Download Problemset 6

1) Sort the drugs below in order of the anticipated onset of their blood glucose lowering
effect:
A. Tolbutamide
B. Insulin
C. Troglitazone
1)Insulin acts immediately. 2) Tolbutamide triggers the release of existing insulin.
3) Glitazones act by transcriptionally upregulating insulin signaling components =
slowest
2)
Nicorandil is a new drug of the nitrate group (NO donor) that is used to treat angina
pectoris. An additional effect of nicorandil is the opening of ATP-gated potassium
channels. What are likely side effects and drug interactions of this drug?
As an activator of ATP-gated potassium channels Nicorandil will inhibit insulin
secretion from the beta-islet cells. It opposes in its mechanism the actions of
sulfonyl-urea based drugs (tolbutamide, glyburide, etc.) that are used to treat
diabetes.
3) Glucocorticoid therapy leads to the suppression of ACTH release and consequently to
decreased concentrations of aldosterone. Nevertheless, GCs cause sodium and water
retention, and hypertension. Explain!
GCs have low affinity for the mineralcorticoid receptors. At physiological GC
concentrations, GC display no binding to the aldosterone receptor. However, at
elevated GC concentrations (therapy, Cushing’s syndrome), aldosterone receptors are
engaged by GC, and mineralcorticoid effects are elicited.
4) The anti-estrogen clomiphene and the synthetic Gonadotropin releasing hormone
Leuprorelin are both used to treat infertility. Explain the distinct underlying mechanism of
these drugs.
Leuprorelin, if given as pulse, stimulates FSH and LH release => ovulation.
Clomiphene blocks the negative feed-back of estrogens on the hypothalamus and
anterior pituitary gland => FSH and LH release => ovulation.
5) Which of the following drugs can interfer with the effects of oral contraceptives?
A) Phenobarbital
B) Mucolytic cough medications
C) Laxatives
D) Cholestyramine
E) Lovastatin
All except E: Barbiturates induce P450 enzymes => increased metabolism of the
steroids. Mucolytica reduce the viscosity of vaginal/uterine mucus => loss of barrier
function (only applies to progesterone-only contraceptives). Laxatives reduce the time
for absorption of the steroids. Cholestyramine binds and traps steroids in the intestine =>
no absorption.
6) Barbiturates have more side effects than benzodiazepines, even though both increase
GABA function. What might account for this difference?
Barbiturates also block glutamate receptors, whereas benzodiazepines act specifically
on GABA receptors.