Guanadrel

Guanadrel is an adrenergic-blocking drug used to treat hypertension. Specifically, it is a postganglionic sympathetic nerve blocker, meaning it inhibits the release of norepinephrine from sympathetic nerve endings. This action leads to vasodilation and a decrease in blood pressure.

Mechanism of Action: Guanadrel works by being actively transported into the postganglionic sympathetic neuron via the norepinephrine transporter (NET). Once inside, it accumulates in the norepinephrine storage vesicles, displacing norepinephrine. It also inhibits the release of norepinephrine in response to nerve stimulation. This leads to a depletion of norepinephrine available to stimulate adrenergic receptors on blood vessels, reducing vasoconstriction.

Indications: Guanadrel was primarily used in the management of moderate to severe hypertension, particularly when other antihypertensive medications were insufficient.

Adverse Effects: Common side effects of guanadrel include orthostatic hypotension (a drop in blood pressure upon standing), dizziness, weakness, diarrhea, and nasal congestion. It can also cause sexual dysfunction. The potential for significant orthostatic hypotension required careful monitoring of patients, especially when initiating treatment or adjusting the dosage.

Pharmacokinetics: Guanadrel is absorbed from the gastrointestinal tract. Its onset of action is typically within 1 to 2 hours, and its duration of action can last for several days. The drug is primarily excreted unchanged in the urine.

Contraindications: Guanadrel is contraindicated in patients with pheochromocytoma (a tumor of the adrenal gland), severe heart failure, and hypersensitivity to the drug. It is also generally avoided in patients taking monoamine oxidase inhibitors (MAOIs) due to the risk of severe hypertension.

Drug Interactions: Guanadrel interacts with several other medications, including tricyclic antidepressants, which can block its uptake into sympathetic neurons and reduce its effectiveness. MAOIs can also interact, potentially leading to a hypertensive crisis.

Discontinuation: Abrupt cessation of guanadrel can lead to rebound hypertension. Therefore, gradual tapering of the dosage is recommended when discontinuing the medication.

Note: Guanadrel is less commonly used today due to the availability of newer and more effective antihypertensive drugs with better side effect profiles. However, its mechanism of action and historical use are still relevant in understanding the pharmacology of hypertension management.