PHTX 537-Fall Semester 1999

PMC 537 EXAMINATION 5 1999

DATE: December 15th

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

PHTX 537-Fall SemesterExamination 5Wed. Dec 15th, 1999

DiureticsDr. Costanzo 13 points total

Question 1 (13 points).

A.What is the site and mechanism of action of carbonic anhydrase inhibitors? What acid-base disturbance is caused by this class of drugs, and why? (4 points).

B.What is the effect and mechanism of action of loop diuretics on calcium reabsorption? (4 points).

C.What is the effect of thiazide diuretics on: (5 points)

(a)the ability to produce dilute, hyposmotic urine in a person who is drinking water

(b)the ability to produce concentrated, hyperosmotic urine in a person who is dehydrated? In each case, state whether it is impaired, enhanced, or not changed, and why.

Lipid MetabolismDr. Lamb13 points total

Question 1 (13 points).

Premature atherosclerosis is associated with increases in various plasma lipoproteins. List the lipoprotein profiles associated with types II (a & b), III and IV hyperlipoproteinemias and discuss what drugs (alone or in combination) and diet you would recommend for the treatment of these lipoprotein disorders. Include in your discussion the rationale of your decisions.

Antiarrhythmics/Calcium BlockersDr. Satin19 points total

1.Briefly contrast the mechanisms of action of verapamil and nifedipine. Why is verapamil more useful as an antiarrythmic agent? (7 points)

2.For each of the Vaughan-Williams classes, indicate the prototype drug and briefly characterize the major mechanism of action (6 points).

3.Explain what is meant by 'reentry', and indicate the conditions necessary for it to occur. How in general can antiarrythmic drugs abolish reentry? (6 points).

Antihypertensive/Cardiac StimulantsDr. Ishac36 points total

You have a choice of four (4) questions, answer any three (3) questions. Each question is worth 12 points.

Question 1 (12 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.

Lifestyle changes and risk factors are important in the management of hypertension. List four lifestyle changes/risk factors (2 points).
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).
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 (12 points).

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 (6 points).

B.Describe the proposed mechanism of action of the beta-adrenoceptor blocking agents. Use flow diagrams with arrows. Name two commonly used beta-adrenoceptor antagonists (6 points).

Question 3. (12 points)

A.Briefly discuss the cellular mechanism(s) of action of the cardiac glycosides in the treatment of Congestive heart failure (CHF) (6 points).

Discuss the significance of the Therapeutic index in relationship to the cardiac glycosides (2 points).
Discuss the importance of serum K+ level on the actions of cardiac glycosides. List a class of drug which may affect the serum potassium level (4 points).

Question 4. (12 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 eleven (11) scenarios, answer any eight (8) scenarios. Each scenario is worth 1.5 points.

I.A 55 year old, hypertensive white male with CHF and angina pectoris.

II.A 45 year old, hypertensive afro-American woman with diabetes.

III.A 65 year old, hypertensive white woman who is also obese.

IV.A 50 year old, hypertensive white woman who has asthma.

V.A 55 year old, hypertensive white male with benign prostrate hypertrophy

VI.A 70 year old, afro-American male with CHF.

VII.A 35 year old, balding, vain, white male with hypertension.

VIII.A 45 year old, hypertensive white woman who suffers from migraines.

IX.A 50 year old, hypertensive white woman with glaucoma

X.A 50 year old, hypertensive afro-American woman with diffuse pheochromocytoma.

A 50 year old, hypertensive white woman with arrhythmias.

Antianginal AgentsDr. Egle10 points total

1.Possible hemodynamic mechanisms of action of an antianginal drug include all of the following except:

a.a decrease in heart rate

b.dilation of veins

c.an increase in myocardial contractile force

d.dilation of arteries

e.blockade of cardiac beta receptors

2.The vasodilator action of the nitrates is thought to involve initial formation of ______leading to a subsequent increase in ______which in turn promotes ______of calcium from (by) the sarcoplasmic reticulum.

a.cAMP, NO, uptake

b.NO, cGMP, release

c.cGMP, NO, release

d.NO, cAMP, release

e.NO, cGMP, uptake

3.The increased cGMP formed by the action of nitrates promotes muscle relaxation by favoring the ______of phosphate to (from) ______.

a.addition, myosin-LC

b.addition, actin

c.removal, myosin-LC

d.removal, actin

4.If an isolated aortic strip taken from an animal chronically exposed to nitroglycerin ______tolerance to nitroglycerin administered in vitro, this would indicate that nitroglycerin tolerance has a ______basis. (There are two correct answers, choose either one)

a.exhibits, cellular

b.does not exhibit, dispositional

c.does not exhibit, cellular

d.exhibits, dispositional

5.Which of the following observations would not support the concept that cGMP is a mediator of nitroglycerin (GTN) action?

a.inhibition of cyclic guanoside phosphodiesterase inhibits the relaxant effect of GTN

b.GTN activates the cGMP-producing enzyme guanylyl cyclase

c.inhibition of guanylyl cyclase activity reduces the relaxant effect of GTN

d.tolerance development to GTN is accompanied by decreased guanylyl cyclase activity

e.all of the above support the state concept

6.The use of such compounds as amyl and butyl nitrite for pleasurable effects is based upon their ability to:

a.block dopamine receptors

b.release norepinephrine

c.cause vasodilation

d.release dopamine

e.block central alpha-receptors

7.Which of the following combinations of antianginal drugs would pose the highest risk of depression of myocardial contractility and AV conduction?

a.propranolol & nitroglycerin

b.nifedipine & nitroglycerin

c.propranolol & verapamil

d.the risk would be equal for the three combinations

Select the drug(s) most closely related to each statement below

a.propranolol

b.nitroglycerin

c.nifedipine

d.a and c

e.b and c

8.Can produce reflex cardiac stimulation.

9.Reduces cardiac 02 demand by decreasing heart rate and contractile force.

10.Primary effect is a reduction in cardiac preload.

Renal PharmacologyDr. Lichtman 9 points total

Question 1 (9 points).

A.Give four reasons why the kidney is particularly susceptible to the toxic effects of noxious chemicals (3 points).

B.Briefly, discuss the nephrotoxic effects of one of the following four therapeutic drugs: Cisplatin, Cyclosporine, Amphotericin B, Indomethacin, or Methoxyflurane. In your answer describe the primary site of damage, the clinical signs that would be observed, and the most likely mechanism of action for the drug you selected (3 points).

C.Briefly, discuss the nephrotoxic effects of chloroform to the kidney. In your answer describe the primary site of damage, the clinical signs that would be observed, the most likely mechanism of action, and the sex differences that are observed in mouse models. Finally, are there sex differences in the nephrotoxicity of chloroform in humans? (3 points).