Nursing Pharmacology: Autonomic Pharmacology Adrenergic Drugs
Therapeutic uses of indirect-acting adrenoceptor agonists
Ephedrine is classified as an indirect-acting synthetic non-catecholamine
This drug is resistant to MAO metabolism in the gastrointestinal tract.
Routes of administration include oral, IV, and intramuscular.
Pharmacological actions due to both direct and indirect components:
Direct action is mediated by activation of adrenergic receptors.
Indirect action is based on drug-induced endogenous norepinephrine release.
Pharmacokinetics:
40% of ephedrine does excreted unchanged in urine
Hepatic deamination (hepatic MAO) and conjugation reactions are important drug metabolizing pathways for ephedrine.
Ephedrine's prolonged duration of action results from slow inactivation.
Pharmacodynamics:
Cardiovascular Effects:
Ephedrine's cardiovascular activity is similar to epinephrine but shows a reduced pressor effect and is longer lasting.
IV ephedrine:
IV ephedrine administration results in increased systolic & diastolic blood pressure, heart rate, cardiac output, coronary blood flow, skeletal muscle blood flow.
IV ephedrine, by contrast, causes a reduction in both renal and splanchnic blood flow.
Primary mechanism for cardiovascular effects is activation of cardiac ß1 receptors.
A second ephedrine dose causes a lesser blood-pressure response, which is an example of "tachyphylaxis."
The reduced response following a second dose is due to, in part, depletion of norepinephrine storage sites.
Clinical Use
Ephedrine by IV administration may be used to increase systemic blood pressure following sympathetic blockade during regional anesthesia or to reverse a hypotensive response due to injected or inhaled anesthetics.
Chronic, oral ephedrine administration may be helpful in bronchial asthma management.
Mephentermine (Wyamine)
This drug is classified as an indirect-acting synthetic, non-catecholamine sympathomimetic agent.
Mephentermine is similar in chemical structure to methylamphetamine, but with reduced CNS-stimulation.
Mephentermine activates α and β-adrenergic receptors and following IV administration results in ephedrine-like cardiovascular effects.
Metaraminol (Aramine)
Overview:
Metaraminol is classified as a direct and indirect acting, synthetic, non-catecholamine sympathomimetic
This agent activates α and β-adrenergic receptors
Upon uptake into post-ganglionic sympathetic nerve terminals, metaraminol displaces norepinephrine and acts as a weak, false transmitter (i.e. not the normal norepinephrine neurotransmitter).
Metaraminol is not a. substrate for MAO or COMT enzymatic degradation.
Pharmacodynamics:
Cardiovascular Effects:
Metaraminol administration causes significant, peripheral vasoconstriction but exhibits less positive inotropic action compared to ephedrine. (A positive inotropic effect is an increase in force of cardiac contraction; a positive chronotropic effect is an increase in heart rate.)
Following IV administration, metaraminol increases both systolic and diastolic blood pressure as a result of α-adrenergic receptor activation which in turn causes peripheral vasoconstriction.
The increase in blood pressure after metaraminol then activates an autonomic nervous system reflex which compensates for the increase in blood pressure by slowing the heart rate, i.e. , reflex bradycardia
Bradycardia is associated with a reduction in cardiac output.
Renal effects of metaraminol include a decrease in blood flow; moreover, reduction is cerebral blood flow is also noted.
Adverse Effects: β-Adrenoceptor Antagonists
Rebound hypertension and tachycardia upon abrupt drug discontinuation (receptor "up-regulation" with chronic use).
Hypoglycemic episodes in insulin-dependent diabetics.
Increased plasma triglycerides (VLDL); Decreased plasma high-density lipoproteins (HDL)
Non-selective adrenergic antagonists (blockers) adverse effects:
Bronchoconstriction, due to ß2-antagonism therefore use should be limited to non-asthmatics.
Decreased myocardial contractility.
Decreased heart rate (cardiac output).
ß1-selective Adrenergic Antagonists (blockers) adverse effects:
Careful use in asthmatics because selectivity for ß1- vs. ß2- is limited.
Decreased myocardial contractility.
Decreased heart rate (cardiac output).
Stoelting, R.K., "Sympathomimetics", in Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp. 271-272