Download Lesson 12

Lesson 12
Medications (drugs)
Ex 1. Key-words:
1
endocrine problems
2
corticosteroids
3
adrenal cortex
4
blood electrolyte levels
5
behavior
6
the zona fasciculata and reticularis
7
Inhaled steroids
8
to treat the nasal mucosa, sinuses,
bronchii, and lungs
9
injectables for intravenous and parenteral
routes
10
brain tumors
11
adrenal insufficiency and congenital
adrenal hyperplasia
12
hyperglycemia
13
insulin resistance
14
diabetes mellitus
15
gastritis
16
colitis
17
ictus
18
erectile dysfunction
19
hypogonadism
20
hypothyroidism
21
amenorrhoea
22
retinopathy
1 болезни эндокринной системы
2 кортикостероиды
3 надпочечная кора
4 уровень электролита крови
5 поведение
6 опоясывающий лишай fasciculata и
reticularis
7 вдыхавших стероидов
8, рассматривать носовую слизистую
оболочку, пазухи, bronchii, и легкие
9
injectables
для
внутривенных
и
парентеральных маршрутов
10 опухоли головного мозга
11 надпочечные недостаткои и врожденные
надпочечник
12 гипергликемия
13 сопротивление инсулина
14 диабет
15 гастрит
16 колит
17 удар
18 способных выпрямляться дисфункций
19 hypogonadism
20 гипотиреоз
21 аменорея
ретинопатия
Ex 2. Read and translate the following:
C21H30O4, C21H28O5, 17-hydroxy-11-dehydrocorticosterone, 21-hydroxylase and 17αhydroxylase, 11β-hydroxylase, an 18-oxidation, hydrocortisone-17-butyrate, hydrocortisone-17valerate, aclometasone dipropionate, betamethasone valerate, betamethasone dipropionate,
prednicarbate, clobetasone-17-butyrate, clobetasol-17-propionate, fluocortolone caproate,
fluocortolone pivalate, and fluprednidene acetate, 5-HT3 antagonists,
Ex 3. Read some information about “Drugs for endocrine problems”:
For endocrine problems
androgens, antiandrogens, gonadotropin, corticosteroids, human growth hormone,
insulin, antidiabetics (sulfonylureas, biguanides/metformin, thiazolidinediones, insulin), thyroid
hormones, antithyroid drugs, calcitonin, diphosponate, vasopressin analogues.
Text 25. Corticosteroid
Definition. Corticosteroids are a class of steroid hormones that are produced in the
adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress
response, immune response and regulation of inflammation, carbohydrate metabolism, protein
catabolism, blood electrolyte levels, and behavior.

Glucocorticoids such as cortisol control carbohydrate, fat and protein metabolism
and are anti-inflammatory by preventing phospholipid release, decreasing eosinophil action and
a number of other mechanisms.

Mineralocorticoids such as aldosterone control electrolyte and water levels,
mainly by promoting sodium retention in the kidney.
Some common natural hormones are corticosterone (C21H30O4), cortisone (C21H28O5,
17-hydroxy-11-dehydrocorticosterone) and aldosterone.
Biosynthesis. The corticosteroids are synthesized from cholesterol within the adrenal
cortex. Most steroidogenic reactions are catalysed by enzymes of the cytochrome P450 family.
They are located within the mitochondria and require adrenodoxin as a cofactor (except 21hydroxylase and 17α-hydroxylase).
Aldosterone and corticosterone share the first part of their biosynthetic pathway. The
last part is either mediated by the aldosterone synthase (for aldosterone) or by the 11βhydroxylase (for corticosterone). These enzymes are nearly identical (they share 11βhydroxylation and 18-hydroxylation functions) but aldosterone synthase is also able to perform
an 18-oxidation. Moreover, aldosterone synthase is found within the zona glomerulosa at the
outer edge of the adrenal cortex; 11β-hydroxylase is found in the zona fasciculata and reticularis.
Classification. Corticosteroids are generally grouped into four classes, based on
chemical structure. Allergic reactions to one member of a class typically indicate an intolerance
of all members of the class. This is known as the "Coopman classification” 1989.
Group
A
(short
to
medium
acting
glucocorticoids)
hydrocortisone, hydrocortisone acetate, cortisone acetate, tixocortol pivalate, prednisolone,
methylprednisolone, and prednisone.
Group B (triamcinolone acetonide, triamcinolone alcohol, mometasone, amcinonide,
budesonide, desonide, fluocinonide, fluocinolone acetonide, and halcinonide).
Group C (betamethasone, betamethasone sodium phosphate, dexamethasone,
dexamethasone sodium phosphate, and fluocortolone).
Group D (hydrocortisone-17-butyrate, hydrocortisone-17-valerate, aclometasone
dipropionate, betamethasone valerate, betamethasone dipropionate, prednicarbate, clobetasone17-butyrate, clobetasol-17-propionate, fluocortolone caproate, fluocortolone pivalate, and
fluprednidene acetate).
Inhaled steroids for use to treat the nasal mucosa, sinuses, bronchii, and lungs. This
group includes:

Flunisolide

Fluticasone propionate

Triamcinolone acetonide

Beclomethasone dipropionate

Budesonide
Oral forms such as prednisone and prednisolone.
Systemic forms are available in injectables for intravenous and parenteral routes.
Uses of corticosteroids. Synthetic pharmaceutical drugs with corticosteroid-like effect
are used in a variety of conditions, ranging from brain tumors to skin diseases. Dexamethasone
and its derivatives are almost pure glucocorticoids, while prednisone and its derivatives have
some mineralocorticoid action in addition to the glucocorticoid effect. Fludrocortisone (Florinef)
is a synthetic mineralocorticoid. Hydrocortisone (cortisol) is available for replacement therapy,
e.g. in adrenal insufficiency and congenital adrenal hyperplasia.
Synthetic glucocorticoids are used in the treatment of joint pain or inflammation
(arthritis), temporal arteritis, dermatitis, allergic reactions, asthma, hepatitis, systemic lupus
erythematosus, inflammatory bowel disease (ulcerative colitis and Crohn's disease), sarcoidosis
and for glucocorticoid replacement in Addison's disease or other forms of adrenal insufficiency.
Topical formulations are also available for the skin, eyes (uveitis), lungs (asthma), nose
(rhinitis), and bowels. Corticosteroids are also used supportively to prevent nausea, often in
combination with 5-HT3 antagonists (e.g. ondansetron).
Typical undesired effects of glucocorticoids present quite uniformly as drug-induced
Cushing's syndrome. Typical mineralocorticoid side effects are hypertension (abnormally high
blood pressure), hypokalemia (low potassium levels in the blood), hypernatremia (high sodium
levels in the blood) without causing peripheral edema, metabolic alkalosis and connective tissue
weakness. There may also be impaired wound healing or ulcer formation because of the
immunosuppressive effects.
Clinical and experimental evidence indicates that corticosteroids can cause permanent
eye damage by inducing central serous retinopathy (CSR, also known as central serous
chorioretinopathy, CSC). A variety of steroid medications, from anti-allergy nasal sprays
(Nasonex, Flonase) to topical skin creams, to eye drops (Tobradex), to prednisone have been
implicated in the development of CSR.
Side effects. Long-term corticosteroids use has several severe side effects as for
example: hyperglycemia, insulin resistance, diabetes mellitus, osteoporosis, anxiety, depression,
gastritis, colitis, hypertension, ictus, erectile dysfunction, hypogonadism, hypothyroidism,
amenorrhoea, retinopathy.
Text 26. Gliclazide
Definition. Gliclazide is an oral hypoglycemic (anti-diabetic drug) and is classified as a
sulfonylurea. It is marketed as Glyloc and Reclide in India and Diamicron in Canada. The
modified-release formulation are also marketed now.
Its classification has been ambiguous, as literature uses it as both a first-generation and
second-generation sulfonylurea.
Form and Composition. Each tablet contains 80, 60, or 30 mg of gliclazide.
Gliclazide is not marketed in the United States and Philippines. In the Philippines, it is
marketed under the brandname of Glubitor-OD in 30 mg or 80 mg doses.
Indication. Gliclazide is used for control of hyperglycemia in gliclazide-responsive
diabetes mellitus of stable, mild, non-ketosis prone, maturity-onset or adult type. It is used when
diabetes cannot be controlled by proper dietary management and exercise or when insulin
therapy is not appropriate.
Mode of Action. Gliclazide binds to sulfonylurea receptors on the surface of the Beta
islet cells found in the pancreas. This binding effectively closes the K+ ion channels. This
decreases the efflux of potassium from the cell which leads to the depolarization of the cell. This
causes voltage dependent Ca++ ion channels to open increasing the Ca++ influx. The calcium
can then bind to and activate calmodulin which in turn leads to exocystosis of insulin vesicles
leading to insulin release.
Dosage. The dosage is 40 to 320 mg depending on the response of the patient. The drug
is taken once or twice daily before food, with no more than 160 mg being ingested at a time.
Properties

Hypoglycemic sulfonylurea, restoring first peak of insulin secretion, increasing
insulin sensitivity.

Glycemia-independent hemovascular effects, antioxidant effect.

No active circulating metabolites.
Contraindications

Type 1 diabetes

Hypersensitivity to sulfonylureas

Severe renal or hepatic failure

Pregnancy and lactation

Miconazole coprescription
Metabolism. Gliclazide undergoes extensive metabolism to several inactive metabolites
in humans, mainly methylhydroxygliclazide and carboxygliclazide. CYP2C9 is involved in the
formation of hydroxygliclazde in human liver microsomes and in a panel of recombinant human
P450sin vitro. But the pharmacokinetics of gliclazide MR are affected mainly by CYP2C19
genetic polymorphism instead of CYP2C9 genetic polymorphism.
Interactions. Hyperglycemic action may be caused by danazol, chlorpromazine,
glucocorticoids, progestogens, or β-2 agonists. Its hypoglycemic action may be potentiated by
phenylbutazone, alcohol, fluconazole, β-blockers, and possibly ACE inhibitors. It has been found
that rifampin increases gliclazide metabolism in humans in vivo.
Adverse effects

Hypoglycemia

Gastrointestinal disturbance (reported)

Skin reactions (rare)

Hematological disorders (rare)

Hepatic enzyme rises (exceptional)
Overdosage. Gliclazide overdose may cause severe hypoglycemia, requiring urgent
administration of glucose by IV and monitoring.
Ex 4. Speak about side effects of corticosteroids. Why it happens?
Ex 5. Writing. Write a report to the conference “Medications of new century”. Follow
the sample.
A Report to the Conference
Plan
1.
Introduction.
2.
Starting the target. Define clearly the purpose of your report.
3.
Providing an overview. Outline the main points of the report.
4.
Conclusion.
5.
References.