Variant angina, also known as vasospastic angina, is evidenced by pain that occurs without provocation, even at rest, and is due to spasm of the vessels creating insufficient O2 delivery to the heart.

Calcium channel blockers are the DOC for variant angina because they also cause relaxation of the coronary arteries, preventing the vasospasms.

Nitrates may also prove useful because they too can relax the coronary arteries.

You can decrease the oxygen demand of the heart by decreasing the preload, afterload, contractility and rate of the heart. 

Nitrates act mainly by decreasing preload.

Ca++ blockers reduce afterload, contractility, rate

Beta-blockers decrease contractility and rate

Nitrite:

amyl nitrite

Nitrates:

nitroglycerine

isosorbide mononitrate

Use nitrates.  Here there is an anatomical occlusion of the coronary artery (uncomplicated atherosclerotic plaque).  Relaxing the coronary artery doesn't help very much, as it won't increase the blood flow/O2 supply very much.  Instead, it is more useful to reduce the preload of the heart and this is accomplished with NITRATES, which decrease the venous return to the heart.

Beta blockers and Ca++ channel blockers can be used in the prophylaxis of exertional angina, but the quick onset of the nitrates makes drugs like nitroglycerine more effective for treating an acute exertional angina.

Myocardial infarction or sudden death can result from sudden nitrate withrawal.  This is because the body can undergo dependence during nitrate therapy.

Nitrates also show tachyphylaxis, a quick tolerance development that can also be lost rapidly. This is important in developing a treatment regimen.

Remember that nitrates cause vasodilation.  This accounts for many of their side-effects:

Headache: from vasodilation of meningeal vessels

Postural hypotension: due to systemic vasodilation

Syncope: from postural hypotension

Isosorbide mononitrate is a nitrate drug used to treat angina.  It causes hypotension due to vasodilation.  Sildenafil (Viagra) is a cGMP phosphodiesterase inhibitor.  It can cause life threatening hypotension if given with nitrates.  This is because the extreme hypotension will cause reflex tachycardia and precipitate a myocardial infarction.  In people with angina, this tachycardia increases the heart's O2 demand.  This is exactly what you don't want!  Remember that nitrates increase cGMP levels to cause hypotension.

Nitroglycerine is another nitrate commonly used.

Nitrates (nitroglycerine, isosorbide mononitrate, amyl nitrite) should not be used here because the ventricle lumens are already small (myocardium has pushed into lumen) and the reduced preload effect of nitrates reduces the stroke volume (cardiac output) even further.  This is an example of diastolic failure because the failure is in the filling of the heart during diastole. 

Other drugs that reduce preload, such as diuretics, are also contraindicated in patients with hypertrophic cardiomyopathy.

Instead, beta-blockers and Ca++ channel blockers that act on the heart (Verapamil, Diltiazem) are the drugs of choice.  They slow heart rate and contractility, increasing the diastolic period and giving the ventricles more time to fill.

Nitrates are used to treat angina by reducing the preload.  They cause vasodilation. 

They are contraindicated in patients with hypertrophic cardiomyopathy because they further reduce the preload, resulting in an unacceptably low cardiac output.  They should not be used in cases with increased intracranial pressure, again because of the vasodilation.  Do not give to hypotensives.  Do not give to patients with hepatic disease because nitrates are almost completely metabolized by the liver.

Use nitrates to treat unstable angina.

nitroglycerine

isosorbide mononitrate

Beta blockers reduce the O2 demand of the heart and are used only in exertional angina. (variant angina is due to vasospasms of the coronary arteries, and beta-blockers have no effect here)

beta blockers also improve blood flow to the subendocardial regions of the heart because they increase the diastolic period, relieving the systolic pressure on the vessels of the subendocardial regions.

Beta blockers are also the best drugs to give in cases of myocardial infarction.  They are continued indefinitely after an MI (reduce oxygen demand and decrease remodeling).

As with nitrates, you must also be wary of withdrawal effects of beta-blockers, which could precipitate an MI.

Dyhydropyridines block calcium channels only in the vessels. 

They are Nifedipine and Nimodipine

(drugs ending in 'dipine')

nidomipine has a specificity for cerebral vessels.  It is also used in cases of SAH to prevent cerebral ischemia. 'mod' is like 'dome' backwards.  dome=head = cerebral vessels

Whenever there is a hemorrhage there is a reflex vasospasm by the vessel to try to minimize blood loss.  In the brain, this vasospasm can be so strong that it causes ischemia and stroke.  This is why nimodipine, which has a vasodilating effect, is beneficial in cerebral hemorrhage.

Beta-blockers (atenolol etc.) are useful in the chronic prophylaxis of exertional angina because they reduce the heart rate and contractility, thereby decreasing the heart's O2 demand.

They are not used for acute attacks because their onset is too slow.  Instead, use nitrates like nitroglycerin

This woman has Raynaud's phenomenon.   Ca++ channel blockers find use in Raynaud's because they have vasodilating properties.  The dihydropiridines (pure vasodilators) like nifedipine are drugs of choice!

Recall that a1 blockers like prazosin can also be used. 

Why are Ca++ channel blockers contraindicated in:

Cardiogenic shock?

GERD?

Cardiogenic shock: Ca++ channel blockers (verapamil, diltiazem) would further decrease heart contractility and CO

GERD: recall that Ca++ channel blockers relax smooth muscle causing the lower esophageal sphincter to relax.  This worsens the reflux.

MAP= CO x TPR

(MAP = SV x HR x TPR)

Which parameters are influenced by nitrates, beta-blockers, and Ca++ channel blockers?

Nitrates dilate large veins causing a decreased preload.  This translates into a decreased SV and CO.

Beta-blockers decrease HR and SV, thereby reducing CO

Ca++ channel blockers decrease HR and TPR

The pure vasodilators (ex: Nifedipine) can cause flushing of the skin and palpitations/reflex tachycardia.  This is different from Verapamil and diltiazem, which do not produce tachycardia because they block the calcium channels in the heart.  With a high enough dose, these two drugs can even promote bradycardia despite the vasodilation.

In some cases, nifedipine may make the cardiac ischemia worse because of the reflex tachycardia. It may also worsen angina because of the coronary steal phenomenon, in which branching vessels upstream of an atherosclerotic plaque are dilated, funneling more blood through them (path of least resistance) and thereby further reducing the blood volume to locations beyond the plaque!

These drugs decrease the O2 demand of the heart by reducing both the afterload and the contractility.

Recall, the dihydropyridines (nefidipine, nimodipine) are pure vasodilators that do not affect the contractility of the heart. 

Also recall: coronary artery vasodilation

Calcium channel blockers increase O2 delivery to the heart by dilating the coronary vessels. 

Recall that simple dilation of the coronary vessels by pure vasodilators like nifedipine may worsen exertional angina by the coronary steal phenomenon, in which blood is preferentially rerouted upstream of the plaque.  While nifedipine stops the vasospasms by relaxing the coronary vessel, and is therefore useful in variant angina, it is not as good for the exertional ischemias.