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BIMM118 – WI’16 Final
NOTE: WRONG answers on multiple choice questions will result in the
DEDUCTION of the points !!!!!
1) What are the two major drug classes used in the treatment of elevated blood cholesterol and
triglycerides?
Briefly describe their molecular targets! (20)?
a) Statins: inhibit HMG-CoA-Reductase, the rate limiting enzyme in the cholesterol
synthesis pathway => increased uptake of LDL from plasma
b) Fibrates: PPAR agonists that trigger upregulation of fatty acid metabolizing enzymes
and stimulate lipoprotein-lipase activity.
2) Oral antidiabetic drugs are only effective in Type II, but not in Type I diabetes. Explain why? (10)
Oral hypoglycemic drugs stimulate insulin production of beta-cells, or increase sensitivity
of the target tissue to existing insulin, which will improve the symptoms of Type II
diabetes.
In Type I diabetes, the beta-cells are destroyed, therefore no insulin can be produced.
3) Which of the following drugs finds use in the treatment of nausea and emesis (5 pts ea)
a) Dimenhydramine
b) Finasteride
c) Scopolamine
d) Metoclopramide
e) Ceterizine
f) Pirenzepine
4) High glucocorticoid concentrations during therapy lead also to the stimulation of
mineralcorticoid receptor, causing Na+ and water retention and consequently hypertension.
Which of the following drugs would be the OBVIOUS choice to prevent this GC side effect?
Explain your choice! (10)
a) Prazosin
b) Propranolol
c) Spironolactone
d) Captopril
e) Nifedipine
5) Stomach ulcers are a frequent side effect of chronic NSAID use.
a) Explain the mechanism that causes this side effect (10)
Prostacyclin production in the stomach stimulates mucus/bicarbonate production
and inhibits stomach acid production. NSAIDS inhibit PG synthesis => more acid
and less mucus is produced => ulcer
b) Which drug could be added to the NSAID therapy to prevent this problem? (5)
The synthetic PG Misoprostol can be used as a replacement for endogenous PG
6) DHEA is widely consumed by men as a “dietary supplement” because of its supposed
anabolic and “rejuvenating” effects. However, some men experience breast growth,
particularly after high doses of DHEA. Explain why! (10)
DHEA can also be metabolized in the body into estrogens, causing the growth of
breast tissue.
7) Both clomiphene and tamoxifen act as anti-estrogens, however, each finds a very distinct
clinical application.
a) What are the specific indications for each drug?(5)
Tamoxifen: Estrogen-dependent cancers
Clomiphen: Infertility
b) What mechanism accounts for the specificity! (10)
Tamoxifen binds to the type of estrogen receptor found on e.g. breast tissue etc.
Clomiphene specifically antagonizes the estrogen receptors in the pituitary gland
=> loss of feedback inhibition on the secretion of LH and FSH => ovulation.
8) Provide an example for a drug that is now predominantly marketed for a “side effect” rather
than its initially intended use (10)
Sildenafil: used for ED instead of angina pectoris
Minoxidil: used for hair loss instead of hypertension
Finasteride: used for hair loss instead androgen responsive tumors
9) Provide two examples for the clinical use of histamine H1 and H2 receptor antagonists!
H1: Antiallergic; antiemetic; hypnotic (sleeping aid)…
H2: Antacid
a) Name at least one drug in each group and describe the basis for their efficacy (16)
H1 1st Gen: Diphenhydramine; dimehydranate; doxylamine (H1 block in periphery =>
antiallergic; H1 block in CNS => antiemetic, hypnotic)
H1 2nd Gen: Ceterizine, Fexofenadine, etc. (H1 block in periphery => antiallergic; NO
H1 block in CNS !!)
b) Why do 1st generation “anti-histamines” display efficacy against more conditions that the
newer 2nd generation drugs (4)?
H1 1st Gen cross BB barrier => CNS effects (drowsiness)
H1 2nd Gen DO NOT cross BB barrier => no sleepiness
10) The synthetic GnRH Leuprorelin can be used in women to either induce ovulation or to
suppress gonadal function (“medical castration”). Describe the determining factor and the
physiological basis for these apparently opposing effects of Leuprorelin? (20)
When given as a bolus, Leuprorelin triggers release of LH and FSH, thereby inducing
ovulation. A continuous administration of Leuprorelin, however, desensitizes the
GnRH receptors => no further LH/FSH production => reduced sex steroid production =
“medical castration”
11) An elderly patient who is taking propranolol for cardiovascular problems arrives in the ER
with an acute asthma attack. Which ONE of the following drugs to you administer? (10)
a)
b)
c)
d)
e)
Dexamethasone (to slow)
Chromolyn (only prevents an attack, useless for treatment)
Furosemide (not relevant)
Ipratropium
Nifedipine (not relevant)
12) Local anesthetics display a signifcantly reduced effect in inflammed tissue due to the acidic
pH in that environment. Explain the molecular mechanism! (15)
Local anaesthetics are weak bases with pKa 8-9 (only partially ionized at
physiologic pH). The action of local anaesthetics is dependent on their ability to
penetrate the nerve sheath in their non-ionized form and block the Na+ channel
from the inside. Decreased pH would result in significant ionization and reduced
ability to cross membranes and therefore failure to elicit a response.
13) During an outpatient procedure the physician accidentally injects lidocaine directly into the
bloodstream. Within a few seconds the patient goes into cardiac arrest. WHY? (15)
Lidocaine (which in low doses is also used as an anti-arrhythmic drug) disrupts the cardiac
impulse conduction (particularly from the AV node) => Cardiac arrest!
Lidocaine (which in low doses is also used as an anti-arrhythmic drug) disrupts the
cardiac impulse conduction (particularly from the AV node) => Cardiac arrest!
14) Explain the mechanism behind the synergistic analgesic effect between NSAIDs and opioids!
(20)
NSAIDS and Opioids produce analgesia through two different mechanisms leading to
a synergistic analgesic effect.
NSAIDS act via their ability to inhibit cyclooxygenase (COX) and therefore
prostaglandin synthesis. Prostaglandins sensitize pain receptors; therefore, NSAIDs
have an indirect analgesic effect by ‘desensitizing’ pain receptors.
Opiods are opiate receptor agonists. Opioid analgesia is mediated through changes in
the perception of pain at the spinal cord and higher levels in the CNS. Their painreducing effect is caused by their inhibitory effects on the transmission of the action
potential elicited by the pain receptors.
15) Describe two drugs or drug groups (mechanism and use) whose efficacy is based on altering
the conductance of K+ channels (10).
Minoxidil - increases K+ current in vascular smooth muscle cells => membrane
hyperpolarization => less Ca++ influx => vasodilation: reduction in blood pressure
Bretylium, Amiodarone - block K+ current => prolonged repolarization phase =>
extended AP: treatment of cardiac arrhythmias
Sulfonylureas: inhibit ATP-gated K+-channels => lower depolarization threshold =>
opening of voltage-gated Ca2+-channels => increased exocytosis of insulin
16) Provide two examples of drugs acting on receptors on presynaptic neurons (10)
Clonidine, Yohimbine – 2-receptors
Opiates – Opioid receptors (spinal analgesia)
H3-agonists/antagonists (in trial)
17) Describe three mechanistically distinct drug groups that act as vasodilators. Briefly explain
their mechanism of action! (15)
1 antagonists
2 agonists
L-type Ca++ channel antagonists
ACE inhibitors
ATII-R antagonists
Organic nitrates (NO)
Nitroprusside…
18) Glitazones and sulfonylureas have been used for many years as oral antidiabetic drug.
However, in recent years several novel concepts in the treatment of diabetes have emerged.
Describe two distinct classes of these new oral antidiabetic drugs (or drug classes), and
explain their mechanism of action (20)
Alpha-Glucosidase inhibitors: prevent carbohydrate digestions and thus absorption
DPP4 inhibitors: increase half-life (=> amount) of GLP1 and GIP1
SGLT2 inhibitors: prevent glucose re-uptake in the proximal convoluted tube
(Note: Incretin mimetics e.g. exenatide or pramlintide, respectively) are NOT oral
drugs !!)
19) Which drug is acting faster in reducing the symptoms of allergies: Loratidine or Prednisone?
(Classify the drugs, explain their mechanism of action and justify your conclusion)? (15)
Loratidine: H1-R antagonist
Prednisone: Glucocorticoid R agonist
Glucocorticoid Rs are nuclear receptors/transcription factors => responses mediated
via transcriptional modulation => requires time
=> H1-R antagonists act quicker
20) “Saw palmetto extract” contains a 5-reductase inhibitor and is used as a dietary supplement
as it presumably increases testosterone (and consequently - at least according to advertising
- increases hair growth and libido). Nevertheless, 5-reductase inhibitors are used clinically
to treat androgen-dependent malignancies (e.g. prostate cancer). Explain this apparent
contradiction! (15)
Saw palmetto extract inhibits 5-alpha reductase, the enzyme that converts
testosterone into the more potent androgen dihydrotestosterone (DHT). Thus,
testosterone increases, but DHT decreases => reduced androgenic effect.