EX2 Alpha Agonists/Antagonists (P'col)

Non-selective (α1 and α2) Blockers

Phenoxybenzamine

Phentolamine

Selective α1 Blockers

Prazosin

Terazosin

Doxazosin

Tamsulosin

a blocker mechanism

Inhibition of vascular and other peripheral α-adrenergic receptors

Decrease in BP

Pharmacokinetics → Non-competitive inhibition (phenoxybenzamine)

Action slow in onset but irreversible

Competitive inhibition (as caused by all others)

Relatively fast in onset and can be reversed

a blocker ADR

nasal congestion

difficulty in ejaculation

Reflex tachycardia

Systemic extracellular fluid retention

Orthostatic hypotensive symptoms

Phenoxybenzamine

Long-acting, irreversible inhibitor of both α1- and α2-receptors

Pheochromocytoma (a rare tumor, usually benign, that forms in the adrenal gland (above the kidney) and causes it to release too much adrenaline (epinephrine) and noradrenaline, leading to dangerously high blood pressure, pounding heart, headaches, and sweating)

 Treatment of sweating and hypertension associated with pheochromocytoma

 Used during the preoperative period prior to surgery

 Also used to treat patients with inoperable pheochromocytoma

Phentolamine

Non-selective, Reversibly inhibits both α1 and α2 receptors, Short acting

Clinical Uses

Pheochromocytoma

Extravasation management

Local anesthesia reversal

Hypertensive crisis (off-label use)

ADR GI

Prazosin

Prototype of the selective α1- adrenergic blocking agents

for HTN

Used in combination with

diuretics, β-blockers or other

antihypertensive agents

 Attractive drug for hypertensive

patients with BPH

Raynaud phenomenon (off-label)

PTSD-related nightmares and sleep disruption (off-label)

 Likely by inhibition of central α1-receptors

ADR: Orthostatic hypotension with syncope, ECF retention, tachycardia

Doxasosin and Terazosin

Newer α1-receptor blockers

 Mechanism of action, side effects and uses are almost identical to prazosin

half-lives are much longer than prazosin

Helpful in BPH and long term HTN

Tamsulosin (silodosin dont need to know too)

blocking the subtype A alpha-1

receptor (α1A)

 Main subtype in smooth muscle of the bladder neck and prostate

for BPH

ADR: abnormal ejaculation

Centrally-Acting Sympathetic Neuronal Blockers

Methyldopa

Clonidine

Guanfacine

Centrally-Acting Sympathetic Neuronal Blockers effects

α2-receptor agonists

 More prominent effects at CNS α2 sites

Act on vasomotor centers, thereby decreasing sympathetic outflow to peripheral organs like heart, blood vessels, and kidney

Methyldopa

a2 adrenergic agonist

Enzymes that convert Dopa to DA to NE

Dampening outflow of sympathetic nerve activity

to peripheral CV tissues

 Results in a decrease of:

 Renal renin release

 Heart rate

 Cardiac output

 Peripheral resistance

limited to treatment of hypertension in pregnancy

ADR - peripheral fluid retention, dry mouth, sedation, positive coombs test, hemolytic anemia

Clonidine

direct α2 adrenergic agonist

 Like methyldopa, decreases sympathetic outflow from CNS vasomotor centers

Primary hypertension (mechanisms similar to methyldopa)

 Not recommended for the initial treatment of hypertension

Used as patch

ADR - Dry mouth and sedation, Sexual dysfunction, Rebound hypertension

Clonidine other clinical uses

ADHD

 Pain management (epidural)

 Inhibits release of neurotransmitter in afferent pain fibers

 Opioid withdrawal (off-label)

 Imidazoline receptors

 Vasomotor symptoms associated with menopause (off-label)

 Apraclonidine for decreasing postsurgical intraocular pressure

Guanfacine

not 1st choice

Primary Hypertension

 α2 antihypertensive use similar to clonidine

 Slightly less sedation and less tendency toward withdrawal (rebound)

syndrome

 Not recommended for the initial treatment of hypertension

ADHD → Reserved for children and adolescents who respond poorly to or have unacceptable side effects with a trial of stimulants or atomoxetine