Nursing Pharmacology: Autonomic Pharmacology Adrenergic Drugs
Order of agonist potency
Isoproterenol > epinephrine > norepinephrine
ß-receptors are divided into two major categories: ß1 and ß2.
ß1 receptors are associated with the myocardium.
ß2 receptors are associated with smooth muscle and most other sites.
The subdivision of beta receptors followed from the observation that in the heart norepinephrine and epinephrine were equipotent, whereas epinephrine was many fold (10 - 50) more potent at smooth muscle.
Order of agonist potency
Epinephrine > norepinephrine >> isoproterenol
Multiple alpha receptor subtypes have been identified.
Multiple forms were suggested when, after administration of an alpha-receptor antagonist, repetitive nerve stimulation resulted in increasing amount of norepinephrine release. This findings suggested a presynaptic alpha-receptor binding site.
Post-synaptic receptors are classified as α1 .
Pre-synaptic receptors → α2 .
α2 receptors are also present post-synaptically.
This site is involved in the action of some centrally-acting antihypertensive agents, e.g. clonidine.
Some drugs, such as clonidine are more active at α2 receptors.
Clonidine acts in the brain at post-synaptic alpha2 receptors, inhibiting adrenergic outflow from the brainstem. Inhibition of sympathetic outflow results in a decrease in blood pressure.
Clonidine reduces cardiac output (by reducing both stroke volume and heart rate) and peripheral resistance. Reduction in stoke volume occurs due to increased venous pooling (decreased preload).
Clonidine does not interfere with cardiovascular responses to exercise.
Renal blood flow and function is maintained during clonidine treatment.
Clonidine has minimal or no effect on plasma lipids.
Some drugs such as methoxamine (Vasoxyl) or phenylephrine (Neo-Synephrine) are more active at α1 receptors.
Multiple forms of both α1 and α2 receptors have been identified.
Following exposure to catecholamines, there is a progressive loss of the ability of the target site to respond to catecholamines.
For example, stimulation of ß-adrenergic receptors rapidly causes receptor phosphorylation and decreased responsiveness.
This phenomenon is termed tachyphylaxis, desensitization or refractoriness.
Regulation of catecholamine responsiveness occurs at several levels:
Cyclic nucleotide phosphodiesterases
Lefkowitz, R.J, Hoffman, B.B and Taylor, P. Neurotransmission: The Autonomic and Somatic Motor Nervous Systems, 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.112-137.