Minoxidil hypotension caused

A study in 19 healthy subjects found that the absorption of topical minoxidil was increased by almost threefold by the use of topical tretinoin 0.05% applied 1 hour before the minoxidil. The manufacturers note that topical drugs that alter the stratum corneum barrier, such as tretinoin or dithranol, could result in increased absorption of minoxidil if applied concurrently. They suggest that, theoretically, one possible effect of minoxidil absorption would be potentiation of orthostatic hypotension caused by vasodilator drugs. The exact drugs are not stated but this caution would be expected to cover drugs such as the nitrates and hydralazine. 

Hydralazine and minoxidil cause direct arteriolar smooth muscle relaxation. Compensatory activation of baroreceptor reflexes results in increased sympathetic outflow from the vasomotor center, producing an increase in heart rate, cardiac output, and renin release. Consequently, the hypotensive effectiveness of direct vasodilators diminishes over time unless the patient is also taking a sympathetic inhibitor and a diuretic. 

Minoxidil is a peripheral vasodilator that directly relaxes vascular smooth musculature, thus, lowering systolic and diastolic pressure. Its action is linked to the activation of calcium channels. Open calcium channels cause hyperpolarization of smooth muscle cells, which in turn, reduces the flow of calcium ions into the cell, which is necessary for supporting vascular tonicity. However, when taking minoxidil, tachycardia, elevated renin secretion, and water and sodium ion retention all appear simultaneously with hypotension. Because of potentially serious side effects, it is used only for severe hypertension that does not respond to treatment with other drugs, and absolutely in combination with two other antihypertensive drugs. A synonym of this drug is loniten. 

NITRATES ANALGESICS-NSAIDS Hypotensive effects of hydralazine, minoxidil and nitroprusside antagonized by NSAIDs NSAIDs cause sodium and water retention in the kidney and can raise BP due to 1 production of vasodilating renal prostaglandins Monitor BP at least weekly until stable... 

Minoxidil (loniten) is efficacious in patients with the most severe and drug-resistant forms of hypertension. A small fraction of minoxidil is metabolized by hepatic sulfotransferase to the active molecule, minoxidil N-O sulfate. Minoxidil sulfate activates the ATP-modulated channel in smooth muscle, causing hyperpolarization and relaxation of arteriolar smooth muscle. Minoxidil produces arteriolar vasodilation with essentially no effect on capacitance vessels. Minoxidil preferentially increases blood flow to skin, skeletal muscle, the GI tract, and the heart. The disproportionate increase in blood flow to the heart may have a metabolic basis, in that administration of minoxidil is associated with a reflex increase in myocardial contractility and in cardiac output. The cardiac output can increase by as much as three- to fourfold, primarily due to enhanced venous return to the heart. The increased venous return probably results from enhanced flow in vascular beds with a fast response for venous return to the heart. The adrenergic increase in myocardial contractility contributes to the increased cardiac output, but is not the predominant factor. The renal effects of minoxidil are complex it dilates renal arteries, but systemic hypotension produced by the drug actually can decrease renal blood flow. Renal function usually improves in patients who take minoxidil for the treatment of hypertension, especially if renal dysfunction is secondary to hypertension. Minoxidil potently stimulates renin secretion, an effect mediated by renal sympathetic stimulation. 

When minoxidil is administered with diuretics or other hypotensive drugs, the hypotensive effect of minoxidil increases, and concurrent use may cause profound orthostatic hypotensive effects. 

---