Anti-Anginals
12. A woman with frequent migraine headaches develops angina of effort. Which of the following is relatively contraindicated?
(A) Amlodipine (B) Diltiazem (C) Metoprolol (D) Nitroglycerin (E) Verapamil
16. Two years later, Mrs Green returns complaining that her medicine works well for her type of angina but she has frequent attacks of rapid heart rate. Which of the following drugs is the most suitable alternative for her type of angina?
(A) Amlodipine (B) Verapamil (C) Metoprolol (D) Esmolol (E) Sublingual nitroglycerin
3. One year later, the patient returns complaining that his nitroglycerin works well when he takes it for an acute attack but that he is having frequent attacks now and would like something to prevent them. Useful drugs for the prophylaxis of exercise-induced angina include which one of the following?
(A) Amyl nitrite (B) Diltiazem (C) Esmolol (D) Sublingual isosorbide dinitrate (E) Sublingual nitroglycerin
5. When nitrates are used in combination with other drugs for the treatment of angina, which one of the following combinations results in additive effects on the variable specified?
(A) Beta-blockers and nitrates on end-diastolic cardiac size (B) Beta-blockers and nitrates on heart rate (C) Calcium channel blockers and beta-blockers on cardiac force (D) Calcium channel blockers and nitrates on cardiac ejection time (E) Non-dihydropyridine calcium channel blockers and nitrates on heart rate
4. If a β blocker were to be used for prophylaxis in this patient, what is the most probable mechanism of action in angina?
(A) Block of exercise-induced tachycardia (B) Decreased end-diastolic ventricular volume (C) Dilation of constricted coronary vessels (D) Increased cardiac force (E) Increased resting heart rate
13. A new patient presents with hypertension and angina. In considering adverse effects of possible drugs for these conditions, you note that an adverse effect that nitroglycerin and prazosin have in common is?
(A) Bradycardia (B) Impaired sexual function (C) Lupus erythematosus syndrome (D) Orthostatic hypotension (E) Throbbing headache
Questions 1-3 A 60-year-old man presents to his primary care physician with a complaint of severe chest pain when he walks uphill to his home in cold weather. The pain disappears when he rests. After evaluation and discussion of treatment options, a decision is made to treat him with nitroglycerin. 1. Which of the following is common direct or reflex effect of nitroglycerin?
(A) Decreased heart rate (B) Decreased venous capacitance (C) Increased afterload (D) Increased cardiac force (E) Increased diastolic intramyocardial fiber tension
7. A 74-year-old man presents with a history of anterior chest pressure when he walks more than one block. The chest pain is relieved within 3 min when he stops walking. A diagnosis of stable angina in made. Which of the following drugs would be most effective in reducing the acute pain associated with walking and reduce the chance of blood clotting?
(A) Esmolol (B) Nifedipine (C) Verapamil (D) Metoprolol (E) Isosorbide dinitrate
14. A patient being treated for another condition complains that whenever he takes that medication, his angina becomes worse. Which of the following drugs may precipitate angina when used for another indication?
(A) Isoproterenol (B) Metoprolol (C) Propranolol (D) Diltiazem (E) Verapamil
11. Diastolic fiber length and diastolic myocardial fiber tension in the heart are both reduced by?
(A) Metoprolol (B) Diltiazem (C) Isosorbide dinitrate (D) Propranolol (E) Verapamil
10. Which of the following drugs interacts with nitroglycerin by inhibiting the metabolism of cGMP?
(A) Metoprolol (B) Nifedipine (C) Verapamil (D) Sildenafil (E) Isosorbide dinitrate
15. Mrs Green, 60 years old, complains of unpredictable chest pain when she is resting in bed in her apartment. A decision is made to treat her type of angina with a drug that exclusively reduces afterload by which of the following drugs?
(A) Nitroglycerin (B) Esmolol (C) Propranolol (D) Nifedipine (E) Verapamil
Types of Angina (4)
1. "Fixed" (Stable) - is precipitated by exercise and/or excitement. Stable angina is relieved by rest. It is caused by obstruction in one or more of the coronary arteries, and the lesion is usually arteriosclerotic. 2. "Variant Angina" (Prinzmetal's Angina) - it occurs at rest or even during sleep and is unpredictable. It is caused by vasospasm of an artery that is probably injured. 3. "Unstable Angina" - is used to categorize a variety of clinical presentations involving acute ischemic syndromes that are progressive, and in the initial stages, indistinguishable from impending myocardial infarction. The condition is believed to be caused by thrombosis in a blood vessel. 4. "Silent Ischemia" - ischemia of myocardium without pain or symptoms.
NITRATES \ NITRITES: Pharmocological Classification
1. rapidly acting agents used to terminate an acute attack of angina Amyl Nitrite (0.33 ml ampule) given by inhalation *Nitroglycerin given sublingual (0.15-0.6 mg), IV, and oral spray (0.4 mg) Note: Nitroglycerin generally inactive PO (10-20% bioavailability, Hepatic, 1-pass). 2. agents with prolonged action used to prevent attacks of angina and are given orally and topically Nitroglycerin Ointment (2%) *Nitroglycerin Transdermal (2.5 to 15 mg/24 hrs) *Isosorbide Dinitrate Penterythritol Tetranitrate Erythrityl Tetranitrate
6. A patient is admitted to the emergency department following a drug overdose. He is noted to have severe tachycardia. He has been receiving therapy for hypertension and angina. A drug that often causes tachycardia is:
A) Diltiazem (B) Clonidine (C) Isosorbide dinitrate (D) Propranolol (E) Verapamil
2. In advising the patient about the adverse effects he may notice, you point out that nitroglycerin in moderate doses often produces certain symptoms. Which of the following effects might occur due to the mechanism listed?
A) Headache due to meningeal vasodilation (B) Hypertension due to reflex tachycardia (C) Dizziness due to reduced cardiac force (D) Apnea due to cranial vasodilation (E) Diuresis due to sympathetic discharge
9. The major common determinant of myocardial oxygen consumption is:
A. Blood volume B. Cardiac output C. Diastolic blood pressure D. Heart rate E. Myocardial fiber tension
8. Which of the following effects attributed to nitroglycerin therapy would exacerbate symptoms in a patient with variant angina?
A. decrease preload B. increase heart rate C. decrease arterial pressure D. increase venodilation E. decrease ejection time
17. Which of the following effects attributed to metoprolol therapy would help relieve symptoms in a patient with unstable angina?
A. decrease preload B.decrease heart contractility C.increase afterload D.decrease ejection time E. increase venodilation
BETA BLOCKERS: Clinical Uses and ADRs
B-1 effect to dec HR & SV, O2 consumption Dec HR prolongs diastole to increase in diastolic coronary perfusion time B-1 blockers (eg, metoprolol) dec HR leads to dec BP / O2 demand; B-2 block (eg, propranolol) may cause some peripheral vasoconstriction Block tachycardia reflexed by nitrates & Ca antagonists (nifedipine class) Caution when BBs & cardiac depressant Ca antagonist used in combo Not effective for vasospastic angina, but effective for unstable and stable angina
Ca CHANNEL BLOCKERS
Block slow voltage-dependent, L-type Ca channels to prevent influx Ca in sm mus, and cardiac nodal & muscle cells: decrease myocardial contractility to reduce oxygen requirement decreased arteriolar tone results in decreased vascular resistance relief of coronary artery spasm; principally used as prophylactic Verapamil/diltiazem possess both cardiac and vasodilator activity Nifedipine (i.e., dihydropyridines) class has little direct effect on heart, primarily considered vasodilators Mainly use to relieve vasospasm in variant and stable angina
Myocardial Oxygen Supply
Dependent on coronary blood flow Coronary flow mainly dependent on local metabolites (dec O2 , inc H+ , lactate, and adenosine) and endothelial factors (NO) Coronary flow is inversely proportional to coronary vascular bed resistance Arteriolar tone controls vascular resistance and determines systolic wall stress Venous tone controls the amount of blood returned to the heart and determines diastolic wall stress
Cardiac Metabolism
Heart can't tolerate oxygen debt like skeletal muscle Ischemia quickly affects ATP production and contractile function which decreases left ventricular ejection, CO & BP > CHF Corresponding ECG - ST segment / T wave changes reflect ischemia
CORONARY VESSELS
Ischemia is the most potent vasodilator Vasospastic coronary vessels can be relaxed and dilated, can open collaterals Arterio/atherosclerotic vessels do not dilate like normal vessels; dilator drugs may cause a "coronary steal" effect Systemic reduction of preload and afterload which decreases cardiac work & oxygen demand is primary effect
NITRATES \ NITRITES: Mechanism of Action
MA: Nitrate/Nitrite> NO > c-GMP that relaxes sm mus by dec phosphorylation MLC Vasodilation in a gradient manner: Most prominent effect on veins to "pool" blood, this decreases preload; pulm vascular pressures / heart size significantly decreased due to reduced myocardial diastolic fiber length/wall tension arteries/arteriolar dilation, this increases with dosage and decreases afterload and BP; In fixed (stable) angina the above actions decrease cardiac work and the demand for oxygen; In variant or Prinzmetals angina vasodilation (relaxation of smooth muscle) relieves the vasospasm Increase coronary flow via collateral vessels in ischemic area platelet aggregation dec.
NITRATES \ NITRITES: Pharmacokinets, Clinical Indication, ADRs
Nitroglycerin generally inactive PO (Hepatic, 1-pass), but there are sustained release preps Tolerance \ cross tolerance/ rebound; usu w/longer acting preps (i.e., transdermal patch) Uses - stable (exercise-induced), variant, unstable angina, acute attacks (sublingual prep for acute pain) Adverse effects: excessive dilation (dec BP) reflexes HR, dizziness (orthostatic hypotension), vasomotor flushing, headache (meningeal artery dilation)
NIFEDIPINE: Clinical Uses and ADRs
One of dihydropyridines, arteriolar dilators Excessive dilation may trigger reflex HR Use in stable angina and especially vasospastic angina (Prinzmetal's) Adverse effects primarily related to excessive vasodilation: nausea, lightheadedness, dizziness, headache, tachycardia, peripheral edema Other class drugs: amlodipine, nicardipine
Preload / Afterload
Preload is the workload presented to the heart, the blood coming back to the heart to be pumped - venous return; venodilators decrease venous return Afterload is the workload the heart must overcome to pump the blood out of the heart - peripheral resistance or the diastolic pressure; decreasing afterload is the main effect of arteriodilators
VERAPAMIL/DILTIAZEM: Clinical Uses and ADRs
Vasodilation , decrease afterload Dec HR and AV conduction (V>D) Dec myocardial contractility (V>D), usu. high doses or toxicity; may cause CHF Use in variant and stable angina and fast atrial/nodal arrhythmias to slow HR/AV conduction Caution if used with beta blockers due to excessive reduction of contractility/CHF
