Vasospasm

Vasospasm refers to a condition in which blood vessels spasm, leading to vasoconstriction. This can lead to tissue ischemia and death (necrosis). Cerebral vasospasm may arise in the context of subarachnoid hemorrhage. Symptomatic vasospasm or delayed cerebral ischemia is a major contributor to post-operative stroke and death after aneurysmal subarachnoid hemorrhage. Vasospasm typically appears 4 to 10 days after subarachnoid hemorrhage.

Additions:

General Information:

Along with physical resistance, vasospasm is a main cause of ischemia. Like physical resistance, vasospasms can occur due to atherosclerosis.

General pathophysiology of vasospasms:

Normally endothelial cells release prostacyclin and nitric oxide which induce relaxation of the smooth muscle cells, and reduce aggregation of platelets. Aggregating platelets stimulate ADP and 5-HT to act on endothlial cells and help them induce relaxation of the smooth muscle cells. However aggregating platelets also stimulate TXA-2 and 5-HT which can induce contraction of the smooth muscle cells. In general the relaxations outweighs the contractions.

During atherosclerosis we see a dysfunctional endothelium. It does not stimulate as much prostacyclin and NO to induce relaxation on smooth muscle cells. Also there is not as much inhibition of aggregation of platelets. In this case, the greater aggregation of platelets produce ADP, 5-HT, and TXA-2. However the 5-HT and the TXA-2 cause more contraction of the smooth muscle cells and as a result contractions outweigh the relaxations.

Symptoms:

One reason why vasospams are undesirable is because they cause ischemia. This resulting loss of oxygen supply to vital organs can lead to angina, myocardial infarction and even death.

Therapy options:

You can reduce the occurance of vasospams by preventing the occurance of atherosclerosis. This can be done in several ways, most important being lifestyle modifications. Decreasing your bad cholesterol, quiting smoking etc. Also you can chose pharmacological therapy which include hypolipidemics, thrombolytics, anticoagulants etc.

If you already have atherosclerosis and ischemic heart disease, there are some pharmacological options for reducing the severity and occurance of ischemic episodes but these do not eliminate the cause of the problem. These medications are classified as organic nitrates and include long acting(ie.isosorbide dinitrate) and short acting(ie.nitroglycerin) durations of action.

The way these drugs work is by increasing NO levels in the blood and inducing coronary vasodilation which will allow for more coronary blood flow due to a decreased coronary resistance. Therefore, there should be more oxygen supply to the vital organs(myocardium). The nitric oxide increase in the blood seen by these drugs also causes dilation of systemic veins which in turn causes a reduction in venous return, ventricular work load and ventricular radius. All of these reductions contribute to the decrease in ventricular wall stress which is significant because this causes the demand of oxygen to decrease. In general organic nitrates decrease oxygen demand and increase oxygen supply. And it is this favourable change to the body that can decrease the severity of ischemic symptoms, particularly angina.

Adverse effects:

Like most pharmacological therapeutic options, there are risks that should be considered. For these drugs in particular, vasodilation can be associated with some adverse effects which might include orthostatic hypotension, tachycardia, headaches and palpitations. Tolerance may also develop overtime due compensatory response of the body, as well as depletion of -SH groups of glutathione which are essential for the metabolism of the drugs to their active forms.

Contraindications:

These drugs should not be taken with PDE5 inhibitors(ie.sildenafil)since both NO and PDE5 inhibitors increase cyclic GMP levels and the sum of their pharmacodynamic effects will greatly exceed the optimal therapuetic levels. What you could see upon taking both medications at the same time, as caused by the much higher induction of relaxation of smooth muscle cells, include a severe drop in blood pressure and an erection which will make you hate even the thought of arousal.

Other pharmacological options:

Other medications used to reduce the occurance and severity of vasospams and ultimatly ischemia include L-type calcium channel blockers(ie.verapamil, deltiazem, nifedipine)and B-receptor antagonists(ie.propranolol).

How they work:

B-receptor antagonists do not cause vasodilation but they do decrease the heart's demand for oxygen. This decrease is caused by a reduction in heart rate, afterload and wall stress, leading to less contraction force needed by the myocardium. B-antagonists also increase coronary blood flow since they reduce heart rate.

L-type calcium channel blockers induce coronary dilation as well as decrease the heart's demand for oxygen by reducing contractility, heart rate, and wall stress.

ADR's include:

Verapamil: hypotension, bradycardia, constipation

Deltiazem: hypotension, bradycardia

Nifedipine: hypotension

Propranolol: asystole, asthma attacks

Contraindications:

B-receptor agonists should be avoided in patients with reactive pulmonary disease to avoid asthma attacks. Also B-receptor antagonists should be avoided in patients with AV node dysfunction and/or patients on other medications which might cause bradycardia(ie.calcium channel blockers). The potential for these contrainications and drug-drug interaction could lead to asystole and cardiac arrest.

Again some calcium channel blocker should be avoided with some B-receptor blockers since they may cause severe bradycardia and other potential side effects.

Corrective Therapy

Since vasospasms can be caused by atherosclerosis and contribute to the severity of ischemia there are some surgical options which can restore circulation to these ischemic areas. One surgical intervention, referred to as percutaneous coronary intervention or angioplasty, involves placing a stent at the sight of stenosis in an artery and inflating the stent using a balloon catheter. Another surgical intervention is coronary artery bypass.

Reference: This information is a summary of a lecture given by a professor at Albany College of Pharmacy