Antianginal DrugsGarrett J. Gross

Myocardial Preconditioning

• Single or multiple brief periods of ischemia result in a marked reduction in infarct size when the hearts are exposed to a more prolonged period of ischemia.

• Has 2 phases:Acute and Delayed PC• Acute phase lasts 1-2 Hours• Delayed phase lasts 24-72 Hours• Nitrogycerin(GTN) produces delayed PC in animal

and clinical studies.• This effect persists even in the presence of tolerance

to its vasodilator effects

" Decrease in the effect of a drugwhen administered in a long-acting form"

" Decrease in the effect of a drugwhen administered in a long-acting form"

NITRATESTOLERANCE

NITRATESTOLERANCE

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

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

NITRATES

CONTRAINDICATIONSNITRATES

CONTRAINDICATIONS

Previous hypersensitivity

Hypotension ( < 80 mmHg)

AMI with low ventricular filling pressure

1st trimester of pregnancy

Previous hypersensitivity

Hypotension ( < 80 mmHg)

AMI with low ventricular filling pressure

1st trimester of pregnancy

WITH CAUTION:WITH CAUTION:� Constrictive pericarditis� Intracranial hypertension� Hypertrophic cardiomyopathy

� Constrictive pericarditis� Intracranial hypertension� Hypertrophic cardiomyopathy

ß-ADRENERGIC BLOCKERSCONTRAINDICATIONS

ß-ADRENERGIC BLOCKERSCONTRAINDICATIONS

Hypotension: BP < 100 mmHg

Bradycardia: HR < 50 bpm

Chronic bronchitis, ASTHMA

Severe chronic renal insufficiency

Hypotension: BP < 100 mmHg

Bradycardia: HR < 50 bpm

Chronic bronchitis, ASTHMA

Severe chronic renal insufficiency

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