METHODICAL INSTRUCTIONS TO LESSON № 1 FOR STUDENTS
THEME: CLINICAL PHARMACOLOGY OF ANTIANGINAL DRUGS. CLINICAL PHARMACOLOGY OF ANTIARRHYTHMIC DRUGS CLINICAL PHARMACOLOGY OF ANTIHYPERTENSIVE AND ANTIHYPOTENSIVE DRUGS. CLINICAL PHARMACOLOGY OF CARDIAC GLYCOSIDES. CLINICAL PHARMACOLOGY OF DIURETICS
Aim: To acquaint with main groups of antianginal drugs: organic nitrates, b-adrenergic blockers, Ca++ channel blockers. Mechanism of action, pharmacokinetics, pharmacodynamics, adverse effects. Treatment of angina in patients with concomitant deseases.
To acquaint with main groups of antihypertensive drugs, treatment strategies in hypertension, treatment of hypertension in patients with concomitant diseases.
To acquaint with therapeutic strategies in chronic and acute heart failure, digitalis glycosides, indications and contraindications in cardiac glycosides therapy.
Professional Motivation: Angina pectoris is a characteristic chest pain caused by coronary blood flow that is insufficient to meet the oxygen demands of the myocardium. The imbalance between oxygen delivery and utilization may result from a spasm of the vascular smooth muscle or from obstruction of blood vessels caused by atherosclerotic lesions. Angina is characterized by a sudden, severe pressing substernal pain radiating to the left arm. Three classes of drugs are effective, either alone or in combination, in treating patients with stable angina: nitrates, b-blockers, and calcium channel-blockers. Nitrates decrease coronary vasoconstriction or spasm and increase perfusion of the myocardium by relaxing coronary arteries. b-Blockers decrease the oxygen demands of the heart. Variant angina (also called Prinzmetal’s angina) caused by spontaneous coronary spasm, either at work or at rest, rather than by increases in myocardial oxygen requirements, is controlled by organic nitrates or calcium channel-blockers, but b-blockers are contraindicated.
Hypertension is defined as a sustained diastolic blood pressure greater than
Congestive heart failure (CHF) is a condition in which the heart unable to pump sufficient blood to meet the needs of the body. CHF can be caused by an impaired ability of the cardiac muscle to contract or by an increased workload imposed on the heart. CHF is accompanied by abnormal increases in blood volume and interstitial fluid; the heart, veins, and capillaries are therefore generally dilated with blood. Hence the term “congestive” heart failure, since the symptoms include pulmonary congestion with left heart failure, and peripheral edema with right heart failure. Underlying causes of CHF include arteriosclerotic heart disease, hypertensive heart disease, valvular heart disease, dilated cardiomyopathy, and congenital heart disease. Left systolic dysfunction secondary to coronary artery disease is the most common cause of heart failure. The number of newly diagnosed patients with CHF is increasing because more individuals now survive acute myocardial infarction.
Basic Level:
Students’ Independent Study Program
I. Objectives for Students’ Studies
You should prepare for the practical class using exist textbooks and lectures. Special attention should be paid to the following:
1. Clinical pharmacology of organic nitrates group.
2. b-Adrenergic blockers classification. Mechanism of action, pharmacokinetics, pharmacodynamics.
3. b-Adrenergic blockers therapeutic uses and contraindications in clinic. Adverse effects and discontinuance of b– blockers.
4. Ca++ Channel blockers classification. Mechanism of action, pharmacokinetics, pharmacodynamics.
5. Ca++ Channel blockers indications, usage and contraindications. Adverse effects and discontinuance of Ca++ channel blockers.
6. Main principles of myocardial infarction treatment.
7. Antihypertensive drugs classification.
8. Main principles of hypertension treatment strategies.
9. Treatment of hypertension in patients with concomitant diseases
10. Clinical pharmacology of diuretics
11. Clinical pharmacology of ACE inhibitors
12. Clinical pharmacology of centrally-acting adrenergic drugs
13. a-Adrenergic blocking agents clinical pharmacology
14. Hypertensive emergency
15. Digitalis glycosides classification, pharmacokinetics, pharmacodynamics, changes in electrocardiogram.
16. Indications and contraindications in cardiac glycosides therapy.
17. Digitalis toxicity: cardiac and extracardiac signs, prophylaxis and treatment.
Key words: angina pectoris, nitroglycerin, b-adrenergic blockers, calcium channel blockers, hypertension, diuretics, ACE inhibitors, a-blockers, vasodilators.
II. Tests and Assignments for Self-assessment:
Multiple Choice:
1. All of the following statements concerning nitroglycerin are correct EXCEPT:
A. It causes an elevation of intracellular cGMP.
B. It undergoes significant first-pass metabolism in the liver.
C. It may cause significant reflex tachycardia.
D. It significantly decrease AV conduction.
E. It can cause postural hypotension.
2. Which of the following adverse effects is associated with nitroglycerin?
A. Hypertension
B. Throbbing headache
C. Bradycardia
D. Sexual dysfunction.
E. Anemia.
F. Postural hypotension
3. All of the following mechanisms of action correctly match a drug EXCEPT:
A. Quinidine: Blocks Na+ channels
B. Brethylium: Blocks K+ channels
C. Verapamil: Blocks Ca++ channels
D. Propranolol: Blocks b adrenoceptors
E. Procainamide: Blocks K+ channels.
4. Which one of the following statements is INCORRECT?
A. Lidocaine must be given parenterally.
B. Lidocaine is used mainly for atrial arrhythmias.
C. Procainamide is associated with a reversible lupus phenomenon.
D. Quinidine is active orally.
E. All antiarrhythmic drugs can suppress cardiac contractions.
5. Which one of the following statements is INCORRECT?
A. Quinidine prolongs repolarization and the effective refractory period.
B. Mexiletine shortens repolarization and decreases the effective refractory period.
C. Propranolol increases Phase 4 depolarization.
D. Verapamil shortens the duration of the action potential.
E. Amiodarone prolongs repolarization.
6. Which one of the following statements about antiarrhythmic drugs is CORRECT?
A. They may act by converting unidirectional block to a bidirectional block.
B. They often cause an increase in cardiac output.
C. As a group they have mild side effects.
D. They all affect Na+ channels in the cell membrane.
E. They are equally useful in atrial and ventricular arrhythmias.
7. Which of the following patients is most suited for primary therapy with hydrochlorothiazide?
A. patients with gout
B. patients with hyperlipidemia
C. young hypertensive patients with rapid resting heart rates
D. black patients and eldery patients
E. patients with impaired renal function.
8. All of the following produce a significant decrease in peripheral resistance except:
A. chronic administration of diuretics.
B. hydralazine.
C. b-blockers
D. ACE inhibitors
E. clonidine
9. Which one of the following drugs acts at central presynaptic a2 receptors?
A. Minoxidil
B. Verapamil
C. Clonidine
D. Enalapril
E. Hydrochlorothiazide
10. Which one of the following antihypertensives is most likely to cause reflex tachycardia?
A. Prazosin
B. Propranolol
C. Nifedipine
D. Captopril
E. Hydralazine
11. Which one of the following drugs should not be given to a pregnant, hypertensive woman?
A. Hydrochlorothiazide
B. Propranolol
C. a-Methyldopa
D. Lisinopril
E. Verapamil.
12. Which of the following most directly describes the mechanism of action of digitalis?
A. Inhibits sodium-potassium ATPase.
B. Decreases intracellular sodium concentration.
C. Increases the intracellular level of ATP.
D. Stimulates production of cAMP.
E. Decreases release of calcium from the sarcoplasmic reticulum.
13. Which one of the following drugs would be the most appropriate single drug therapy for mild congestive heart failure?
A. A vasodilator such as hydralazine.
B. A cardiac glycoside such as digoxin.
C. A b-adrenergic agonists such as norepinephrine.
D. A diuretic such as hydrochlorothiazide.
E. An ACE inhibitor, such as captopril.
14. All of the following are useful in the treatment of digitalis overdose EXCEPT:
A. Anti-digoxin antibodies.
B. Dietary potassium supplements for patients being treated concomitantly with diuretics.
C. Lidocaine.
D. Phenytoin.
E. Quinidine.
15. Which one of the following aggravates a digitalis induced arrhythmia?
A. Decreased serum calcium.
B. Decreasing heart rate with propranolol.
C. Decreases serum sodium.
D. Decreased serum potassium.
E. Decreased serum angiotensin II.
Real-life Situations to be solved:
Which drugs should have been prescribed in the case? What strategy should be recommended?
What antiarrhythmic drug should have been prescribed next due to the increasing frequency of arrhythmic attacks?
Which drugs should have been prescribed in the case? What strategy should be recommended?
What antiarrhythmic drug should have been prescribed next due to the increasing frequency of arrhythmic attacks?
III. Answers to the Self-assessment:
Multiple Choice:
1. D;
2. B, F.
3. E
4. B
5. C
6. A
7. D; 10. D 13.E
8. C. 11. D 14. E
9. C
Real-life Situations to be solved:
1. Nitrates should be used with protective effect at physical and emotional exertion. Recommendation – diet therapy and stop smoking.
2. Novocainamide, b-blockers, (negative inotropic effect), Ca2+ channel blockers, quinidine are contraindicated to the patient. The drug of choice is cordarone. The initial dose 200 mg 3 times daily and maintenance dose 200 mg 1-2 times daily in 8-15 days period
3.
· Thiazide therapy is causing potassium depletion and resulting in the cramps and fatigue. Hydrochlorothiazide works inhibiting a sodium/chloride transporter, which leads to increased sodium and water excretion into the urine and diuresis. When the elimination of sodium is increased, the kidney exchanges potassium for sodium in the transprter (both are monovalent cations), which over an extended period can lead to potassium depletion. If significant quantities of potassium are not obtained through the diet or by exogenous supplements, an individual may experience cramps, fatigue, and possibly arrhythmias.
· ACE inhibitors are an effective group of antihypertensive medications with a favorable side-effect profile. In addition to preventing vasoconstriction, ACE inhibitors also decrease aldosterone secretion, resulting in less sodium and water reabsorption and less potassium wasting. Since ACE inhibitors do not block b-receptors, they are a good choice for the treatment of asthma patients.
4. Spironolactone develops its effect on 3-5 days from beginning of treatment course. The patient should be prescribed fast-acting diuretics (furosemide, ethacrinic acid, dychlothiazide) in combination with spironolactone.
Visual Aids and Material Tools: Medical documents, tables, slides.
Students Practical Activities
Student must know:
– Clinical pharmacology of organic nitrates group.
– b-Adrenergic blockers classification. Mechanism of action, pharmacokinetics, pharmacodynamics.
– b-Adrenergic blockers therapeutic uses and contraindications in clinic. Adverse effects and discontinuance of b– blockers.
– Ca++ Channel blockers classification. Mechanism of action, pharmacokinetics, pharmacodynamics.
– Ca++ Channel blockers indications, usage and contraindications. Adverse effects and discontinuance of Ca++ channel blockers.
– Main principles of myocardial infarction treatment.
– Antihypertensive drugs classification.
– Main principles of hypertension treatment strategies.
– Treatment of hypertension in patients with concomitant diseases
– Clinical pharmacology of diuretics
– Clinical pharmacology of ACE inhibitors
– Clinical pharmacology of centrally-acting adrenergic drugs
– a-Adrenergic blocking agents clinical pharmacology
– Hypertensive emergency
– Digitalis glycosides classification, pharmacokinetics, pharmacodynamics, changes in electrocardiogram.
– Indications and contraindications in cardiac glycosides therapy.
– Digitalis toxicity: cardiac and extracardiac signs, prophylaxis and treatment.
Student must be able to write a prescription on following drugs:
Nitroglycerin, isosorbide dinitrate, metoprolol, atenolol, nifedipine, metoprolol, bisoprolol, esmolol, sotalol, verapamil, diltiazem, hydochlorothiazide, spironolactone, enalapril, lisinopril, losartan, amlodipine, felodipine, doxazosin, clonidine, captopril, sodium nitroprusside, furosemide, digitoxin, digoxin.
References:
1. Netter’s Cardiology. Marschall, Patterson, George, 2008
2. Pathophysiology of heart disease :a collaborative project of medical students and faculty. 4th ed. – Leonard S. Lilly, 2008.
3.
4. Gibbons RJ et al: ACC/AHA 2002 guideline update for the management of patients with chronic stable angina—summary article: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (Committee on the Management of Patients With Chronic Stable Angina). J Am Coll Cardiol 2003;41:159.
5. Pollack CV, Braunwald E: 2007 Update to the ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: Implications for emergency department practice. Ann Emerg Med 2008;51:591.
Prepared by ass. prof. Meretskyy V.M.
Methodical instruction was discussed
and adopted at the Department sitting
4.01.2013,
Minute № 7
Methodical instruction was adopted
and reviewed at the Department sitting
27.08.2013 Minute № 1
