Chapter 21 Adrenergic Antagonists
● Cause direct blockade of adrenergic receptors
● With one exception, all produce reversible (competitive) blockade
● Most adrenergic antagonists are more selective than the adrenergic agonists
● Two major groups:
○ Alpha-adrenergic blocking agents
○ Beta-adrenergic blocking agents
Therapeutic Applications of Alpha Blockade
● Essential hypertension
○ Lower blood pressure by causing vasodilation by blocking alpha1
receptors on arterioles and veins
○ In response to venous dilation:
■ Return of blood to the heart decreases
■ Cardiac output decreases
■ Arterial pressure is reduced
● Reversal of toxicity from alpha1 agonists
● Overdose of alpha-adrenergic agonist (for example, epinephrine)
● Hypertension due to excessive activation of alpha1 receptors on blood vessels
● Reversal: Alpha-blocking agent
● Extravasated necrosis: Infiltrate the region with phentolamine (an alphaadrenergic antagonist)
● Blocks vasoconstriction and prevents injury
Adverse Effects of Alpha1 Blockade
● Detrimental effects result from the blockade of alpha1 receptors
● Effects from alpha2 receptors are minor
● Orthostatic hypotension
○ Blockade of alpha receptors on veins
○ Reduced muscle tone in the venous wall
○ Upon standing, blood pools in the veins
○ Return of blood to the heart is reduced
○ Cardiac output decreased: Blood pressure drops
● Reflex tachycardia
○ Reflex to increase heart rate via the autonomic nervous system (ANS)
● Nasal congestion
○ Dilates the blood vessels of the nasal mucosa
● Inhibition of ejaculation
○ Alpha1 activation required for ejaculation
○ Impotence is reversible; resolves when drug is discontinued
● Sodium retention and increased blood volume
○ Reduced blood pressure promotes renal retention of sodium and water
○ Usually combined with diuretic when used for hypertension
Adverse Effects of Alpha2 Blockade
● Most significant adverse effect associated with alpha2 blockade: Potentiation of
reflex tachycardia
Doxazosin [Cardura]
Actions and uses
● Selective competitive inhibitor of alpha1-adrenergic receptors
● Treatment of hypertension and BPH
Pharmacokinetics
● Administered orally
● Peak effects: Develop after 2 to 3 hours
● Half-life: 22 hours
● Once-a-day dosing
● Protein bound
● Extensive hepatic metabolism
● Biliary excretion
Adverse effects
● Orthostatic hypotension
● Reflex tachycardia
● Nasal congestion
● First-dose effect
Tamsulosin [Flomax]
Actions and uses
● Alpha1-adrenergic antagonist
● Causes ÒselectiveÓ blockade of alpha1 receptors of the smooth muscle of
the bladder neck (trigone and sphincter), the prostatic capsule, and the
prostatic urethra
● Blockade of vascular alpha1 receptors is weak
● Approved only for BPH
Adverse effects
● Headache
● Dizziness
● Abnormal ejaculation
● Rhinitis
Drug interactions
● Cimetidine: Possible toxicity
● Hypotensive drugs and phosphodiesterase type 5 inhibitors (such as sildenafil
[Viagra]): Significant reduction in blood pressure
Phentolamine [OraVerse, Regitine]
Actions and uses
Competitive adrenergic antagonist
● Blocks alpha2 receptors as well as alpha1 receptors
● Approved applications:
○ Diagnosis and treatment of pheochromocytoma
○ Prevention of tissue necrosis after the extravasation of drugs that
produce alpha1-mediated vasoconstriction (such as norepinephrine)
○ Reversal of soft tissue anesthesia
Adverse effects
● Orthostatic hypotension
● Reflex tachycardia
● Nasal congestion
● Inhibition of ejaculation
● Contraindicated in patients with angina pectoris and myocardial infarction
● Profound hypotension: Treat with norepinephrine