Treatment Of Coronary Artery Disease

Explanation
(D) is the correct answer here and the following will explain why that is the case.

Statement 1 is true. This is because nitrates will relax venous smooth muscle, increasing capacitance. By doing so, venous return is decreased and the end diastolic volume (when the heart fills) is decreased as well. The volume work of the heart decreased, which is the reduction in preload.

Statement 2 is true. Nitrates will also relax arterial smooth muscle, decreasing TPR. Decreasing TPR will lower the systolic pressure so the pressure work the heart has to do is decreased. This is known as a reduction in the afterload.

Statement 3 is true, but with a grain of salt. While it is true that the coronary arteries would dilate in the presence of nitrates, autoregulation would have dilated those vessels. So this effect still exists but is diminished.

Individuals who exercise may experience anginal pain. Fortunately, because nitrates are able to reduce the workload of the heart, they can help with exercise performance since the heart will require less oxygen.

Explanation
(E) is the correct answer as they are all associated with nitrates.

Headaches are associated with nitrates as the dilation of the cranial blood vessels occurs.

Orthostatic hypotension can occur because nitrates relax venous smooth muscle, pooling the blood and decreasing cardiac output. This is desired as that reduces preload. However, when cardiac output decreases to the brain dizziness, weakness, and fainting may occur when going from sitting to standing.

As you may recall from the hypertension quiz, the fall in blood pressure from nitrates will be sensed by the carotid baroreceptors. Sympathetic neurons in the heart will compensate by stimulating the heart via beta-1 receptors. This is actually why nitrates may be combined with beta-blockers for treatment.

Taking nitrates chronically may actually lessen the effects of them over time. Having time during the day when nitrates aren't used (nitrate-free period) is desirable to lessen the tolerance problem.

Explanation
(C) is the correct answer here and the explanation is as follows.

Statement 1 is true. Calcium channel blockers, as per their mechanism of action, will relax the smooth muscle of arteries, which will decrease the TPR and decrease the afterload. This means the heart has to do less pressure work.

Statement 3 is true as well. Coronary blood flow will increase due to dilation of the arteries, but autoregulation will have already dilated the vessels. Therefore, this effect is diminished, but still occurs.

Statement 2 is actually FALSE. The reason is that calcium channel blockers do not significantly relax the venous smooth muscle. Since they are not as relaxed, they won't contribute to reducing venous return. Preload remains relatively steady.

Explanation
(A) is the false statement here. Calcium channel blockers are actually effective in vasospastic angina, which is caused by a spasm in the coronary arteries.

(B) is true due to the dilation of the cranial arteries.

(C) is true, believe it or not. While this is uncommon at common doses, CCBs will block L-type voltage-gated calcium channels, which are utilized by cardiac muscle cells. When these agents are combined with beta-blockers, the effect is more pronounced because beta-blockers will disrupt the sympathetic activation of the heart, also reducing contractility.

Explanation
(D) is the correct answer here. All three statements are true.

Statement 1 is true. Beta-blockers will reduce the heart rate and cardiac contractility because they will block the effects of norepinephrine on the beta-1 receptors on the heart AND the atrial and ventricular muscles. By blocking these receptors, the heart does less work and the oxygen demand is decreased.

Statement 2 is true. Afterload is decreased because beta-blockers are useful in hypertension. Recall that beta-blockers will decrease TPR and thus decrease afterload.

Statement 3 is true but not for the same reasons as nitrates and CCBs. Beta-blockers will decrease the heart rate and thus increase the diastolic filling time. This allows for greater perfusion of the heart during diastole and will increase the blood supply, especially to the coronary arteries.

Explanation
(B) is the false statement here. The capacity for exercise is actually INCREASED in patients with coronary artery disease. However, peak performance will be reduced.

(A) is true. This is because when exercising, the sympathetic nervous system will be stimulated and norepinephrine will be released. These will act on beta-1 receptors to increase the heart rate. Additionally, there is decreased activity from the parasympathetic nervous system. In an individual taking a beta-blocker, the heart rate will still increase but since some of the receptors are blocked (from the drug), the increase is smaller.

(C) is a true statement. This is one of the reasons why beta-blockers are used for angina. At any exercise intensity, the heart rate for an individual is lower taking a beta-blocker is lower than that same individual when not. However, the heart rate at which angina occurs will be the same. The key here is that with the beta-blocker, the individual must exercise to a higher intensity to reach that heart rate (from the discussion about increases in heart rate). So there will be a decrease in angina attacks if the individual stays below that established heart rate.

(D) is also true. As will be discussed later, beta-blockers are extremely useful in individuals who had just had a myocardial infarction in order to prevent a subsequent one.

Explanation
(B) is the correct answer here. Only nitrates will reduce preload. Recall that nitrates will relax the venous smooth muscle and increase the capacitance of veins. By doing so, blood pools to the veins and reduces venous return. This decreases the amount of volume work that the heart has to do and thus reduces preload.

Calcium channel blockers don't really affect the veins. They really just relax the arteries (reduce afterload).

Beta-blockers also decrease TPR to thus decrease afterload.

Explanation
(C) is the combination that must be used with caution. Cardiac depression can occur when the contractility is reduced too much, which can be the case with NON-dihydropyridines and beta-blockers. Examples of non-DHP drugs are verapamil and diltiazem.

(A) is actually a combination that makes intuitive sense. The administration of nitrates can lead to reflex tachycardia or palpitations. This is because the body will adjust to the decrease in cardiac output by activating the sympathetic nervous system to increase heart rate. That is through beta-1 receptors on the heart and is mediated via norepinephrine. Beta-blockers can be used to lessen the effects of the sympathetic nervous system.

(B) is a combination that works as well. The effects of DHP drugs can be augmented in the presence of beta-blockers. Examples of DHP drugs are nifedipine and amlodipine.

(D) is also true. Since the mechanism of actions of these agents are all different, control of coronary artery disease can be achieved through multiple agents. It's generally avoided to use multiple drugs of the same class, so using three different classes of drugs may provide the most benefit for the patient.