Drugs for Ischemic Heart Disease

Question 1

myocardial oxygen demand

Answer 1

• Heart rate
• Systolic blood pressure (afterload)
• Contractility
• Left ventricular (LV) wall stress, which is proportional to LV end diastolic volume(preload) and myocardial mass

Question 2

myocardial oxygen supply is dependent on…

Answer 2

• Coronary blood flow
• Coronary perfusion pressure (aortic diastolic blood pressure)

Question 3

classes of antiischemic drugs

Answer 3

1. organic nitrates
2. beta blockers
3. calcium channel blockers

Question 4

nitroglycerin

Answer 4

• organic nitrate
• biotransformed to NO
• Marked venodilation with sublingual use

Decreased ventricular preload

Decreased EDV Decreased end-diastolic pressure

NET EFFECT: Decreased oxygen demand The beneficial effect of nitroglycerin results from reduced cardiac O2 demand rather than an increase in the delivery of O2 to ischemic regions of myocardium.

• also for heart failure
• USES:

Angina pectoris-prophylaxis & treatment,SL

Heart failure, IV

ACS – Pain relief SL,IV

•SIDE EFFECTS:

Tolerance

Headache

Syncope

Interaction with sildenafil (Viagra & others)

Genetic consideration

Direct relaxation of all vascular smooth muscle

Venous relaxation with SL or topical use

Arteriolar and venous relaxation with IV use

To minimize the development of tolerance ensure nitrate-free intervals (nights)

Question 5

isosorbide dinitrate

Answer 5

• organic nitrate
• biotransformed to NO

ACTION Venous relaxation – Slow onset but Long acting

USES Oral Angina pectoris – prophylaxis ADR Headache,

Nitrate tolerance (ensure a nitrate - free interval)

Interaction with sildenafil and other ED drugs

Question 6

sodium nitroprusside

Answer 6

• organic nitrate
• biotransformed to NO

Intravenous nitroglycerin or sodium nitroprusside may be useful in the management of the pain associated with acute myocardial infarction i.e., pain that has not responded adequately to morphine. The relief of pain occurs as the result of decreases in ventricular preload and afterload (reduced O2 demand).

•also for hypertension, heart failure

Question 7

metoprolol

Answer 7

• beta blocker
• Effective for:

Angina pectoris

Reduce myocardial oxygen demand

Limit heart rate

Decrease contractility

Lower blood pressure during exercise

• Decrease O₂ demand
• BETA BOCKERS – ADVERSE EFFECTS

CNS Cardiovascular Bad dreams

Aggravation of severe HF

Depression

Aggravation of occlusive arterial disease

Slow A-V conduction

Pulmonary Bronchospasm in severe asthmatics

Drug interactions

With drugs that impair A-V conduction (digoxin and some calcium channel blockers)

Question 8

diltiazem and verapamil

Answer 8

• Ca++ channel blockers, non-dihydropyridine CCBs
• block L type Ca channels in cardiac tissue
• slow conduction throgh AV node, angina
• side effects: bradycardia and AV block, negative ionotropic effect
• Ca channels mediate Ca entry into into smooth muscle and cardiac myocytes and SA and AV nodal cells in response to electrical depolarization. All channel blockers induce vascular relaxation and in cardiac myocytes negative inotropic effects.
• But there are differences related to differing binding to the channel constituents.
• nifedipine: dihydropyridine, does not affect conduction throug the AV node
• verapamil and diltiazem:non-dihydropyridines, depress the rate of sinus node pacemaker and slow AV conduction

•CALCIUM CHANNEL ANTAGONISTS MECHANISM OF BENEFICIAL ACTION IN ANGINA PECTORIS

Decrease in myocardial oxygen demand

Decrease in afterload

Decrease in cardiac contractility ( V & D)

Increase in supply Coronary vasodilation

•CALCIUM CHANNEL ANTAGONISTS ADVERSE EFFECTS

Hypotension

Heart failure

Headache

AV Block

Constipation

Peripheral edema

Question 9

propranolol

Answer 9

•beta blocker

Question 10

amlodipine and nifedipine

Answer 10

• Ca2+ channel block, dihydropyridine CCBs
• hypertension
• block L-type Ca channels in vascular smooth muscle
• side effects: hypotension, peripheral edema, headache