Anti-Anginal Drugs

• Sensation of intense compression and tightness at the level below the sternum.

• Pain sometimes radiates to jaw or left arm

• Results from myocardial ischemia

• Imbalance between oxygen supply and demand

• Metabolic by-products accumulate; lactic acid.

What primarily causes Angina Pectoris?

Angina occurs d/t impairments in the determinants of:

• Myocardial Oxygen Demand

• Coronary blood flow and myocardial oxygen supply

• Vascular tone

• Wall stress - intraventricular pressure, ventricular radius (volume), wall thickness

• Heart rate

• Contractility

• Coronary blood flow is inversely proportiona to coronary vascular bed resistance

• Resistance is determined mainly by intrinsic factors including metabolic products and autonomic activity and various pharmacologic agents

• Increasing cGMP (Cyclic Guanosine Monophosphate)

• Decrease intracellular Ca

• Stabilizing or preventing depolarization of the vascular smooth muscle cell membrane

• Increase cAMP (Cyclic Adenosine Monophosphate) in vascular smooth muscle cells

• Converted to Nitrous Oxide (activates)> Cyclic Guanosine Monophosphate > causing vasodilation

• Primary anti-anginal effect: general vasodilation in vasculature thruout the body

• Decreases myocardial demand d/t decrease work in arteries and veins.

• Organic Nitrates

• Most well known

• primarily a powerful explosive but is diluted with lactose, alcohol or propylene glycol

• Use: to prevent and treat anginal attacks

• Routes: Buccal, Oral, Sublingual, Transdermal, Ointment

• best route

• therapeutic within 2 minutes

• no first-pass effect

• easy and convenient

• for prophylaxis

• tolerance is able to be developed.

• intermittent administration provides beneficial effects.

• daily administration may be optimized by wearing the patch for 12 to 16 then an 8 to 12 interval.

• messy

• tolerance can be developed

• higher plasma levels of drug

• longer lasting effect

• Effect last longer: long acting nitrates

• Use: Prevent onset treatment of acute episode of anginal attack

• Routes: Buccal, Sublingual, Oral (as a chewable tablet)

• Long acting

• Long onset of action, long duration of action

• Use: Prevention of anginal attack

• Route: Oral/Buccal (chewable tablet), Sublingual

• Long acting nitrate similar in function to erythrityl tetranitrate

• Use: primary in the prevention of anginal attacks

• Route: Oral

• Limited clinical use

• Ampules: inhalation and absorption is through the nasal membranes

• Use: primary in the prevention of anginal attacks (during)

• Headache and Dizziness

• Orthostatic hypotension

• Decrease heart rate and force of myocardial contraction

• Decrease work = decrease demand

• Nonselective: bronchoconstriction

• Excessive cardiac depression

• Block entry of calcium into vascular smooth muscle

  • Relaxation = vasodilation - increase oxygen supply

• Some degrees of systemic vasodilation

  • Decrease cardiac preload and afterload = decrease demand

• Primary beneficial effect: ability to dilate coronary arteries and peripheral vasculature

Factors that affect the rate at which cardiac muscle fibers contract.

Factors that affect the amount of force at which cardiac muscle fibers contract.

• Calcium Channel Blocker

• (Nonselective)

• Inhibits calcium influx to vascular smooth muscle and cardiac striated muscle.

• Dilates coronary and peripheral vessels.

• Inhibitory effect on heart: dec. HR (negative chronotropic)

• Decrease cardiac contractility (negative inotropic)

• Vasodilate coronary arteries and peripheral vasculature.

• Depresses electrical conduction in SA and AV node slight bradycardia.

• Relatively selective for vascular smooth muscle

• Vasodilate coronary arteries and peripheral vasculature.

• No major effect on cardiac excitability and contractility.

• Vasodilates coronary vessels (moderately effective)

• Exerts considerable effects on myocardial excitability.

• Used mainly for arrhythmias.

• Peripheral vasodilation, headache, flushing, feeling of warmth, dizziness.

• Peripheral edema and nausea

• Nonselective blocker - cardiac rhythmic disturbance (Verapamil, Bepridil)

• Reflex tachycardia (Nifedipine and Dihydropyridine)

• Skeletal muscle fatigue and weakness (Animal study)

Heart rate reaction to Nitrate alone, Beta blockers or Calcium channel blockers or a combination of both (nitrate + beta blocker or Ca channel blocker)

Arterial Pressure reaction to Nitrate alone, Beta blockers or Calcium channel blockers or a combination of both (nitrate + beta blocker or Ca channel blocker)

End Diastolic Volume reaction to Nitrate alone, Beta blockers or Calcium channel blockers or a combination of both (nitrate + beta blocker or Ca channel blocker)

Contractility reaction to Nitrate alone, Beta blockers or Calcium channel blockers or a combination of both (nitrate + beta blocker or Ca channel blocker)

Ejection time reaction to Nitrate alone, Beta blockers or Calcium channel blockers or a combination of both (nitrate + beta blocker or Ca channel blocker)

• Partial Fatty Acid Oxidation (pFOX) inhibitors in the myocardium

• Inhibition of oxidation of fatty acids to ATP requires heart muscles to take up glucose as a fuel, requiring less oxygen in the process, not requiring more work for the heart to function. (hypothetically fatty acid needs 200 O2 molecules to function, and glucose only needs 100) (layman’s MOA)

• Relatively selective sodium channel blockers

• Inhibits the hyperpolarization-activated sodium channel in the SA node

• Ivabradine

• Inhibits intake of Na+ to the Funny current, inhibiting the rise in hypepolarization, causing bradycardia (low bpm)

• Most common form; also known as exertion angina.

• d/t physical exertion

• Primary problem: myocardial demand greatly exceeds oxygen supply.

• Treated with beta blockers, organic nitrates, calcium channel blockers.

• Ranolazine (metabolic modulator) is another option for treating this.

• Low-dose aspirin therapy or other antiplatelet strategies are important as to decrease risk of thrombus formation and coronary infarction.

• Primary problem: decrease oxygen supply to myocardium due to coronary artery vasospasm.

• Occurs even at rest.

• Drug of choice: calcium channel blocker

• Long acting nitrates can also be used.

• Potentially life threatening; may occur anytime.

• Often initiated by sudden rupture of atherosclerotic plaques within the coronary arteries, which precipitates coronary vasoconstriction and thrombus formation.

• Oxygen demand increases while supply decreases.

• Treated with drug combination.

  • Calcium channel blocker with long-acting nitrates

  • Beta blocker maybe added.

  • Aspirin, Heparin, and Thrombolytic agents