Direct-acting vasodilators are a class of antihypertensive medications that are used for severe refractory hypertension, malignant hypertension, and hypertensive emergencies. These medications include hydralazine, which can be administered orally, intravenously, and intramuscularly; minoxidil, which can be administered orally or topically; and sodium nitroprusside, which is given intravenously.
Once administered, direct acting vasodilators rapidly work on the vascular smooth muscle cells by preventing the increase of intracellular calcium concentration.
As a result, direct acting vasodilators prevent vasoconstriction and promote vasodilation, leading to a reduction in the total peripheral resistance and blood pressure.
Keep in mind that hydralazine and minoxidil mainly work on arterioles, while sodium nitroprusside works on both arterioles and venules.
Now, since direct acting vasodilators tend to work rapidly, they can result in sudden vasodilation and hypotension. This may lead to side effects, including dizziness, headache, reflex tachycardia, palpitations, and edema.
Other side effects include nausea, vomiting, and gastrointestinal distress. So to counteract side effects like reflex tachycardia and edema, direct acting vasodilators can be used in combination with beta-blockers or diuretics, but under close monitoring for adverse effects.
Now, through an unclear mechanism, hydralazine may trigger a lupus-like syndrome, which can involve multiple organs. Clients may experience severe malaise, myalgia, arthralgia, pericarditis, and hepatosplenomegaly, and upon blood tests, they may present with leukopenia, thrombocytopenia, and positive autoantibodies.
What’s important to keep in mind is that hydralazine-induced lupus-like syndrome mainly affects clients who take higher doses for a prolonged period of time, and can be reversed upon discontinuation of hydralazine.
Regarding minoxidil, an important boxed warning is that it can cause pericardial effusion, which may progress to cardiac tamponade, and it can exacerbate angina pectoris.
On that account, minoxidil should be reserved for hypertensive clients who don’t respond adequately to the maximum therapeutic doses of two other antihypertensive medications and a diuretic.
Another interesting side effect of minoxidil is hypertrichosis, which means excessive hair growth! In fact, minoxidil can be applied topically to promote hair growth and treat hair loss or alopecia.
Finally, sodium nitroprusside has a boxed warning because it contains cyanide, which is released when nitroprusside is metabolized; normally the liver is able to convert the cyanide into a less toxic byproduct called thiocyanate, but if nitroprusside is given over several days, the cyanide can accumulate and cause problems such as disorientation and delirium.
Moreover, if sodium nitroprusside is administered too quickly, clients may develop cyanide poisoning, which can lead to hypoxia and metabolic acidosis.
Cyanide poisoning typically presents with dizziness, confusion, headache, mydriasis, tachypnea, and tachycardia; while severe cases can develop hypotension, apnea, seizures, and even coma.
Finally, sodium nitroprusside can also suppress iodine uptake by thyroid cells, which can lead to hypothyroidism.
Direct-acting vasodilators are contraindicated in clients with cerebrovascular insufficiency and any other condition that could be worsened by a sudden decrease in blood pressure, like peripheral vascular disease, coronary artery disease, heart failure, and mitral valve disease, as well as septic shock.
