Pharm Adrenocortigoids and Antag Part 1

Answer: C
(Katzung, pp 640, Brunton, pp 1600)
Glucocorticoids inhibit the synthesis of almost all known cytokines, including the macrophagemediated
production of tumor necrosis factor (TNF). This cytokine has proinflammatory,
oncostatic and chemotactic properties which play interacting roles in the function of the immune
system.
A, B, D, E) Glucocorticoids can exert all these actions but they do not contribute significantly to
the immunosuppressive effect of these drugs.

Answer: D
(Katzung, pp 644, Brunton, pp 1595)
Immunologic thrombocytopenic purpura is, in most adults, a chronic disorder that results from
development of an antibody directed against a structural platelet antigen. Treatment in the adult
is usually begun with a large dose of an oral glucocorticoid, like prednisone. The mechanism of
action of all steroid drugs involves binding to a receptor-heat-shock protein complex in the
cytoplasm.
A, C, E, F) The mechanism of action of these drugs also involves binding to a receptor-heatshock
protein complex in the cytoplasm, but these drugs are not used in autoimmune diseases.
B) Azathioprine is an immunosuppressant drug sometimes used in immunologic
thrombocytopenic purpura, but its mechanism of action is different from the one described
above.

Answer: E
(Katzung, pp 1032, Brunton, pp 1600)
Crohn disease is a chronic inflammatory bowel disease of unknown origin. The antiinflammatory
effect of glucocorticoids, which may dramatically reduce fever diarrhea and abdominal pain in
the acute stage of the disease, is due to many actions, including inhibition of lymphocytemediated
production of interleukin-2. This cytokine induces proliferation of B and T cells (including cytotoxic T cells) and activation of natural killer cells and lymphokine-activated killer
cells, an therefore it plays a main role in inflammatory processes.
A) Glucocorticoids have no effect on the metabolism of prostaglandins
B, C, D) Glucocorticoids have effect opposite to those listed.

Answer: C
(Katzung, pp 636, Brunton, pp 1596)
Corticosteroids are sufficiently lipid soluble to cross the membrane of the target cells. In the
cytoplasm they bind to a corticosteroid receptor-heat-shock protein complex and this binding
releases the heat-shock protein. The hormone-receptor complex is then transported into the
nucleus where it binds to specific nucleotide sequences along the DNA, called glucocorticoid (or
mineralocorticoid) response elements. This binding alters the transcription so modulating the
expression of specific genes.
A, B, D, E, F) (see explanation above)

Answer: C
(Katzung, pp 646, Brunton, pp 1609)
Because of their antiinflammatory and immunosuppressive actions glucocorticoids are generally
contraindicated in infectious disease. Few infectious diseases however (i.e. Pneumocystis carinii
pneumonia and Haemophilus influenzae meningitis in infants) can be effectively treated with
corticosteroids.
A, B, D, E) glucocorticoid are use extensively, not rarely, in these diseases.

Spironolactone is a mineralocorticoid antagonist. It blocks the effects of aldosterone, a hormone that regulates sodium and water balance in the body. By inhibiting aldosterone, spironolactone helps to reduce fluid retention and lower blood pressure. It is commonly used to treat conditions such as hypertension, heart failure, and edema.

Ketoconazole is a drug that inhibits several steps of steroidogenesis requiring cytochrome P450 enzymes.

Mifepristone is a drug that blocks the cytoplasmic glucocorticoid receptors.

Answer: B
(Katzung, pp 647, Brunton, pp 1603)
In a person under treatment for adrenal insufficiency the high blood pressure, the low K+ levels
and the ECG data suggest that the symptoms and signs of the patient are due to an excessive
dose of fludrocortisone, a mineralocorticoid currently used to treat Addison disease.
A, D) Hyperglycemia or myopathy induced by cortisol excess would not cause the patient’
symptoms and signs.
C) An inadequate therapy of adrenal insufficiency would have caused symptoms opposite to
those exhibited by the patient.
E) The patient has a high blood pressure, but in a person with adrenal insufficiency essential
hypertension is unlikely. The high blood pressure is more likely due to an excessive dose of the
mineralocorticoid used for treatment.

Dexamethasone is a glucocorticoid that does not have salt retaining activity.

Aminoglutethimide is a drug that blocks the conversion of cholesterol to pregnenolone.

Fludrocortisone is a mineralocorticoid that is used to treat adrenal insufficiency. It helps to replace or supplement the body's natural mineralocorticoids, which are hormones that regulate salt and water balance in the body. By taking fludrocortisone, it can help to prevent low blood pressure, electrolyte imbalances, and other symptoms associated with adrenal insufficiency.

Answer: E
(Katzung, pp 302, Brunton, pp 657)
The antiinflammatory effects of glucocorticoids is mediated by a vast array of actions including
the induction of the synthesis of lipocortins. These enzymes act as inhibitors of phospholipase
A2, the enzyme that catalyzes the release of arachidonic acid from membrane phospholipids.
Since arachidonic acid is the precursor of eicosanoids, the corticosteroid induced induction of
lipocortins leads to an inhibition of phospholipase A2 and in turn to an inhibition of biosynthesis
of all eicosanoids, which are proinflammatory compounds.
A) Glucocorticoids inhibit ACTH release but this contributes very little to the antiinflammatory
effect.
B, C D) Glucocorticoids do not influence the catabolism of prostaglandins and decrease, not
increase capillary permeability and the release of interleukin 1.

(Katzung, pp 636, Brunton, pp 1601, Koda-Kimble pp 44-7)
Corticosteroids are very lipid soluble drugs and therefore they can be easily absorbed by oral
route and even though the intact skin. Their plasma half lives are short (1-6 hours) but since they
lives) can be quite long.
C) Since corticosteroids are very lipid soluble they widely distribute in all tissues, including brain
E) As a rule a lipid soluble drug is mainly biotransformed by the liver and corticosteroids are not
exceptions to this rule.

Answer: CD
(Katzung, pp 640, Brunton, pp 1597)
Effects of glucocorticoids on intermediary metabolism can be viewed as protecting glucose
dependent tissue (brain and heart) from starvation. To this end they increase glycogen synthesis
and storage in liver and diminish glucose utilization in the periphery, therefore decreasing
glucose uptake by adipose tissue. The net results of all these effect is to increase blood glucose
levels.
A, B, E) Actually glucocorticoids have actions opposite to those listed .