New Paradigm of Anti Anginal Therapy dr.Yerizal Karani SpPD,SpJP(K)

Angina Pectoris Angina pectoris  sudden severe pressing chest pain or heaviness radiating to the neck, jaw, back and arms  associated with diaphoresis, tachypnea and nausea. Angina  insufficient coronary flow to meet oxygen demands of the myocardium  precipitated by any activity/process that creates an imbalance in O2 supply and demand

Types of Angina Angina occurs in three overlapping patterns: Stable angina Unstable angina Prinzmetal (variant) angina

Nitrat Nitrogliserin (gliseril trinitrat)  very fast onset sublingually  acute condition Isosorbide dinitrate  fast onset sublingually (substitute of gliseril trinitrat) Isosorbide mononitrate  slow onset  used in preventing angina

Nitrates Tolerance " Decrease in the effect of a drug when administered in a long-acting form" Develops with all nitrates Is dose-dependent Disappears in 24 h. after stopping the drug Tolerance can be avoided Using the least effective dose Creating discontinuous plasma levels Treatment of Heart Failure. Nitrates: Tolerance Repetitive administration of nitrates over days is accompanied by a reduction in intensity and duration of its effects (tolerance), that obligates sequential increases in dose to obtain the desired effect. Nitrate tolerance appears with all nitrates, crosses over from one nitrate preparation to another (explaining the poor effect that IV NTG can have in patients on oral nitrate therapy), and is not dose dependent. Additionally, tolerance appears within 8-24 hours of administration of preparations that allow for maintenance of stable plasma nitrate levels (i.v., patch), but disappears rapidly (<48hrs) after stopping treatment. Increasing dosage does not overcome the tolerance effect. Tolerance can be avoided, however, by using the lowest effective dose, and by avoiding continuous plasma levels (drug-free periods).

Nitrates Contraindications Previous hypersensitivity Hypotension ( < 80 mmHg) AMI with low ventricular filling pressure 1st trimester of pregnancy Treatment of Heart Failure. Nitrates: Contraindications Nitrates are contraindicated in patients with histories of nitrate hypersensitivity, marked hypertension or shock, acute infarction with low filling pressures, and first-trimester pregnancy. They should also not be given to patients with anemia, increased intracranial pressure, severe aortic or mitral stenosis, cardiac tamponade, constrictive pericarditis or coronary thrombosis. Nitrates can aggravate angina in the setting of hypertrophic cardiomyopathy. WITH CAUTION: Constrictive pericarditis Intracranial hypertension Hypertrophic cardiomyopathy

Contraindication B-Blocker Hypotension: BP < 100 mmHg Bradycardia: HR < 50 bpm Chronic bronchitis, ASTHMA Severe chronic renal insufficiency Treatment of Heart Failure. Beta-Blockers: Contraindications Contraindications to beta-blocker therapy in heart failure patients are the same as those for the general population.

Reasons for Using Nitrates and Beta Blockers in Combination in Angina Beta Blockers prevent reflex tachycardia and contractility produced by nitrate-induced hypotension. Nitrates prevent any coronary vasospasm produced by Beta Blockers. Nitrates prevent increases in left ventricular filling pressure or preload resulting from the negative inotropic effects produced by Beta Blockers. Nitrates and Beta Blockers both reduce myocardial oxygen consumption by different mechanisms. Nitrates and Beta Blockers both increase subendocardial blood flow by different mechanisms

Anti Anginal Effect Endocardial blood flow Collateral Wall tension Nitrate B-Blocker CCB Endocardial blood flow ↑↑ ↑ Collateral → Wall tension ↓ →↑ Heart rate ↑ (reflex) ↓↓ ↑↓ Contractility ↓→↑ Cardiac work

Take Home Messages Angina pectoris  imbalance of O2 in supply & demand of the myocardium Nitrogliserin: very fast onset of nitrate in angina pectoris

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