Indications
Minoxidil is primarily indicated for the management of severe hypertension. Additionally, it is utilized in the topical treatment of androgenic alopecia for both males and females. It aids in hair regrowth and helps stabilize hair loss in patients experiencing androgenic alopecia.
Pharmacodynamics
Minoxidil acts as a direct-acting peripheral vasodilator when administered orally. It effectively reduces elevated systolic and diastolic blood pressure by lowering peripheral vascular resistance. In its topical form, minoxidil is applied to treat androgenetic alopecia. Studies demonstrate that minoxidil enhances or maintains microcirculatory blood flow across systemic vascular beds in animals while reducing forearm and renal vascular resistance in humans. It increases forearm blood flow without affecting renal blood flow and glomerular filtration rate. The principal site of its action is the arterial system, and venodilation does not occur. Consequently, postural hypotension is uncommon. The antihypertensive effects are attributed to its active metabolite, minoxidil sulfate.
Absorption
Minoxidil exhibits high absorption rates, with at least 90% being absorbed from the gastrointestinal tract in both experimental animals and humans. This efficient absorption underscores its efficacy in systemic applications.
Metabolism
Approximately 90% of minoxidil undergoes metabolic transformation, primarily through conjugation with glucuronic acid at the N-oxide position within the pyrimidine ring. It is also converted into more polar metabolites, which have significantly reduced pharmacologic activity compared to the parent compound.
Mechanism of Action
Minoxidil functions by enhancing the survival of human dermal papillary cells (DPCs), or hair cells, through the activation of extracellular signal-regulated kinase (ERK) and Akt pathways. It prevents apoptosis by increasing the BCl-2/Bax ratio, thereby exerting both proliferative and anti-apoptotic effects, which may prolong the anagen phase of hair growth. Furthermore, as a vasodilator, Minoxidil opens adenosine triphosphate-sensitive potassium channels in vascular smooth muscle cells, potentially improving the viability of hair cells or follicles through enhanced blood flow.
