VASODILATORS AND THE TREATMENT OF ANGINA

Question 0

Variant Angina (aka Angiospastic Angina)

Answer 0

● oxygen delivery decreases as a result of reversible coronary vasospasm

Question 1

Classic Angina (aka Angina of Effort)

Answer 1

● myocardial oxygen requirement increases (as during exercise), but coronary blood flow does not increase proportionally, usually due to atheromatous obstruction of coronary vessels.

Question 2

Unstable Angina (aka Acute Coronary Syndrome)

Answer 2

● characterized by the progression of stable angina to repeated episodes, even at rest
●usually due to atherosclerotic plaque rupture
●very often a precursor of acute myocardial infarction

Question 3

Goals of Therapy for angina

Answer 3

● increase the delivery of oxygen to cardiac tissue by increasing coronary blood flow
and/or

● decrease oxygen demand by decreasing cardiac work

● for angina of effort, pharmacological interventions usually only decrease
cardiac work through systemic vasodilation

● for variant angina, pharmacological agents can be used to reverse coronary vasospasm

Question 4

PATHOPHYSIOLOGY OF ANGINA

Determinants of Myocardial Oxygen Demand

Answer 4

• heart rate
• cardiac contractility
• arterial pressure
• ventricular volume

Question 5

PATHOPHYSIOLOGY OF ANGINA

Determinants of Coronary Blood Flow

Answer 5

• aortic diastolic pressure
• duration of diastole
• coronary vascular bed resistance

Question 6

PATHOPHYSIOLOGY OF ANGINA

Determinants of Vascular Tone

Answer 6

• ateriolar and venous tone play a role in peripheral vascular resistance and
  arterial blood pressure

Question 7

PATHOPHYSIOLOGY OF ANGINA

Ways to Relax Vascular Smooth Muscle

Answer 7

● increase cGMP: cGMP facilitates dephosphorylation of myosin light chain,preventing myosin’s interaction with actin
example: organic nitrates (nitroglycerin, etc.)

●decreasing intracellular Ca++ by preventing Ca++ entry: reduces activity of myosin light chain kinase
example: Ca++ channel blockers (verapamil, diltiazem,

● stabilizing or preventing depolarization of membrane potential by increasing K+permeability: prevents activation of voltage-gated Ca++ channels
example: K+ channel openers (e.g., minoxidil, hydralazine)

●increase cAMP: cAMP increases the rate of inactivation of myosin light chain kinase (NOTE: THESE AGENTS ARE NOT USED IN THE TREATMENT OF ANGINA DUE TO EFFECTS ON HEART RATE AND CONTRACTILITY!!)

Question 8

ORGANIC NITRATES

Answer 8

● these agents release nitric oxide (NO) at target tissues
● released NO activates guanylate cyclase, which leads to an elevation cGMPcontent
● at therapeutic doses, their action is largely confined to smooth muscle
● however, the main effect of NO in terms of angina is venodilation, which reduces preload and ventricular filling, which in turn reduces myocardial O2 demand.
● dilation of large coronary arteries and arterioles leads to a redistribution of
blood flow from epicardial to endocardial regions, providing some relief from ischemia