Alpha Antagonist

Question 1

Phenoxybenzamine

Answer 1

nonselective alpha adrenergic receptor antagonist
But blocks A1 > A2 100x
(also inhibits Ach, histamine, 5-HT)

Uses;

• pre-op to pts with pheochromocytoma to prevent HTN episode during surgery
• tx HTN crisis after sympathomimetic OD
• Tx vasospastic peripheral vascular disorders (Raynaud’s Syndrome)

MOA;
irreversible antagonist at the alpha adrenergic receptors blocking catecholamine and sympathomimetic effects; causing decrease BP, postural hypotension; reflex tachycardia (baroreceptor activation/ increased NE activity at beta receptors)

Dose;
PO; 10 - 120 mg/day in divided doses for 2 -3 weeks before surgery

Pharmacokinetics;
*Pro-drug
-onset; 60 min
-E1/2t; 24 hours 
 metabolized by the liver and excreted by the kidneys 

Side Effects;

• hypotension
• tachycardia
• flushing
• dry mouth
• nasal congestion
• miosis

BP drop is amplified with preexisting hypotension, hypovolemia, blood loss, vasodilation drugs, VA

Contraindicated;
-severe hypotension or hypovolemia

Caution;
-pregnant women (neonatal hypotension and respiratory distress in the first 72 hours of life

Question 2

Phentolamine

Answer 2

Competitive A1 and A2 adrenergic Receptor Antagonist
Short acting

Uses;

• Tx for pt with pheochromocytoma to prevent HTN crisis during surgery
• Tx IV infiltration of NE
• Tx of HTN associated with clonidine withdrawl
• Tx of HTN w/ tyramine injection on MAOI

MOA;
-reversible and competitive block of alpha 1 and alpha 2 receptors;
producing peripheral vasodilation and decrease in SBP

Dose;
-HTN crisis; 1 - 5 mg IV q 5 min
(max 20 mg)
-Tx Extravasation of NE; 5 -10mg in 10 mL of saline injected into the infiltrated area within 12 hrs

Pharmacokinetics;

• onset; 2 - 5 min
• E1/2 life; 19 min
• DOA; 10 - 15 min

metabolized by the liver
10 - 13% excreted unchanged in urine

Side Effects;

• ab cramping/ diarrhea (tx with atropine)
• hypotension & orthostatic hypotension
• tachycardia (reflex)
• angina –> MI
• cardiac arrhythmias
• N/V
• flushing

*severe hypotension can be treated with NE

Contraindicated;

• hypersensitivity
• severe hypotension
• CAD
• Hx of MI and Angina
• PUD
• breast feeding or pregnant women

Question 3

Prazosin

Answer 3

Selective Post- Synaptic Alpha 1 adrenergic receptor blocker 
A1 >>>> A2 1,000x 
alpha 1 receptors in vein >>>> arteries 
**no reflex tachycardia 
**most selective 
Uses;
-tx HTN
-decrease after load in CHF
-Pre-op in pt with pheochromocytoma
-Reduces vasospasm in Raynauds
-HTN r/t t BPH (can reduce prostate size) 
-combination with diuretics to tx HTN

MOA;
-selectively binds to post synaptic A1 adrenergic receptors blocking catecholamines and sympathomimetics; causing arterial and venous vasodilation
-decreases SVR without causing reflex tachycardia
[[maintains inhibitor of alpha 2 release of NE; no reflex tachycardia]]

Dose; initial 1 mg PO; titrate to effect
max dose 20 mg/day in divided doses

Pharmacokinetics;

• Peak; 3 hrs
• E1/2t; 3 - 4 hours
• Pb; high

First pass effect with PO dose <60% bioavailability
metabolized by the liver and excreted in bile and feces

Side Effects;

• syncope after 1st dose
• dizziness
• vertigo
• headache
• drowsiness
• orthostatic hypotension
• palpitations
• anticholinergic effects (dry mouth, nasal congestion)

Contraindicated;

• hypersensitivity
• epidural anesthesia hypotension can be exaggerated (alpha 1 antagonist prevents compensatory vasoconstriction in unblocked part of body)

Caution;
pregnancy (category C)