Guanethidine

Guanethidine

Guanethidine chemical structure

Guanethidine is a medication that was historically used as an antihypertensive agent. It is a sympatholytic drug that works by inhibiting the release of norepinephrine from sympathetic nerve endings, thereby reducing blood pressure. Guanethidine was once a common treatment for hypertension, but its use has declined with the development of newer antihypertensive drugs.

Mechanism of Action

Guanethidine acts by entering the adrenergic neurons through the norepinephrine transporter (NET). Once inside the neuron, it is stored in synaptic vesicles, displacing norepinephrine. This displacement prevents the release of norepinephrine into the synaptic cleft, leading to decreased stimulation of adrenergic receptors on the vascular smooth muscle, resulting in vasodilation and reduced blood pressure.

Pharmacokinetics

Guanethidine is poorly absorbed from the gastrointestinal tract, and its bioavailability is variable. It is metabolized in the liver and excreted primarily in the urine. The onset of action is slow, and the full antihypertensive effect may take several days to develop. The drug has a long half-life, which allows for once-daily dosing.

Clinical Use

Guanethidine 3D ball model

Guanethidine was primarily used to treat moderate to severe hypertension. It was often reserved for patients who did not respond to other antihypertensive medications. Due to its side effect profile and the availability of more effective and better-tolerated drugs, guanethidine is now rarely used.

Side Effects

Common side effects of guanethidine include orthostatic hypotension, diarrhea, and sexual dysfunction. Orthostatic hypotension is particularly problematic, as it can lead to dizziness and fainting upon standing. Other side effects may include nasal congestion, fatigue, and edema.

History

Guanethidine was first introduced in the 1950s and was widely used in the treatment of hypertension during the 1960s and 1970s. However, with the advent of newer classes of antihypertensive agents, such as ACE inhibitors, beta blockers, and calcium channel blockers, the use of guanethidine has significantly declined.

Related Pages

• Hypertension
• Sympatholytic
• Adrenergic receptor
• Norepinephrine