Anginal syndromes What is it TYPES OF ANGINA

Anginal syndromes What is it? ?

TYPES OF ANGINA I Chronic stable angina I Unstable angina I Prinzmetals variant

pathophysiology of anginal syndromes Oxygen demand Oxygen supply Heart rate Cornory blood flow Heart size Oxygen extraction Contractility Oxygen availability

nitrates l a n i g n a i ant s g u dr CCB’S verapamil diltiazem nifedipine β blockers K+ channel opener nicorandil Antiplateletes aspirin ticlopidin Miscellanous trimetazidine

organic nitrates Short acting long acting drugs route dose nitroglycerin e S. L I. V Tr. lin Amyl nitrate inhal nitroglycerin e Isosorbide dinitrate Oral Tr. der 6 -9 6 -10 mg 30 30 -40 4 -8 hrs 24 hrs S. L oral 5 -10 mg 10 -60 mg 5 -10 15 -20 2 -4 hrs 2 -6 hrs Isosorbide mononitrate Erythrityl Oral S. R tab 10 -40 mg 60 mg 15 -30 30 -60 8 -10 hrs 8 -12 hrs S. L 5 -10 mg 5 -15 2 -4 0. 4 – 0. 6 mg 5 mcg/min 0. 4/melu Min 1 -3 1 -2 2 -4 Onset duration 10 -30’ 3 -5’ 10 -30’

how nitrates act ? ? ? nitrates R. SNO NO GC Inhibit Ca+ Release + block Ca+ entrance MLC C. GMP MLC. PO 4 contraction GTP MLC (relaxation)

how vascular dilation cause beneficial effect Dominently venous capacitence vessel Pooling of blood in veins venous return VEDP myocardial wall tension Subendocardial perfusion arterial dilatation Arterial load

u s e s Angina MI Heart failure Cyanide poisoning Biliary colic a d Vasodilation headache, dizziness v e tachycardia r tolerance s methenoglobinemiae e f f e c t

Important kinetics of Nitrates Nitroglycerin • Short and fast acting • Undergo first pass metabolism by glutathione reductase • Adm. S. L / Transling. in acute angina • S. R oral, Transdermal as prophylactic

Isosorbide Dinitrate • Long and slow acting • Metabolized at slower rate than nitroglycerin • Intermediate metabolite i. e Mononitrate is active and long acting • Bioavailability of Mononitrate is 100 percent

Drug Interaction Sildenafil ( ) PD – 5 Cytosole Ca++ ↑ C. GMP ↓ Activity of MLC K (-) MLC (+) MLC PO 4 ------- MLC (contraction) Exaggerate response of Nitrate Leading Hypotension , MI

Calcium Channel Blockers Commonly used CCBs in angina Phenylalkylamines - VERAPAMIL Benzodiazepines - DILTIAZEM Dihydropyridine -NIFEDIPINE -NICARDIPINE -NITRENDIPINE -AMLODIPINE

Properties of CCBs • Block voltage sensitive calcium channel L – type • Location of L. channel – Cardiac and other smooth muscle S. A Node and A. V Node • Function – Regulate Excitation and Contraction, Regulate pace maker activity and conduction

Pharmacological effects of CCBs • Reduce Myocardial oxygen demand - ↓ H. R, ↓ Contractility and ↓ conduction velocity VERAPAMIL > DILTIAZEM > NIFEDIPINE - Vasodilation of peripheral vessel → ↓ Resistant to outflow → ↓ work load → ↓ Oxygen demand NIFEDIPINE > VERAPAMIL > DILTIAZEM ↑ Myocardial Oxygen supply - Dilates epicardial and transmyocardial Arteries – prevent coronary spasm NIFEDIPINE > VERAPAMIL > DILTIAZEM

Clinical uses of CCBs • Hypertension • Angina • Cardiac arrhythmias

Adverse Effects Arterial Vasodilatation Cardiac Depression Effect on other smooth muscle Flushing, Head ache, Hypotension, tachycardia Bradycardia, hypotension, A. V Block Constipation, difficult to void urine

Drugs Interact with CCBs • β Blockers • Quinidine - Exaggerate S. A Nadal, Depression, A. V Conduction defects • Digoxin - ↑ Plasma level of digoxin

β Antagonist ↓ O 2 demand ↓ H. R, ↓ Contractility Spasm of coronary artery ↑ O 2 demand Tachycardia. Relax smooth muscle ↓ Arterial pressure Vasodilatation Nitrates

Coronary Steal? ? ? Arteriolar Dilator drugs may worsen anginal pain (dipyrimadole). But not the drugs that dilate veins and larger arteries. Note: ↑ Blood flow to the normal area at the expense of ischemic area where the arteries are fully dilated – coronary steal phenomenon.