Alpha Blockers, 5-Alpha Reductase Inhibitors, and Alpha-2 Antagonists Pharmacology

Flashcards covering alpha-1 antagonists, 5-alpha reductase inhibitors, and alpha-2 antagonists based on clinical pharmacology lecture charts.

Prazosin (Minipress®)

Selective $\alpha_1$ antagonist that blocks postsynaptic $\alpha_1$ receptors in vascular smooth muscle $\rightarrow$ vasodilation, and relaxes smooth muscle in the bladder neck and prostate. Used for hypertension, PTSD-associated nightmares (off-label), and BPH (less common). Major ADRs include first-dose syncope, orthostatic hypotension, dizziness, and headache. Has the shortest half-life of the $\alpha_1$ blockers; start with a low bedtime dose to minimize first-dose syncope.

Terazosin (Hytrin®)

Selective $\alpha_1$ antagonist that blocks postsynaptic $\alpha_1$ receptors to cause vasodilation and smooth muscle relaxation. Used for hypertension and BPH. Effective for both conditions and features a longer duration of action than prazosin. Major ADRs include orthostatic hypotension, dizziness, and fatigue.

Doxazosin (Cardura®, Cardura XL®)

Selective $\alpha_1$ antagonist used for hypertension and BPH. It is not considered first-line for HTN because of an increased heart failure risk observed in the ALLHAT trial. Major ADRs include orthostatic hypotension, dizziness, and peripheral edema.

Alfuzosin (Uroxatral®)

Functionally uroselective $\alpha_1$ antagonist that relaxes smooth muscle in the prostate and bladder neck, improving urinary flow in benign prostatic hyperplasia (BPH). Features a lower incidence of ejaculatory dysfunction than tamsulosin or silodosin. Contraindicated in moderate-to-severe hepatic impairment.

Tamsulosin (Flomax®)

Selective $\alpha_1\text{A}$ antagonist that selectively relaxes smooth muscle in the prostate, bladder neck, and urethra. Used for BPH and off-label medical expulsive therapy for ureteral stones. Major ADRs include ejaculatory dysfunction, dizziness, orthostasis, and rhinitis. Strongly associated with intraoperative floppy iris syndrome (IFIS) during cataract surgery.

Silodosin (Rapaflo®)

Highly selective $\alpha_1\text{A}$ antagonist and the most prostate-selective $\alpha_1$ blocker. Used for BPH. Associated with the highest incidence of ejaculatory dysfunction (retrograde ejaculation). Contraindicated in severe renal impairment and severe hepatic impairment.

Intraoperative Floppy Iris Syndrome (IFIS)

A potential surgical complication during cataract surgery strongly associated with the selective $\alpha_1\text{A}$ antagonist Tamsulosin (Flomax®).

Finasteride (Proscar, Propecia)

Inhibitor of type II $5\alpha\text{-reductase} \rightarrow \downarrow \text{DHT}$. Clinical uses include BPH (Proscar) and male pattern baldness (Propecia). Major ADRs include sexual dysfunction ($\downarrow$ libido, ED) and gynecomastia. It is a teratogen (pregnancy exposure risk). Takes months to take effect, and decreases PSA, requiring adjusted interpretation.

Dutasteride (Avodart)

Inhibits both type I and type II $5\alpha\text{-reductase}$, leading to decreased DHT. Used for BPH. It is more potent than finasteride and has a long half-life. Teratogenic pregnancy exposure risk.

Dutasteride + Tamsulosin (Jalyn)

Combination $5\alpha\text{-reductase}$ inhibitor + $\alpha_1\text{A}$ antagonist causing $\downarrow \text{DHT}$ plus smooth muscle relaxation. Used for moderate-severe BPH with an enlarged prostate. Combination therapy beats monotherapy; defer cataract surgery due to floppy iris risk. Contraindicated in pregnancy, women, children, and sulfa allergy.

Yohimbine

Available as a dietary supplement with no FDA-approved prescription product. Historically used for erectile dysfunction; blocks presynaptic $\alpha_2$ receptors, increasing norepinephrine release. Supplement quality and potency are highly variable.

Atipamezole

Veterinary medicine only agent that reverses sedation produced by dexmedetomidine and medetomidine in animals. Not approved for routine human use.

Idazoxan

Investigational research compound used to study $\alpha_2$ receptor pharmacology.

Mirtazapine (Remeron®)

FDA-approved antidepressant that is not a selective $\alpha_2$ blocker. Its antidepressant effects result from central presynaptic $\alpha_2$ antagonism combined with potent $5\text{-HT}_2$, $5\text{-HT}_3$, and $H_1$ receptor antagonism.