Download Sheet#6,Dr.Alia,Marwh Nsour

6-3-2014
pharma sheet #6
marwh nsour
In the last lecture , we talked about adrenalin glands starting with Glucocorticoid hormones
which secreted from fasciculate layer in adrenalin gland and we said that glucocorticoid can be
used as anti-inflammatory or immunosuppressive agent ,due to the fact that glucocorticoid
work in( inhibit ) phospholipaseA enzyme and COX 11 enzyme , that has role in synthesis of
leukotreines , prostaglandin , interleukins ( inflammatory mediators ) , there is other
mechanisms by which glucocorticoid work but this is the main one . Also we discuss some of
disease related to adrenals gland , now we will start by another adrenal disorder which is
conn’s syndrome .
Primary Aldosteronism also known >>(Conn’s Syndrome)
•
This disease happens due to Excess mineralocorticoid (aldosteron ) production , due to
hyperactivity or tumor of the adrenals cortex particularly in it’s Outer layer : zona
glomerulosa .
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Remember : Aldosterone work in Na and water reabsorbtion and on (Ca, Mg )
excretion from kidney , due to this fact when there excessive production of aldosteron
the patient will suffer from hypertension “ hyper volumic “ .
•
We all know that renin-angiotensin pathway play a role in aldosteron secretion from
kidneys, and because we have high level of this hormone so PRA ( plasma renin
activity )and angiotensin II not needed and it will be suppressed .
•
Treatment: spironolactone (aldosteron anatagonist ) but this drug has a major side
effect in male which is gynaecomastia ( enlargement of the breast in males) .
Glucocorticoid and blood cancers
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We can use glucocorticoid drugs ( ex :Prednisolone ,Dexamethasone ) as a perfect
treatment of blood cancer : multiple myeloma , leucocytic leukemia .
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Glucocorticoid attach to a specific receptors inside the nucleus and together work as a
nuclear transcription factor. They increase transcription of certain genes related to
apoptosis “ programed cell death “ or genes play role in cell cycle arrest so by that
glucocorticoid stop multiplication and proliferation of these cancer cells .
•
multiple myeloma : tumor affect plasma cells in blood this can be treated also
by thalidomide , very old drug used in prevention of nausea in pregnant women but
unfortunately these women deliver babies with missing or fused limbs , so thalidomide
is consider as teratogenic drug ( malformed baby ) so must not be used by pregnant
women . But later on they discover that this drug can be used in treatment of multiple
6-3-2014
pharma sheet #6
marwh nsour
myeloma so nowadays is consider as drug can be use beside glucocorticoid to treat
multiple myeloma .
note : thalidomide involved in X category of drugs. X categeory mean that : drugs
which included in it has a teratogenic effect so must not be used in pregnant women.
Another example of drugs related to x category is isotretinoin ( related to "topical
retenoids" ) ,, a common effective drug used to treat acne valgaries used in a long term
treatment for 3-6 months. They are very effective but has many side effects .
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Again , glucocorticoid as an anti -inflammatory or immunosuppressive agent
work by :
1- inhibit synthesis of prostaglandins, by inhibiting phospholipase A enzyme.
2- affect cell mediated immunity ((supress cytokines which attract a phagocytic immune
cell (cell migration) and other cytokines play roles in antigen recognition)).
Important note : Steroids are NOT effective inhibitors of antibody synthesis.
Glocucorticoid sides effect :
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symptoms like those which appear in cushing syndrome ( is a disease characterized by
excessive production of gloucocorticoid hormones from adrenaline gland ) :
 Buffalo Hump
 Moon Face
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Symptoms like those which appear in Conn’s disease : hypertension
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peptic ulcer ( by inhibition OF prostaglandin synthesis which has an important role in
inhibition of gastric acid secretion and activate mucous production in GIT ). SO when
there is no prostaglandin --> peptic ulcer may occur .
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hyperglycemia, protein wasting, hyperlipidemia, obesity.
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myopathy, growth failure, osteopenia , osteoporosis .
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cataracts, glaucoma.
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In relation to aldosteron : Na+ retention, K+ loss, negative Ca++ balance,
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glucosuria.
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pharma sheet #6
marwh nsour
•
On Skin : Purpura (bleeding under skin ) .
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Cushingoid appearance with truncal obesity ( appear obese around trunk )
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increased risk for bacterial, fungal, viral infections due to that it has
immunocompromised effect .
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Suppression HPA “ hypothalamus pituitary adrenaline axis “ when use in chronic way
more than 1 month or in high doses. SO in this case must not to withdrawal
glucocorticoid suddenly (Cold turkey ) since the HPA is suppressed so there will be no
normal level of cortisone in our body for a period of time after discontinuation so
preferable to stop drug in graduate manner .
Note : we can’t tell exactly how and when we can stop these drugs ,, just from the
duration ,, that also depend in many factors :
1- kind of drug “ mainly the potency “
2-dose
3-the clinical condition the drug used for it
4- duration of action
There is slide has alots of disorders can be treated by glucoctricoid , what we need to know is
just a general idea about these disorder ,that most of them : immune disorders ;
autoimmunodisease , inflammatory conditions but later in this sheet we will focus about some
of these disorders which realted to dentistry .
Now we will talk about some of glucocorticoid synthetic drugs :
Prednisolone
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Predominant glucocorticoid activity and low mineralocorticoid activity.
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useful for the treatment of a wide range of inflammatory and auto-immune conditions.
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Directly can be used as ophthalmic suspension (eye drops) to treat certain inflammatory
rxn in eye.
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Used in multiple myeloma and leukemia
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an immunosuppressive drug for organ transplants --> ( suppress body immune response
against the new transplanted organ )
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pharma sheet #6
marwh nsour
Dexamethasone
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Another drug Used in many inflammatory and autoimmune conditions .
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It is also given after some forms of dental surgery, such as the extraction of the
wisdom teeth , an operation which often leaves the patient with puffy, swollen
cheeks,, but of course this drug will not prevents infection so we must use
antibiotic and the first antibiotic of choice in dentistry is amoxiclline
Antiglucocorticoid drugs (synthetic inhibitors )
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Metyrapone: blocks 11-hydroxylase
increases ACTH synthesis .
•
Aminoglutethimide : blocks conversion of cholesterol to pregnenalone (first step of
conversion is cholesterol --> glucocorticoid ) .
Used in Cushing’s syndrome .
•
Ketoconazole ( antifungal ): Inhibit steroid synthesis at high doses / affect multiple
enzymes in pathway of synthesis .
Used in Cushing’s syndrome .
•
Mifepristone (RU486):
It is a progesterone antagonist, so one of its main uses abortifacien “eliminate
pregnancy “ .
note : this drug used in treatment , when other mentioned drugs will not work will .
6-3-2014
pharma sheet #6
marwh nsour
Dental uses of corticosteroids
There is a lot of uses for corticosteroid in dentistry , some of these drugs used
topically others used systematically :
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In minor conditions like pulp capping, pulpotomy we can use topical corticosteroid.
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But there is also more serious autoimmune disease that affect oral cavity like : oral
pemphigus, oral lichen planus.
•
Other serious diseases affect oral cavity ; TMJ arthritis symptoms , desquamative
gingivitis.
oral lichen planus
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is an autoimmune disease of unknown etiology. There is antibodies attack parts
of skin or mucous membrane so may affect membrane of the GIT or urinary
tract and also the oral cavity .
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appear as purple lesion has stria !! “ white lines “
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the important about lichen planus that , certain dental material can induce it
like amalgam ( make lichenoid rxn )
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treatment topical : if it localized
systemic : if the disease affect more than one region in the body
oral pemphigus
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another auoimmuno disease cuze destruction to epithelium cell and can cuze
ulceration for skin and mucosa of oral cavity
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pharma sheet #6
marwh nsour
•
these lesions make the patient more susceptible to infection like whitish
candidia appear in figure below
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treatment : Dexamethasone ointment , Triamcinolone acetonide oral gel ( can
also be used to treat aphtas ! “” which is ulceration of oral mucosa that occur
due stress or may occur without underlining cuze “”” ....so we use to treat
signs of any inflammation in oral cavity .
note ; these ointments may contain analgesia to relieve pain that associated
with these inflammation.
* also we can use a combination of : “”Nystatin””
which is antifungal drug + Triamcinolone Acetonide (Mycogen) , in treatment
of Candidiasis in oral cavity .
Lupus erythematosus : wolf syndrome
( systematic autoimmune disease can affect oral cavity )
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auto immune disease
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more serious than oral lichen planus
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skin lesion and mucosa lesion
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ulceration on oral cavity
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can affect kidney , liver ,heart
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need systematic treatment of glucocorticoid
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face of patient has a butterfly appearance around the nose
6-3-2014
pharma sheet #6
marwh nsour
Erythema Multiforme
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autoimmune disease can predispose by viral infection , EBV
(Epstein Barr virus ), this virus stimulate autoimmuno rxn in
people who’s infected.
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something special about this disease is target lesion : red
circular lesion surrounding ulceration .
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also it can affect other tissue mainly the eye and in this case
called , Steven-Johnson Syndrome .
Now , as a dentist when we deal with patient at our chair . FIRSTLY ,we must
take a good medical history , so if your patient in past is on a corticosteroid
therapy at least for 2 weeks and he stop it before coming to ur clinic by 1-2
years , discontinuous it ,or he still in corticosteroid therapy ,u must know , why
? that important due to fact in a stressful situation our glucocorticoid level must
be at normal level or more , on the other hand , those patient who in past
used steroid treatment and stop it or still on treatment , there glands need
about 9 month or more to retain it’s ability to produce normal amount of
corticosteroid which needed to be higher than normal while doing ur dental
procedure on them . so as a dentist u must give them cortisone supplement
before starting any dental procedure .
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so what’s occur to your patients if you not adjust there corticosteroid level while you
do dental procedure for them : ((Hypotension/ Severe weakness/Progressive mental
confusion/ Nausea and vomiting/ Abdominal, lower back or leg pain /Hyperthermia
/Hypoglycemia/ Hyperkalemia /Loss of consciousness /Coma /death)) .
6-3-2014
pharma sheet #6
marwh nsour
Dental patient taking steroid supplementation not required, when ?
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Patient taking low dose (<20 mg of cortisol daily)
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Patient taking large dose: for less than 2 weeks
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for minor dental procedure with minimal stress “” but that depend on state of patient
some of them even with minor procedure will be in fair and high stress “” .
Dental patient taking steroid supplementation required, when ?
1-
Patient taking large dose ( >20 mg ) : for greater than 2 weeks and still on therapy
for extensive major or stressful dental procedure .
how adjust the that ?
＃ Double usual daily dose on the day before, the day of dental surgery , and the day after
surgery
＃ take it (corticosteroid ) in the morning of the above mentioned days “ to have larger effect
since in normal situation corticosteroid reach there highest level at morning “ .
＃ Good pain control
＃ Resume normal maintenance dose ,2 days post-operative .
2- If the patient received at least 20mg of cortisol for more than 2 weeks within past year .
How to adjust that ?
＃ give them 60mg cortisol(or equivalent) the day before and the day of surgery at morning
＃ On first 2 post-operative days, give 40mg cortisol
＃ Then take 20mg cortisol thereafter, until post-operative 6 days ( ya3ne for 4 days ).
Management of adrenal crisis
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Transportation of patient to a medical facility as soon as possible while that :
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Place the patient in a supine position with leg elevated ( to elevate blood pressure )
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pharma sheet #6
marwh nsour
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200 mg hydrocortisone IV stat repeated as necessary
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Do Oxygen and CPR if necessary “ to maintain his conciseness to not go in coma “
In one of dr slides there is a table u need to know the below things about :
Short Acting GC : Cortisol /Cortisone /Prednisone /Prednisolone /Methylprednisolone .
Intermediate Acting GC : Triamcinolone /Fluprednisolone .
Long Acting GC : Betamethasone /Dexamethasone .
Mineralocorticoids : Fludrocortisone /Desoxycorticosterone citrate
Drug Interactions
•
Anticonvulsant drugs (phenytoin and carbamazepine): potent inducer of glucocorticoid
metabolism “” inducer for cyp53 enzymes which responsible for glucocorticoid
metabolism “”
Finally , dr add extra note about Congenital Adrenal Hyperplasia “from previous lecture “ :
which is Familial disorder of cortisol synthesis enzyme deficiency , with Excessive ACTH
production , since ACTH can affect synthesis of androgen not just cortisone , and there is
excessive production of ACTH so there will be over production of androgens ,,what important to
know is the side effects :



virilization ( female get male characteristics )
accelerated growth
early epiphyseal plate closure
note that : cortisol synthesis is decreased although ACTH level is high , cuze there is a
deficiency in the enzymes that have a role in cortisole synthesis , and the Most common
enzyme affected but not the only one is 21 hydroxylase enzyme .
Marwh nsour
Good luck :D