indication

For the treatment of symptomatic BPH and mild to moderate hypertension.

pharmacology

Terazosin, classified as a quinazoline, is similar to doxazosin and prazosin. As an α-adrenergic blocking agent, terazosin is used to treat hypertension and BPH. Terazosin produces vasodilation and reduces peripheral resistance but in general has only a slight effect on cardiac output. The antihypertensive effect with chronic dosing is not usually accompanied by reflex tachycardia.

mechanism of action

In general, α₁-adrenergic receptors mediate contraction and hypertrophic growth of smooth muscle cells. α₁-Receptors are 7-transmembrane domain receptors coupled to G proteins, G_q/11. Three α₁-receptor subtypes, which share approximately 75% homology in their transmembrane domains, have been identified: α_1A (chromosome 8), α_1B (chromosome 5), and α_1D (chromosome 20). Terazosin is the first α₁-receptor antagonist to demonstrate selectivity for the α_1A-receptor. All three receptor subtypes appear to be involved in maintaining vascular tone. The α_1A-receptor maintains basal vascular tone while the α_1B-receptor mediates the vasocontrictory effects of exogenous α₁-agonists. Activation of α₁-receptors activates G_q-proteins, which results in intracellular stimulation of phospholipases C, A₂, and D. This results in mobilization of Ca²⁺ from intracellular stores, activation of mitogen-activated kinase and PI₃ kinase pathways and subsequent vasoconstriction. Terozosin produces its pharmacological effects by inhibiting α_1A-receptor activation. Inhibition of these receptors in the vasculature and prostate results in muscle relaxation, decreased blood pressure and improved urinary outflow in symptomatic benign prostatic hyperplasia.

toxicity

LD₅₀=259.3mg/kg (IV in mice)

biotransformation

Hepatic. One of the four metabolites identified (piperazine derivative of terazosin) has antihypertensive activity.

absorption

Essentially completely absorbed in man (90% bioavailability).

half life

12 hours

route of elimination

Approximately 10% of an orally administered dose is excreted as parent drug in the urine and approximately 20% is excreted in the feces.

drug interactions

Acebutolol: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Alfuzosin: Additive antihypertensive effects may occur. Increase risk of orthostatic hypotension and syncope. Concomitant therapy should be avoided.

Amifostine: Terazosin may increase the hypotensive effect of Amifostine. At chemotherapeutic doses of Amifostine, Terazosin should be withheld for 24 hours prior to Amifostine administration. Use caution at lower doses of Amifostine.

Atenolol: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Betaxolol: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Bisoprolol: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Carteolol: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Carvedilol: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Esmolol: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Labetalol: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Metoprolol: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Nadolol: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Nebivolol: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Oxprenolol: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Penbutolol: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Pindolol: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Propranolol: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Rituximab: Additive antihypertensive effects may occur. Increased risk of hypotension. Consider withholding Terazosin for 12 hours prior to administration of Rituximab.

Sildenafil: Increased risk of hypotension.

Sotalol: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Tadalafil: Tadalafil may enhance the hypotensive effect of Terazosin. Monitor for hypotension during concomitant therapy.

Tamsulosin: Concomitant use of alpha1-adrenergic antagonists, Tamsulosin and Terazosin, may result in additive antihypertensive effects. Combination therapy is not recommended.

Timolol: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Treprostinil: Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.

Vardenafil: Additive hypotensive effects of the PDE5 inhibitor, Vardenafil, and alpha1-blocker, Terazosin, may occur. Monitor for hypotension during concomitant therapy.