Nursing Pharmacology: Autonomic Pharmacology Adrenergic Drugs
α-Adrenergic Antagonists (Blockers)
α-adrenergic receptor activation is responsible for many actions of both endogenous catecholamine and drugs.
α1-adrenergic receptor activation results in contraction of arterial and venular smooth muscle.
α-adrenergic receptor activation causes:
Decreased sympathetic outflow.
Increased vagal tone.
Increased platelet aggregation.
Decreased release of the transmitters acetylcholine and norepinephrine (presynptic inhibitory effect).
Metabolic regulation effects, e.g.:
Decreased insulin release
α-adrenergic receptor antagonists:
Phentolamine (Regitine) exhibits comparable potency at α1 and α2-adrenergic receptors
Prazosin (Minipress) is more potent at α1 compared to α2-adrenergic receptors
Yohimbine (Yocon) is more potent at α2 compared to α1-adrenergic receptors
α1-adrenergic receptor antagonists- Cardiovascular Effects
α1-adrenergic receptor blockade inhibits vasoconstriction caused by endogenous catecholamines.
α1-adrenergic receptor blockers cause an arteriolar and venular vasodilation (a reduction in peripheral resistance) that decreases blood pressure. (BP = Cardiac Output x Total Peripheral Resistance)
Hypotensive responses trigger baroreceptor reflexes that act to increase
If the drug blocks both α1 and α2 adrenergic receptors, then the α2 presynaptic effect serves to increase norepinephrine release further increasing heart rate through ß1 cardiac stimulation.
α1-adrenergic antagonists block effects of sympathomimetic amines. For example:
pure α-adrenergic agonist effects (phenylephrine (Neo-Synephrine)) are nearly completely blocked
norepinephrine α-receptor mediated effects are blocked but ß1 effects remain.
"Epinephrine reversal": epinephrine blood pressure increases (pressor effects) are converted to vasodepressor effects due to a receptor blockade in the presence of continued ß2 receptor activation.
Recall that ß2 receptor activation causes vasodilation by meanse of ß2 receptor activation that leads to relaxation of vascular smooth muscle.
α2-adrenergic receptor antagonists
α2-adrenergic antagonists increase norepinephrine release from nerve endings.
Activation of central nervous system (CNS) α2-adrenergic receptors cause a decrease in sympathetic outflow and consequently a decrease in blood pressure.
α2-adrenergic antagonists such as yohimbine (Yocon) increase sympathetic outflow and increase blood pressure.
Activation of a2-adrenergic receptors can result in smooth muscle contraction or relaxation, depending on vascular beds.
Phenoxybenzamine blocks both α1 and α2 adrenergic receptors.
Phenoxybenzamine reacts with a adrenergic receptors to form a covalent bond.
Receptor blockade is "irreversible" (covalent) and reactivation of receptor function requires de novo receptor synthesis
Pharmacological effects are secondary to α adrenergic blockade. Such effects include:
A decrease in peripheral resistance
Reflex cardiac stimulation
Impaired response to hypovolemia and anesthetic-induced vasodilation
Impaired response to exogenous pressors
Therapeutic Uses for α-adrenergic blocking drugs
Treatment of elevated and fluctuating blood pressure due to pheochromocytoma.
Pheochromocytomas are adrenal medullary tumors secreting into the circulation large amounts of catecholamines.
High blood catecholamine levels cause severe hypertension.
Phenoxybenzamine (Dibenzyline) or phentolamine (Regitine) are used to control blood pressure prior to definitive surgical treatment.
Drugs in this category are useful in controlling autonomic hyperreflexia in patients with spinal injury.
Some α adrenergic antagonists (blockers) are effective in treating benign prostatic hypertrophy by relaxing smooth muscle that otherwise would impede urine flow.
Major adverse effects of α-adrenergic blockade:
Inhibition of ejaculation
Phentolamine (Regitine) and Tolazoline (Priscoline)
Competitive antagonist at both α1 and α2 adrenergic receptor
Phentolamine also blocks 5-HT (serotonin) receptors.
Phentolamine causes mast cell histamine release.
Tolazoline is less potent, but otherwise similar to phentolamine.
Some clinical uses for phentolamine:
Short-term management of pheochromocytoma
Counteracts dermal necrosis following extravasation of vasoconstrictive, α-adrenergic receptor agonists
Major adverse effects
Prazosin (Minipress) and Terazosin (Hytrin)
Prazosin and terazosin are selective α1 adrenergic receptor blockers.
Both cause a significant reduction in peripheral vascular resistance and venous return, a combination which reduces reflex tachycardia.
Prazosin and trazosin decrease preload: no significant increase cardiac output or heart rate.
Possible CNS effect: suppression of sympathetic outflow.
Significant orthostatic hypotension following first-dose.
Some therapeutic uses for prazosin/terazosin:
Congestive heart failure (arteriolar and venular dilatation)
Reduction in preload and afterload improves cardiac output
Reduction in pulmonary congestion
Prazosin has not been shown to improve longevity (by contrast to treatment with an angiotensin converting enzyme (ACE) inhibitor or by a combination of the vasodilator hydralazine and an organic nitrate.
Benign prostatic hypertrophy
Mechanism is: α1-adrenergic receptor blockade reduces bladder and urethral trigone muscle tone.
Other α-adrenergic receptor blockers
Yohimbine (Yocon) α2 adrenergic receptor blocker
Labetalol (Trandate, Normodyne) (α and ß receptor blocker)
Ketanserin (5-HT [serotonin] and alpha-adrenergic receptor blocker)
Some antipsychotic drugs (e.g. haloperidol (Haldol), chlorpromazine (Thorazine))
Hoffman, B.B and Lefkowitz, R.J, Catecholamines, Sympathomimetic Drugs, and Adrenergic Receptor Antagonists, In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp.225-232.