Part A.

1. Explain why sympathetic activity is important to many vascular beds. What is a main difference in mechanism of action in case of using centrally acting sympatholytics vs peripheral sympatholytics in patients with hypertension?

2. Give your rationale in decision making process why beta blockers are highly recommended and used in patients with cardiovascular disease.

What is a role of cardiac glycosides? How they can affect cardiac contractility?

3. Identify the most commonly used antihypertensives that can produce orthostatic hypotension. Which of the drugs affecting the sympathetic nervous system can also cause bradycardia?

4. Describe the most significant adverse effects of direct acting vasodilators. Compare their effects to phosphodiesterase inhibitors.

5. Describe the mechanism of the action of loop diuretics. Why there is a significant different in the clinical effect based on the dose? How dosing can be changed in patients with renal insufficiency?

6. What are major advantages and disadvantages of diuretics use? What are major site effects and drug interactions? Give some examples.

7. Briefly describe the importance of ACE inhibitors and ARBs for clinical use. Why ACE inhibitors are not recommended to use in patients taking NSAIDs? Which one of these drugs can cause salty metallic taste?

8. If antiarrhythmic drug belongs to class III, what is a mechanism of action? What side effects would require cardiac rhythm monitoring during acute or chronic use.

9. Describe the major mechanism by which statins reduce circulating cholesterol. Compare this activity to other agents that reduce blood cholesterol by decreasing cholesterol absorption. Give some examples of drugs.

10. What is the major mechanism of action of anticoagulants? How different is this action from antiplatelet drugs? What is a major role of aspirin and why is this drug so widely used?

Part B.

1. Dopamine, epinephrine (or norepinephrine) and histamine are important neurotransmitter agonists. When these ligands interact with their cellular receptors, how do they mainly elicit their responses?

A. Activate adenylyl cyclase directly, leading to increased intracellular cAMP levels

B. Activate phospholipase C

C. Induce or inhibit synthesis of ligand specific intracellular proteins

D. Open or close ligand gated ion channels

E. Regulate intracellular second messengers through G-protein-coupled receptors

2. A patient with chronic-stable angina is on prophylactic beta-blocker therapy, with sublingual nitroglycerin used PRN (as needed) for managing acute angina. One day he experiences particularly severe angina and takes the usually recommended dose of sublingual nitroglycerin (NTG). His discomfort is not reduced at all. Seeking relief, he repeats the usual recommended dose of NTG dose 6 times over a period of about 10 minutes, and now has taken far too much of the nitrovasodilator.

An electrocardiogram taken by the paramedics, who were called for the patient's emergency, shows changes consistent with myocardial ischemia. The patient incurs a massive infarction, goes into cardiac arrest, and cannot be resuscitated.

Which of the following is the most likely cause of or contributing factor to the patient's ultimately fatal response to the excessive dosage of NTG? Assume the patient was taking no other drugs except the NTG and a beta-blocker.

A. Cyanide, or toxic metabolite of NTG, accumulated.

B. NTG directly induced coronary vasoconstriction.

C. NTG lowered arterial (coronary perfusion) pressure excessively

D. Beta-blocker counteracted the effects of NTG and increased the risk of ischemia

3. A 65-year old man with heart failure is unable to climb a flight of stairs without experiencing dyspnea. After several years of therapy with carvedilol, captopril and furosemide, the therapeutic plan probably needs to change now. You empirically add digoxin to improve cardiac muscle contractility. Within 4 week he has a marked improvement in his symptoms. Which of the following best describes the main cellular action of digoxin that accounts for its ability to improve his cardiovascular function?

A. Activates beta1-adrenergic receptors

B. Facilitates GTP binding to specific proteins

C. Increases mitochondrial calcium (Ca++) release

D. Inhibits sarcolemmal Na/K-ATP-ase

4. A patient has frequent episodes of paroxysmal supraventricular tachycardia (PSVT). Which of the following drugs would be most suitable for outpatient prophylaxis of these events?

A. Adenosine

B. Lidocaine

C. Nifedipine

D. Verapamil

5. A patient with chronic-stable angina begins taking metoprolol, and once blood levels reach the therapeutic range the frequency and severity of angina attacks and the need for sublingual nitroglycerin were reduced. Which of the following states the direct pharmacologic action by which the beta-blocker produced the desired effects?

A. Decreased myocardial oxygen demand

B. Dilated coronary vasculature

C. Directly inhibited angiotensin II synthesis

D. Reduced total peripheral resistance

6. A patient with newly diagnosed essential hypertension starts treatment with a commonly used antihypertensive drug at a dose that is considered to be therapeutic for the vast majority of patients. Soon after starting therapy the patient experiences crushing chest discomfort. ECG changes show myocardial ischemia. Studies in the cardiac catheterization lab show episodes of coronary vasospasm, and it is likely the antihypertensive drug provoke the vasospasm. Which antihypertensive drug most likely caused the ischemia and the angina?

A. Atenolol

B. Diltiazem

C. Hydrochlorothiazide

D. Lozartan

7. A 28-year-old woman is receiving drug therapy for essential hypertension. She subsequently becomes pregnant. You realize that the drug she's been taking for her blood pressure can have serious, if not fatal, effects on the fetus. As a result, you stop the current antihypertensive drug and substitute it with another drug that is deemed to be equally effective in terms of her blood pressure, and safer for the fetus.  Which of the following drugs was she most likely taking before she became pregnant?

A. Alpha-Methyldopa

B. Captopril

C. Furosemide

D. Labetalol

E. Verapamil

8. The use of propranolol as an antiarrhythmic agent is contraindicated in patients with:

A. COPD

B. Asthma

C. Severe heart failure

D. A and C

E. All of the above

9. A patient has frequent episodes of paroxysmal atrial fibrillation. He has received a medication for prophylaxis of these events. Which of the following is the most suitable for long term use?

A. Nifedipine

B. Adenosine

C. Amiodarone

D. Heparin

E. Lidocaine

10.  A 52-year-old woman with essential hypertension, hypercholesterolemia, and chronic-stable angina, develops severe constipation. Which of the following drugs is the most likely cause?

A. Atorvastatin

B. Captopril

C. Labetalol

D. Nitroglycerin

E. Verapamil

Case #1. A patient (76 years old female) with compromised cardiac function was hospitalized due to significant volume overload and generalized edema.

Chest X-ray confirmed pulmonary edema, ejection fraction was estimated - 20%.

Patients' heart rate and blood pressure have been monitored. Despite intravenous use of diuretics she still feels significant shortness of breath, her blood pressure is now 90/60 mm Hg. Blood tests confirmed that renal function is worsening. Blood creatinine - 2.0 mg/L, Na - 132 mEq/L; K - 3.9 mEq/L.

Intravenous therapy with Dobutamine was initiated.

Questions:

What group of cardiovascular drugs does dobutamine belong to?

What is mechanism of action?

What effect this drug has on cardiac and vascular adrenergic receptors?

After intensive treatment at the hospital for more than a week, this patient was released home and will be followed by primary care physician. Along other medication lisinopril was prescribed.

Questions:

What group of cardiovascular drugs does lisinopril belong to?

What is mechanism of action?

What effect this drug has on patient's neurohumoral responses?

What potential side effects can be related to long term lisinopril use?

Two months later this patient was readmitted for an episode for cardiac arrhythmia. She was diagnosed with atrial fibrillation.

Amiodarone was initiated for her arrhythmia treatment.

Questions:

What group of cardiovascular drugs does Amiodarone belong to?

What is the mechanism of action?

What effect this drug has on patient's heart rate?

What potential side effects can be related to long term Amiodarone use?

Extra

1. A 51-year-old man asks his physician for a prescription for sildenafil to improve his sexual performance. Because of risks from a serious drug interaction, this drug should not be prescribed and the patient should be urged not to try to obtain it from other sources, if he is also taking which of the following drugs? 

A. Angiotensin-converting enzyme inhibitor

B. Beta-adrenergic blocker

C. Nitrovasodilator (eg. Nitroglycerin)

D. Thiazide or loop diuretic

2. A patient with heart failure, hypertension and hyperlipidemia is taking furosemide, captopril, atenolol, and simvastatin.

During a scheduled physical examination, about a month after starting all the drugs, the patient reports a severe, hacking and relentless cough.

Which of the following is the most likely cause of the cough?

A. An expected effect of the captopril

B. An allergic reaction to the statin

C. Dyspnea due to captopril's bronchoconstrictor action

D. Hyperkalemia caused by an interaction between furosemide and captopril

E. Excessive doses of furosemide, which lead to hypovolemia

3. Flecainide and propafenone are in Vaughan-Williams (antiarrhythmic) Class IC. What is the clinically relevant "take home" message about this class of drugs?

A. Are only given for arrhythmias during acute myocardial infarction (MI)

B. Are particularly suited for patients with low ejection fraction or cardiac output

C. Are preferred drugs for relatively non-severe ventricular arrhythmias

D. Have a significant pro-arrhythmic effect (induction of lethal arrhythmias)

E. Cause pulmonary fibrosis and a hypo-thyroid syndrome when given long term.