Alpha Blockers and Adrenergic Neuronal Blockers

non-selective alpha receptor blockers

phenoxybenzamine

phentolamine

selective alpha 1 blockers

prazosin

terazosin

doxazosin

tamsulosin

alpha blockers MOIs

inhibition of vascular and other peripheral alpha adrenergic receptors

decrease in BP by decrease in peripheral vascular resistance due to inhibition of alpha1 mediated arterial vasoconstriction

alpha blockers pharmacokinetics

non-competitive inhibition (phenoxybenzamine)

• slow onset but irreversible

• only synthesis of new receptors can restore a-adrenergic function

competitive inhibition (phentolamine)

• fast onset but can be reversed

alpha blocker local side effects

nasal congestion

difficulty in ejaculation

alpha blocker systemic side effects

reflex tachycardia

systemic extracellular fluid retention

orthostatic hypotensive sx

phenoxybenzamine pharmacokinetics

long acting irreversible inhibitor of both a1 and a2 receptors

phenoxybenzamine clinical use

pheochromocytoma

• treatment of sweating and HTN associated w pheochromocytoma

• preoperative period prior to surgery

• inoperable pheochromocytoma

blocks both alpha receptors

non-competitive

phentolamine pharmacokinetics

nonselective reversibly inhibits both alpha receptors

short acting

phentolamine clinical uses

pheochromocytoma releases excess epinephrine, HTN caused by this is also treated phentolamine associated resulting from stress or manipulation during the perioperative period

extravasation management: dermal necrosis/sloughing after extravasation of norepi

local anesthesia reversal: epinephrine used with local anesthetics

phentolamine adverse effects

primarily gastrointestinal

prazosin MOI

prototype of selective a1 adrenergic blocking agents

prazosin clinical use

mild to moderate primary HTN

• not as monotherapy

• combo with diuretics, B-blockers or other antiHTN agents

• good for HTN with BPH

raynaud phenomenon - reserved for pts resistant to initial therapy (CCBs)

PTSD nightmares and sleep disruptions

prazosin adverse effects

orthostatic hypotension with syncope

• severe first day (first dose phenomenon)

• initial dose usually taken at bedtime to avoid syncopal rx

• dose titration helps to prevent these sx

systemic extracellular fluid retention - diuretics not included in therapy

reflex tachycardia but not as much as with nonselective agents because a2 still working

doxazosin and terazosin MOI

a1 receptor blockers, side effects and uses almost identical to prazosin

half lives longer than prazosin

• better compliance for long term HTN

induces apoptosis in prostate smooth muscle cells

what is benign prostatic hyperplasia (BPH)

enlarged prostate can cause obstructive urinary symptoms

relaxation of smooth muscle of the bladder neck and prostatic urethra can improve sx

what can you use to treat BPH

long acting alpha 1 antagonists: doxazosin, terazosin

subtype selective a1a antagonists: tamsulosin

tamsulosin MOI

selective blocking subtype A alpha1 receptor

• smooth muscle of the bladder neck and prostate

tamsulosin clinical use

BPH

• less frequent and less severe systemic side effects

• little effect on BP

• does not require dose titration

tamsulosin adverse effects

high incidence of abnormal ejaculation

• local side effect due to alpha 1a receptors in vas deferens

centrally-acting adrenergic neuronal inhibitors

methyldopa

clonidine

guanfacine

centrally acting adrenergic neuronal inhibitors MOI

a2 receptor agonists

more prominent effects at CNS a2 sites

act on vasomotor centers to decrease sympathetic flow to peripheral organs (heart, blood vessels, kidney)

methyldopa MOI

enzymes that convert Dopa to DA to NE convert this drug to methylnorepinephrine

a2 adrenergic agonist in central vasomotor centers

dampens outflow of sympathetic nerve activity to peripheral CV tissue

• decrease in HR, CO, renal renin release, peripheral resistance

methyldopa clinical use

treatment of HTN in pregnancy

methyldopa adverse effects

peripheral fluid retention and central mediated dry mouth and sedation

positive Coombs test (hemolytic anemia reversed with drug cessation)

abnormal liver function tests (severe hepatic necrosis)

what does adrenergic neuronal inhibitor mean

dampen effects of sympathetic system (a2 agonists for negative feedback acting on sympathetic system)

clonidine MOI

direct a2 adrenergic agonist

decreases sympathetic outflow from CNS vasomotor centers

clonidine clinical use

primary HTN

immediate release tablet

transdermal patch

• smoother BP control, less sedation, can have skin rx

not first line for HTN

clonidine other clinical uses

ADHD: sustained release, children who respond poorly to or have bad side effects of stimulants

opioid withdrawal (imidazoline receptors)

vasomotor sx with menopause

apraclonidine for decreasing postsurgical IOP

• little systemic effects

clonidine adverse effects

dry mouth and sedation (at least 50% of pts)

sexual dysfunction

rebound HTN with abrupt cessation of the drug (except for methyldopa)

guanfacine clinical use

primary HTN

a2 hypertensive

• less sedation and less withdrawal

not first line

ADHD: sustained release, children who respond poorly to or have bad side effects of stimulants