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PMC 537 EXAMINATION 5 2000
DATE: December 11th
FROM: Edward JN Ishac, Course Director
NOTE: This exam is scheduled to last for 2 HOURS. Apportion your time to approximate 1
minute per point value.
Please write the last 4 digits of your social security number on each page of the exam.
Also please answer the questions from each lecturer on separate pages from those of the
others.
Finally, before answering the following questions, read and analyze them carefully to
identify the information being requested. When you have done this, write your response,
using the same organizational format as the question. Be sure to address each point
raised in the question, but you are strongly discouraged from including extraneous
information not asked for (even though you may be very eager to demonstrate your
knowledge).
There are FIVE exams scheduled for this course. The questions will be as they were in the
past, i.e., short answer and/or essay type. Each exam will be worth 100 points, so figure
on an 7 point question that should take 7 minutes to answer per lecture hour. There is no
cumulative final exam, so all exams are weighted evenly in the final grade.
GOOD LUCK
Multiple Choice Questions Answers:
Balster
1.____
Egle
1.____
2.____
2.____
3.____
3.____
4.____
4.____
5.____
5.____
6.____
6.____
7.____
7.____
8.____
8.____
9.____
9.____
10.___
10.___
11.___
11.___
12.___
12.___
2
Diuretics
Dr. Costanzo
12 points total
1. For each group of diuretics, give the name of one drug in this class, the site of action in the
nephron, and the transporter (or transport process) that is inhibited when the drug produces an
increase in Na+ excretion. (3 points, 1/4 point each response).
Diuretic class
Name of drug
Site in nephron
Transporter inhibited
CA inhibitors
Loop diuretics
Thiazide diuretics
K-sparing diuretics
2. For each diuretic group below, name the acid-base disorder it produces and, in one or two
sentences, explain why. (3 points, 1 point for each diuretic group.)
CA inhibitors
Loop diuretics
K-sparing diuretics
3. For each diuretic group below, state the expected effect on Ca2+ excretion and, in a few
sentences, why this effect on Ca2+ occurs. (3 points, 1.5 points for each diuretic group.)
Loop diuretics
Thiazide diuretics
4. What is the effect of loop diuretics on the ability to concentrate the urine in a person who is
dehydrated? (1.5 points)
5. What happens to the serum Na+ concentration in a person taking a thiazide diuretic who is
drinking large volumes of water, and why? (1.5 point)
3
Drug Abuse
1.
B.
C.
D.
E.
D.
E.
Receptor down-regulation
Receptor upregulation
Changes in biodisposition
Altered signal transduction
Changes in levels of endogenous opioids
Relative to drugs with short durations of action, long-acting drugs
A.
B.
C.
D.
E.
6.
they have no positive reinforcing effects
most do not produce cross-dependence with heroin
they have a slow onset of action
they are not available clinically
more than one of the above
The cellular basis for opioid tolerance probably involves
A.
B.
C.
5.
N-methyl-D- aspartate (NMDA)
gamma-amino-butyric acid (GABA)
5-HT2
D2
5-HT1A
Opioid mixed-agonist/antagonists have lower abuse potential than full opioid agonists
because.
A.
B.
C.
D.
E.
4.
The ability of antagonists to maintain opiate dependence insures patient
participation in the treatment program.
The primary use of antagonists is to precipitate abstinence.
Patients are usually medicated with antagonists before being placed on methadone.
Patients are detoxified before being placed on antagonist therapy.
Antagonists are particularly suited for in-patient treatment
Which of the following receptors is most likely to serve as the basis of hallucinogen
intoxication?
A.
B.
C.
D.
E.
3.
12 points total
Which of the following statements is true about the use of opiate antagonists such as
naltrexone in the treatment of heroin abuse.
A.
2.
Dr. Balster
have a less intense withdrawal syndrome
require more frequent use to produce physical dependence
have a delayed emerging withdrawal syndrome
have a prolonged withdrawal syndrome
more than one of the above
Alcohol withdrawal symptoms are similar to the withdrawal symptoms from
A.
B.
C.
D.
E.
heroin
barbiturates
phenothiazines
benzodiazepines
more than one of the above
4
7.
Which of the following is a representative indolamine hallucinogen?
A.
B.
C.
D.
E.
8.
A heroin addict receives this drug and experiences an immediate, severe withdrawal
syndrome. He was probably given
A.
B.
C.
D.
E.
9.
heroin
cocaine
barbiturate
haloperidol
marihuana
Which drug(s) of abuse can produce a personality deterioration which resembles paranoid
schizophrenia?
A.
B.
C.
D.
E.
12.
physical dependence
psychological dependence
cross-dependence
tolerance
drug addiction
Convulsions are more likely to occur with____________withdrawal.
A.
B.
C.
D.
E.
11.
naloxone
methadone
dextropropoxyphene
disulfiram
heroin
A heroin addict seeks a prescription from a physician for hydromorphone (Dilaudid) for the
treatment of back pain. If, in truth, the patient is trying to relieve heroin withdrawal
symptoms, this is best considered an example of
A.
B.
C.
D.
E.
10.
LSD
PDQ
PCP
MDMA
mescaline
toluene
marihuana
amphetamine
LSD
more than one of the above
To which drug are the effects of phencyclidine (PCP) most similar?
A.
B.
C.
D.
E.
LSD
dimethyl-tryptamine
amphetamine
ibogaine
ketamine
5
Neurobehavioral Toxicology
Dr. Wiley
7 points total
1.
List the four major classes / targets of neurotoxicants. (2 points)
2.
Which of these targets is the primary target of MPTP? (one word answer, 1 point).
3.
Describe the presumed mechanism of action for the neurotoxic effects of MPTP,
including specification of which system it affects and why it affects that system.
Use a diagram if desired (4 points)
Antiarrhythmics/Calcium Blockers
Dr. Satin
20 points total
1.
For each of the Vaughan-Williams classes and subclasses of antiarrythmic drugs,
provide a brief description of the typical class effect, and list a prototype drug (12
points).
2.
Briefly mention two limitations of the Vaughan-Williams classification? (1 points)
3.
Briefly describe reentry arrythmias, and how antiarrytmic drugs in general interfere
with their generation (3 points)
4.
Discuss the relative clinical usefulness of the Ca channel blockers nifedipine vs.
verapamil, and describe their mechanisms of action in very basic terms (4 points)
Renal Pharmacology
1.
Dr. Lichtman
7 points total
Select acetaminophen, cadmium, or chloroform to illustrate why the kidney is more
susceptible to the toxic effects of the selected agent than other organs. (In your
answer, include the most likely mechanism of action for the drug you selected,
describe the clinical signs that would be observed, the primary site of damage, and
of course why the kidney is particularly susceptible to toxicity). Remember to select
only one agent (7 points).
6
Antihypertensive/Cardiac Stimulants
Dr. Ishac
30 points total
You have a choice of four (4) questions, answer any three (3) questions. Each question is
worth 10 points.
Question 1 (10 points).
A 38 year old man over four separate office visits, has documented blood pressure of
160/100 mmHg. Upon further examination and many (expensive) tests, no underlying
cause of the hypertension can be found and he is given a diagnosis of essential
hypertension.
A.
The managing physician wishes to give a single drug treatment to control the
hypertension. Assuming there is no other complicating disease present. List the
four front-line classes of drugs that would be suitable to treat the hypertension in
this individual (4 points).
B.
Assuming the use of a single agent was not sufficient to lower the blood pressure to
an acceptable level. What combination therapy (2 or 3 agents) would complement
each other in the treatment of the hypertension with fewer side-effects. Use flow
diagrams with arrows to explain your rationale (6 points).
Question 2 (10 points).
A.
Describe the mechanism of action of the Angiotensin converting enzyme (ACE)
inhibitors. Use flow diagrams with arrows to illustrate your answer. Name one
commonly used ACE inhibitor (5 points).
B.
Describe the proposed mechanism of action of the beta-adrenoceptor blocking
agents. Use flow diagrams with arrows. Name two commonly used betaadrenoceptor antagonists (5 points).
Question 3. (10 points)
A.
Briefly discuss the cellular mechanism(s) of action of the cardiac glycosides in the
treatment of Congestive heart failure (CHF) (5 points).
B.
Discuss the significance of the Therapeutic index in relationship to the cardiac
glycosides (2 points).
C.
Discuss the importance of serum K+ level on the actions of cardiac glycosides. List
a drug class which may affect the serum potassium level (3 points).
7
Question 4. (10 points)
Ishac continued
For the follow individuals select a suitable agent or agents to treat their medical conditions
with the least potential for side-effects. Also any drug class which may be contraindicated.
You have a choice of ten (10) scenarios, answer any five (5) scenarios. Each scenario is
worth 2 points.
1.
A 55 year old, hypertensive white male with CHF and angina pectoris.
2.
A 45 year old, hypertensive afro-American woman with diabetes.
3.
A 65 year old, hypertensive white woman who is also obese.
4.
A 50 year old, hypertensive white woman who has asthma.
5.
A 55 year old, hypertensive white male with benign prostrate hypertrophy
6.
A 70 year old, afro-American male with CHF.
7.
A 35 year old, balding, vain, white male with hypertension.
8.
A 45 year old, hypertensive white woman who suffers from migraines.
9.
A 50 year old, hypertensive white woman with glaucoma
10.
A 50 year old, hypertensive afro-American woman with diffuse pheochromocytoma.
8
Antianginal Agents
1.
ATP,
NO,
NO,
disulfide bonds,
beta receptors,
calmodulin
calmodulin
cGMP
calcium
MLCK
exhibit,
exhibit,
not exhibit,
not exhibit,
cellular
dispositional
cellular
dispositional
According to the Needleman hypothesis, the development of tolerance to the nitrates is due
to the formation of:
a.
b.
c.
d.
e.
5.
decreased
unchanged
increased
unchanged
decreased
You would expect an isolated aortic strip taken from an animal chronically administered
nitroglycerin (GTN) to __________ tolerance to GTN administered in vitro, indicating that
GTN tolerance has a __________ basis.
a.
b.
c.
d.
4.
unchanged,
decreased,
unchanged,
increased,
increased,
It appears that the vasodilator action of nitrates involves the formation of ________ and an
increase in the amount of ________ in the vascular smooth muscle cell.
a.
b.
c.
d.
e.
3.
12 points total
In typical (or effort, exertional, etc.) angina, 02 supply to the heart is and 02 demand is:
a.
b.
c.
d.
e.
2.
Dr. Egle
cyclic AMP
sulfhydral groups
excessive amounts of NO
disulfide bonds
inactive metabolites at an unusually high rate
An increase in cGMP in a vascular smooth muscle cell results in __________ of myosin-LC
and a(n) __________ in calcium uptake by the sarcoplasmic reticulum.
a.
b.
c.
d.
phosphorylation,
phosphorylation,
dephosphorylation,
dephosphorylation,
increase
decrease
increase
decrease
9
6.
Which of the following observations would not support the concept that cGMP is a mediator
of nitroglycerin (GTN) action?
a.
b.
c.
d.
e.
7
The duration of action of nitroglycerin is approximately __________ hours for the sublingual
tablet and __________ hours for the transdermal membrane.
a.
b.
c.
d.
e.
8
3,
0.5,
12,
0.5,
3,
12
6
24
24
72
Adverse effect(s) closely associated with nitroglycerin and related drugs:
a.
b.
c.
d.
e.
9.
inhibition of cyclic guanoside phosphodiesterase enhances the relaxant effect of
GTN
GTN activates the cGMP-producing enzyme guanylyl cyclase
inhibition of guanylyl cyclase activity reduces the relaxant effect of GTN
tolerance development to GTN is accompanied by decreased guanylyl cyclase
activity
all of the above support the stated concept
increased hepatic transaminases
headache
GI irritation
nephrotoxicity
all of the above
Which of the following combinations of antianginal drugs would pose the lowest risk of
cardiac depression (contractility, conduction) or reflex tachycardia?
a.
b.
c.
d.
propranolol
and
nitroglycerin
nifedipine
and
nitroglycerin
propranolol
and
verapamil
the risk would be equal for the three combinations
Select the drug(s) most closely related to each statement below
a.
b.
c.
d.
e.
nitrate
beta blocker
dihydropyridine calcium blocker
a and c
all of the above
10
May cause a reflex tachycardia
11
Tolerance associated with chronic use
12
Reduce(s) cardiac preload more than afterload through peripheral vasodilation
10
Extra
A 50 year old, hypertensive white woman with arrhythmias.