Pharmacology I
Angina & Antianginal Drugs Objectives

Learning Objectives:

Know the therapeutic goals for treating angina.
See also Brody p 240 – table citing "therapeutic overview"
Coronary artery insufficiency – increase effective flow through the coronary arteries and ¯ O2 consumption by the heart. Goal is also to prevent vasospasm of coronary arteries.

Know the cardiovascular effects of nitric oxide (NO) and how endothelial dysfunction might lead to vasoconstriction.
Endothelial dysfunction might lead to vasoconstriction. NO activates guanylate cyclase which cGMP which leads to dephosphorylation of myosin-light-chain-kinase (MLCK). Effects on the CV system:

  1. Dilation of large veins resulting in pooling of blood in veins which ¯ ’es preload and ¯ ’es workload.
  2. Dilates coronary vasculature, providing increased blood supply to heart muscle.  (Lippincott, p 176)

Note: Brody, p 240 comments on "steal" phenomenon: The ischemic are of heart is already vasodilated due to the metabolic end products; vasodilation by drugs does "little to enhance blood flow to ischemic region."

Acetylcholine, histamine, bradykinin, ATP – many vasodilator substances depend on the endothelium to generate nitric oxide. Endothelial dysfunction would prevent that (class example was atherosclerosis).

Understand the mechanisms of action of nitrates and Ca+2 channel blockers, and relate them to the rationale for using these drugs for treating angina.
NO activates guanylate cyclase which cGMP which leads to dephosphorylation of myosin-light-chain-kinase (MLCK). Effects on the CV system:

  1. Dilation of large veins resulting in pooling of blood in veins which ¯ ’es preload and ¯ ’es workload.
  2. Dilates coronary vasculature, providing increased blood supply to heart muscle.  
    Ca+2 channel blockers block the inward movement of calcium by binding to the L-type Ca+2 channel in the © and in smooth muscle of the coronary and peripheral vasculature thus causing relaxation and dilating the arterioles. Ca+2 channel blockers also ¯ smooth muscle tone and ¯ vascular resistance. This can also decrease spasm in coronary vessels. A ¯ in conduction of AV node will ¯ HR and subsequently ¯ MVO2. (Lippincott p 177, 188-9).

Angina is O2 demand > supply.
    Nitrates ¯ demand, also vasodilate the coronary arteries but the "steal phenomenon means ischemic tissue doesn’t necessarily benefit. Nitrates also supply.
    Ca+2 channel blockers ¯ demand by ¯ afterload of arterial beds and supply.

Discuss the rationale of co-administering b -blockers with vasodilators, in the treatment of angina.
    Vasodilators can cause reflex tachycardia via SNS stimulation. b -blockers inhibit the HR (which would have ed O2 demand and worsened angina.

Be able to distinguish the vascular and cardiac effects of the 3 classes of Ca+2 channel blockers.
  

Phenylalkylamine
Verapamil

Dihydropyridines
Nifedipine

Benzothiazepine
Diltiazem

Vasodilation

Peripheral

++

+++

+

Coronary

++

+++

+++

Cerebral

+

+

+

Heart rate

¯

¯

SA node

¯

   

¯ ¯

AV node

¯ ¯

   

¯

Contractility

¯ ¯

¯
Indications For Use

Prinzmetal’s angina, Chronic stable angina, PSVT, Afib/flutter, essential HTN

Angina caused by spasm, chronic stable angina, HTN

Prinzmetal’s angina, chronic stable angina, HTN
Notes

Open channel blocker so channel must be open to work.

Called L-type channel blockers.  Prefers channel closed & more negative.

   

 

Know the pharmocokinetics (routes of administration, relative time of absorption, onset and duration) of each class of antianginal drug.

See drug cards on website

Know the clinical problems for each class (especially related to the mechanisms of action).

Nitrates: 

b -blockers: 

Ca+2 channel blockers: 

 

Last updated 09/06/01 08:53 PM
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