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DRUGS AFFECTING CARDIOVASCULAR
FUNCTION
ANTIHYPERTENSIVE DRUGS:-
Hypertension is a common cardiovascular disease affecting worldwide population. A persistent and sustained high blood pressure has damaging effects on the heart, brain, kidneys and eyes. Could be:
- Primary or essential hypertension: It is the most common type. There is no specific
underlying cause.
- Secondary hypertension: It can be due to renal, vascular, endocrine disorders, etc.
Blood Pressure :- Systolic blood pressure (SBP): It is the maximum pressure recorded during ventricular systole. Diastolic blood pressure (DBP): It is the minimum pressure recorded during ventricular diastole. Pulse pressure (PP): It is the difference between systolic and diastolic blood pressure PP = SBP –DBP)
Classification of antihypertensive drugs:-
- Diuretics
- Thiazides and related agents : hydrochlorothiazide,indapamide.
- Loop diuretics : Furosemide, bumetanide, torsemide.
- Potassium-sparing diuretics : spironolactone, Amiloride, triamterene.
- ACE inhibitors: Captopril, enalapril, lisinopril, ramipril.
- Angiotensin II receptor antagonists : Losartan, candesartan, valsartan.
- Calcium channel blockers:
- Non- Dihydropyridine : Diltiazem, verapamil.
- Dihydropyridine : nifedipine, amlodipine …etc.
- Sympatholytic agents
- Centrally acting adrenergic drugs : Clonidine, methyldopa.
- Adrenergic blockers : Atenolol, metoprolol, propranolol etc
- Adrenergic blockers with additional a -blocking activity : Labetalol, carvedilol.
- α -Adrenergic blockers :
Selective : Prazosin, terazosin, doxazosin. Nonselective : Phenoxybenzamine, phentolamine.
- Vasodilators
- Arteriolar : Hydralazine, minoxidil, Diazoxide
- Arteriolar and venodilator : Sodium nitroprusside
DIURETICS:-
ACE INHIBITORS:- ANGIOTENSIN II RECEPTOR ANTAGONISTS :-
CALCIUM CHANNEL BLOCKERS:-
VASODILATORS:- SYMPATHOLYTIC AGENTS:- HYPERTENSIVE CRISIS [HYPERTENSIVE EMERGENGIES]:-
It is characterized by a very high blood pressure ( systolic >220 and/or diastolic >120 mmHg) with progressive end-organ damage such as renal dysfunction and/or hypertensive encephalopathy. The BP should be reduced by not more than 25% within minutes to 2 h, and then to 160/100 mm of Hg within 2–6 h. • The preferred drug to treat the condition is sodium nitroprusside (i.v. infusion). • The other drugs :
- nitroglycerin (i.v. infusion)
- hydralazine (i.v.)
- labetalol (i.v.)
ANTIANGINAL DRUGS:-
Angina pectoris:-
Angina pectoris is a symptom of ischaemic heart disease. It is due to an imbalance
between oxygen supply and oxygen demand of the myocardium. Types of angina pectoris Stable angina (classical angina): It is characterized by episodes of chest pain commonly associated with exertion. Unstable angina: It is characterized by angina at rest or increased frequency and duration of anginal attacks. – due to rupture of an atheromatous plaque and platelet deposition in the coronary artery, leading to progressive thrombosis. Prinzmetal’s angina (variant angina): Angina that occurs at rest and is due to spasm of coronary arteries. –
Pathophysiology:-
-Angina occurs due to imbalance in oxygen supply and demand by the myocardium
F 0 D 2Headache F 0 D 2Usually diminish in intensity and frequency with continued use F 0 D 2Tachycardia, postural hypotension F 0 D 2Tolerance may develop (Monday disease)
sosorbide dinitrate F 0 D 2Isosorbide dinitrate has active initial metabolites. F 0 D 2This drug is administered orally or sublingually; F 0 D 2it has better oral BA and a longer half-life (up to 1 h) than nitroglycerin. F 0 D 2Timed-release oral preparations are available with durations of action up to 12 hours. Therapeutic uses
- Sublingual nitroglycerin is most often used for severe, recurrent Prinzmetal's angina.
- Continuous infusion or slowly absorbed preparations of nitroglycerin (including the ransdermal patch) or derivatives with longer half-lives have been used for unstable angina and for CHF in the presence of MI. Adverse effects F 0 C 9Nitrates and nitrites produce vasodilation, which can lead to orthostatic hypotension, eflex tachycardia, throbbing headache (may be dose limiting), blushing, and a burning sensation. F 0 C 9Tolerance. F 0 C 9Large doses produce methemoglobinemia and cyanosis.
BETA BLOCKERS:-
F 0 C 9Atenolol (Tenormin) F 0 C 9Metoprolol (Lopressor) F 0 C 9Propranolol (Inderal) F 0 C 9Nadolol (Corgard)
Mechanism of Action:-
F 0 C 9Decrease the HR, resulting in decreased myocardial oxygen demand and increased oxygen delivery to the heart F 0 C 9Decrease myocardial contractility, helping to conserve energy or decrease demand Therapeutic Uses:- F 0 C 9Antianginal F 0 C 9Antihypertensive F 0 C 9Cardioprotective effects, especially after MI
Side Effects:-
Calcium channel blocker:-
F 0 C 9 Phenyl alkylamine: Verapamil F 0 C 9 Benzothiazepine: Diltiazem F 0 C 9 Dihydropyridines: Nifedipine,Felodipine,Amlodipine,Nitrendipine,Nimodipine,Lacidipine Mechanism: F 0 C 9Calcium channel-blocking agents produce a blockade of L-type (slow) calcium channels, which decreases contractile force and oxygen requirements. F 0 D 8Agents cause coronary vasodilation and relief of spasm
F 0 D 8they also dilate peripheral vasculature and decrease cardiac afterload. Preload refers to total volume of blood in the left ventricle of the heart and the pressure it exerts before the left ventricle contracts. Afterload then is the amount of pressure exerted by the left ventricle when it does contract.
Pharmacologic properties
F 0 C 9C C blocking agents can be admi orally. F 0 C 9When admi intravenously, they are effective within minutes. F 0 C 9The therapeutic use of these drugs in angina is generally reserved for instances in which nitrates are ineffective or when β-Blks C/I. F 0 C 9Serum lipids are not increased. F 0 C 9These drugs produce hypotension.
Selected CCB drugs:-
Verapamil:- F 0 C 9Verapamil produces slowed conduction through the AV node (predominant effect); this may be an unwanted effect in some situations (especially in the treatment of hypertension). F 0 C 9Verapamil may produce AV block when used in combination with β-blks. F 0 D 7The toxic effects of verapamil include myocardial depression, heart failure, and edema. F 0 D 7Verapamil also has peripheral vasodilating effects that can reduce afterload and BP F 0 D 7The peripheral effects of verapamil can produce headache, reflex tachycardia, and fluid etention. Nifedipine,Isradipine,Nisoldipine And Nicardipine:- F 0 D 7These dihydropyridine CCBls have predominant actions in the peripheral vasculature; hey decrease afterload and to a lesser extent preload and lower blood pressure. F 0 D 7These drugs have significantly less direct effect on the hear t than verapamil. Diltiazem:- F 0 D 7Diltiazem, a benzothiazepine, is intermediate in properties between verapamil and the dihydropyridines. F 0 D 7Diltiazem is used to treat variant (Prinzmetal's) angina, either naturally occurring or drug-induced and stable angina. Bepridil:- F 0 D 7Bepridil blocks both slow and fast sodium channels and both voltage-dependent and eceptor-mediated calcium channels. F 0 D 7Bepridil is used only when other agents have failed or have elicited intolerable A/E. F 0 D 7Bepridil may cause ventricular arrhythmias.
Therapeutic Uses:-
F 0 D 7First-line agents for treatment of angina, hypertension, and supraventricular tachycardia F 0 D 7Short-term management of atrial fibrillation and flutter F 0 D 7Several other uses
POTASSIUM CHANNEL OPENERS:- F 0 D 7Their efficacy is similar to nitrates, beta blockers, CCBs F 0 D 7Main advantages of Nicorandil, it has longer DOA and does not cause tolerance F 0 D 7Administered orally Mechanism of action:-
Side effects:- F 0 D 7Headache F 0 D 7Hypotension
Effect in Heart: F 0 D 8In failing heart; it ↑ force of contraction (Dose dependent ) → ↑ CO F 0 D 8Slow AV conduction → bradycardia F 0 D 8More complete emptying of failing and dilated ventricles F 0 D 8SA node and A-V node automaticity is reduced at therapeutic concentration F 0 D 8They increase myocardial contractility and output in a hypodynamic heart without a proportionate increase in O2 consumption Mechanism of action:- Increase intracellular Ca2+ by blocking Na+-K+ATPase
Effect in Blood vessels:- F 0 D 8No prominent effect in BP so can be given in hypertensive patient Effect CNS:- F 0 D 8Little effect in therapeutic dose F 0 D 8Higher dose- activate CTZ, hyperapnoea, central sympathetic stimulation, mental confusion , disorientation, visual disturbances PHARMACOKINETICS:- F 0 D 8Digitoxin: more lipid soluble ; slow & long acting F 0 D 8Digoxin:
- Fast and short acting than digitoxin
- Relatively polar (……….)
- Bioavailability differ from manufacture to manufacturer
- Food delay absorption
- Concentrate in heart, Skeletal muscle, kidney and liver : large volume of distribution (6- L/Kg) ADVERSE EFFECTS:- F 0 D 8Toxicity is high F 0 D 8Margin of safety is low (therapeutic index 1.5-3) F 0 D 8Extracardiac:
- Initially: Anorexia, nausea, vomiting, diarrhea and abdominal pain
- Fatigue, malaise, headache, mental confusion, restlessness, hyperapnoea, disorientation,psychosis, visual disturbances
- Skin rashes and gynaecomastia rarely F 0 D 8Cardiac: Bradycardia, A-V block, any type of arrhythmias TREATMENT OF DIGITALIS TOXICITY:- F 0 D 8Stop digitalis on earliest sign of toxicity F 0 D 8Pot. Chloride administration (if toxicity is due to chronic use/ use of diuretics ) which is guided by serum pot. Measurement F 0 D 8Treatment of arrhythmias (if required) a. Ventricular arrhythmias: Lignocaine i.v. b. Supraventricular arrhythmias: Propranolol (oral/ i.v.) c. A-V block & bradycardia: Atropine (i.m.) F 0 D 8Digoxin antibody- very effective Orphan drug. CONTRAINDICATIONS:- F 0 D 8Hypokalemia F 0 D 8Elderly, renal or severe hepatic disease (pt. more sensitive) F 0 D 8Hypothyroidism (low elimination, cumulation) F 0 D 8Ventricular tachycardia F 0 D 8Partial A-V Block
USES:-
- Congestive Heart Failure: F 0 D 8Not commonly used because: a. Have low margin of safety b. Inable to reverse/ retard the disease progression F 0 D 8Drug of choice in CHF patient: a) With dilated heart and low ejection fraction b) With atrial fibrillation c) Not controlled by other drugs (resistant case) F 0 D 8Prescribe in dose that provides plasma concentration (0.8 -1.2ng/dl)- digitalization F 0 D 8Stable clinical state for 2-3 months, withdrawal of digitalis therapy can be attempted
- Cardiac arrhythmias: F 0 D 8Atrial fibrillation (AF) F 0 D 8Atrial flutter (AFl) F 0 D 8Paroxysmal supraventricular tachycardia (PSVT) F 0 A 7Atrial flutter and atrial fibrillation are both abnormal heart rhythms. F 0 A 7In atrial fibrillation, the atria beat irregularly. In atrial flutter, the atria beat regularly, but aster than usual and more often than the ventricles F 0 A 7Dose: 0.125-0.25 mg PO/IV Shock:- Types of shocks:- 1.Hypovolemic 2.Septic 3.Cardiogenic 4.Anaphylactic 5.Neurogenic 6.Obstructive Haemodynamic characteristics:-
