Angina Pectoris

y Angina pectoris is a characteristic sudden severe pressing chest pain or heaviness radiating to the neck, jaw, back and arms. It is often associated with diaphoresis, tachypnea and nausea. y Caused by coronary flow that is insufficient to meet oxygen demands of the myocardium. y Typically angina lasts for seconds to minutes, up to 15 minutes. Classically angina is not associated with ischemic cell death, anginal symptoms lasting longer than 60 minutes indicates myocardial death.

Types of Angina
y Angina occurs in three

overlapping patterns:
y Stable angina y Unstable angina y Prinzmetal (variant)

angina

Stable Angina
y Angina indicates that myocardial oxygen demand is exceeding supply. Stable indicates the reproducible nature of the angina; the same activity at the same intensity faithfully produces symptoms. Typically this type of angina is relieved by rest or acute use of nitroglycerin.

Unstable Angina
y Unstable angina occurs when

anginal symptoms occur with less cardiac demand; previously tolerated activities elicit symptoms, of great concern is angina at rest. These episodes are less or un-responsive to nitroglycerine or rest. Crescendo angina describes a rapid progression of myocardial ischemia often heralding infarction.

Prinzmetal (Variant) Angina

y This is a relatively uncommon

pattern of myocardial ischemia usually occurring at rest and often in young individuals (particularly women) lacking classic risk factors or significant demonstrable coronary disease. y These attacks can be triggered by alcohol, drinking iced drinks, rapid eye movement sleep, ergonovine, atrial pacing, cocaine, nicotine, acetylcholine, and hyperventilation. y It is induced by coronary artery vasospasm it generally responds promptly to vasodilators.

Classification
y Nitrates y Short acting: Gylceryl Trinitrate (nitroglycerin) y Long Acting: Isosorbide dinitrate, Isosorbide mononitrate, erythrityl tetranitrate y -blockers: y Propranolol, metoprolol, atenolol y Calcium Channel Blockers: y Verapamil, nifedipine, diltiazem, felodipine, amlodipine y Potassium Channel Opener: y Nicorandil y Others: y Dipyridamole, trimetazidine, oxyphedrine

Nitrates (Pharmacological Action)

y Non-specific smooth muscle relexation y Preload reduction: y Nitrates dilate veins more than arteries>peripheral pooling of blood>decreased venous return>preload is reduced>decreased cardiac work>decreased O2 consumption. y Afterload reduction: y Some arteriolar dilation>slightly decrease t.p.r>BP falls (systolic more than diastolic)>reduced cardiac work

Nitrates (Pharmacological Action)

y Redistribution of coronary flow: y Nitrates relax bigger coronary arteries more than arterioles>favourable redistribution of blood flow to ischaemic areas in angina pectoris y Relief of angina: y Dilator effect on large coronary arteries (by counteracting vascular spasm) in variant angina. y Reduction of cardiac work in classical angina

Nitrates (Pharmacological Action)

y Heart and peripheral blood flow: y No direct stimulant or depressant action on the heart. y Dilate cutaneous (face and neck) vessels>flushing>memengial vessels>headache y Splanchic and renal blood flow decreases y Other smooth muscle: y Bronchi, biliary tract and esophagus are relaxed

Mechanism of action
Nitrates are rapidly denitrated enzymatically in smooth muscle cell to release Nitric Oxide Activates cytosolic guanylyl cyclase (increased cGMP) Dephosphorylation of Myosin light chain kinase (MLCK) Reduced availability of MCLK interferes with activation of myosin It fails to interact with actin to cause contraction Raised intracellular cGMP reduces Ca2+ entry (relaxation)

Mechanism of Action

Pharmacokinetics
y Well absorbed from buccal mucosa, intestines and skin. y Undergo extensive first pass metabolism y Rapidly denitrated by liver enzymes y The rate of absorption and the rate of metabolism determines the duration of action of nitrates

Adverse effects
y Fullness of head, throbbing headache y Fluching, weakness, sweating, palpitation, dizziness

and fainting.

y Withdrawal symptoms may occur (an indication of

tolerance) when nitrate agents are tapered or discontinued, this may precipitate anginal attacks.
Methemoglobinemia Rashes Tolerance Dependence

y y y y

Indications/Uses
y Angina pectoris: y For classical and variant angina, aborting and terminating an attack. y CHF and LVF: y Relief by venous pooling of blood, reduced venous return, decreased end diastolic volume y Myocardial infarction: y Area of necrosis can be reduced by favourably altering O2 balance in marginal partially ischemic zone by reducing cardiac work

Indications/Uses
y Interventional cardiac procedures: y Percutaneous coronary angioplasty, thrombolytic therapy of acute MI y Biliary colic y Esophageal spasm y Cyanide poisoning

Potassium Channel Openers

y Nicorandil, minoxidil and diazoxide y Used in severe hypertension and hypertensive

emergencies y Intracellular concentration of K+ is much higher than extracellular>K+ channel opening results in outflow of K+ ions and hyperpolarization>smooth muscle relaxation>vascular as well as visceral. y Adverse effects include: flushing, palpitation, weakness, headache, dizziness, mouth ulcers, nausea and vomiting.