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Project Title
Corticosteroids & Associated Diseases
A research presented by
Student name:
Student No:
Mohammad khrais
9750079
Project supervisor Dr.Rafiq R. A. Abou-Shaaban
Jan.2001
Ajman University for Science and Technology
Abu Dhabi Branch
UAE
Research for this project was carried out by me during the period of Hospital
Pharmacy Training-1 no.700315(academic year 2000-2001)
Signed
Date Jan 10th 2000
ACKNOWLEDGMENTS
Sincere gratitude were extended to Dr. Rafeeq Abu Shaaban from the
pharmaceutical department, to the support, encouragement and fruitful
accompaniment through out the training and presentation of this
project.
The author is indebted to project supervisor Dr Asim Ahmed, for the
continuous follow up , constructive criticism , and valuable comments.
The author wishes to express special gratitude and thanks to those
contributing in this revolutionary, distinctive and advanced Hospital
Pharmacy training 1; namely Dr.Danna Sallam and the staff of the New
Medical Center Hospital.
Finally the author wishes to express heartfelt thanks to Dr. Abduelmula inCharge of the Central training committee for furnishing the entire Clinical
Pharmacy Services as far as this term is concerned.
INDEX
Description
Section l
1.0 Introduction to corticosteroids
1.1 Unlabeled uses of corticosteroids
1.2 Pharmacokinetics of corticosteroids
1.3 Classification of corticosteroids
1.4 Availability of corticosteroids
Section II
2.0 Adverse effects of corticosteroids
2.1 Treatment of adverse effects
2.2 Withdrawal of corticosteroids
Section III
3.0Uses and administration of corticosteroids
3.1 Routes of administration of corticosteroids
3.2 Disorders in which corticosteroids are administered
Section IV
4.0 Precautions for corticosteroids
4.1 Drug interactions
Section V
5.0 Absorption and fate of corticosteriods
Section VI
6.0 Antagonists of adrenocortical agents
6.1 Synthesis inhibitors & glucocorticoid antagonists
6.2 Mineralocorticoid antagonists
Section VII
7.0 Topical corticosteroids
7.1 Properties of topical steroid
7.2 Guidance for the use of topical corticosteroids
Section VIII
8.0 Corticosteroids for ophthalmic uses
8.1 Classes of corticosteroids used in eye disorders
Section IX
9.0 Drugs names and properties
Section X
The indications, contra-indications, warnings, precautions…etc, of each
class of the corticosteroids
10.0 Glucocorticoids
10.1 Mineralocorticoids
References
Basic and clinical pharmacology (Bertram G. Katzung)
Martindale the extra pharmacopoeia (30th addition)
Clinical drug data
Clinesphere
Section I: Introduction
1.0 Introduction toCorticosteroids
Corticosteroids are used for the replacement therapy in adrenal insufficiency and are also
given for their palliative anti-inflammatory and immunosuppressant effects in a wide
variety of disorders. High doses may be needed for emergencies but in general the lowest
effective dose should be given for the shortest possible time; local administration is
preferable. Withdrawal of systemic treatment should be gradual since abrupt cessation of
corticosteroids may precipitate acute adrenal insufficiency. To prevent adrenal
insufficiency resulting from increased corticosteroids requirements during periods of
stress or trauma, it may be necessary to increase the dose. Adverse effects of
corticosteroids mainly result from an excessive action on electrolyte balance, metabolism
and tissue repair, and an inhibitory effect on secretion of corticotrophin (leading to
adrenal insufficiency). Susceptibility to all kinds of infection may be increased and there
may be growth retardation in children.
The adrenal cortex produces a number of steroids, which may be divided into 3 classes;
glucocorticoids, mineralocorticoid, and sex corticoids that include mainly androgens. The
glucocorticoids (cortisone and hydrocortisone or cortisol) principal pharmacological
actions are upon gluconeogenesis, glycogen deposition, and protein, lipid, and calcium
metabolism, together with inhibition of corticotrophin secretion, anti-inflammatory
activity, and effects on tissue repair, the heart, kidneys, and CNS. The principal actions of
the mineralcorticoids (deoxycortone and aldosterone) are upon electrolyte and water
metabolism.
Glucocorticoids and mineralcorticoids are collectively known as corticosteroids and apart
from aldosterone, the endogenous corticosteroids (cortisone, deoxycortone, and
hydrocortisone) are secreted under the influence of the interior pituitary hormone,
corticotrophin. All 4 naturally occurring corticosteroids have mineralocorticoid actions to
a varying degree and they all, with possible exception of deoxycortone, have some
glucocrticoid actions.
In addition to the naturally occurring corticosteroids, many synthetic steroids with similar
properties have been introduced. In developing these synthetic analogues the aim has
usually been firstly to produce enhanced potency generally and secondly to separate the 2
main pharmacological actions so that, for example, an increase in glucocorticoid actions
is not accompanied by a parallel increase in the mineralocorticoid effects.
It appears that a measure of corticosteroids potency as a glucocorticoid is the degree of
inhibition of corticotrophin secretion it produces.
The chemical structures of the corticosteroids are very similar to each other.
The main corticosteroids used systemically are hydroxy compounds (alcohol). They are
relatively insoluble in water and the sodium salt of the phosphate or succinate ester is
generally used to provide water-soluble forms for the injections or solutions. Such esters
are readily hydrolyzed in the body.
Esterification of corticosteroids at the 17 or 21 positions with fatty acids generally
increases the activity on the skin. The formation of cyclic acetonides at the 16 and 17
positions further increases topical anti-inflammatory activity, usually without increasing
systemic glucocorticoid activity, and fluorinated corticosteroids also generally have
increased topical activity.
Some corticosteroids esterified at the 17 position are much more potent topically than
systemically, e.g. beclomethasone dipropionate and betamethasone valerate; they are
used by inhalation where their potent anti-inflammatory effect on the lungs has little
systemic effect.
In the medical and pharmacological the name of unesterified corticosteroids have
frequently been used for both the unesterified and esterified forms and it is not always
apparent to which form is being made. The unesterified form is sometimes qualified by
the phrase ‘free alcohol’.
1.1 Unlabeled uses of corticosteroids :
Use
Drug/Comment
Acute mountain sickness
Dexamethasone 4 mg q 6 h; prevention or treatment
Antiemetic
Bacterial meningitis
Dexamethasone most common, 16 to 20 mg
Dexamethasone 0.15 mg/kg q 6 h; to decrease incidence of
hearing loss
Dexamethasone 0.5 mg/kg, then taper.
Bronchopulmonary dysplasia in
preterm infants
COPD
Depression
Duchenne's muscular dystrophy
Prednisone 30 to 60 mg/day for 1 to 2 weeks, then taper
Diagnosis of Dexamethasone 1 mg
Prednisone 0.75 to 1.5 mg/kg/day; to improve strength and
function
Graves ophthalmopathy
Hepatitis, severe alcoholic
Prednisone 60 mg/day, taper to 20 mg/day
Methylprednisolone 32 mg/day; to reduce mortality
Hirsutism
Respiratory distress syndrome
Dexamethasone 0.5 to 1 mg/day
Prevention in premature neonates (beta methasone most
common); adults, methylprednisolone 30 mg/ kg (controversial)
Septic shock
Methylprednisolone 30 mg/kg IV most common (very
controversial)
Acute Methylprednisolone IV within 8 hrs of injury; to improve
neurologic function
Prednisolone 0.75 mg/kg/day, then taper; concurrently with
antituberculous therapy
Spinal cord injury
Tuberculosis pleurisy
1.2 Pharmacokinetics of corticosteroids:
The major glucocorticoid in humans is cortisol. It is synthesized from cholesterol by the
cells of the zona fasciculata and zona reticularis and released into the circulation under
the influence of ACTH.
In the normal adult in the absence of stress, 10-20mg of cortisol is secreted daily. The
rate of secretion changes in a circadian rhythm governed by irregular pulses of ACTH
that peak in the early morning hours and after meals and that are also influenced by light.
In plasma, cortisol is bound to plasma protiens. Corticosteroids-binding globulin (CBG),
an α2-globulin synthesized by the liver, binds 75% of the circulating hormone under
normal circumstances. The remainder is free (about 20%) or loosely bound to albumin
(about 5%) and is available to exert its effect on target cells. When plasma cortisol levels
exceed 20-30 μg/dL, CBG is saturated, and the concentration of free cortisol rises
rapidly. CBGis increased in pregnancy and with estrogen adminstration, which increases
its synthesis by the liver, and in hyperthyroidism. It is decreased by hypothyroidism,
genetic defects in synthesis, and protien deficiencystates. Albumin has a large capacity
but low affinityfor corisol. Synthetic corticosteroids such as dexamethasone are largely
bound to albumin.
The half-life of cortisol in the circulation is normally about 60-90 minutes; half-life may
be increased when hydrocortisone (the pharmaceutical preparations of cortisol) is
administered in large amounts or when stress, hypothyroidism, or liver disease is present.
Only 1% of cortisol is converted to cortisone by 11-hydroxysteroid dehydrogenase in the
kidney and other tissues with mineralocorticoid receptors before reaching the liver. Most
of the cortisone and the remaining cortisone and the remaining cortisol is inactivated in
the liver by reduction of the 4,5 double bond in the A ring and subsequent conversion to
tetrahydrocortisol and tetrahydrcortisone by 3-hydroxysteroid dehydrogenase.
1.3 Classification of corticosteroids:
Very potent
potent
Moderatly potent
Mild
clobetasol propionate 0.05% amcinonide 0.1%
alcometasone dipropionate 0.05% fluocinolone acetonide 0.0025%
diflcortolone valerate 0.3% beclomethasone dipropionate
betamthasone valerate 0.025%
Hydrocortisone 0.5 and 1%
flucinolone acetonide 0.2% betamethasone benzoate 0.025% clobetasone butyrate 0.05%
Hydrocortisone acetate 1%
halcinonide 0.1%
methylprednisolone acetate0.25%
betamethasone valerate 0.1%
desoxymethasone 0.05%
budesonide 0.025%
flumethasone pivalate 0.02%
desonide 0.05%
flucinolone acetonide 0.01%
desoxymethasone 0.25%
and 0.00625%
doflorasone diacetate 0.05%
fluocortin butyl 0.75%
difucortolone valerate 0.1%
fluocortolone preparations
fluclorolone acetonide 0.025%
fluocinolone acetonide 0.025%
fluocinoide 0.05%
fluprednidene acetate 0.1%
Hydrocortisone butyrate 0.1%
mometasone furoate 0.1%
trimcinolone acetonide 0.1%
1.4 Availability of corticosteroids.
Glucocorticoid
Approximate
equivalent
dose (mg)
Relative antiinflammatory
(glucocorticoid)
potency
Relative
mineralocorticoid
potency
Halflife
Plasma
(min)
Half-life
biological
(hrs)
Type of the
glucocorticoid
Cortisone
Hydrocortisone
Prednisone
25
20
5
0.8
1
4
2
2
1
30
118-80
60
12-8
12-8
36-18
Short acting
Short acting
Intermediate
acting
Intermediate
acting
Prednisolone
5
4
1
212-115
36-18
Triamcinolone
4
5
0
+200
36-18
Methylprednisolone
4
5
0
188-78
36-18
Dexamethasone
0.75
30-20
0
210-110
54-36
Intermediate
acting
Intermediate
acting
Long acting
Betamethasone
0.75-0.6
30-20
0
+300
54-36
Long acting
Section II: Adverse reactions
2.0Adverse effects of corticosteroids
The side-effects associated with the use of corticosteroids in the large doses often
necessary to produce a therapeutic response result from excessive action on electrolyte
balance, excessive action on other aspects of metabolism including gluconeogenesis, the
action on tissue repair and healing, and an inhibitory effect on the secretion of
corticotrophin by the anterior lobe of the pituitary gland.
Disturbance of the electrolyte balance is manifest in the retention of sodium and water,
with edema and hypertension, and in the increased excretion of potassium with the
possibility of hypokalaemic alkalosis. In susceptible patients, cardiac failure may be
induced. Disturbances of electrolyte balance are common with the naturally occurring
corticosteroids, such as cortisone, deoxycortone, and hydrocortisone, but are less frequent
with many synthetic derivatives, such as betamethasone, dexamethasone,
methylprednisolone, prednisolone, prednisone, and triamcinolone, which have little or no
mineralocorticoid activity.
Other excessive metabolic effects lead to mobilization of calcium and phosphorus, with
osteoporosis and spontaneous fractures, nitrogen depletion, and hyperglycemia with
accentuation or precipitation of the diabetic state. The insulin requirements of diabetic
patients are increased. Increased appetite is often reported.
The effect on tissue repair is manifest in delayed wound healing, and increased liability to
infection; infections may also be masked since corticosteroids have marked antiinflammatory properties with analgesic and antipyretic effects. Increased susceptibility to
all kinds of infection, including sepsis, tuberculosis, fungal infections, and viral
infections, has been reported in patients on corticosteroids therapy; for example, Candida
infections of the mouth in patients treated with corticosteroids, especially if these are
given concomitantly with antibiotics, are not uncommon.
The dose of corticosteroid required to diminish corticotrophin secretion with consequent
atrophy of the adrenal cortex and the time required for its occurrence vary from patient to
patient. Acute adrenal insufficiency may occur during prolonged treatment or on
cessation of treatment and may be precipitated by stressful situations, for example,
infection or trauma. Growth retardation in children has been reported. High doses of
corticosteroids administered during pregnancy may cause foetal or neonatal adrenal
suppression.
Large doses of corticosteroids, or of corticotrophin, may produce Cushingoid symptoms
typical of hyperactivity of the adrenal cortex, with moon-face, sometimes with
hairsutism, buffalo hump, flushing, increased bruising, ecchymoses, atriae, and acne,
sometimes leading to a fully developed Cushing’s syndrome. If administration is
discontinued these symptoms are usually reversed, but sudden cessation is dangerous.
Rapid intravenous administration of large doses of corticosteroids may cause
cardiovascular collapse.
Other adverse effect include amenorrhoea, hyperhidrosis, skin thinning, mental and
neurological disturbances, intracranial hypertension, acute pancreatitis, and aseptic
necrosis of bone. An increase in the coagulability of the blood may lead to thromboembolic complications. Peptic ulceration has been reviews do not always agree that
corticosteroids are responsible for an increased incidence. Muscle weakness and wasting
occur occasionally, particularly when corticosteroids are taken in large doses. The former
arises from the mineralcorticoid properties of corticosteroids, the latter from their
glucocorticoid properties and is most evident with triamcinolone.
Adverse effects of corticosteroids appear equally with all types of preparations, and vary
with the different strength of each preparation. Short courses at high doses for
emergencies appear to cause less side effects than prolonged courses with lower doses.
Most topically applied corticosteroids may, under certain circumstances, be absorbed in
sufficient amounts to produce systemic effects. The topical application of corticosteroid
preparations to the eyes has produced corneal ulcers, raised intra-ocular pressure, and
reduces visual function, and systemic administration has caused posterior subcapsular
cataract. Application of corticosteroids to the skin has led to loss of skin collagen and
subcutaneous atrophy; local hypopigmentation of deeply pigmented skins has been
reported following both the intradermal injection and topical application of potent
corticosteroids.
1. Adrenal suppression
2. Effects on bones and joints
3. Effects on carbohydrates metabolism
4. Effects on cardiovascular system
5. Effects on the cerebrovascular system
6. Effects on the eyes
7. Effects on the gastro-intestinal tract
8. Effects on the growth
9. Effects on lipid metabolism
10. Effects on the mental state
11. Effects on the nervous system
12. Effects on the pancreas
13. Effects on the skin
14. Effects on the voice
15. Hypersensitivity and anaphylaxis
16. Pregnancy and neonate
17. Tumor lysis syndrome
2.1 Treatment of adverse effects of corticosteroids
The adverse effects of corticosteroids are nearly always due to their use in excess of
normal physiological requirements. They should be treated symptomatically, where
possible the dosage being reduced or the drug slowly withdrawn.
The treatment of acute adrenal insufficiency in corticosteroid-treated patients, whether it
be due to accidental abrupt withdrawal of the corticosteroid or the inability of the
patient’s adrenals to cope with the increases stress of infection or accidental or surgical
trauma.
2.2 Withdrawal of corticosteroids
The use pharmacological doses of corticosteriods to treat disease suppresses the
endogenous secretion of corticotrophin by the anterior pituitary, with the result that the
adrenal cortex becomes atrophied. Sudden withdrawal or reduction in dosage, or an
increase in corticosteroids requirements associated with the stress of infection or
accidental or surgical trauma, may then precipitate acute adrenal insufficiency.
Symptoms of adrenal insufficiency include malaise, muscle weakness, mental changes,
muscle and joint pain, desquamation of the skin, dyspnoea, anaroxia, nausea, vomiting,
fever, hypoglycaemia, hypotension, and dehydration; deaths have followed the abrupt
withdrawal of corticosteroids.
Other effects that may occur during withdrawal or change of corticosteroids therapy
include benign intracranial hypertension with headache and vomiting and papilloedema
caused by cerebral edema. Latent rhinitis or eczema may be unmasked.
Duration of treatment and dosage appear to be important factors in determining
suppression of the pituitary-adrenal response to stress on cessation of corticosteroid
treatment, and individual liability to suppression is also important.
Corticosteroids withdrawal should therefore always be gradual, the rate depending upon
individual patient’s response, the dose, the disease being treated, and the duration of
therapy. Recommendations for initial reduction vary according to different steps.
Adrenal function should be monitored throughout the withdrawal period. The gradual
withdrawal of corticsteroids therapy permits a return of adrenal function adequate for
daily needs, but a further one to two years may be required for the return of function
necessary to meet the stress of infection, surgical operations, or trauma. On such
occasions patients with a history of recent corticosteroid withdrawal should be protected
by means of supplementary corticosteroid therapy.
Section III: Uses of corticosteroids
3.0Uses and adminstration of corticosteroids
The corticosteroids are used in physiological doses for replacment therapy in adrenal
insufficiency. Pharmacological doses are used when palliative anti-inflammatory or
immunosuppressant effects are required. Before instituting therapy the benefits and risks
of corticosteroids should be considered; where appropriate, local rather than systemic
therapy should be used for the shortest possible duration of time; high doses may be
neede for life-threatening situations.
In primary adrenal insufficiency, such as Addison's disease or after adrenalectomy, both
mineralocorticoid and glucocorticoid replacementis needed; hydrocortisone is generally
given by mouth together with fludrocortisone.In secondary adrenal insufficiency,
associated with inadequate coticotrophin secretion, glucocorticoid replacement alone is
adequate. The emergancy treatment of adrenal insufficiency usually involves the
intravenous adminstration of hydrocortisone sodium succinate or another suitable
synthetic corticosteroids, together with infusions of sodium chloride and glucose to
correct electrolyte disturbances. The anti-inflammatory and immunosuppressant
glucocorticoid properties of corticosteroids are used to suppress manifestations of disease
in a wide range of disorders. For these purposes, the synthetic analogues with enhanced
glucorticoid properties linked with enhanced glucocorticoid properties, are preferred to
cortisone and hydrocortisone. Despite the existance of very powerful synthetic
glucocorticoids with virtually no mineralcorticoid activity, the hazards of inappropriately
high glucocorticoid therapy are such that the less powerful prednisolone and prednisone
are the glucorticoids of choice for most conditions, since they allow for a greater margin
of safety. There is a little to choose between prednisolone and prednisone; prednisolone
may be preferred since, like hydrocortisone, it exists in a metabolically active form,
whereas prednisone, like cortisone, is inactive and must be converted into its active form
by the liver; hence, particularly in some liver disorders, prednisone's bioavailability is
less reliable.
Doses of corticosteroids higher than those required for physiological replacement will
eventually lead to some degree of adrenal suppression, the extent depending on the dose
given, and the route, frequency, time, and duration of administration. The adrenal glands
have a daily output equivalent to approximatly 20mg of hydrocortisone (cortisol), but
individual blood-cortisol concentrations may vary widely, and can increase up to ten-fold
or more during stress. Therefore, during periods of stress, such as during and when
suffering from intercurrent infections, the corticosteroid dosage of patients must be
increased. Intramuscular or intravenous injection of hydrocortisone 100mg (usually as the
sodium succinate) with the premedication and repeated every 8 hours has been used in
patients on long-term corticosteroid therapy undergoing minor surgical procedures. This
dose is generally tapered off 5 days to reach a typical maintenancedose of 20 to 30mg
daily. Some studies, however, have suggested that such routine supplementation may not
always be necessary and that in some patients only postoperative supplements need to be
given when clinical symptoms of insufficiency arise.
3.1Routes of administration of corticosteroids:
1.
2.
3.
4.
5.
6.
7.
8.
9.
Oral therapy
Parentral therapy
Intr-articular injection
Topical application
intralesional injection
Opthalmic preparations
Ear drops
Inhalational therapy
Rectal adminstration
3.2 Disorders in which corticosteroids are administered:
Administration in kidney failure
Administration in liver failure
Adrenal insufficiency
AIDS
Anaphilactic shock
Aspiration syndromes
Behcet's syndrome
Bites and stings
Blood disorders
Bone disorders
Cerebral oedema
Cogan's syndrome
Congenital adrenal hyperplasia
Connective tissue disorders
Epilepsy
Eye disorders
Gastro-intestinal disorders
Hypercalcaemia
Infections:
 Eye infections
 Leishmaniasis
 Leprosy
 Meningitis
 Pneumocystis Carini Pneumonia
 Septic shock
 Tuberculosis
 Viral encephalitis
Kawasaki disease
Organ and tissue transplantation
Kidney disorders
Pain
Pancreatitis
Pregnancy and neonate
Respiratory disorders
Rheumatoid disease and osteoarthritis
Rhinitis
Sarcoidosis
Skin disorders
Spinal cord injury
Thyroid disorders
Vascular disorders
Some therapeutic indications for the use of glucocorticoids in nonadrenal disorders
Disorder
Examples
Angioneurotic edema, asthma, bee sting, contact dermatitis, drug reactions, allergic rhinitis,
urticaria, serum sickness
Giant cell arteritis, lupus erythematosus, mixed connective tissue syndrome,
Collagen-vascular disorder polymyalgia rheumatica, rheumatoid arthritis
Eye disease
Acute uveitis, allergic conjunctivitis, choroiditis, optic neuritis
Gastrointestinal disease
Inflammatory bowel disease, nontropical sprue, subacutal hepatic necrosis
Acquired and autoimmune hemolytic anemia, allergic purpura, leukaemia, idiopathic
Hematologic disorder
thrombocytopenic purpura, multiple myeloma
Infections
Gram-negative septicemia; occasionally helpful to suppress excessive inflammation
Inflammatory conditions of
bones and joints
Arthritis, bursitis, tenosynovitis
Cerebral edema (large doses of dexamethasone are given after brain surgery),
Neurologic disorder
multiple sclerosis
Organ transplants
Prevention and treatment of rejection (immunosuppression)
Pulmonary diseases
Aspiration pneumonia, asthma, prevention of infant respiratory distress syndrome, sarcoidosis
Renal disorder
Nephrotic syndrome
Atopic dermatitis, dermatoses, lichen simplex chrnicus, mycosis fungoides, pemphigus,
Skin diseases
seborrheic dermatitis, xerosis
Thyroid diseases
Malignant exophthalmos, sub acute thyroiditis
Allergic reactions
Miscellaneous
Hypocalcaemia, mountain sickness
Section IV: Precautions and interactions
4.0 Precautions for corticosteroids
Unless considered life-saving, systemic administration of corticosteroids is contraindicated in patients with peptic ulcer, osteoporosis, psychoses, or severe
psychoneuroses, and they should be used only with great caution in the presence of
congestive heart failure or hypertension, in patients with diabetes mellitus, epilepsy,
glaucoma, infectious diseases, ocular herpes simplex, chronic renal failure and ureamia,
and in elderly persons. Patients with active or doubtfully quiescent tuberculosis should
not be given corticosteroids except, very rarely, as adjuncts to treatment with
antitubercular drugs, patients with quiescent tuberculosis should be observed closely and
should receive chemoprophylaxis if corticosteroid therapy is prolonged.
Corticosteroids are usually contra-indicated in the presence of acute infections, because
of interference with inflammatory and immunological response. Similarly, patients
already receiving corticosteroid are more susceptible to infection, the symptoms of
which, moreover, may be masked until an advanced stage has been reached. Because of
the risk of precipitating a serious infection, live vaccines should not be given to patients
receiving high-dose systemic corticosteroid therapy; killed vaccines or toxoids may be
given although the response may be attenuated. Children are at special risk of infection
and may require prophylaxis with immunoglobulin.
During long courses of corticosteroid therapy, patients should be examined regularly and
checked for hypertension, glycosuria, hypokalaemia, gastric discomfort, and mental
changes. Sodium intake may need to be reduced and potassium supplements may be
necessary. Monitoring of the fluid intake and output, and daily weight records may give
early warning of fluid retention. Back pain may signify osteoporosis. Children are at
special risk from raised intracranial pressure. Infections should be treated as an
emergency. Patients should carry cards (and preferably also wear bracelets) giving full
details of their corticosteroid therapy; they and their relatives should be fully conversant
with the implications of their therapy and the precautions to be taken.
Measures to compensate for the adrenals’ inability to respond to stress include increasing
the dose to cover minor intercurrent illnesses or trauma such as surgery (with
intramuscular administration to cover vomiting).
Rapid intravenous injection of massive doses of corticosteroids may sometimes cause
cardiovascular collapse and injections should therefore be given slowly or by infusions.
High doses should not be used for prolonged treatment.
Concurrent administration of barbiturates, carbamazepine, phenytoin, or rifampicin may
enhance the metabolism and reduce the effects of corticosteroids. Concurrent
administration of corticosteroids with potassium-depleting diuretics, such as thiazides or
frusemide, may cause excessive potassium loss. There may be an increased incidence of
gastro-intestinal bleeding and ulceration when corticosteroids are given with nonsteroidal anti-inflammatory agents. Response to anticoagulants may be altered by
corticosteroids and requirements of antidiabetics and antihypertensives may be increased.
Corticosteroids may decrease serum concentrations of salicylates and may decrease the
effect of antimuscarinics in myasthenia gravis.
Many drugs have been reported to interfere with certain assay procedures for
corticosteroids themselves may interfere with or alter the results of assays for some
endogenous substances or drugs.
Topical applications of corticosteroids should not be made with an occlusive dressing to
large areas of the body because of the increased risk of systemic toxicity and should not,
in general, be used in the presence of infection. They should not be used for the treatment
of rosacea and should not be used indiscriminately for pruritus. Occasionally they may be
used with the addition of a suitable antimicrobial substance in the treatment of infected
skin but there is a risk of sensitivity reactions occurring. Corticosteroids should not be
applied to ulcers of the leg and long-term topical use is best avoided, especially in
children.
Caution is required when corticosteroids are used locally in the treat eye disorders.
4.1 Drug Interactions:
Corticosteroid Drug Interactions
Precipitant drug
Object drug
Aminoglutethimide
Dexamethasone
Barbiturates
Cholestyramine
Oral Contraceptives
Ephedrine
Estrogens
Hydantoins
Ketoconazole
Macrolide antibiotics
Rifampin
Anticholinesterases
Oral anticoagulants
Cyclosporine
Description
Possible loss of dexamethasone-induced
adrenal suppression.
Corticosteroids
Decreased pharmacological effects of the
corticosteroid may be observed.
Hydrocortisone
The hydrocortisone AUC may be
decreased.
Corticosteroids
Corticosteroid half-life and concentration
may be increased and clearance
decreased.
Dexamethasone
A decreased half-life and increased
clearance of dexamethasone may occur.
Corticosteroids
Corticosteroid clearance may be
decreased.
Corticosteroids
Corticosteroid clearance may be
increased, resulting in reduced therapeutic
effects.
Corticosteroids
Corticosteroid clearance may be
decreased and the AUC increased.
Methylprednisolone Significant decrease in
methylprednisolone clearance has been
used to decrease methylprednisolone
dose.
Corticosteroids
Corticosteroid clearance may be increased
resulting in decreased therapeutic effects.
Corticosteroids
Anticholinesterase effects may be
antagonized in myasthenia gravis.
Corticosteroids
Anticoagulant dose requirements may be
reduced. Conversely, corticosteroids may
oppose the anticoagulant action.
Corticosteroids
Although this combination is
therapeutically beneficial for organ
transplants, toxicity may be enhanced.
Digitalis glycosides
Corticosteroids
Isoniazid
Corticosteroids
Nondepolarizing
muscle relaxants
Corticosteroids
Potassium-depleting
agents (e.g. diuretics)
Salicylates
Corticosteroids
Somatrem
Corticosteroids
Theophyllines
Corticosteroids
Corticosteroids
Coadministration may enhance the
possibility of digitalis toxicity associated
with hypokalemia.
Isoniazid serum concentrations may be
decreased.
Corticosteroids may potentiate,
counteract or have no effect on the
neuromuscular blocking action.
Observe patients for hypokalemia.
Corticosteroids will reduce serum
salicylate levels and may decrease their
effectiveness.
Growth-promoting effect of somatrem
may be inhibited.
Alterations in the pharmacological
activity of either agent may occur.
Section V: Absorption and fate
Absorption and fate of corticosteroids
Corticosteroids are in general, readily absorbed from the gastro-intestinal tract. They are
also well absorbed from sites of local application. When administered by topical
application, particularly under an occlusive dressing or when the skin is broken, or as a
pulmonary aerosol inhalation or a rectal enema, sufficient corticosteroid may be absorbed
to give systemic effects. Water-soluble forms of corticosteroids are given by intravenous
injection for a rapid response; more prolonged effects are achieved using lipid-soluble
forms of corticosteroids by intramuscular injection.
Corticosteroids are rapidly distributed to all body tissues. They cross the placenta and
may be excreted in small amounts in breast milk.
Most corticosteroids in the circulations are extensively bound to plasma proteins, mainly
to globulin and less so to albumin. The corticosteroid-binding globulin has high affinity
but low binding capacity, while the albumin has low affinity but large binding capacity.
The synthetic corticosteroids are less extensively protein bound than hydrocortisone
(cortisol). They also tend to have longer half-lives.
Corticosteroids are metabolized mainly in the liver but also in the kidney, and are
excreted in the urine. The slower metabolism of the synthetic corticosteroids with their
lower protein-binding affinity may account for their increased potency compared with the
natural corticosteroids.
Section VI: corticosteroids antagonist
6.0 Antagonists of adrenocortical agents
6.1 Synthesis inhibitors & glucocorticoid antagonists
1. Metyrapone
Metyrapone is a relatively selective inhibitor of steroid synthesis.
Mechanism of action:
It inhibits 11-hydroxylation, interfering with cortisol and corticosterone synthesis and
leading to secretion of 11-deoxycortisol. In the presence of a normal pituitary gland, there
is a compensatory increase in 11-deoxycortisol production. This response is adapted for
clinical use as a diagnostic test for the pituitary gland.
Adverse reactions:
The drug doses produce transient dizziness and gastrointestinal disturbances. The major
adverse effects observed are salt and water retention and hairsutism.
Indications:
This agent has not been widely used in Cushing’s syndrome. However, in doses of 0.25 g
twice daily to 1 g four times daily, metyrapone can reduce cortisol production to normal
levels in some patients with adrenal tumor, ectopic ACTH syndromes, and hyperplasia. It
may be useful in the management of severe manifestations of cortisol excess while the
cause is being determined or in conjunction with radiation or surgical treatment.
Metyrapone most commonly used in tests of adrenal function.
Biopharmaceutics of metyrapone:
The blood levels of 11-deoxycortisol and the urinary excretion of 17-hydroxycorticoids
are measured before and after administration of the compound. Normally, there is a
twofold or greater increase in the urinary 17-hydroxycorticoid excretion.
2. Aminoglutethimide
Aminoglutethimide blocks the conversion of cholesterol to pregnenolone and causes a
reduction in the synthesis of all hormonally active steroids. It has been used in the
conjunction with dexamethasone or hydrocortisone to reduce or eliminate estrogen and
androgen production in patients with carcinoma of the breast. In a dosage of 1 g/d it was
well tolerated; however, with higher dosage, lethargy was a common effect. This drug
can be used in conjunction with ketoconazole to reduce steroid secretion in patients with
Cushing’s syndrome due to adrenocortical cancer that does not respond to mitotane.
Aminoglutethimide also apparently increases the clearance of some steroids. It has been
shown to enhance the metabolism of dexamethasone, reducing its half-life from 264
minutes to 120 minutes.
Indications:
 Cushing's syndrome: For the suppression of adrenal function in selected patients
with Cushing's syndrome.
 Unlabeled uses: Aminoglutethimide has been used successfully in
postmenopausal patients with advanced breast carcinoma and in patients with
metastatic prostate carcinoma.

Aminoglutethimide was previously marketed as an anticonvulsant, but was
withdrawn for that use in 1966.
Drugs proprietary name
Cytadren (Ciba)
250 mg tablets (Ciba 24). White, scored tablets in 100 tabs box.
Administration and Dosage:
 Institute treatment in a hospital until a stable dosage regimen is achieved.
 Give 250 mg 4 times daily, preferably at 6 hour intervals. Follow adrenal cortical
response by careful monitoring of plasma cortisol until the desired level of
suppression is achieved. If cortisol suppression is inadequate, dosage may be
increased in increments of 250 mg daily at intervals of 1 to 2 weeks to a total
daily dose of 2 g.
 Dose reduction or temporary discontinuation may be required in the event of
adverse responses (ie, extreme drowsiness, severe skin rash or excessively low
cortisol levels). If skin rash persists for > 5 to 8 days or becomes severe,
discontinue the drug. It may be possible to reinstate therapy at a lower dosage
following the disappearance of a mild or moderate rash.
 Mineralocorticoid replacement therapy (ie, fludrocortisone) may be necessary. If
glucocorticoid replacement therapy is needed, 20 to 30 mg hydrocortisone orally
in the morning will replace endogenous secretion.
Actions:
 Pharmacology: Aminoglutethimide inhibits the enzymatic conversion of
cholesterol to d5–pregnenolone, thereby reducing the synthesis of adrenal
glucocorticoids, mineralocorticoids, estrogens and androgens. Aminoglutethimide
blocks several other steps in steroid synthesis, including the hydroxylations
required for the aromatization of androgens to estrogens. A decrease in adrenal
secretion of cortisol is followed by an increased secretion of pituitary
adrenocorticotropic hormone (ACTH), which will overcome the blockade of
adrenocortical steroid synthesis by aminoglutethimide.
 Pharmacokinetics: Aminoglutethimide is effectively absorbed orally and is
minimally bound to plasma protein. Its half-life is 11 to 16 hours initially, but
decreases after 1 to 2 weeks to 5 to 9 hours. Approximately 34% to 54% is
excreted unchanged in the urine and 20% to 50% is excreted as the acetylated
metabolite (less than one-fifth as active as the parent compound). The acetylation
mechanism is genetically controlled .
 Clinical trials: Morning levels of plasma cortisol in patients with adrenal
carcinoma and ectopic ACTH-producing tumors were reduced on the average to
about one half of the pretreatment levels, and in patients with adrenal hyperplasia
to about two thirds of the pretreatment levels, during 1 to 3 months of therapy
with aminoglutethimide. Data available from the few patients with adrenal
adenoma suggest similar reductions in plasma cortisol levels. Measurements of
plasma cortisol showed reductions to >= 50% of baseline or to normal levels in
one third or more of the patients studied, depending on the diagnostic groups and
time of measurement.
Contraindications:
 Hypersensitivity to glutethimide or aminoglutethimide.
Warnings:
 Duration of therapy: Because aminoglutethimide does not affect the underlying
disease process, it has been used primarily until more definitive therapy (ie,
surgery) can be undertaken, or in cases where such therapy is not appropriate.
Only a small number of patients have been treated for less than 3 months. A
decreased effect or escape from a favorable effect occurs more frequently in
pituitary-dependent Cushing's syndrome, probably because of increasing ACTH
levels in response to decreasing glucocorticoid levels.
 Cortical hypofunction: May cause adrenal cortical hypofunction, especially
under conditions of stress such as surgery, trauma or acute illness. Monitor
patients carefully and give hydrocortisone and mineralocorticoid supplements as
indicated. Do not use dexamethasone.
 Hypotension: Aminoglutethimide may suppress aldosterone production by the
adrenal cortex and may cause orthostatic or persistent hypotension. Monitor blood
pressure in all patients at appropriate intervals.
 Pregnancy: Category D. Aminoglutethimide can cause fetal harm when
administered to pregnant women. In about 5000 patients, two cases of
pseudohermaphroditism were reported in female infants whose mothers took
aminoglutethimide and concomitant anticonvulsants. Normal pregnancies have
also occurred during the administration of the drug. When administered to rats at
doses 1/2 to 3 times the maximum human dose, aminoglutethimide caused a
decrease in fetal implantation, and increased fetal deaths, teratogenic effects and
pseudohermaphroditism. If this drug must be used during pregnancy, or if the
patient becomes pregnant while taking the drug, apprise her of the potential
hazard to the fetus.
 Lactation: It is not known whether this drug is excreted in breast milk. Decide
whether to discontinue nursing or to discontinue the drug, taking into account the
importance of the drug to the mother.
 Children: Safety and efficacy have not been established.
Precautions:
 Monitoring:
 Hypothyroidism may occur. Make appropriate clinical observations and perform
thyroid function studies as indicated. Supplementary thyroid hormone may be
required.
 Hematologic abnormalities have been reported. Elevations in AST, alkaline
phosphatase and bilirubin have been reported. Perform appropriate clinical
observations and regular laboratory studies before and during therapy. Determine
serum electrolytes periodically.
Drug Interactions:
Aminoglutethimide Drug Interactions:
Precipitant drug
Aminoglutethimide
Aminoglutethimide
Aminoglutethimide
Aminoglutethimide
Object drug
Anticoagulants
Dexamethasone
Digitoxin
Medroxyprogesterone
Description
Anticoagulant effects may be decreased.
Possible loss of dexamethasone-induced adrenal suppression.
Digitoxin clearance may be increased.
Medroxyprogesterone serum levels may be decreased.
Aminoglutethimide
Theophylline
The action of theophyllines may be reduced.
Adverse Reactions:
 Untoward effects have been reported in » 67% of patients treated for >= 4 weeks
in Cushing's syndrome. The most frequent effects are: Drowsiness (33%),
morbilliform skin rash (17%), nausea and anorexia (12.5%). These are reversible
and often disappear spontaneously within 1 or 2 weeks of continued therapy.
 Cardiovascular: Hypotension, occasionally orthostatic (3%); tachycardia (2.5%).
 CNS: Headache and dizziness, possibly caused by decreased vascular resistance
or orthostasis (5%.)
 Dermatologic: Rash (17%, often reversible on continued therapy); pruritus (5%).
These may be allergic or hypersensitivity reactions. Urticaria has occurred rarely.
 Endocrine: Adrenal insufficiency occurred during >= 4 weeks of therapy in 3%
of patients with Cushing's syndrome. Hypothyroidism, occasionally associated
with thyroid enlargement, may be detected early or confirmed by measuring the
plasma levels of the thyroid hormones. Masculinization and hirsutism in females
and precocious sex development in males have occasionally occurred.
 Hematologic: In 4 of 27 patients with adrenal carcinoma who were treated for at
least 4 weeks, there were single occurrences of neutropenia, leukopenia (patient
received mitotane concomitantly) and pancytopenia. One patient with adrenal
hyperplasia showed decreased hemoglobin and hematocrit during treatment. In
1214 non-cushingoid patients, transient leukopenia was reported once. Coombsnegative hemolytic anemia was reported in one patient. In » 300 patients with
nonadrenal malignancy, 4% of cases showed some degree of anemia and two
developed
 pancytopenia. Thrombocytopenia and agranulocytosis have also occurred.
 Hepatic: Isolated abnormal liver function tests; suspected hepatotoxicity (less
than 0.1%), cholestatic jaundice (hypersensitivity mechanism suspected).
 Miscellaneous: Vomiting, myalgia (3%). Fever, possibly related to therapy,
occurred in several patients on aminoglutethimide for < 4 weeks when given with
other drugs.
Over dosage:
 Symptoms: Over dosage has caused ataxia, somnolence, lethargy, dizziness,
fatigue, coma, hyperventilation, respiratory depression, nausea and vomiting, loss
of sodium and water, hyponatremia, hypochloremia, hyperkalemia,
hypoglycemia, hypovolemic shock due to dehydration and hypotension. Extreme
weakness has been reported with divided doses of 3 g/day. No reports of death
following doses estimated as large as 7 g.
 The signs and symptoms of acute over dosage with aminoglutethimide may be
aggravated or modified if alcohol, hypnotics, tranquilizers or tricyclic
antidepressants have been taken at the same time.
 Treatment: Gastric lavage and supportive treatment have been employed. Full
consciousness following deep coma was regained <= 40 hours after ingestion of 3
or 4 g without lavage. No evidence of hematological, renal or hepatic effects were
subsequently found. Consider dialysis in severe intoxication. Treatment includes
usual supportive measures.
Patient Information:
 May produce drowsiness or dizziness; patients should observe caution while
driving or performing other tasks requiring alertness, coordination or physical
dexterity.
 May cause rash, fainting, weakness or headache; notify physician if pronounced.
 Nausea and loss of appetite may occur during the first 2 weeks of therapy; notify
physician if these persist or become pronounced.
3. ketoconazole
Ketoconazole, is a potent and rather nonselective inhibitor of adrenal and gonadal steroid
synthesis. This compound inhibits the cholesterol side chain cleavage, P450c17,
C17,20-lyase, 3ß-hydroxysteroid dehydrogenase, and P450c11 enzymes required for
glucocrticoid synthesis. The sensitivity of the P450 enzymes to this compound in
mammalian tissues is much lower than that of the fungal enzymes, so that the inhibitory
effects are seen only in high doses. This inhibition is compensated for by increased
ACTH production and leads to increases in 17-deoxy steroids such as progesterone and
aldosterone and to suppression of plasma rennin activity. Ketoconazole also has other
endocrine effects. It displaces estradiol and dihydrotestosterone from sex
hormone-binding protein in vitro and increases estradiol-testosterone ratioin plasma in
vivo by different mechanism. The latter may be responsible for the gynecomastia
sometimes seen with ketoconazole therapy.
Ketoconazole has been used for the treatment of patients with Cushing’s disease due to
several causes. Dosages of 200-1200 mg/d have produced a reduction in hormone levels
and impressive clinical improvement in some patients in these preliminary studies.
4. Mifepristone (RU 486)
Mifepristone is a synthetic partial agonist steroid binds to glucocorticoid as well as to
progesterone receptors and has been used experimentally in the treatment of Cushing’s
syndrome.
5. Mitotane
Mitotane produces adrenal atrophy in dogs and interferes with biosynthetic pathways in
the human adrenal cortex. This drug was administered 6-12 mg daily. About one-third of
patients with adrenal carcinoma showed a reduction tumor mass and steroid production
was decreased in tow-thirds. In 80% of patients, the toxic effects were sufficiently severe
to require dose reduction. These included diarrhea, nausea, vomiting, depression,
somnolence, and skin problems. The drug has been withdrawn from the market in the
USA.
6. Amphenone B
Amphenone B is a more inhibitor of synthesis than mitotane, blocking hydroxylation at
the 11, 17, and 21 positions. It does not have a destructive effect on the tissue, and the
block of steroid leads to increased production of ACTH and hyperplasia of the gland.
Amphenone causes central nervous system depression and gastrointestinal tract and skin
disorders and impairs liver and thyroid function. It is considered too toxic for use in
humans.
7. Trilostane
Trilostane is also a 3ß-17-hydroxysteroid-dehydrogenase inhibitor that interferes with the
synthesis of adrenal and gonadal hormones and is comparable to aminoglutethimide. Its
side effects are predominantly gastrointestinal rather than the rashes and drowsiness seen
with aminoglutethimide; side effects occur in about 50% of patients with both agents.
There is no cross-resistance or crossover of side effects between these compounds.
6.2 Mineralocorticoid antagonists
In addition to agents that interfere with aldosterone synthesis, there are steroids that
compete with aldosterone for binding sites and decreases its effect peripherally.
Progesterone is mildly active in this respect.
Spironolactone is a 17α-aceylthiospironolactone. Little is know about its metabolism.
The onset of activity is slow, and the effects last for 2-3 days after the drug is
discontinued. Its used in the treatment of primary aldosteronism in dosages of 50-100
mg/d. This agent reverses many of the findings of aldosteronism. It has been useful in
establishing the diagnosis in some patients and in ameliorating the signs and symptoms
when surgical removal of an adenoma is delayed. When used diagnostically for the
detection of aldosteronism in hypokalemic patients with hypertension, dosage of 400-500
mg/d for
4-8 days with an adequate intake of sodium and potassium will restore potassium levels
to or toward normal. This agent is useful in preparing these patients for surgery. Dosages
of 300-400 mg/d for 2 weeks are used for this purpose and may reduce the incidence of
cardiac arrhythmias.
Spironolactone is also used in the treatment of hirsutism in women. Dosages of 50-200
mg/d cause a reduction in the density, diameter, and rate of growth of facial hair in
patients with idiopathic hirsutism or hirsutism secondary to androgen excess. The effect
con usually be seen in 2 months and becomes maximal in about 6 months. It may b due to
inhibition of androgen production and an action at the hair follicle.
Adverse effects reported for the spironolactone include hyperkalemia, menstrual
abnormalities, gynecomastia, sedation, headache, gastrointestinal disturbances, and skin
rashes.
Drospirenone, a progestin is a new oral contraceptive, also antagonizes the effects of
aldosterone.
Section VII: Corticosteroids for topical use
7.0 Topical corticosteroids
The basic principles are to use ointments rather than creams, and to use the least potent
formulations as sparingly as possible. The first choice is 1% hydrocortisone ointment.
More potent preparations are to be avoided for children and should be restricted to
refractory cases. When other steroids are used, the potency must be checked.
The different potencies of topical steroids cause confusion among doctors and parents.
Most parents think that topical steroids are dangerous and any prescription must be
accompanied by an explanation of the different potencies. Skin atrophy is in fact the main
hazard of topical steroids. It results from regular use of the more potent preparations,
especially on the face, but topical hydrocortisone virtually never causes atrophy. In older
children, it is common to see severe and heavily lichenified patches of eczema confined
to the front of the knees, the wrists and the ankles. Such lesions may not respond well to
low- potency steroids and in these sites it makes no sense to withhold a moderately potent
steroid because of the fear of skin atrophy.
The larger the areas of skin affected, and the more inflamed the skin, the greater the risk
of systemic absorption of a topical steroid. There is therefore a theoretical risk of
iatrogenic Cushing’s syndrome with widespread application of topical steroid. While
eczema is not a fatal condition, the resulting handicap and damage can be severe. To
withhold mild or moderately potent steroids in such patients for fear of adverse effects is
unreasonable. Growth impairment occurs in up to 10% of children with atopic eczema
but there is no evidence that use of low or moderate-potency topical steroid contributes to
this. Nevertheless, long-term use of potent or very potent drugs over large areas of skin
may inhibit growth.
7.1 Properties of topical steroid
Topical corticosteroids have an anti-inflammatory activity on the skin as a result of four
main actions: vasoconstriction, antipruritic, antimitotic, and immunosuppression.
Topical corticosteroids into four potency groups according to their vasoconstrictive
activity: mildly potent, moderately potent, potent very potent. The potency groupings
give some indication of therapeutic efficacy and the likelihood of side effects. The
potency of topical steroids can also be affected by the base used in the formulation
producing changes in skin penetration. Effective treatment with topical steroids depends
on the selection of the correct potency and formulation to meet the needs of the
individual patient.
Skin penetration is required for the anti-inflammatory activity of the topical steroids, but
excessive penetration of potent steroids can lead to local and systemic side effects. Less
potent steroids should be used in areas of thin skin such as the face,and in the children
and the elderly.
Topical steroids are generally well tolerated. Prolonged use, particularly of potent
steroids, increases the risk of skin atrophy or suppression of the HPA axis.
Treatment failure may result from under use and side effects may result from excessive
use or use at inappropriate sites. Patients therefore need clear guidance on the quantities
of steroid to apply and the frequency of treatment.
7.2 Guidance for the use of topical corticosteroids
1-Always start with low-potency preparations such as 1% hydrocortisone
2-Avoid using fluorinated steroids in infants
3-Avoid using high-potency steroids on face, neck and intertriginous areas
4-Always warn patients and parents of the side effects of steroid medications
5-Do not authorize repeat prescriptions for steroid preparations without proper follow-up
6-For eyelids and perioral areas, use ophthalmic steroid preparations
7-When using long-term topical steroid therapy with high-potency steroids, discuss the
possibility of systemic absorption, HPA suppression and possible growth retardation
8-When inflammatory condition do not respond, or worsen, with treatment, suspect
allergic contact dermatitis to one or more ingredients in the preparation used.
9-Avoid occlusive therapy involving plastic wrapping as side effects tend to be hastened
and complication are more common.
10-Avoid abrupt discontinuation of topical steroid therapy. It is better to switch to lowerpotency steroid medication and then gradually taper off.
11-The basic principles for topical corticosteroids are to use ointments rather than creams
and to use the least potent drugs as sparingly as possible.
Section VIII: Corticosteroids for ophthalmic use
8.0Corticosteroids for ophthalmic uses:
Indications:
Inflammatory conditions: For the treatment of steroid-responsive inflammatory
conditions of the palpebral and bulbar conjunctiva, cornea, lid, sclera and anterior
segment of the globe, such as: Allergic conjunctivitis; acne rosacea; superficial punctate
keratitis; herpes zoster keratitis; iritis; cyclitis; selected infective conjunctivitis; vernal
conjunctivitis; episcleritis; epinephrine sensitivity; and anterior uveitis.
Ocular surgery: For treatment of postoperative inflammation following ocular surgery.
Corneal injury: For corneal injury from chemical, radiation or thermal burns or
penetration of foreign bodies.
(See individual monographs for specific indications and administration and dosage.)
Administration and Dosage:
Treatment duration varies with type of lesion and may extend from a few days to several
weeks, depending on therapeutic response. If signs and symptoms fail to improve after 2
days, the patients should be re-evaluated. Relapse may occur if therapy is reduced too
rapidly; taper over several days. Relapses, more common in chronic active lesions than
in self-limited conditions, usually respond to retreatment.
Actions:
Pharmacology – Topical opthalmic corticosteroids exert an anti-inflammatory action.
Aspects of the inflammatory process such as edema, fibrin deposition, capillary dilation,
leukocyte migration, capillary proliferation, deposition of collagen, scar formation and
fibroblastic proliferation are suppressed. Steroids inhibit inflammatory response to
inciting agents of mechanical, chemical or immunological nature. Topical ophthalmic
corticosteroids are effective in acute inflammatory conditions of the conjunctiva, sclera,
cornea, lids, iris and anterior segment of the globe; and in ocular allergic conditions. In
ocular disease, route of administration depends on site and extent of disorder.
The mechanism of the anti-inflammatory action is thought to be potentiation of
epinephrine vasoconstriction, stabilization of lysosomal membranes, retardation of
macrophage movement, prevention of kinin release, inhibition of lymphocyte and
neutrophil function, inhibition of prostaglandin synthesis and, in prolonged use, decrease
of antibody production.
Inhibiting fibroblastic proliferation may prevent symblepharon formation in chemical and
thermal burns. Decreased scarring with clearer corneas after topical corticosteroids is a
result of inhibiting fibroblastic proliferation and vascularization.
Contraindications:
 Acute epithelial herpes simplex keratitis (dendritic keratitis).
 Fungal diseases of ocular structures.
 Vaccinia.
 Varicella and most other viral diseases of the cornea and conjunctiva.
 Ocular tuberculosis.
 Hypersensitivity.
 After uncomplicated removal of a superficial corneal foreign body.
 Mycobacterial eye infection.

Acute, purulent, untreated eye infections that may be masked or enhanced by the
presence of steroids (see Warnings).
Medrysone: Medrysone is not for use in iritis and uveitis; its efficacy has not been
demonstrated.
Warnings:
Moderate-to-severe inflammation: Use higher strengths for moderate-to-severe
inflammations. In difficult cases of anterior segment eye disease, systemic therapy may
be required. When deeper ocular structures are involved, use systemic therapy.
Ocular damage: Prolonged use may result in glaucoma, elevated IOP, optic nerve
damage, defects in visual acuity and fields of vision, posterior subcapsular cataract
formation or secondary ocular infections from pathogens liberated from ocular
tissues. Check IOP and lens frequently if used for >= 10 days. In diseases that cause
thinning of cornea or sclera, perforation has occurred with topical steroids.
Cataract surgery: The use of steroids after cataract surgery may delay healing and
increase the incidence of bleb formation.
Mustard gas keratitis or Sjögren's keratoconjunctivitis: Topical steroids are not
effective.
Infections: Prolonged use may result in secondary ocular infections caused by
suppression of host response. Acute, purulent, untreated eye infections may be
masked or the activity enhanced by steroids. Fungal infections of the cornea have
been reported with long-term local steroid applications. Therefore, suspect fungal
invasion in any persistent corneal ulceration where a steroid has been used or is being
used. Take fungal cultures when appropriate.
Stromal herpes simplex keratitis treatment with steroid medication requires great
caution; frequent slit-lamp microscopy is mandatory.
Pregnancy: Category C. There are no adequate and well-controlled studies in pregnant
women. Use only when clearly needed and when potential benefits outweigh potential
hazards.
Lactation: Topically applied steroids are absorbed systemically. It is not known if
sufficient systemic absorption occurs to produce detectable quantities in breast milk.
Therefore, because of the potential for serious adverse reactions in nursing infants, decide
whether to discontinue nursing or discontinue the drug, taking into account the
importance of the drug to the mother.
Children: Safety and efficacy have not been established.
Fluorometholone: Safety and efficacy in children < 2 years of age have not been
established.
Adverse Reactions:
 Glaucoma (elevated IOP) with optic nerve damage.
 Loss of visual acuity and field defects.
 Posterior subcapsular cataract formation.
 Delayed wound healing.
 Secondary ocular infection from pathogens, including herpes simplex and fungi
liberated from ocular tissues.
 Acute uveitis.
 Perforation of globe where there is corneal or scleral thinning.
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Exacerbation of viral, bacterial and fungal corneal infections.
Transient stinging or burning.
Chemosis.
Dry eyes.
Epiphora.
Photophobia.
Keratitis.
Conjunctivitis.
Corneal ulcers.
Mydriasis.
Ptosis.
Blurred vision.
Discharge.
Discomfort.
Ocular pain.
Foreign body sensation.
Hyperemia.
Pruritus (rimexolone).
Rarely, filtering blebs have been reported with steroid use after cataract surgery.
Systemic: Systemic side effects may occur with extensive use (eg, hypercorticoidism)
Patient Information:
Medical supervision during therapy is recommended.
Instruct patients that use of contaminated ocular solutions can cause ocular infections and
serious damage to the eye with subsequent loss of vision. To avoid contamination, do not
touch applicator tip to any surface. Replace cap after using.
If improvement in the condition being treated does not occur within 2 days, or if pain,
redness, itching or swelling of the eye occurs, discontinue medication and notify the
physician. Take care not to discontinue prematurely.
Advise patients to immediately seek physician's advice concerning continued use of the
present multidose container if they develop an intercurrent ocular condition (eg, trauma,
ocular surgery, infection).
Benzalkonium chloride is absorbed by contact lenses. Do not administer medications
containing benzalkonium chloride while wearing soft contact lenses. Instruct patients to
wait >= 15 minutes after instilling medication before inserting their lenses.
8.1 Classes of corticosteroids used in eye disorders
1. FLUOROMETHOLONE
1- With 0.004% benzalkonium chloride, EDTA, polysorbate 80 and 1.4% polyvinyl
alcohol.
2- With 0.004% benzlkonium chloride, EDTA, polysorbate 80 and polyvinyl alcohol.
3- With 0.01% benzalkonium chloride, EDTA, hydroxyethylcellulose and tyloxapol.
4- With 0.005% benzalkonium chloride, EDTA, polysorbate 80 and 1.4% polyvinyl
alcohol.
5- With 0.0008% phenylmercuric acetate, white petrolatum, mineral oil and lanolin
alcohol.
Indications:
Inflammatory conditions: For steroid-responsive inflammation of the palpebral and
bulbar conjunctiva, cornea and anterior segment of the globe.
Administration and Dosage:
Consult a physician if there is no improvement after 2 days. Do not discontinue therapy
prematurely. In chronic conditions, withdraw treatment by gradually decreasing the
frequency of applications.
Suspension: Shake well before using. Instill 1 to 2 drops into the conjunctival sac(s) 2 to
4 times daily. During the initial 24 to 48 hours, the dosage may be increased to 2 drops
every 2 hours.
Ointment: Apply a small amount (» 1/2 inch ribbon) of ointment to the conjunctival sac
1 to 3 times daily. During the first 24 to 48 hours, the dosing frequency may be increased
to one application every 4 hours.
2. MEDRYSONE
1- With 0.004% benzalkonium chloride, EDTA, 1.4% polyvinyl alcohol and
hydroxypropyl methyl-cellulose.
Indications:
Inflammatory conditions: For the treatment of allergic conjunctivitis, vernal
conjunctivitis, episcleritis and ephinephrine sensitivity.
Administration and Dosage:
Shake well before using. Instill 1 drop into the conjunctival sac up to every 4 hours.
3. PREDNISOLONE
1- With benzalkonium chloride, EDTA, polysorbate 80, hydroxypropyl methylcellulose
and sodium bisulfite.
2- With 0.01% benzalkonium chloride, EDTA, polysorbate 80, hydroxypropyl
methylcellulose and glycerin.
3- With 0.01% benzalkonium chloride and EDTA.
Indications:
Inflammatory conditions: For the treatment of steroid-responsive inflammatory
conditions of the palpebral and bulbar conjunctiva, cornea and anterior segment of the
globe, such as allergic conjunctivitis, acne rosacea, superficial punctate keratitis, herpes
zoster keratitis, iritis, cyclitis, selected infective conjunctivitis when the inherent hazard
of steroid use is accepted to obtain an advisable diminution in edema and inflammation.
Mild-to-moderate: For the treatment of mild-to-moderate noninfectious allergic and
inflammatory disorders of the lid, conjunctiva, cornea and sclera (including chemical and
thermal burns).
Moderate-to-severe: Use higher strengths for moderate-to-severe inflammations. In
difficult cases of anterior segment eye disease, systemic therapy may be required. When
deeper ocular structures are involved, use systemic therapy.
Corneal injury: Corneal injury from chemical, radiation or thermal burns or penetration
of foreign bodies.
Administration and Dosage:
Solutions: Depending on the severity of inflammation, instill 1 or 2 drops of solution into
the conjunctival sac up to every hour during the day and every 2 hours during the night as
necessary as initial therapy.
When a favorable response is observed, reduce dosage to 1 drop every 4 hours. Further
reduction in dosage to 1 drop 3 to 4 times daily may suffice to control symptoms.
Suspensions: Shake well before using. Instill 1 to 2 drops into the conjunctival sac 2 to 4
times daily. During the initial 24 to 48 hours, the dosing frequency may be increased if
necessary.
In cases of bacterial infections, concomitant use of anti-infective agents is mandatory.
If signs and symptoms do not improve after 2 days, re-evaluate the patient.
Dosing may be reduced, but advice patients not to discontinue therapy prematurely. In
chronic conditions, withdraw treatment by gradually decreasing the frequency of
applications.
4. DEXAMETHASONE
1- With polysorbate 80, EDTA, 0.1% sodium bisulfite, 0.25% phenylethanol, 0.02%
benzalkonium chloride.
2- With 0.01% benzalkonium chloride, EDTA, 0.5% hydroxypropylmethylcellulose,
polysorbate 80.
3- With lanolin anhydrous, parabens, PEG-400, white petrolatum and mineral oil.
4- With white petrolatum and mineral oil.
Indications:
Inflammatory conditions: Treatment of steroid-responsive inflammatory conditions of
the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe, such as
allergic conjunctivitis, acne rosacea, superficial punctate keratitis, herpes zoster keratitis,
iritis, selected infective conjunctivitis when the inherent hazard of steroid use is accepted
to obtain advisable edema and inflammation diminution.
Corneal injury: Corneal injury from chemical, radiation or thermal burns or penetration
of foreign bodies.
Administration and Dosage:
Solutions: Instill 1 to 2 drops into the conjunctival sac every hour during the day and
every 2 hours during the night as initial therapy. When a favorable response is observed,
reduce dosage to 1 drop every 4 hours. Further reduction in dosage to 1 drop 3 or 4 times
daily may suffice to control symptoms.
Suspension: Shake well before using. Instill 1 or 2 drops in the conjunctival sac(s). In
severe disease, drops may be used hourly, being tapered to discontinuation as
inflammation subsides. In mild disease, drops may be used <= 4 to 6 times daily.
Ointment: Apply a thin coating of ointment 3 to 4 times a day. When a favorable
response is observed, reduce the number of daily applications to twice daily and later to
once daily as a maintenance dose if this is sufficient to control symptoms.
The ointment is particularly convenient when an eye pad is used. It may also be the
preparation of choice for patients in whom therapeutic benefit depends on prolonged
contact of the active ingredients with ocular tissues.
5. RIMEXOLONE
1- With 0.01% benzalkonium chloride, polysorbate 80 and EDTA.
Complete prescribing information begins in the Ophthalmic Corticosteroids group
monograph. (Reference)
Indications:
Inflammatory conditons: Treatment of anterior uveitis.
Ocular surgery: Treatment of postoperative inflammation after ocular surgery.
Administration and Dosage:
Shake well before using.
Postoperative inflammation: Apply 1 to 2 drops into the conjunctival sac of the affected
eye(s) 4 times daily begining 24 hours after surgery and continuing throughout the first 2
weeks of the postoperative period.
Anterior uveitis: Apply 1 to 2 drops into the conjunctival sac of the affected eye every
hour during waking hours for the first week, 1 drop every 2 hours during waking hours of
the second week, and then taper until uveitis is resolved.
6. LOTEPREDNOL ETABONATE
1- With 0.01% benzalkonium chloride and EDTA.
Complete prescribing information begins in the Ophthalmic Corticosteroids group
monograph. (Reference)
Indications:
0.2% suspension:
Inflammatory conditions: For the temporary relief of the signs and symptoms of seasonal
allergic conjunctivitis.
0.5% suspension:
Inflammatory conditions: For the treatment of steroid-responsive inflammatory
conditions of the palpebral and bulbar conjunctiva, cornea and anterior segment of the
globe such as allergic conjunctivitis, acne rosacea, superficial punctate keratitis, herpes
zoster keratitis, iritis, cyclitis, selected infective conjunctivitis, when the inherent hazard
of steroid use is accepted to obtain an advisable dimunition in edema and inflammation.
Ocular surgery: Treatment of postoperative inflammation following ocular surgery.
Administration and Dosage:
Approved by the FDA: March 9, 1998.
Shake well before using.
0.2% suspension: Instill 1 drop into the affected eye(s) 4 times daily.
0.5% suspension:
Steroid responsive disease: Apply 1 to 2 drops into the conjunctival sac of the affected
eye(s) 4 times daily. During the initial treatment within the first week, the dosing may be
increased up to 1 drop every hour. Advise patients not to discontinue therapy
prematurely. If signs and symptoms fail to improve after 2 days, re-evaluate the patient.
Postoperative inflammation: Apply 1 to 2 drops into the conjunctival sac of the operated
eye(s) 4 times daily beginning 24 hours after surgery and continuing throughout the first
2 weeks of the postoperative period.
Section IX: Corticosteroids chemical and proprietary names
9.0 Drugs names and properties:
1. Alclometasone Dipropionate




It’s a corticosteroid of general properties.
Store in airtight container.
Used topically in the treatment of various skin disorders.
It is usually employed as a cream or ointment containing 0.05%.
Proprietary names
Aclosone, Aclovate, Delonal, Legederm, Logoderm, Modrason, Modrasone.
2. Aldosterone





Aldosterone is the main mineralocorticoid secreted by the adrenal cortex.
It has no anti-inflammatory properties.
It has been used in association with a glucocorticoid in the treatment of
adrenocortical insufficiency.
Doses of 500 μg have been given by slow intravenous injection or by
intramuscular injection.
It has also been used as the sodium succinate.
Proprietary names
Aldocorten.
3. Amcinonide



It’s a corticosteroid of general properties.
Amcinonide is a corticosteroid used topically in the treatment of various skin
disorders.
It is usually employed as a cream, lotion, or ointment containing 0.1%.
Proprietary names
Amciderm, Amcinil, Amicla, Cyclocort, Penticort.
4. Beclomethasone dipropionate.


It’s a corticosteroid of general properties
Adrenal suppression may occur in some patients treated with high-dose long-term
inhalation therapy for asthma.
Adrenal suppression: some cases have occurred with patients receiving doses below 1.5
mg daily.
Candidiasis: its uncommon finding in children compared to adults using beclomethasone
inhalation for asthma. But the incidence increase in children receiving steroids than in
those who do not.
Effects on the bones: studies have shown that beclomethasone dipropionate can suppress
bone metabolism.
Effects on the lungs: the developments of pulmonary eosinophilia have been reported inpatient treated with inhaled beclomethasone.
Hypersensitivity.
 Beclomethasone dipropionate is used for asthma, skin disorders, and ulcerative
colitis
Asthma: compound used to exert topical effect on the lungs without producing any
systemic action (in order to avoid systemic side effect). An inhalation aerosol is used to
administer the drug. Dosage size varies from patient to another; according to the severity,
age…etc. Children aged 2 years or under are not allow to use steroids therapy unless if
they are not responding to other drugs or if the asthma attack is very severe.
Skin disorders: different dosage forms (e.g. cream, lotion, and ointment), and different
concentrations are used for skin disorders.
Ulcerative colitis: beclomethasone dipropionate 5 mg enemas were found to be very
effective in the treatment of acute attacks of ulcerative colitis.
Proprietary names
Aerobec, Aldécine, Aldecin, Béconase, Bécotide, Beclo Asma, Beclo Rino, Beclodisk,
Becloforte, Beclorhinol, Beclosona, Becloturmant, Beclovent, Becodisk, Becodisks,
Beconase, Beconase AQ, Beconase Aquosum, Beconase Dosier-Spray, Beconasol,
Becotide, Bronco-Turbinal, Cleniderm, Clenil, Clenil-A, Dereme, Dermisone Beclo,
Inalone, Menaderm Simple, Menaderm Simplex, Propaderm, Rino-Clenil, Rino Clenil,
Sanasthmax, Sanasthmyl, Turbinal, Vancenase, Vancenase AQ, Vanceril, Viarin, Viarox.
Aerosoma, Beclonarin, Batasol, Clenil Compositum, Clenil Compositum-A, Menaderm,
Menaderm Clio, Menaderm Otologico, Propaderm-A, Propaderm-C, Recto Menaderm,
Venoflavan, Ventide, Ventolin Flogo, Ventolin Plus.
5. Betamethasone

It is a glucocorticoid given orally, parentrally, by local injection, by inhalation, or
applied topically in the management of various disorders in which corticosteroids
are indicated.
 Its lack of mineralocorticoid properties makes betamethasone particularly suitable
for treating cerebral edema and congenital adrenal hyperplasia.
 It’s a corticosteroid of general properties.
 Subtypes of betamethasone:
a- Betamethasone acetate
b- Betamethasone benzoate
c- Betamethasone dipropionate
d- Betamethasone sodium phosphate
e- Betamethasone valerate
Proprietary names
Alphatrex, Beben, Bedermin, Bentelan, Betacort, Betaderm, Betagel, Betamatil,
Betapred, Betatrex, Betnelan, Betnelan-V, Betnasol, Betnasol-V, Betnasol-WL, Betneval,
Betnovat, Betnovate, Betnovate RD, Betoid, Bextasol, B-S-P, Célestène, Célestoderm,
Celestan, Celestan—V, Celestoderm, Celestoderm-V, Celeston, Celeston valerate,
Celestone, Celestone M, Celestone Phosphate, Celestone V, Cordes Beta, Diproderm,
Diprolène, Diprolene, Diprolene Glycol, Diprosis, Diprosone, durabetason, Ecoval,
Ectosone, Euvaderm, Maxivate, Minisone, Novobetamet, Paucisone, Persivate,
Prevex B, Sclane, Topilene, Topisone, Valisone, Vista-Methasone,
Alergical, Alfaflor, Anauran, Antibioticoedermin B, Beben Clorossina, Bentelan,
Beta Micutrin, Betabioptal, Betamatil con Neomicina, Betamida, Betnelan-VC, BetnelanVN, Betnesalic, Betnesol, Betnesol-N, Betnesol-VN, Betneval-Néomycine,
Betnovat mad chinoform, Betnovate Rectal ointment, Betnovate-N, Biorinil, Bronsal,
Brumeton Colloidale S, Célestamine, Célestène Chronodose, Célestoderm Néomycine,
Celesemine, Celestamine, Celestan Depot, Celestoderm Gentamic,
Celestoderm met Garamycin, Celestoderm met Neomycine, Celestoderm-V with
Garamycin, Celestoform, Celeston bifas, Celeston valerat comp., Celeston valerat med
chinoform, Celeston valerat med gentamicin, Celestone Soluspan, Celestone-VG,
Cuatroderm, Deltavagin, Diproform, Diprogen, Diprogenta, Diprophos, Diprorecto,
Diprosalic, Diprosept, Diprosone Depot, Diprosone Duopack, Diprosone Néomycine,
Diprostène, durabetagent, Eucoval con Neomicina, Eubetal, Eubetal Anibiotico,
Euvaderm, Fenistil Plus, Flourorinil, Fucibet, Fucicort, Garasone, Gentalyn Beta, Glido,
Glido Néomycine, Lotricomb, Lotriderm, Lotrisone, Micomplex, Micutrin Beta,
Nasotic Oto, Ophtasone, Otocusi Enzimatico, Quadriderm, Quadriderme, Ramatocina,
Raquivit, Resorborina, Rinofluimucil, Rinojet, Rinojet Sf senza Fenilefrina, Scalmine,
Sclane, Stanoval, Sulmycin mit Celestan-V, Triderm, Valisone-G, Vipsgal, VistaMethasone N, Visbulefarite, Visumetazone Antibiotico, Visumidriatic Antiflogistico.
6. Budesonide





It’s a corticosteroid of general properties.
Budesonide is a glucocorticoid used by inhalation for asthma (administered by
metered aerosol, dry powder inhaler, and pressurized inhaler).
Budesonide can be used for children (including those under 1 year old) for the
treatment of asthma or to control wheezing.
Budesonide is also used topically for the treatment of various skin disorders.
It’s employed as a cream or ointment containing 0.025%.
Proprietary names
Bidien, Preferid, Pulmicort, Rhinocort, Topinasal.
7. Ciclomethasone


Ciclomethasone is a glucocorticoid, which has been applied topically in
allergic and inflammatory skin disorders.
It has also been given by inhalation in asthmatic conditions.
Proprietary names
Cycloderm, Telocort.
8. Clobetasol Propionate



It’s a corticosteroid of general properties.
Clobetasol propionate is used topically in the treatment of various skin disorders.
It is usually employed as a cream, ointment, or scalp preparation containing
0.05%.
Proprietary names
Clobesol, Clovate, Declban, Dermoval, Dermovat, Dermovate, Dermoxin, Dermoxinale,
Termovate, Dermovate-NN.
9. Clobetasone Butyrate





It’s a corticosteroid of general properties.
Clobetasone butyrate is used as an eye drops for the treatment of intra-ocular
pressure.
It has been reported that clobetasone butyrate eye drops have less side effects
on the eyes than other eye drops containing corticosteroids such as
hydrocortisone, betamethasone, prednisolone, or dexamethasone.
It is also applied topically for the treatment of various skin disorders.
It is usually employed as a cream or ointment containing 0.05%, and is also
used as eye drops containing 0.1%.
Proprietary names
Cloptison, Emovat, Emovate, Eumovate, Visucloben, Cloptison-N, Eumovate-N,
Trimovate.
10. Clocortolone Pivalate
 It’s a corticosteroid of general properties.
 It is used topically in the treatment of various skin disorders
 Clocortolone hexanoate has been used similarly.
Proprietary names
Lenen, Cort-Tavegil, Crino-Kaban N, Kaban, Kabanimat, Procto-Kaban.
11.Cloprednol


It’s a corticosteroid of general properties.
It has been given by mouth in various disorders.
Proprietary name
Cloradryn, Novacort, Syntestan.
12.Cortisone Acetate

It’s a corticosteroid of general properties.






Cortisone acetate is readily absorbed from the gastro-intestinal tract, and the
cortisone is rapidly converted in the liver to its active metabolite,
hydrocortisone (cortisol).
The biological half-life of cortisone itself is only about 30 minutes.
Absorption of cortisone from intramuscular sites is slower than absorption it
orally.
Cortisone is a glucocorticoid secreted by the adrenal cortex.
Cortisone acetate has some mineralocorticoid properties and has been used
mainly for the replacement in Addison’s disease or chronic adrenocortical
insufficiency secondary to hypothyroidism.
Cortisone acetate has been used in the treatment of many allergic and
inflammatory disorders, but other corticosteroids are preferred since cortisone
has sodium-retaining properties.
Proprietary names
Adreson, Altesona, Cortal, Cortate, Cortelan, Cortstab, Cortisyl, Cortogen, Cortone,
Cortone Acetate, Cortone Acetato, Antiblefarica, Belfarida, Cortisona Neomi, Dutimelan,
Gingilone.
13.Cortivazol


It’s a glucocorticoid with general properties.
It has been given orally, and by intra-articular injection.
Proprietary names
Altim, Diaster.
14.Deflazacort



It’s a glucocorticoid with general properties.
It is said to have fewer systemic side effects than other corticosteroids such as
prednisone or methylprednisolone.
It has been given orally.
Proprietary names
Calcort, Deflan, Fentadin.
15.Deoxycortone Acetate





Deoxycortone pivalate is a derivative of deoxycortone acetate.
It’s a corticosteroid of general properties.
Overdoses of deoxycortone acetate may produce excessive sodium and water
retention leading to hypertension, edema, pulmonary congestion, and signs and
symptoms of congestive heart failure.
Salt restriction is advisable in such cases.
Excessive loss of potassium may result in muscular weakness and paralysis.



Deoxycortone is a mineralocorticoid secreted by the adrenal cortex and has its
general properties.
It has been used in the treatment of Addison’s disease and other adrenocortical
deficiency states.
Deoxycortone acetate has benn administered as a subcutaneous implant, and as
oily intramuscular injection.
Proprietary names
Cortiron, Syncortyl.
16.Desonide




It’s a corticosteroid of general properties.
It’s used topically in the treatment of various skin disorders.
It is usually employed as a cream or ointment or ear drops containing 0.05%.
The pivalate ester has also been used in dermatological preparations and the
sodium phosphate in ophthalmological preparations.
Proprietary names
Apolar, Cirkan a la Prednacinolone, Desonicx, Desowen, Locapred, Reticus, Reticus
Antimicotico, Sine Flour, Sterax, Topifug, Tridésonit, Tridesilon.
17.Desoxymethasone



It’s a corticosteroid of general properties.
Desoxymethasone is a corticosteroid used topically in the treatment of various
skin disorders.
It is usually employed as a cream, gel, lotion, or ointment; concentrations used
range is from 0.05% to 0.25%.
Proprietary names
Flubason, Ibril, Ibril med salicylsyra, Stiedex, Stiedex LP, Stiedex LPN, Topicort,
Topicort Composto, Topicorte, Topiderm, Topifram, Topisalen, Topisolon.
18. Dexamethasone
 Dexamethasone is a glucocorticoid given orally, parenterally, by local injection,
by inhalation, and applied topically in the management of various disorders in
which corticosteroids are indicated.
 Subtypes of dexamethasone:
a. Dexamethasone Acetate (1.1 mg is equivalent
to 1 mg of dexamethasone).
b. Dexamethasone Isonicotinate (1.3 mg is
equivalent to 1 mg of dexamethasone).
c. Dexamethasone Phosphate.
d. Dexamethasone Sodium Metasulphobenzoate
(1.5 mg is equivalent to 1 mg of
dexamethasone).













e. Dexamethasone Sodium Phosphate (1.1 mg is
equivalent to 1 mg of dexamethasone).
It’s a corticosteroid of general properties.
Serum concentrations of dexamethasone are reported to be
decreased by phenytoin, and vice versa.
Dexamethasone is readily absorbed from the gastrointestinal tract.
Its biological half-life in the plasma is about 190 minutes
Binding of dexamethasone to plasma is less than for most
other corticosteroids.
Dexamethasone has been used in the form of free alcohol
or in one of the esterified forms in the treatment of all
conditions in which corticosteroid therapy is indicated.
Its lack of mineralocorticoid properties makes
dexamethasone suitable for treating cerebral edema and
suppressing corticotrophin secretion in congenital adrenal
hyperplasia.
Dexamethasone is also used orally in the dexamethasone
suppression tests for the diagnosis of Crushing’s syndrome.
Dexamethasone is administered parentrally for intensive
therapy or in emergencies.
For ophthalmic disorders or for topical applications in the
treatment of various skin disorders, dexamethasone or
sodium phosphate ester is usually employed; concentrations
are usually expressed in terms of dexamethasone or
dexamethasone phosphate and are commonly 0.05 to 1%
for eye drops or ointments, and 0.1% for topical skin
preparations.
Dexamethasone is also used by inhalation in the
management of asthma.
Dexamethasone has been administered intravenously and
orally for the prevention of nausea and vomiting induced
by cancer chemotherapy.
Dexamethasone is said to be effective in the treatment of
alcohol withdrawal syndrome, hirsutism, malaria,
meningitis, and mountain sickness.
Proprietary names
Aeroseb-Dex, afpred-1, Ak-Dex, Anemul Mono, Artosone, Auxiloson, Auxisone,
Baldex, Cébédex, Cortidexason, Cortisumman, Dalalone D.P., Décadron, Decaderm in
Estergel, Decadran, Decadron, Decadron Depot, Decadron Phosphat, Decadron
Phosphate, Decadron-LA, Decaspray, Decoflour, Dectancyl, Deronil, Desalark,
Deseronil, Dexa in der Ophtiole, Dexabene, Dexa-Brachialin N, Dexa-Clinit, Dexacortal,
Dexa-Effecton, Dexa-Inject, Dexalocal, Dexamed, Dexamiso, Dexamonozon,
Dexamonozon N, Dexane, Dexaplast, Dexapos, Dexa-ratiopharm, Dexa-sine SE,
Dexasone, Dexasone 10, Dexasone 4, Dexasone LA, Dexamethasone, Etacortilen,
Firmalone, Fortecortin, Fosfodex, Hexadrol, Hexadrol Phosphate, Isopto Maxidex,
Lokalison-F, Lokalison-universale, Luxazone, Maxidex, Megacort, Mephamésone,
Millicortène, Oradexon, Predni-F-Tablinen, Sokaral, Soldesam, Solone, Soludécadron,
Spresadex, Spondy-Dexa, Totocortin, Tuttozem N, Visumetazone.
19.Dichlorisone Acetate



It’s a corticosteroid of general properties.
It is used topically in the treatment of various skin disorders.
It is usually employed as a cream or ointment containing 0.25% or 1%.
Proprietary names
Astroderm, Dermaren, Diclasone, Diclasone Gentamicina, Dicloderm Forte.
20.Diflorasone Diacetate



It’s a corticosteroid of general properties.
It is used topically in the treatment of various skin disorders.
It is usually employed as a cream or ointment containing 0.05%.
Proprietary names
Bexilona, Dermaflor, Dermonilo, Florone, Flutone, Fulixan, Maxiflor, Murode, Psorcon,
Soriflor, Sterodelta.
21.Diflucortolone Valerate



It’s a corticosteroid of general properties.
It is a corticosteroid used topically in the treatment of various skin disorders.
It is usually employed as a cream or ointment containing 0.1% or 0.3%.
Proprietary names
Binerisona, Claral, Corti-floural, Dermaflogil, Dermobios, Dermobios Oto, Dermaval,
Dicortal, Impetex, Flu-Cortanest, Nérisone C, Neriforte, Nerisona, Nerisona C, Nerisone,
Temetex, Temetex C, Temetex Compositum, Travocort.
22.Difluprednate



It’s a corticosteroid of general properties.
It has been used topically in the treatment of various skin disorders
It is usually employed as a cream, gel, or ointment; concentrations used range
from 0.02% to 0.05%.
Proprietary names
Épitopic, Epitopic Néomycine.
23.Domoprednate


It’s a corticosteroid of general properties.
It is under investigation for use topically in the treatment of various skin
disorders.
(The drug is still under examinations; no brand has been produced yet).
24.Endrysone


It’s a corticosteroid of general properties.
It is used as eye drops and eye ointments, containing 0.5%.
Proprietary names
Aldrisone, Aldrisone VC.
25.Fluazacort



It’s a corticosteroid of general properties.
It has been used topically in the treatment of various skin disorders.
It is usually employed as a cream containing 0.025%.
Proprietary names
Azacortid.
26.Fluclorolone Acetonide



It’s a corticosteroid of general properties.
It is used topically in the treatment of various skin disorders.
It is usually employed as a cream or ointmentcontaining 0.025%.
Proprietary names
Cutanit, Topilar.
27.Fludrocortisone Acetate









Fludrocortisone acetate is a corticosteroid with potent mineralocorticoid activity.
It is given orally in the treatment of primary adrenal insufficiency, usually as an
adjunct to hydrocortisone replacement therapy.
The main side effects are fluid retention, hypokalaemia, and hypertension.
Fludrocortisone acetate has a glucocorticoid action about 10 times as potent as
hydrocortisone and mineralocorticoid effects more than 100 times as potent.
Their side effects are mainly due to the mineralocorticoid activity.
Fludrocortisone is readily absorbed from the gastro-intestinal tract.
Fludrocortisone is applied topically to the skin, eye, and ear in the treatment of
various disorders.
It has been employed as cream, ointment, gel, or drops, usually in a concentration
of 0.1%.
The main indications of fludrocortisone are:
a. Adrenal insufficiency
b. Congenital adrenal hyperplasia
c. Hyperkalaemia
d. Hypoaldosteronism
e. Orthostatic hypotension
f. And various skin disorders
Proprietary names
Bléphaseptyl, Florinef, Florinef Acetaat, Florinef Acetate, Fludronef, Novicort, Panotile,
Panotile N.
28.Flumethasone




It’s a corticosteroid of general properties.
Flumethasone pivalate is a glucocorticoid used topically in the treatment
of various skin disorders.
It is usually employed as cream, ointment, or lotion containing 0.02%.
Flumethasone pivalate is also used in eardrops in a concentration of 0.02%
with clioquinol 1%.
Proprietary names
Locacortène, Locacortène-Vioforme, Locacorten, Locacorten c. Neomycin, Locacorten
Tar, Locacorten Vioform, Locacorten-Vioform, Localasen, Locasalène, Locasalen,
Locorten, Locorten Neomicina, Locorten Tar, Locortene, Locortene Vioformo, LocortenVioformo, Locorten-Vioformio, Logamel, Losalen, Psocortène.
29.Flunisolide



It’s a corticosteroid of general properties.
Flunisolide is a glucocorticoid used as a nasal spray for the prophylaxis and
treatment of allergic rhinitis.
Flunisolide is also used by inhalation from a metered aerosol in the management
of asthma.
Proprietary names
AeroBid, Bronalide, Bronilide, Gibiflu, Inhacort, Lokilan, Nasal, Lunibron-A, Lunis,
Nasalide, Rhinalar, Syntaris, Syntaris Bronchiale.
30.Fluocinolone Acetonide




It’s a corticosteroid of general properties.
Fluocinolone acetonide is used topically in the treatment of various skin
disorders.
It is usually employed as a cream, gel, lotion, or ointment; concentration used
range from 0.0025% to 0.2%.
Fluocinolone acetonide has also been used topically in the treatment of
inflammatory eye, ear, and nose disorders.
Proprietary names
Alfabios, Alfa-Fluorone, Alvadermo Fuerte, Abrasone Rectal, Alergical, Anatopic,
Anasilpiel, Antibio-Synalar, Artrodesmol Extra, Bazalin, Co Fluocin Fuerte, Coderma,
Cortalar, Cortamide, Cortiespec, Cortiplastol, Cortoderm, Cortanest Plus, Cranolona,
Dermaisom, Dermaplus, Dermobeta, Dermofil, Dermoersa, Dermolin, Doricum
Semplice, Doricum, Elasven, Elasven Neomicina, Esacinone, Esilon, Fluo Fenicol, Fluo
Vaso, Fluocid Forte, Fluocinil, Fluocit, Fluoderm, Fluodermo Fuerte, Fluodermol,
Fluomix Same, Fluomicetina, Fluonid, Fluonide, Fluovitef, Gelidina, Intradermo Cort,
Intradermo Corticosteroi, Intradermo Cort Ant Fung, Isnaderm, Jellin, Jellin polyvalent,
Jellin-Neomicina, Lauromicina, Leniderm, Localyn, Localyn S.V., Localyn-Neomicina,
Mecloderm F, Meclutin, Midacina, Myco Synalar, Myco-Jellin, Myco-Synalar, Nefluan,
Neo Analsona, Neo-Synalar, Neoderm Ginecologico, Omniderm, Otomidrin, Oxidermiol
Fuerte, Poxider, Procto-Jellin, Proctolyn, Procto-Synalar, Radiocin, Sterolone, Straderm,
Synalar, Synalar + D.B.O., Synalar Bi-Otic, Synalar C, Synalar med chinoform, Synalar
N, Synalar Néomycine, Synalar Neomicina, Synamol, Synemol, Synobel, Topiflour,
Ultraderm, Vinciseptil Otico.
31.Fluocinonide



It’s a corticosteroid of general properties.
Fluocinonide is a corticosteroid used topically in the treatment of various skin
disorders.
It is usually employed as a cream, gel, lotion, ointment, or scalp application
containing 0.05%.
Proprietary names
Combiderm, Cusigel, Flu 21, Garia, Klariderm, Lidecomb, Lidemol, Lidex, Lyderm,
Metosyn, Novoter, Novoter Gentamicina, Proctonide, Topsym, Topsym polyvalent,
Topsyn Neomicina, Topsyn Néomycine, Topsyne, Trisyn,Vasoderm E, Vipsogal.
32.Fluocortin Butyl




Fluocortin butyl is a corticosteroid of general properties.
It is used topically in the treatment of various skin disorders.
It has been employed as a cream or ointment containing 0.75%.
Fluocortin butyl has also been used in the form of a dry powder inhalation for the
management of allergic rhinitis.
Proprietary names
Bi-Vaspit, Lenen, Vaspit.
33.Fluocortolone




It’s a corticosteroid of general properties.
Fluocortolone and its esters are corticosteroids used topically in the treatment of
various skin disorders.
They are usually employed as a cream or ointment; concentrations usually used
are 0.1% of the hexanoate with 0.1% of the pivalate and 0.25% of the hexanoate
with 0.25% of either the free alcohol or pivalate ester.
The pivalate and hexanoate esters have also been used together in ointments or
suppositories for the treatment of anorectal disorders.
Proprietary names
Dermocur, Doloproct, Eczecur, Mycocur, Myco-Ultralan, Protocort, Syracort, Ultracur,
Ultradil, Ultradil Plain, Ultralan, Ultralan-crinale, Ultralan-D, Ultralan M, Ultralanum,
Ultralanum Plain, Ultraproct.
34.Fluorometholone






It’s a corticosteroid of general properties.
Fluorometholone acetate 1.1 mg is equivalent to 1 mg of fluorometholone.
It is used with topramycin in ophthalmic suspensions.
Fluorometholone is a glucocorticoid employed, usually as eye-drops
containing 0.1% in the treatment of allergic and inflammatory conditions of
the eye.
Prolonged application to the eye has caused raised intra-ocular pressure and
reduced visual functions.
Fluorometholone has also been used topically in the treatment of various skin
disorders.
Proprietary names
Bexicortil, Cortisdin Urea, Delmeson, Efemolin, Efemoline, Efflumycin, Efflumidex,
Flarex, Fluaton, Flucon, Flumetol, Fluometol Semplice, Flumetol Antibiotico, Fluorvas,
FML, FML Forte, FML Liquifilm, FML-S Liquifilm, FML Neo, FML-Neo, Isopto
Flucon, Loticort, Psoriasdin Corticoide, Regresin, Regresin Hemorroidal.
35.Fluprednidene Acetate



It’s a corticosteroid of general properties.
It is used topically in the treatment of various skin disorders.
It is usually employed as a cream, lotion, or ointment containing 0.1%, and
sometimes 0.05% is also used.
Proprietary names
Candio-Hermal, Corticoderm, Corticoderm comp., Crinohermal FEM, Crinohermal fem
neu, Decoderm, Decoderm comp., Decoderm compositum, Decoderm trivalent,
Decoderm Trivalente, Sali-Decoderm, Vobaderm, Vobaderm Plus.
36.Fluprednisolone


It’s a glucocorticoid of general properties.
It has been used orally in the form of free alcohol.
Proprietary names
Selectren.
37.Flurandrenolone

It’s a corticosteroid of general properties.


It is used topically in the treatment of various skin disorders.
It is usually employed as a cream or ointment containing 0.0125%.
Proprietary names
Cordran, Cordran-N, Cordran SP, Dernison, Dernison con Neomicina, Dernison
Neomicina, Haelan, Haelan-C, Haelan-X, Sermaform, Sermaka, Sermaka N.
38.Fluticasone Propionate





It’s a corticosteroid of general properties.
Fluticasone propionate is poorly absorbed from the gastro-intestinal tract and
undergoes extensive first pass metabolism.
Fluticasone propionate is administered by nasal spray in the prophylaxis treatment
of allergic rhinitis.
It has been tried orally in the treatment of inflammatory bowel disease.
Fluticasone propionate, administered orally, was reported to be useful in the
treatment of Crohn’s disease.
Proprietary names
Flixonase, Flutide Nasal, Flutinase.
39.Formocortal



Formocortal is a corticosteroid of general properties.
It has been used in the treatment of inflammatory eye disorders as eye drops and
eye ointments containing 0.05%.
Prolonged application to the eye has caused raised intra-ocular pressure and
reduced visual functions.
Proprietary names
Formoftil, Formomicin.
40.Halcinonide



Halcinonide is a corticosteroid of general properties.
It’s used topically in the treatment of various skin disorders.
It is usually employed as a cream, lotion, or ointments in concentrations ranges
from 0.025% to 0.1%.
Proprietary names
Halciderm, Halcimat, Halog, Halog-E, Heyden Dermol.
41. Halobetasol Propionate
 Halobetasol Propionate is a corticosteroid of general properties.
 It’s used topically in the treatment of various skin disorders.
 It is usually employed as an ointment containing 0.05%.
Proprietary names
Ultravate.
42.Halometasone



Halometasone is a corticosteroid of general properties.
It’s used topically in the treatment of various skin disorders.
It is employed as a cream or ointment containing 0.05% of halometasone
monohydrate.
Proprietary names
Sicorten, Sicorten plus.
43.Hydrocortamate Hydrochloride


Hydrocortamate Hydrochloride is a corticosteroid of general properties.
It is used topically in the treatment of various skin disorders.
Proprietary names
Cortanest, Etamicina.
44.Hydrocortisone

Hydrocortisone, the main glucocorticoid secreted by the adrenal cortex, is given
as the free alcohol or in esterified form.
 It is given orally, parentrally, by local injection, or applied topically in the
management of various disorders in which corticosteroids are indicated.
 Intravenous therapy with water-soluble esters is used in emergencies to give a
rapid response.
 Hydrocortisone is used with fludrocotisone for replacement therapy in adrenal
insufficiency.
 Hydrocortisone is a corticosteroid of general properties.
 Hydrocortisone is readily absorbed from the gastro-intestinal tract and peak blood
concentrations are attained in about an hour.
 Hydrocortisone is metabolized in the liver and most body tissues to hydrogenated
and degraded forms such as tetrahydrcortisone and tetrahydrocortisol.
 The metabolized hydrocortisone forms are excreted in the urine.
 Hydrocortisone is preferred over cortisone; since cortisone need to convert in the
liver to hydrocortisone.
 Sub-types of hydrocortisone:
A- Hydrocortisone Acetate
B- Hydrocortisone Butyrate
C- Hydrocortisone Cypionate
D- Hydrocortisone Hemisuccinate
E- Hydrocortisone Sodium Phosphate
F- Hydrocortisone Sodium Succinate
G- Hydrocortisone Valerate
Proprietary Names
Actocortina, Adacor, Aeroseb-HC, A-Hydrocort Univial, Alfason,
Algicortis, Alocort, Anflam, Anuprep HC, Barriere-HC, Buccalsone,
Carmol HC, Colifoam, Colofoam, Cordes H, Corlan, Cortacream Bandgage,
Cortaid, Cortamed, Corlan, Cortacet,Cortacream Bandage, Cortaid, Cortamed,
Cortate, Cort-Dome, Cortef, Cortenema, Cortic, Ccorticream, Cortidro, Corttifair,
Cortifoam, Cortiment, Cortoderm, Corril, Covocort, Crema Transcutan Astier,
Cutaderm, Dermacalm, Dermacort, Derm-Aid, Dermocortal, dermolate,
Dermosa Cusi Hidrocort, Dilucort, Dioderm, Efcortelan, efcortelan Soluble,
Efcortesol, Egocort Cream, Ekzesin, Emocort, Ficortril,flebocortid, Glycocrtison H,
Glocortisone H, Hc45, Hemril-HC, Hidroaltesona, Hycor, Hycort, Hyderm,
Hydro-adreson, Hydrocortistab, Hydrocortisyl, Hidrocortone, Hidrocortone Acetate,
Hidrocortone Phosphate, Hidrosone, Hysone, Hysone-A, Hytone, Idracemi,
Idrocortigamma, Lanacort, Lenirit, Locoid, Locoidon, Massengill, Medicated, Mildison,
Mildison Lipocream, Munitren H, Mylocort, Nordicort, Novohydrocort, Nutracort,
Orabase HCA, Oralsone, Pandel, Paro, Penecort, Prevex HC, Procort, Proctocort,
Procutan, Rapicort, Rectocort, Retef, sagittacortin, Sanatison Mono, Sarna HC,
Schericur, Scheroson F, Sigmacort, Siguent Hycor, Sintorat, Skincalm, Solu-Cortef,
Solu-Glyc, Squibb-HC, Supralef, Synacort, Texacort, Timocort, Unicort, Uniderm,
Urecortyn, Velopural, Waspeze Hydrocortisone, Westcort, Zenoxone.
45.Medrysone


Medrysone is a corticosteroid of general properties.
It is a glucocorticoid employed usually as eye drops containing 1%, in the topical
treatment of allergic and inflammatory conditions of the eye.
Proprietary names
HMS Liquifilm, Medriusar, Ophtocortin, spectramedryn.
46.Meprednisone


It’s a glucocorticoid with general properties.
It has been given by mouth and injection.
47.Methylprednisolone





Methylprednisolone is a corticosteroid of general properties.
Methylprednisolone is indicated orally, parenterally, by local injection, or applied
topically in the management of various disorders in which corticostroids are
indicated.
The half-life of methylprednisolone is slightly longer than prednisolone.
Methylprednisolone is absorbed from joints over a week but is more slowly
absorbed following deep intramuscular injection.
Methylprednisolone is administered for blood disorders, organ and tissue
transplantation, bone disorders, eye disorders, lupus erythematoses, cerebral
edema, rheumatoid disease, septic shock, skin disorders, spinal cord injury, and
for vertigo.
Proprietary names
A-Methapred Univial, Asmacortne, Caberdelta M, Dépo-Médrol, Depo Moderin, DepoMedrate, Depo-Medrol, Depomedrone, Depo-Predate, Esametone, Firmacort, Médrol,
Medrate, Medrol, Medrol Topical, Medrol Veriderm, Medrone, Mega-Star,
Metilbetasone Solubile, Metypresol, Prednilen, Urbason, Vériderm Médrol.
Section X: The indications, contra-indications,
warnings, precautions…etc, of each class of the corticosteroids.
10.1 Glucocorticoids
Corticotropin (ACTH)
CORTICOTROPIN INJECTION
1-With 9 mg hydrolyzed gelatin.
2-With 5 mg amino acetic acid.
3-With 14 mg hydrolyzed gelatin.
Administration and Dosage:
Give IM or SC. May be given IV for diagnostic purposes.
REPOSITORY CORTICOTROPIN INJECTION
Administration and Dosage:
Give IM or SC., and not for IV use.
Indications:
 ACTH and cosyntropin: Diagnostic testing of adrenocortical function.
Cosyntropin is more potent and less allergenic than the exogenous ACTH
preparations.
 ACTH: Corticotropin has limited therapeutic value in conditions responsive to
corticosteroid therapy; in such cases, corticosteroid therapy is the treatment of
choice. Corticotropin may be used in the following disorders:
 Endocrine: Nonsuppurative thyroiditis; hypercalcaemia associated with cancer.
 Nervous system diseases: Acute exacerbations of multiple sclerosis.

Miscellaneous: Tuberculosis meningitis with subarachnoid block or impending
block when accompanied by antituberculosis chemotherapy; trichinosis with
neurologic or myocardial involvement; rheumatic, collagen, dermatologic,
allergic, ophthalmic, respiratory ,hematologic, neoplastic, edematous, and GI
diseases in the same manner as the glucocorticoids.
Unlabeled uses: Treatment of infantile spasms.
Administration and Dosage:
 Standard tests for verification of adrenal responsiveness to corticotropin may
utilize as much as 80 units as a single injection, or one or more injections of a
lesser dosage. Perform verification tests prior to treatment with corticotrophins.
The test should utilize the route(s) of administration proposed for treatment.
Following verification, individualize dosage. Attempt only gradual change in
dosage schedules after full drug effects have become apparent.
 In the short test (single injection) for the ACTH stimulation test, a normal
response is plasma cortisol > 20 mcg/dl on any sample. A blunted response
indicates primary or secondary adrenal insufficiency. In the long test (8 hour
infusion on 3 consecutive days), an absent or subnormal rise in plasma cortisol
and 17-OHCS indicates primary adrenal failure. Plasma cortisol > 20 mcg/dl and
a two- to threefold urinary 17-OHCS increase over baseline on day 4 indicate
ACTH deficiency.
 For diagnostic purposes: 10 to 25 units dissolved in 500 ml of 5% Dextrose
Injection infused IV over 8 hours.
 The usual IM or SC dose is 20 units 4 times daily. Chronic administration of > 40
units/day may be associated with uncontrollable adverse effects.
 When indicated, reduce dosage gradually by increasing the duration between
injections or decreasing the quantity of corticotropin injected or both.
 Acute exacerbations of multiple sclerosis: 80 to 120 units/day IM for 2 to 3
weeks.
 Infantile spasms: 20 to 40 units daily or 80 units every other day IM for 3 months
or 1 month after cessation of seizures has been recommended.
 Repository corticotropin injection: 40 to 80 units IM or SC every 24 to 72 hours.
Preparation and storage: Reconstitute powder by dissolving in Sterile Water for
Injection or Sodium Chloride Injection so that the individual dose will be contained in 1
to 2 ml of solution. Refrigerate reconstituted solution. Use within 24 hours.
Actions:
Pharmacology- Corticotropin (adrenocorticotropic hormone, ACTH) is secreted by the
anterior pituitary and stimulates the adrenal cortex to produce and secrete adrenocortical
hormones. Adequate adrenal function is necessary for corticotropin to elicit a
pharmacological response. ACTH secretion is regulated by a negative feedback
mechanism, whereby elevated plasma corticosteroid levels suppress ACTH secretion.
Chronic administration of exogenous corticosteroids will decrease ACTH stores and
induce morphological changes in the pituitary. In absence of ACTH stimulation, the
adrenal cortex may atrophy.
Cosyntropin is a synthetic peptide corresponding to the amino acid residues 1 to 24 of
human ACTH, which exhibits the full corticosteroidogenic activity of natural ACTH. A
dose of 0.25 mg cosyntropin is pharmacologically equivalent to 25 units of natural
ACTH. Cosyntropin is less allergenic than natural ACTH. Because it is unavailable in a
repository form, it is not used therapeutically, only diagnostically.
Pharmacokinetics - ACTH injection has a rapid onset. Plasma half-life is about 15
minutes. After IM or rapid IV administration of 25 units, peak plasma concentrations are
usually achieved within 1 hour and begin to decrease after 2 to 4 hours. Repository
corticotropin contains ACTH incorporated in a gelatin menstruum designed to delay the
absorption rate and increase the period of effectiveness. Repository corticotropin has a
slower onset but may sustain effects for up to 3 days.
Contraindications:
Scleroderma; osteoporosis; systemic fungal infections; ocular herpes simplex; recent
surgery; history of or presence of peptic ulcer; congestive heart failure (CHF);
hypertension; sensitivity to porcine proteins. IV administration (except in the treatment of
idiopathic thrombocytopenic purpura). IV administration may be used for diagnostic
testing of adrenocortical function. Treatment of conditions accompanied by primary
adrenocortical insufficiency or adrenocortical hyperfunction.
Warnings:
Do not administer: Do not administer until adrenal responsiveness has been verified
with the route of administration (IM or SC) which will be used during treatment. A rise in
urinary and plasma corticosteroid values provides direct evidence of a stimulatory effect.
 Chronic administration: Chronic administration may lead to irreversible
adverse effects. ACTH may suppress signs and symptoms of chronic disease
without altering the natural course of the disease. Since complications with
corticotropin use are dependent on the dose and duration of treatment, a risk to
benefit decision must be made in each case.
 Prolonged use: Prolonged use increases the risk of hypersensitivity reactions and
may produce posterior subcapsular cataracts and glaucoma with possible damage
to the optic nerve.
 Stress: Although the action of ACTH is similar to that of exogenous
adrenocortical steroids, the quantity of adrenocorticoid secreted may be variable.
In patients who receive prolonged corticotropin therapy, use additional rapidly
acting corticosteroids before, during and after an unusually stressful situation.
 Infection: ACTH may mask signs of infection including fungal or viral eye
infections that may appear during its use. There may be decreased resistance and
inability to localize infection. When infection is present, administer appropriate
anti-infective therapy.
 Tuberculosis - Observe patients with latent tuberculosis or tuberculin reactivity
that receives ACTH, as reactivation of the disease may occur. During prolonged
ACTH therapy, administer chemoprophylaxis.
 Immunosuppression: Perform immunization procedures with caution, especially
when high doses are administered, because of the possible hazards of neurological
complications and lack of antibody response. Immunization with live vaccines is
usually contraindicated in patients on ACTH or corticosteroid therapy.
 Electrolytes: Corticotropin can elevate blood pressure, cause salt and water
retention and increase potassium and calcium excretion. Dietary salt restriction
and potassium supplementation may be necessary.

Hypersensitivity: Cosyntropin exhibits slight immunologic activity, does not
contain foreign animal protein, and is less risky to use than natural ACTH. Most
patients with a history of a previous hypersensitivity reaction to natural ACTH or
a preexisting allergic disease will tolerate cosyntropin without incident; however,
hypersensitivity reactions are possible. Refer to Management of Acute
Hypersensitivity Reactions. (Reference )
 Pregnancy: Category C. ACTH has embryocidal effects. Fetal abnormalities
have been observed in animals. Use in pregnancy only when clearly needed and
when potential benefits outweigh potential hazards to the fetus. Monitor infants
born of mothers who have received substantial doses during pregnancy for signs
of hyperadrenalism.
 Lactation: It is not known whether this drug is excreted in breast milk. Because
of the potential for serious adverse reactions in nursing infants from ACTH,
decide whether to discontinue nursing or to discontinue the drug.
 Children: Prolonged use of corticotropin in children will inhibit skeletal growth.
If use is necessary, give intermittently and carefully observe the child.
Precautions:
 Concomitant therapy: Since maximal corticotropin stimulation of the adrenals
may be limited during the first few days of treatment, administer a rapidly acting
corticosteroid (e.g. hydrocortisone) when an immediate therapeutic effect is
desirable.
 Administer for treatment only when disease is intractable to more conventional
therapy; ACTH should be adjunctive and not the sole therapy.
 Use the lowest possible dose: Use the lowest possible dose to control the
condition, and when reduction in dosage is possible, it should be gradual.
 Sensitivity to porcine proteins: Perform skin testing prior to treatment in
patients with suspected sensitivity to porcine proteins. During or following
administration, observe for sensitivity reactions.
 Adrenocortical insufficiency: Adrenocortical insufficiency induced by
prolonged ACTH therapy may be minimized by gradual reduction of dosage.
Insufficiency may persist for months after therapy discontinuation; therefore, in
any situation of stress during that period, reinstitute corticosteroid therapy.
 Hypothyroidism and cirrhosis: An enhanced effect of corticotropin may occur.
 Multiple sclerosis: Although ACTH may speed the resolution of acute
exacerbations of multiple sclerosis; it does not affect the ultimate outcome or
natural course of the disease. Relatively high doses of ACTH are necessary to
demonstrate a significant effect.
 Acute gouty arthritis: Limit treatment of acute gouty arthritis to a few days.
Since rebound attacks may occur when corticotropin is discontinued, administer
conventional concomitant therapy during corticotropin treatment and for several
days after it is stopped.
 Mental disturbances: Psychic derangements may appear, ranging from
euphoria, insomnia, mood swings, personality changes, and depression to frank
psychosis. Existing emotional instability or psychotic tendencies may be
aggravated.
Use with caution: Use with caution in patients with diabetes, abscess, pyogenic
infections, diverticulitis, renal insufficiency and myasthenia gravis.
Drug abuse and dependence: Although drug dependence does not occur, sudden
withdrawal of corticotropin after prolonged use may lead to recurrent symptoms, which
make it difficult to stop. It may be necessary to taper the dose and increase the injection
interval to gradually discontinue the medication.
Drug Interactions:
Corticotropin (ACTH) Drug Interactions
Precipitant drug
Object drug
Description
Corticotropin
Amphotericin B
Amphotericin B depletes potassium and may enhance
the potassium wasting effect of corticotropin; it may
also decrease adrenocortical responsiveness to
corticotropin. Closely monitor serum potassium.
Corticotropin
Aspirin,
indomethacin
Because of its known ulcerogenic effects, use aspirin
cautiously in conjunction with corticotropin, especially
in hypoprothrombinemia. Corticosteroids may increase
the renal clearance of salicylates. Increased serum levels
of salicylates and salicylate toxicity may occur when
steroid therapy is discontinued.
Corticotropin
Insulin
Increased requirements for insulin or oral hypoglycemic
agents in diabetes have occurred in patients taking
ACTH, due to the intrinsic hyperglycemic activity of
glucocorticoids.
Corticotropin
Diuretics
Diuretics that deplete potassium may enhance the
potassium wasting effect of corticotropin. Closely
monitor serum potassium.
Drug/Lab test interactions: Corticotropin may decrease I131 uptake and may suppress
reactions to skin tests. It may affect the method of Brown used for determination of
urinary estradiol and estriol, causing falsely decreased concentrations of these estrogens.
The drug may also interfere with colorimetric/fluorometric procedures for determination
of urinary estrogens causing a falsely decreased concentration of urinary estrogens.
Adverse Reactions:
 Infections: Pneumonia, abscess and septic infection, and GI and GU infections
(more frequent with higher doses).
 Cardiovascular: Hypertension; CHF; necrotizing angiitis.
 CNS: Convulsions; vertigo; headache; increased intracranial pressure with
papilledema, pseudotumor cerebri, usually after treatment.
 Dermatologic: Impaired wound healing; petechiae and ecchymoses; increased
sweating; hyperpigmentation; thin fragile skin; facial erythema; acne; suppression
of skin test reactions.
 Electrolyte disturbances: Sodium and fluid retention; potassium and calcium loss;
hypokalemic alkalosis.
 Endocrine: Menstrual irregularities; suppression of growth in children;
hirsutism; development of Cushingoid state; manifestations of latent diabetes
mellitus; decreased carbohydrate tolerance; increased requirements for insulin or
oral hypoglycemic agents in diabetics; secondary adrenocortical and pituitary
unresponsiveness, especially during stress.
 GI: Pancreatitis; ulcerative esophagitis; abdominal distention; peptic ulcer with
possible perforation and hemorrhage has been associated with steroid therapy
(this association has been disputed).
 Hypersensitivity: Dizziness; nausea; vomiting; shock; skin reactions.
 Metabolic: Negative nitrogen balance due to protein catabolism.
 Musculoskeletal: Muscle weakness; steroid myopathy; loss of muscle mass;
osteoporosis; vertebral compression fractures; pathologic fracture of long bones;
aseptic necrosis of femoral and humeral heads.
 Ophthalmic: Posterior subcapsular cataracts; increased intraocular pressure;
glaucoma with possible damage to optic nerve; exophthalmos.
 Miscellaneous: Prolonged use may result in antibody production and subsequent
loss of the stimulatory effect of ACTH.
Patient Information:
 ACTH may mask signs of infection. There may be decreased resistance and
inability to localize infection.
 Avoid immunizations with live vaccines.
 Diabetics may have increased requirements for insulin or oral hypoglycemics.
 Notify physician if marked fluid retention, muscle weakness, abdominal pain,
seizures, or headache occurs.
COSYNTROPIN
1- With 10 mg mannitol.
Administration and Dosage:
Administer IM or IV as a rapid screening test of adrenal function. It may also be given as
an IV infusion over 4 to 8 hours to provide a greater stimulus to the adrenal glands. Doses
of 0.25 to 0.75 mg have been used and a maximal response noted with the smallest dose.
The suggested dose is 0.25 mg dissolved in sterile saline injected IM.
 Children (less than or 2 years old): 0.125 mg will often suffice.
 IV infusion: Add 0.25 mg cosyntropin to dextrose or saline solutions and give at
a rate of approximately 0.04 mg/hour over 6 hours.
 For test procedure and interpretation of results, refer to manufacturer's insert.
Glucocorticoids
Indications:
 Endocrine disorders: Primary or secondary adrenal cortical insufficiency
(hydrocortisone or cortisone is the drug of choice; synthetic analogs may be used
in conjunction with mineralocorticoids; in infancy, mineralocorticoid
supplementation is important ;)congenital adrenal hyperplasia; nonsuppurative
thyroiditis; hypercalcaemia associated with cancer).
 Parenteral: Acute adrenal cortical insufficiency (hydrocortisone or cortisone is
drug of choice); preoperatively or in serious trauma or illness with known adrenal
insufficiency or when adrenal cortical reserve is doubtful; shock unresponsive to
conventional therapy if adrenal cortical insufficiency exists or is suspected.
 Rheumatic disorders: Adjunctive therapy for short-term use (acute episode or
exacerbation) in: Ankylosing spondylitis; acute and subacute bursitis; acute
nonspecific tenosynovitis; acute gouty arthritis; psoriatic arthritis; rheumatoid
arthritis, including juvenile (selected cases may require low-dose maintenance
therapy); posttraumatic osteoarthritis; synovitis of osteoarthritis; epicondylitis.
 Collagen diseases: For exacerbation or maintenance therapy in selected cases of
systemic lupus erythematosus, acute rheumatic carditis or systemic
dermatomyositis (polymyositis).
 Dermatologic diseases: Pemphigus; bullous dermatitis herpetiformis; severe
erythema multiforme (Stevens-Johnson syndrome); mycosis fungoides; severe
psoriasis; angioedema or urticaria; exfoliative, severe seborrheic, contact or atopic
dermatitis.
 Allergic states: Control of severe or incapacitating allergic conditions intractable
to conventional treatment in serum sickness and drug hypersensitivity reactions.
 Parenteral therapy is indicated for urticarial transfusion reactions and acute
noninfectious laryngeal edema (epinephrine is the drug of first choice).
 Ophthalmic: Severe acute and chronic allergic and inflammatory processes
involving the eye and its adnexa such as: Allergic conjunctivitis; keratitis; allergic
corneal marginal ulcers; herpes zoster ophthalmicus; iritis and iridocyclitis;
chorioretinitis ;diffuse posterior uveitis and choroiditis; optic neuritis; sympathetic
ophthalmia and anterior segment inflammation.
 Respiratory diseases: Symptomatic sarcoidosis; bronchial asthma (including
status asthmaticus); Loeffler's syndrome not manageable by other means;
berylliosis; fulminating or disseminated pulmonary tuberculosis when
accompanied by appropriate antituberculous chemotherapy; aspiration
pneumonitis; seasonal or perennial allergic rhinitis.
 Hematologic disorders: Idiopathic thrombocytopenic purpura and secondary
thrombocytopenia in adults (IV only; IM use is contraindicated); acquired
(autoimmune) hemolytic anemia; erythroblastopenia (RBC anemia); congenital
(erythroid) hypoplastic anemia.
 Neoplastic diseases: For palliative management of leukemias and lymphomas in
adults and acute leukemia of childhood.
 Edematous states: To induce diuresis or remission of proteinuria in the
nephrotic syndrome (without uremia) of the idiopathic type or that due to lupus
erythematosus.
 GI diseases: To tied the patient over a critical period of the disease in ulcerative
colitis, regional enteritis (Crohn's disease) and intractable sprue.
 Nervous system: Acute exacerbations of multiple sclerosis (see Precautions).
 Miscellaneous: Tuberculous meningitis with subarachnoid block or impending
block when accompanied by appropriate antituberculous chemotherapy; in
trichinosis with neurologic or myocardial involvement.
Intra-articular or soft tissue administration: Short-term adjunctive therapy (to tide the
patient over an acute episode) in synovitis of osteoarthritis; rheumatoid arthritis; acute
and subacute bursitis; acute gouty arthritis; epicondylitis; acute nonspecific tenosynovitis;
post-traumatic osteoarthritis.
Intralesional administration: Keloids; localized hypertrophic, infiltrated, inflammatory
lesions of lichen planus, psoriatic plaques, granuloma annulare, lichen simplex chronicus
(neurodermatitis); discoid lupus erythematosus; necrobiosis lipoidica diabeticorum;
alopecia areata. May be useful in cystic tumors of an aponeurosis or tendon (ganglia).
Dexamethasone: Dexamethasone is also indicated for testing of adrenal cortical
hyperfunction; cerebral edema associated with primary or metastatic brain tumor,
craniotomy or head injury.
Triamcinolone: Triamcinolone is also indicated for the treatment of pulmonary
emphysema where bronchospasm or bronchial edema plays a significant role, and diffuse
interstitial pulmonary fibrosis (Hamman-Rich syndrome); in conjunction with diuretic
agents to induce a diuresis in refractory congestive heart failure (CHF) and in cirrhosis of
the liver with refractory ascites; and for postoperative dental inflammatory reactions.
Administration and Dosage:
The maximal activity of the adrenal cortex is between 2 and 8 am, and it is minimal
between 4 pm and midnight. Exogenous corticosteroids suppress adrenocortical activity
the least when given at the time of maximal activity (am). Therefore, administer
glucocorticoids in the morning prior to 9 am. When large doses are given, administer
antacids between meals to help prevent peptic ulcers.
Initiation of therapy: The initial dosage depends on the specific disease entity being
treated. Maintain or adjust the initial dosage until a satisfactory response is noted. If after
a reasonable period of time there is a lack of satisfactory clinical response, discontinue
the drug and transfer the patient to other appropriate therapy. It should be emphasized
that dosage requirements are variable and must be individualized. For infants and
children, the recommended dosage should be governed by the same considerations rather
than by strict adherence to the ratio indicated by age or body weight.
Maintenance therapy: After a favorable response is observed, determine the
maintenance dosage by decreasing the initial dosage in small amounts at intervals until
the lowest dosage that will maintain an adequate clinical response is reached. Constant
monitoring of drug dosage is required. Situations which may make dosage adjustments
necessary are changes in the disease process, the patient's individual drug responsiveness,
and the effect of patient exposure to stress; in this latter situation it may be necessary to
increase the dosage for a period of time consistent with the patient's condition.
Withdrawal of therapy: If, after long-term therapy, the drug is to be stopped, it must be
withdrawn gradually. If spontaneous remission occurs in a chronic condition, discontinue
treatment gradually. Continued supervision of the patient after discontinuation of
corticosteroids is essential, since there may be a sudden reappearance of severe
manifestations of the disease.
Alternate day therapy: Alternate day therapy is a dosing regimen in which twice the
usual daily dose is administered every other morning. The purpose is to provide the
patient requiring long-term treatment with the beneficial effects of corticosteroids while
minimizing pituitary-adrenal suppression, the cushingoid state, withdrawal symptoms and
growth suppression in children. The benefits of alternate day therapy are only achieved
by using the intermediate-acting agents.
The rationale for this treatment schedule is based on two major premises: (a) The
therapeutic effect of intermediate-acting corticosteroids persists longer than their physical
presence and metabolic effects; (b) administration of the corticosteroid every other
morning allows for reestablishment of a more normal hypothalamic-pituitary-adrenal
(HPA) activity on the off-steroid day. Keep the following in mind when considering
alternate day therapy:
1-Benefits of alternate day therapy do not encourage indiscriminate steroid use.
2-Alternate day therapy is primarily designed for patients in whom long-term
corticosteroid therapy is anticipated.
3-In less severe disease processes, it may be possible to initiate treatment with alternate
day therapy. More severe disease states usually require daily divided high-dose therapy
for initial control. Continue initial suppressive dose until satisfactory clinical response is
obtained, usually 4 to 10 days in the case of many allergic and collagen diseases. Keep
the period of initial suppressive dose as brief as possible, particularly when alternate day
therapy is intended. Once control is established, two courses are available: (a) Change to
alternate day therapy, then gradually reduce the amount of corticosteroid given every
other day or (b) reduce daily corticosteroid dose to the lowest effective level as rapidly as
possible, then change over to an alternate day schedule. Theoretically, course (a) may be
preferable.
4-Because of the advantages of alternate day therapy, it may be desirable to try patients
on this form of therapy who have been on daily corticosteroids for long periods of time
(eg, patients with rheumatoid arthritis). Since these patients may already have a
suppressed HPA axis, establishing them on alternate day therapy may be difficult and not
always successful; however, it is recommended that such regular attempts be made. It
may be helpful to triple or even quadruple the daily maintenance dose and administer this
every other day rather than just doubling the daily dose if difficulty is encountered. Once
the patient is controlled, attempt to reduce this dose to a minimum.
5-Long-acting corticosteroids (eg, dexamethasone, betamethasone), due to their
prolonged suppressive effect on adrenal activity, are not recommended for alternate day
therapy.
6-It is important to individualize therapy. Complete control of symptoms will not be
possible in all patients. An explanation of the benefits of alternate day therapy will help
the patient to understand and tolerate the possible flare-up in symptoms, which may occur
in the latter part of the off-steroid day. Other therapy to relieve symptoms may be added
or increased at this time if needed.
7-In the event of an acute flare-up of the disease process, it may be necessary to return to
a full suppressive daily corticosteroid dose for control. Once control is established,
alternate day therapy may be reinstituted.
Intra-articular injection: Dose depends on the joint size and varies with the severity of
the condition. In chronic cases, injections may be repeated at intervals of 1 to 5 or more
weeks depending upon the degree of relief obtained from the initial injection. Injection
must be made into the synovial space. Do not inject unstable joints. Repeated intraarticular injection may result in joint instability. X-ray follow-up is suggested in selected
cases to detect deterioration.
Suitable sites: Suitable sites for injection are the knee, ankle, wrist, elbow, shoulder, hip
and phalangeal joints. Since difficulty is frequently encountered in entering the hip joint,
avoid any large blood vessels in the area. Joints not suitable for injection are those that
are anatomically inaccessible and devoid of synovial space such as the spinal joints and
the sacroiliac joints. Treatment failures frequently result from failure to enter the joint
space; little or no benefit follows injection into surrounding tissue. If failures occur when
injections into the synovial spaces are certain, as determined by aspiration of fluid,
repeated injections are usually of no benefit. Local therapy does not alter the underlying
disease process; whenever possible ,employ comprehensive therapy including
physiotherapy and orthopedic correction.
Miscellaneous (tendinitis, epicondylitis, ganglion): In the treatment of conditions such
as tendinitis or tenosynovitis, inject into the tendon sheath rather than into the substance
of the tendon. When treating conditions such as epicondylitis, outline the area of greatest
tenderness and infiltrate the drug into the area. For ganglia of the tendon sheaths, inject
the drug directly into the cyst. In many cases, a single injection markedly decreases size
of the cystic tumor and may affect disappearance. The dose varies with the condition
being treated. In recurrent or chronic conditions, repeated injections may be needed.
Injections for local effect in dermatologic conditions: Avoid injection of sufficient
material to cause blanching, since this may be followed by a small slough. One to four
injections are usually employed. Intervals between injections vary with the type of lesion
being treated and duration of improvement produced by initial injection.
Actions:
Pharmacology - The naturally occurring adrenocortical steroids have both antiinflammatory (glucocorticoid) and salt-retaining (mineralocorticoid) properties.
Glucocorticoids cause profound and varied metabolic effects. In addition, they modify
the body's immune responses to diverse stimuli.
These compounds, including hydrocortisone (cortisol) and cortisone, are used as
replacement therapy in adrenocortical deficiency states and may be used for their antiinflammatory effects. The synthetic steroid compounds prednisone, prednisolone and
fludrocortisone also have both glucocorticoid and mineralocorticoid activity. Prednisone
and prednisolone are used primarily for their glucocorticoid effects.
In addition, a group of synthetic compounds with marked glucocorticoid activity are
distinguished by the absence of any significant salt-retaining activity. These include
triamcinolone, dexamethasone, methylprednisolone and betamethasone. These agents are
used for their potent anti-inflammatory effects.
Pharmacokinetics:
 Absorption: Hydrocortisone and most of its congeners are readily absorbed from
the GI tract; greatly altered onsets and durations are usually achieved with
injections of suspensions and esters.
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Distribution: Hydrocortisone is reversibly bound to corticosteroid-binding
globulin (CBG or transcortin) and corticosteroid binding albumin (CBA).
Exogenous glucocorticoids are bound to these proteins to a significantly lesser
degree. In hypoproteinemic or dysproteinemic states, the total endogenous
hydrocortisone levels are decreased. Conversely, with increased CBG (pregnancy,
estrogen therapy), the total plasma hydrocortisone levels are elevated. These
alterations are not of clinical significance because it is the unbound fraction of the
hormone that is metabolically active. However, the administration of exogenous
glucocorticoids to patients with altered protein binding capacities will result in
significant differences in glucocorticoid pharmacological effects.
 Metabolism/Excretion: Hydrocortisone is metabolized by the liver, which is the
rate-limiting step in its clearance. The metabolism and excretion of the synthetic
glucocorticoids generally parallel hydrocortisone. Induction of hepatic enzymes
will increase the metabolic clearance of hydrocortisone and the synthetic
glucocorticoids. About 1% of its usual daily production, or about 200 mcg
unchanged hormone is excreted in urine daily. Renal clearance is increased when
plasma levels are increased. Prednisone is inactive and must be metabolized to
prednisolone. The following table summarizes the approximate dosage
equivalencies (based on glucocorticoid properties) of the various glucocorticoid
preparations and several of their pharmacokinetic parameters. The half-life values
refer to the intrinsic activity of each agent; insoluble salts of these drugs are used
as repository injections and have sustained effects due to delayed absorption from
the injection site.
Contraindications:
Systemic fungal infections; hypersensitivity to the drug; IM use in idiopathic
thrombocytopenic purpura; administration of live virus vaccines (eg smallpox) in patients
receiving immunosuppressive corticosteroid doses.
Warnings:
 Infections: Corticosteroids may mask signs of infection, and new infections may
appear during their use. There may be decreased resistance and inability of the
host defense mechanisms to prevent dissemination of the infection. If an infection
occurs during therapy, it should be promptly controlled by suitable antimicrobial
therapy.
1. Tuberculosis - Restrict use in active tuberculosis to cases of fulminating or
disseminated disease in which the corticosteroid is used for disease management
with appropriate chemotherapy. If corticosteroids are indicated in latent
tuberculosis or tuberculin reactivity, observe closely; disease reactivation may
occur. During prolonged corticosteroid use, these patients should receive
chemoprophylaxis.
2. Fungal - Corticosteroids may exacerbate systemic fungal infections; do not use in
such infections, except to control drug reactions due to amphotericin B.
Concomitant use of amphotericin B and hydrocortisone has been followed by
cardiac enlargement and CHF.
3. Amebiasis - Corticosteroids may activate latent amebiasis. Rule out amebiasis
before giving to a patient who has been in the tropics or has unexplained diarrhea.
4. Cerebral malaria - A double-blind trial has shown corticosteroid use is
associated with prolongation of coma and a higher incidence of pneumonia and
GI bleeding.
5. Hepatitis: Although advocated for use in chronic active hepatitis, corticosteroids
may be harmful in chronic active hepatitis positive for hepatitis B surface antigen.
 Ocular effects: Prolonged use may produce posterior subcapsular cataracts,
glaucoma with possible damage to the optic nerves, and may enhance the
establishment of secondary ocular infections due to fungi or viruses. Use
cautiously in ocular herpes simplex because of possible corneal perforation.
 Fluid and electrolyte balance: Average and large doses of hydrocortisone or
cortisone can cause elevation of blood pressure, salt and water retention and
increased excretion of potassium. These effects are less likely to occur with the
synthetic derivatives except when used in large doses. Dietary salt restriction and
potassium supplementation may be necessary. All corticosteroids increase
calcium excretion.
 Peptic ulcer: The relationship between peptic ulceration and glucocorticoid
therapy is unclear. Patients who appear to be at risk are those being treated for
nephrotic syndrome or liver disease, or who are comatose postcraniotomy. Other
predisposing factors include a total prednisone intake exceeding 1g, a history of
ulcer disease, concomitant use of known gastric irritants (as in arthritic patients)
and stress. It may be desirable to use prophylactic antacids pending clarification
of the relationship.
 Immunosuppression: During therapy, do not use live virus vaccines (eg,
smallpox). Do not immunize patients who are receiving corticosteroids, especially
high doses, because of possible hazards of neurological complications and a lack
of antibody response .This does not apply to patients receiving corticosteroids as
replacement therapy. Corticosteroids may suppress reactions to skin tests.
 Adrenal suppression: Prolonged therapy of pharmacologic doses may lead to
hypothalamic-pituitary-adrenal suppression. The degree of adrenal suppression
varies with the dosage, relative glucocorticoid activity, biological half-life and
duration of glucocorticoid therapy within each individual. Adrenal suppression
may be minimized by the use of intermediate-acting glucocorticoids (prednisone,
prednisolone, methylprednisolone) on an alternate day schedule. Following
prolonged therapy, abrupt discontinuation may result in a withdrawal syndrome
without evidence of adrenal insufficiency. To minimize morbidity associated with
adrenal insufficiency, discontinue exogenous corticosteroid therapy gradually.
During withdrawal therapy, increased supplementation may be necessary during
times of stress. Symptoms of adrenal insufficiency as a result of too rapid
withdrawal include: Nausea; fatigue; anorexia; dyspnea; hypotension;
hypoglycemia; myalgia; fever; malaise; arthralgia; dizziness; desquamation of
skin; fainting. Continued supervision after therapy termination is essential; severe
disease manifestations may reappear suddenly.
 Stress: In patients receiving or recently withdrawn from corticosteroid therapy
subjected to unusual stress, increased dosage of rapidly acting corticosteroids is
indicated before, during and after stressful situations, except in patients on highdose therapy. Relative adrenocortical insufficiency may persist for months after
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therapy ends; in any stress situation occurring during that period, reinstitute
therapy. Since mineralocorticoid secretion may be impaired, administer salt or a
mineralocorticoid concurrently.
Cardiovascular: Reports suggest an apparent association between corticosteroid
use and left ventricular free wall rupture after a recent myocardial infarction. Use
with great caution in these patients.
Hypersensitivity reactions: Anaphylactoid reactions have occurred rarely with
corticosteroid therapy; take precautionary measures, especially in patients with a
history of allergies. Refer to Management of Acute Hypersensitivity Reactions.
(Reference )
Renal function impairment: Edema may occur in the presence of renal disease
with a fixed or decreased glomerular filtration rate. Use with caution in renal
insufficiency, acute glomerulonephritis and chronic nephritis.
Elderly: Consider the risk/benefit factors of steroid use. Consider lower doses
because of body changes caused by aging (ie, diminution of muscle mass and
plasma volume). Monitor blood pressure, blood glucose and electrolytes at least
every 6 months.
Pregnancy: (Category C - Prednisolone sodium phosphate). Corticosteroids
cross the placenta (prednisone has the poorest transport). In animal studies, large
doses of cortisol administered early in pregnancy produced cleft palate, stillborn
fetuses and decreased fetal size. Chronic maternal ingestion during the first
trimester has shown a 1% incidence of cleft palate in humans. If used in
pregnancy, or in women of childbearing potential, weigh benefits against the
potential hazards to the mother and fetus .Carefully observe infants born of
mothers who have received substantial corticosteroid doses during pregnancy for
signs of hypoadrenalism.
Lactation: Corticosteroids appear in breast milk and could suppress growth,
interfere with endogenous corticosteroid production or cause other unwanted
effects in the nursing infant. Advise mothers taking pharmacologic corticosteroid
doses not to nurse .However, several studies suggest that amounts excreted in
breast milk are negligible with prednisone or prednisolone doses <= 20 mg/day or
methylprednisolone doses <= 8 mg/day, and large doses for short periods may not
harm the infant. Alternatives to consider include waiting 3 to 4 hours after the
dose before breastfeeding and using prednisolone rather than prednisone
(resulting in a lower corticosteroid dose to the infant).
Children: Carefully observe growth and development of infants and children on
prolonged corticosteroid therapy .
Benzyl alcohol: Some of these products contain benzyl alcohol, which has been
associated with a fatal "gasping syndrome" in premature infants.
Precautions:
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Monitoring: Observe patients for weight increase, edema, hypertension, and
excessive potassium excretion, as well as for less obvious signs of adrenocortical
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steroid-induced untoward effects. Monitor for a negative nitrogen balance due to
protein catabolism. A liberal protein intake is essential during prolonged therapy.
Evaluate blood pressure and body weight, and do routine laboratory studies,
including 2-hour postprandial blood glucose and serum potassium and a chest xray at regular intervals during prolonged therapy. Upper GI x-rays are desirable in
patients with known or suspected peptic ulcer disease or significant dyspepsia or
in patients complaining of gastric distress. Observe growth and development of
infants and children on prolonged therapy.
Use the lowest possible dose: Make a benefit/risk decision in each individual
case as to the size of the dose, duration of treatment and the use of daily or
intermittent therapy, since complications of treatment are dependent on these
factors.
Use with caution in :
1. GI - Nonspecific ulcerative colitis if there is a probability of impending
perforation, abscess or other pyogenic infection; diverticulitis; fresh intestinal
anastomoses; active or latent peptic ulcer.
2. Cardiovascular - Hypertension; CHF; thromboembolitic tendencies;
thrombophlebitis.
3. Miscellaneous - Osteoporosis; exanthema; Cushing's syndrome; antibioticresistant infections; convulsive disorders; metastatic carcinoma; myasthenia
gravis; vaccinia; varicella; diabetes mellitus.; hypothyroidism, cirrhosis (enhanced
effect of corticosteroids).
4. Steroid psychosis: Steroid psychosis is characterized by a delirious or toxic
psychosis with clouded sensorium. Other symptoms may include euphoria,
insomnia, mood swings, personality changes and severe depression. The onset of
symptoms usually occurs within 15 to 30 days. Predisposing factors include doses
> 40 mg prednisone equivalent, female predominance, and, possibly, a family
history of psychiatric illness. A patient history of psychiatric problems does not
correlate well with predisposition to steroid-induced psychosis. Incidence appears
to correlate with dose. One study of 718 patients treated with prednisone revealed
<= 40 mg/day = 1.3%; 41 to 80 mg/day = 4.6%; >= 80 mg/day = 18.4%. If the
steroids cannot be discontinued, psychotropic medication is effective.
5. Multiple sclerosis: Although corticosteroids are effective in speeding the
resolution of acute exacerbations of multiple sclerosis, they do not affect the
ultimate outcome or natural history of the disease. Relatively high doses of
corticosteroids are necessary to demonstrate a significant effect.
6. Repository injections: To minimize the likelihood and severity of atrophy, do
not inject SC, avoid injection into the deltoid and avoid repeated IM injections
into the same site, if possible. Repository injections are not recommended as
initial therapy in acute situations.
7. Local injections: Intra-articular injection may produce systemic and local
effects. A marked increase in pain accompanied by local swelling, further
restriction of joint motion, fever and malaise is suggestive of septic arthritis.
Appropriate examination of any joint fluid present is necessary. If a diagnosis of
sepsis is confirmed, institute appropriate antimicrobial therapy. Avoid local
injection into an infected site and into unstable joints.
8. Strongly impress patients with the importance of not overusing joints in which
symptomatic benefit has been obtained as long as the inflammatory process
remains active. Frequent intra-articular injection may damage joint tissues.
9. Avoid overdistention of the joint capsule and deposition of steroid along the
needle track in intra-articular injection, as it may lead to subcutaneous atrophy.
While crystals of adrenal steroids in the dermis suppress inflammatory reactions,
their presence may cause disintegration of the cellular elements and
physiochemical changes in the ground substance of the connective tissue.
10. The resultant dermal or subdermal changes may form depressions in the skin at
the injection site; the degree will vary with the amount of adrenal steroid
injection. Regeneration is usually complete within a few months or after all
crystals of the adrenal steroid has been absorbed. In order to minimize the
incidence of dermal and subdermal atrophy, exercise care not to exceed
recommended doses in injections. Make multiple small injections into the area of
the lesion whenever possible.
11. Tartrazine sensitivity: Some of these products contain tartrazine, which may
cause allergic-type reactions (including bronchial asthma) in susceptible
individuals. Although the incidence of tartrazine sensitivity in the general
population is low, it is frequently seen in patients who also have aspirin
hypersensitivity. Specific products containing tartrazine are identified in the
product listings.
12. Sulfite sensitivity: Some of these products contain sulfites which may cause
severe allergic reactions in certain susceptible individuals, particularly asthmatics.
Anaphylactoid and hypersensitivity reactions have occurred. Do not use in
patients allergic to sulfites. Products containing sulfites are identified in product
listings.
Drug/Lab test interactions: Urine glucose and serum cholesterol levels may
increase.
Decreased serum levels of potassium, triiodothyronine (T3), and a minimal decrease of
thyroxine (T4) may occur. Thyroid I131 uptake may be decreased. False-negative results
with the nitroblue-tetrazolium test for bacterial infection. Dexamethasone, given for
cerebral edema, may alter the results of a brain scan (decreased uptake of radioactive
material).
Adverse Reactions:
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Parenteral therapy: Rare instances of blindness associated with intralesional
therapy around the face and head; hyperpigmentation or hypopigmentation;
subcutaneous and cutaneous atrophy; sterile abscess; Charcot-like arthropathy;
burning or tingling, especially in the perineal area (after IV injection); scarring,
induration, inflammation, paresthesia, occasional irritation at the injection site or
occasional brief increase in joint discomfort; transient or delayed pain or soreness;
muscle twitching, ataxia ,hiccoughs and nystagmus (low incidence following
injection); anaphylactic reactions with or without circulatory collapse; cardiac
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arrest; bronchospasm; arachnoiditis after intrathecal use; foreign body
granulomatous reactions involving the synovium with repeated injections.
Intra-articular: Osteonecrosis; tendon rupture; infection; skin atrophy;
postinjection flare; hypersensitivity; facial flushing. Systemic reactions may also
occur.
Intraspinal: Meningitis (tuberculous, bacterial, cryptococcal, aseptic, chemical);
adhesive arachnoiditis; conus medullaris syndrome.
Cardiovascular: Thromboembolism or fat embolism; thrombophlebitis;
necrotizing angiitis; cardiac arrhythmias or ECG changes due to potassium
deficiency; syncopal episodes; aggravation of hypertension; myocardial rupture
following recent MI (see Warnings .)There are reports of cardiac arrhythmias,
fatal arrest or circulatory collapse following the rapid administration of large IV
doses of methylprednisolone (0.5 to 1 g in < 10 to 120 minutes). See Electrolyte
Disturbances.
CNS: Convulsions; increased intracranial pressure with papilledema
(pseudotumor cerebri), usually after stopping treatment; vertigo; headache;
neuritis/paresthesias; aggravation of pre-existing psychiatric conditions; steroid
psychoses.
Dermatologic: Impaired wound healing; thin fragile skin; petechiae and
ecchymoses; erythema; lupus erythematosus-like lesions; suppression of skin test
reactions; subcutaneous fat atrophy; purpura; striae; hirsutism; acneiform
eruptions; other cutaneous reactions such as allergic dermatitis; urticaria;
angioneurotic edema; perineal irritation.
Endocrine: Amenorrhea, postmenopausal bleeding and other menstrual
irregularities; development of cushingoid state (eg, moonface, buffalo hump,
supraclavicular fat pad enlargement, central obesity); suppression of growth in
children; secondary adrenocortical and pituitary unresponsiveness, particularly in
times of stress (eg, trauma, surgery, illness); increased sweating; decreased
carbohydrate tolerance; hyperglycemia; glycosuria; increased insulin or
sulfonylurea requirements in diabetics; manifestations of latent diabetes mellitus;
negative nitrogen balance due to protein catabolism; hirsutism.
Electrolyte disturbances: Sodium and fluid retention; hypokalemia;
hypokalemic alkalosis; metabolic alkalosis; hypocalcemia; CHF in susceptible
patients; hypotension or shock-like reactions; hypertension (see Warnings.)
GI: Pancreatitis; abdominal distension; ulcerative esophagitis; nausea; vomiting;
increased appetite and weight gain. Peptic ulcer with perforation and hemorrhage.
Perforation of the small and large bowel, particularly in inflammatory bowel
disease.
Musculoskeletal: Muscle weakness; steroid myopathy; muscle mass loss; tendon
rupture; osteoporosis; aseptic necrosis of femoral and humeral heads (1% to
37%); spontaneous fractures, including vertebral compression fractures and
pathologic fracture of long bones.
Ophthalmic: Posterior subcapsular cataracts; increased IOP; glaucoma;
exophthalmos.
Miscellaneous: Anaphylactoid/hypersensitivity reactions, aggravation/masking
of infections (see Warnings); malaise; leukocytosis (including neonates receiving
dexamethasone via maternal injection); fatigue; insomnia; increased or decreased
motility and number of spermatozoa.
Over dosage:
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Symptoms: There are two categories of toxic effects from therapeutic use of
glucocorticoids:
Acute adrenal insufficiency: Acute adrenal insufficiency due to too rapid
corticosteroid withdrawal after long-term use resulting in fever, myalgia,
arthralgia, malaise, anorexia, nausea, skin desquamation, orthostatic hypotension,
dizziness, fainting, dyspnea and hypoglycemia.
Cushingoid changes: Cushingoid changes from continued use of large doses
resulting in moonface, central obesity, striae, hirsutism, acne, ecchymoses,
hypertension, osteoporosis, myopathy, sexual dysfunction, diabetes,
hyperlipidemia, peptic ulcer, increased susceptibility to infection and electrolyte
and fluid imbalance. Reports of acute toxicity or death are rare.
Treatment: Recovery of normal adrenal and pituitary function may require up to
9 months. Gradually taper the steroid under the supervision of a physician.
Frequent lab tests are necessary. Supplementation is required during periods of
stress (eg, illness ,surgery, injury). Eventually reduce to the lowest dose that will
control the symptoms or discontinue the corticosteroid completely. For large,
acute overdoses, treatment includes gastric lavage or emesis and usual supportive
measures.
Patient Information:
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May cause GI upset; take with meals or snacks. Take single daily or alternate day
doses in the morning prior to 9 am. Take multiple doses at evenly spaced intervals
throughout the day.
Patients on chronic steroid therapy should wear or carry identification to that
effect.
Notify physician if unusual weight gain, swelling of the lower extremities, muscle
weakness, black tarry stools, vomiting of blood, puffing of the face, menstrual
irregularities, prolonged sore throat, fever, cold or infection occurs.
Signs of adrenal insufficiency include fatigue, anorexia, nausea, vomiting,
diarrhea, weight loss, weakness, dizziness and low blood sugar. Notify physician
promptly if these symptoms occur following dosage reduction or withdrawal of
therapy.
High dose or long-term therapy: Avoid abrupt withdrawal of therapy.
BETAMETHASONE
Administration and Dosage:
Initial dosage: 0.6 to 7.2 mg/day.
BETAMETHASONE SODIUM PHOSPHATE
1-With EDTA, phenol and sodium bisulfite.
Administration and Dosage:
Betamethasone phosphate is highly soluble, has a prompt onset and may be given IV.
Systemic and local: The initial dosage may vary up to 9 mg/day.
BETAMETHASONE SODIUM PHOSPHATE AND BETAMETHASONE ACETATE
1-With EDTA and benzalkonium chloride.
Administration and Dosage:
Betamethasone sodium phosphate provides prompt activity, while betamethasone acetate
is only slightly soluble and affords sustained activity.
Systemic: Not for IV use.
Initial dose: 0.5 to 9 mg/day. Dosage ranges are 1/3 to 1/2 the oral dose given every 12
hours. In certain acute, life-threatening situations, dosages exceeding the usual may be
justified and may be in multiples of oral dosage.
Intrabursal, intra-articular, intradermal and intralesional :
1. Bursitis, tenosynovitis, and peritendinitis: 1 ml.
2. Rheumatoid arthritis and osteoarthritis: 0.5 to 2 ml.
3. Very large joints: 1 to 2 ml.
4. Large joints: 1 ml.
5. Medium joints: 0.5 to 1 ml.
6. Small joints: 0.25 to 0.5 ml.
7. Dermatologic conditions: 0.2 ml/cm2 intradermally.
8. Maximum dose: 1 ml/week.
9. Foot disorders: The following doses are recommended at 3 to 7 day intervals:
10. Bursitis: Under heloma durum or heloma molle – 0.25 to 0.5 ml. Under calcaneal
spur – 0.5 ml. Over hallux rigidus or digiti quinti varus – 0.5 ml.
11. Tenosynovitis, periostitis of cuboid: 0.5 ml.
12. Acute gouty arthritis: 0.5 to 1 ml.
Corticosteroid Retention Enemas
Indications:
Adjunctive therapy in the treatment of ulcerative colitis, including ulcerative proctitis,
ulcerative proctosigmoiditis and left-sided ulcerative colitis. It has proved useful in some
cases involving the transverse and ascending colons.
Actions:
Pharmacology - Hydrocortisone is partially absorbed following rectal administration.
Ulcerative colitis patients have absorbed up to 50% of hydrocortisone administered by
enema.
Contraindications:
Systemic fungal infections; ileocolostomy during immediate or early postoperative
period.
Warnings:
If improvement fails to occur within 2 or 3 weeks, discontinue therapy. Symptomatic
improvement may be misleading and should not be used as the sole criterion in judging
efficacy. Sigmoidoscopic examination and x-ray visualization are essential for adequate
monitoring.
Precautions:
Use with caution where there is a probability of impending perforation or abscess;
pyogenic infections; intestinal anastomoses; obstruction; extensive fistulas and sinus
tracts.
Adverse Reactions:
Local pain or burning; rectal bleeding; apparent exacerbations or sensitivity reactions.
HYDROCORTISONE RETENTION ENEMA
1- In aqueous solution with carboxypolymethylene, polysorbate 80 and methylparaben.
Administration and Dosage:
Usual course of therapy is 100 mg nightly for 21 days, or until clinical and proctological
remission occurs. Clinical symptoms usually subside in 3 to 5 days. Improvement in
mucosal appearance may lag behind clinical improvement. Difficult cases may require 2
or 3 months of treatment. If therapy exceeds 21 days, discontinue gradually.
Corticosteroid Intrarectal Foam
HYDROCORTISONE ACETATE INTRARECTAL FOAM
Indications:
Adjunctive therapy in the treatment of ulcerative proctitis of the distal portion of the
rectum in patients who cannot retain corticosteroid enemas.
Administration and Dosage:
Usual dose is 1 applicatorful once or twice daily for 2 or 3 weeks, and every second day
thereafter. Do not insert any part of the aerosol container into the anus. Satisfactory
response usually occurs within 5 to 7 days. Sigmoidoscopy is recommended to judge
dosage adjustment, duration of therapy and rate of improvement.
Contraindications:
Obstruction; abscess; perforation; peritonitis; recent intestinal anastomoses; extensive
fistulas and sinus tracts.
Warnings:
Because the foam is not expelled, systemic hydrocortisone absorption may be greater
than with corticosteroid enema formulations.
If no clinical or proctologic improvement occurs within 2 or 3 weeks, or if the patient's
condition worsens, discontinue use.
Administer with caution to patients with severe ulcerative disease because these patients
are predisposed to perforation of the bowel wall.
CORTISONE
Administration and Dosage:
The drug is insoluble in water.
Initial dosage: 25 to 300 mg/day (oral). In less severe diseases, lower doses may suffice.
DEXAMETHASONE
Administration and Dosage:
Initial dosage: 0.75 to 9 mg/day.
Acute, self-limited allergic disorders or acute exacerbations of chronic allergic disorders:
In acute, self-limited allergic disorders or acute exacerbations of chronic allergic
disorders, the following dosage schedule combining parenteral and oral therapy (0.75 mg
tablets) is suggested: Dexamethasone sodium phosphate injection, 4 mg/ml:
First day: 1 or 2 ml IM.
Second day: 4 tablets in 2 divided doses.
Third day: 4 tablets in 2 divided doses.
Fourth day: 2 tablets in 2 divided doses.
Fifth day: 1 tablet.
Sixth day: 1 tablet.
Seventh day: No treatment.
Eighth day: Follow-up visit.
Suppression tests :
For Cushing's syndrome: Give 1 mg at 11 pm. Draw blood for plasma cortisol
determination the following day at 8 am. For greater accuracy, give 0.5 mg every 6 hours
for 48 hours. Collect 24 hour urine to determine 17-hydroxycorticosteroid excretion.
Test to distinguish Cushing's syndrome due to pituitary ACTH excess from Cushing's
syndrome due to other causes: Give 2 mg every 6 hours for 48 hours. Collect 24 hour
urine to determine 17-hydroxycorticosteroid excretion.
Unlabeled uses: The dexamethasone suppression test has been used for the detection,
diagnosis and management of depression; however, pending further evaluation and
research, its value is unproven.
DEXAMETHASONE ACETATE
1- With creatinine, polysorbate 80, carboxymethylcellulose, sodium bisulfite, EDTA,
benzyl alcohol.
Administration and Dosage:
A long-acting repository preparation with prompt onset of action.
Not for IV use.
Systemic: 8 to 16 mg IM, may repeat in 1 to 3 weeks.
Intralesional: 0.8 to 1.6 mg .
Intra-articular and soft tissue: 4 to 16 mg; may repeat at 1 to 3 week intervals.
DEXAMETHASONE SODIUM PHOSPHATE
1- With sodium sulfite and benzyl alcohol.
2- With methyl and propyl parabens and sodium bisulfite.
3- With sodium metabisulfite, EDTA and methyl and propyl parabens.
4 - With EDTA, methyl and propyl parabens and sodium bisulfite.
Administration and Dosage:
Has a rapid onset and short duration of action compared to less soluble preparations.
Systemic :
Initial dosage: 0.5 to 9 mg daily. Usual dose ranges are 1/3 to 1/2 the oral dose given
every 12 hours. However, in certain acute, life-threatening situations, dosages exceeding
the usual may be justified and may be in multiples of the oral dosages.
Cerebral edema: In adults, administer an initial IV dose of 10 mg, followed by 4 mg IM
every 6 hours until maximum response has been noted. Response is usually noted within
12 to 24 hours. Dosage may be reduced after 2 to 4 days and gradually discontinued over
5 to 7 days. For palliative management of patients with recurrent or inoperable brain
tumors, maintenance therapy with either the injection or tablets in a dosage of 2 mg 2 or 3
times daily may be effective.
Unresponsive shock: Reported regimens range from 1 to 6 mg/kg as a single IV
injection, to 40 mg initially followed by repeated IV injections every 2 to 6 hours while
shock persists.
Intra-articular, intralesional or soft tissue :
Large joints: 2 to 4 mg.
Small joints: 0.8 to 1 mg.
Bursae: 2 to 3 mg.
Tendon sheaths: 0.4 to 1 mg.
Soft tissue infiltration: 2 to 6 mg.
Ganglia: 1 to 2 mg.
DEXAMETHASONE SODIUM PHOSPHATE WITH LIDOCAINE HCl
1- With EDTA, parabens and sodium bisulfite.
Administration and Dosage:
Dexamethasone sodium phosphate provides prompt activity. Lidocaine HCl is a local
anesthetic with a rapid onset and a duration of 45 minutes to 1 hour (see Local
Anesthetics). (Reference) Steroid activity usually begins by the time the anesthesia
wears off.
Soft tissue injection: Acute and subacute bursitis: 0.5 to 0.75 ml.
Acute and subacute nonspecific tenosynovitis: 0.1 to 0.25 ml.
HYDROCORTISONE (Cortisol)
Administration and Dosage:
Cortisol suspension is insoluble in water.
Initial dosage: 20 to 240 mg/day.
HYDROCORTISONE ACETATE
2-With 4 mg polysorbate 80, 5 mg sodium carboxymethylcellulose and 9 mg benzyl
alcohol per ml.
Administration and Dosage:
Hydrocortisone acetate has a slow onset but long duration of action when compared with
more soluble preparations. Because of its insolubility, it is suitable for intra-articular,
intralesional and soft tissue injection where its anti-inflammatory effects are confined
mainly to the area in which it has been injected, although it is capable of producing
systemic hormonal effects.
For intralesional, intra-articular or soft tissue injection only. Not for IV use.
Large joints (e.g. knee): 25 mg; occasionally, 37.5 mg.
Small joints (e.g. interphalangeal, temporomandibular): 10 to 25 mg.
Tendon sheaths: 5 to 12.5 mg.
Soft tissue infiltration: 25 to 50 mg; occasionally, 75 mg.
Bursae: 25 to 37.5 mg.
Ganglia: 12.5 to 25 mg.
If desired, a local anesthetic may be injected before hydrocortisone acetate or mixed in a
syringe and given simultaneously.
If used prior to intra-articular injection of the steroid, inject most of the anesthetic into the
soft tissues of the surrounding area and instill a small amount into the joint.
If given together, mix in the injection syringe by drawing the steroid in first, then the
anesthetic. In this way, the anesthetic will not be introduced inadvertently into the vial of
the steroid. The mixture must be used immediately and any unused portion discarded.
HYDROCORTISONE CYPIONATE
Administration and Dosage:
Initial dosage: 20 to 240 mg/day.
HYDROCORTISONE SODIUM PHOSPHATE
1- With 3.2 mg sodium bisulfite, and 1.5 mg methylparaben and 0.2 mg propylparaben.
Administration and Dosage:
A water-soluble salt with a rapid onset but short duration of action.
Administer by IV, IM or SC injection.
Initial dosage: 15 to 240 mg/day. Usually, 1/3 to 1/2 the oral dose every 12 hours.
Acute diseases: Doses higher than 240 mg may be required.
HYDROCORTISONE SODIUM SUCCINATE
1- With benzyl alcohol.
Administration and Dosage:
A water-soluble salt which is rapidly active.
May be administered IV or IM. The initial dose is 100 to 500 mg, and may be repeated at
2, 4 or 6-hour intervals depending on patient response and clinical condition.
METHYLPREDNISOLONE
1- With lactose and sucrose.
Administration and Dosage:
Initial dose: 4 to 48 mg/day; adjust until a satisfactory response is noted. Individualize
dosage. Determine maintenance dose by decreasing initial dose in small decrements at
appropriate intervals until reaching the lowest effective dose.
Dosepak 21 therapy: Follow manufacturer's directions.
Alternate day therapy (ADT): Twice the usual dose is administered every other morning.
The patient on long-term treatment receives the beneficial effects of corticosteroids while
minimizing certain undesirable effects. In less severe diseases requiring long-term
therapy, treatment may be initiated with ADT.
METHYLPREDNISOLONE ACETATE
1- With polyethylene glycol and myristyl-gamma-picolinium chloride.
Administration and Dosage:
Because of its low solubility, methylprednisolone acetate has a sustained effect.
Systemic: Not for IV use. As a temporary substitute for oral therapy, administer the total
daily dose as a single IM injection. For prolonged effect, give a single weekly dose.
Adrenogenital syndrome: A single 40 mg injection IM every 2 weeks.
Rheumatoid arthritis: Weekly IM maintenance dose varies from 40 to 120 mg.
Dermatologic lesions: 40 to 120 mg IM weekly for 1 to 4 weeks. In severe dermatitis
(eg, poison ivy), relief may result within 8 to 12 hours of a single dose of 80 to 120 mg
IM. In chronic contact dermatitis, repeated injections every 5 to 10 days may be
necessary. In seborrheic dermatitis, a weekly dose of 80 mg IM may be adequate.
Asthma and allergic rhinitis: 80 to 120 mg IM.
Intra-articular and soft tissue :
Large joints: 20 to 80 mg.
Medium joints: 10 to 40 mg.
Small joints: 4 to 10 mg.
Ganglion, tendinitis, epicondylitis and bursitis: 4 to 30 mg.
Intralesional: 20 to 60 mg.
METHYLPREDNISOLONE SODIUM SUCCINATE
1-With sodium phosphate anhydrous (1.6 mg monobasic, 17.5 mg dibasic), 25 mg lactose
and 9 mg benzyl alcohol.
2-With sodium phosphate anhydrous (1.6 mg monobasic, 17.4 mg dibasic), » 18 mg
benzyl alcohol.
3-With sodium phosphate anhydrous (6.4 mg monobasic, 69.6 mg dibasic). May contain
36 to 70.2 mg benzyl alcohol.
4-With sodium phosphate anhydrous (12.8 mg monobasic, 139.2 mg dibasic). May
contain 66.8 to 141 mg benzyl alcohol.
5-With sodium phosphate anhydrous (25.6 mg monobasic, 278 mg dibasic), 273 mg
benzyl alcohol.
Administration and Dosage:
Highly soluble; has rapid effect by IV or IM routes.
Initial dose: 10 to 40 mg IV, administered over 1 to several minutes. Give subsequent
doses IV or IM.
Infants and children: Not less than 0.5mg/kg/24 hours.
For high dose therapy, give 30 mg/kg IV, infused over 10 to 20 minutes. May repeat
every 4 to 6 hours, not beyond 48 to 72 hours.
PREDNISOLONE
Administration and Dosage:
Initial dosage: 5 to 60 mg/day.
Multiple sclerosis: In treatment of acute exacerbations of multiple sclerosis, 200 mg
daily for a week followed by 80 mg every other day for 1 month.
PREDNISOLONE ACETATE
1- With polysorbate 80, carboxymethylcellulose and benzyl alcohol.
Administration and Dosage:
Relatively insoluble.
Systemic: Not for IV use.
Initial dosage: 4 to 60 mg/day, IM.
Intralesional, intra-articular or soft tissue injection: 4 mg, up to 100 mg.
Multiple sclerosis: 200 mg daily for a week, followed by 80 mg every other day or 4 to 8
mg dexamethasone every other day for 1 month.
PREDNISOLONE TEBUTATE
1- With polysorbate 80, sorbitol and benzyl alcohol.
Administration and Dosage:
Slightly soluble with a slow onset and prolonged duration of action.
Intra-articular, intralesional or soft tissue administration :
Large joints: Large joints (eg, knee) – 20 mg; occasionally, 30 mg. Doses > 40 mg are
not recommended.
Small joints: Small joints (eg, interphalangeal, temporomandibular) - 8 to 10 mg .
Bursae: 20 to 30 mg .
Tendon sheaths: 4 to 10 mg .
Ganglia: 10 to 20 mg.
PREDNISOLONE SODIUM PHOSPHATE
1- With niacinamide, EDTA, phenol and sodium bisulfite.
Administration and Dosage:
Water soluble and rapid acting, but has a short duration of action.
Prednisolone sodium phosphate oral liquid produces a 20% higher peak plasma level of
prednisolone which occurs approximately 15 minutes earlier than the peak seen with
tablet formulations.
Parenteral: For IV or IM use.
Initial dosage: 4 to 60 mg/day.
Intra-articular, intralesional or soft tissue administration :
Large joints (eg, knee) : 10 to 20 mg.
Small joints (eg, interphalangeal, temporomandibular): 4 to 5 mg.
Bursae: 10 to 15 mg.
Tendon sheaths: 2 to 5 mg.
Soft tissue infiltration: 10 to 30 mg.
Ganglia: 5 to 10 mg.
Oral: Initial dosage - 5 to 60 ml (5 to 60 mg base) per day.
Multiple sclerosis (acute exacerbations): 200 mg daily for a week, followed by 80 mg
every other day or 4 to 8 mg dexamethasone every other day for 1 month.
PREDNISONE
Administration and Dosage:
Initial dosage varies from 5 to 60 mg/day. Prednisone is inactive and must be
metabolized to prednisolone. This may be impaired in patients with liver disease.
TRIAMCINOLONE
Administration and Dosage:
Initial daily dosage in specific disorders is :
Adrenocortical insufficiency: 4 to 12 mg, in addition to mineralocorticoid therapy.
Rheumatic and dermatological disorders and bronchial asthma: 8 to 16 mg.
Allergic states: 8 to 12 mg.
Ophthalmological diseases: 12 to 40 mg.
Respiratory diseases: 16 to 48 mg.
Hematologic disorders: 16 to 60 mg.
Tuberculous meningitis: 32 to 48 mg.
Acute rheumatic carditis: 20 to 60 mg.
Acute leukemia and lymphoma (adults): 16 to 40 mg. It may be necessary to give as
much as 100 mg/day in leukemia.
Acute leukemia (children): 1 to 2 mg/kg.
Edematous states: 16 to 20 mg (up to 48 mg) until diuresis occurs.
Systemic lupus erythematosus: 20 to 32 mg.
TRIAMCINOLONE ACETONIDE
1-With polysorbate 80, carboxymethlcellulose and benzyl alcohol.
Administration and Dosage:
Relatively insoluble. Has an extended duration which may be permanent or sustained for
several weeks.
Systemic :
Initial IM dose: 2.5 to 60 mg/day. Not for IV use.
Intra-articular or intrabursal administration and for injection into tendon sheaths :
Initial dose: 2.5 to 5 mg for smaller joints and 5 to 15 mg for larger joints. For adults,
doses up to 10 mg for smaller areas and up to 40 mg for larger areas are usually
sufficient.
Intradermal: Use only 3 mg/ml or 10 mg/ml. Initial dose varies; limit to 1 mg per site.
Clumping results from exposure to freezing temperatures; do not use.
TRIAMCINOLONE DIACETATE
1-With polysorbate 80, polyethylene glycol and benzyl alcohol.
Administration and Dosage:
Slightly soluble providing a prompt onset of action and a longer duration of effect.
Systemic: Not for IV use. May be administered IM for initial therapy; however, most
clinicians prefer to adjust the dose orally until adequate control is attained. The average
dose is 40 mg IM per week. In general, a single parenteral dose 4 to 7 times the oral daily
dose controls the patient from 4 to 7 days, up to 3 to 4 weeks.
Intra-articular and intrasynovial: 5 to 40 mg.
Intralesional or sublesional: 5 to 48 mg. Do not use more than 12.5 mg per injection site.
The usual average dose is 25 mg per lesion.
TRIAMCINOLONE HEXACETONIDE
1- With polysorbate 80, sorbitol and benzyl alcohol.
Administration and Dosage:
Relatively insoluble, slowly absorbed and has a prolonged action.
Not for IV use.
Intra-articular: 2 to 20 mg average.
Large joints (eg, knee, hip, shoulder): 10 to 20 mg.
Small joints (eg, interphalangeal, metacarpophalangeal): 2 to 6 mg.
Intralesional or sublesional: Up to 0.5 mg per square inch of affected area.
10.1 Mineralocorticoids
FLUDROCORTISONE ACETATE
Indications:
 Partial replacement therapy for primary and secondary adrenocortical
insufficiency in Addison's disease and for the treatment of salt-losing
adrenogenital syndrome.
 Unlabeled uses: Fludrocortisone 100 to 400 mcg/day has been used in the
management of severe orthostatic hypotension.
 Administration and Dosage:
 Addison's disease: The usual dose is 0.1 mg/day (range 0.1 mg 3 times a week to
0.2 mg/day). If transient hypertension develops as a consequence of therapy,
reduce the dose to 0.05 mg/day. Administration in conjunction with cortisone (10
to 37.5 mg/day )or hydrocortisone (10 to 30 mg/day) is preferable.
 Children and adults: Another recommended dose is 0.05 to 0.1 mg/24 hours.
 Infants: A recommended dose is 0.1 to 0.2 mg/24 hours.
 Salt-losing adrenogenital syndrome: 0.1 to 0.2 mg/day.
Actions:
Pharmacology - Fludrocortisone is an adrenal cortical steroid with potent
mineralocorticoid activity and high glucocorticoid activity (about 15 times as potent as
hydrocortisone), but is used only for its mineralocorticoid effects. Mechanism:
Mineralocorticoids act on the renal distal tubules to enhance the reabsorption of sodium.
They increase urinary excretion of both potassium and hydrogen ions. The consequence
of these three primary effects together with similar actions on cation transport in other
tissues appears to account for the spectrum of physiological activities characteristic of
mineralocorticoids.
In small oral doses, fludrocortisone produces marked sodium retention and increased
urinary potassium excretion. It also causes a rise in blood pressure, apparently because of
these effects on electrolyte levels. In larger doses, fludrocortisone inhibits endogenous
adrenal cortical secretion, thymic activity, and pituitary corticotropin excretion, it
promotes the deposition of liver glycogen, and, unless protein intake is adequate, it
induces negative nitrogen balance.
Pharmacokinetics - Fludrocortisone is readily absorbed from the GI tract with peak
concentrations in 1.7 hours. Plasma half-life is approximately 3.5 hours, but biological
half-life ranges from 18 to 36 hours.
Contraindications:
Hypersensitivity to fludrocortisone; systemic fungal infections.
Warnings:
Supplemental measures: Use mineralocorticoid therapy preferably in conjunction with
other supplemental measures (eg, glucocorticoids, control of electrolytes, control of
infection).
Adrenal insufficiency: To avoid drug-induced adrenal insufficiency, supportive dosage
may be required in times of stress (eg, trauma, surgery, severe illness), both during
treatment with fludrocortisone and for a year afterwards.
Pregnancy: Category C. Safety for use during pregnancy has not been established. Use
only when clearly needed and when the potential benefits outweigh the potential hazards
to the fetus. If it is necessary to give steroids during pregnancy, observe the newborn
infant for signs of adrenocortical insufficiency and institute appropriate therapy, if
necessary.
Lactation: Corticosteroids are found in the breast milk of lactating women. Exercise
caution when administering to nursing women.
Children: Safety and efficacy for use in children have not been established. Monitor
growth and development of infants and children on prolonged therapy.
Precautions:
Addison's disease: Patients with Addison's disease are more sensitive to the action of
the hormone and may exhibit side effects in an exaggerated degree. Closely monitor
patients and stop treatment if a significant increase in weight or blood pressure, edema or
cardiac enlargement occurs.
Sodium retention and potassium loss: Sodium retention and potassium loss are
accelerated by a high sodium intake. If edema occurs, restrict dietary sodium. Perform
frequent blood electrolyte determinations; potassium supplementation may be necessary.
Infection: Monitor patients for evidence of intercurrent infection. Should this occur,
initiate appropriate anti-infective therapy.
Adverse Reactions:
Side effects may occur if dosage is too high or prolonged or if withdrawal is too rapid.
Because it possesses glucocorticoid activity, fludrocortisone may cause side effects
similar to those of the glucocorticoids.
Cardiovascular: Edema; hypertension; CHF; enlargement of the heart.
Dermatologic: Bruising; increased sweating; hives or allergic skin rash.
Miscellaneous: Hypokalemic alkalosis.
Overdosage:
 Symptoms: Hypertension; edema; hypokalemia; excessive weight gain; increase
in heart size.
 Treatment: Discontinue the drug; symptoms usually subside within several
days. Resume subsequent treatment with reduced doses. Muscular weakness may
develop due to excessive potassium loss; treat with potassium supplements.
Monitor blood pressure and serum electrolytes regularly.
 Patient Information:
 Notify physician if dizziness, severe or continuing headaches, swelling of feet or
lower legs, or unusual weight gain occurs