Pharmacology - Adrenergics


1. Drug identification type questions that involve mechanism of action. You need to know the following types of facts:

a. Receptor blockers: alpha or beta adrenergic drugs such as prazosin or propranolol act by competitive inhibition of postjunctional adrenergic receptors

b. Drugs that inhibit the action of adrenergic nerves:
•Reserpine: depletes NE by inhibiting reuptake
•Guanethidine: inhibits the release of catecholamines
•Alpha methyldopa: acts centrally as a false neurotransmitter which gets taken up into storage vesicles and released with NE, thus decreasing sympathetic activity
•Clonidine: stimulates alpha2 receptors in CNS with a resulting decrease in sympathetic outflow

c. Indirect acting sympathomimetic drugs:
•amphetamine, tyramine, and ephedrine act by stimulating the release of stored NE
•TCAs and cocaine block reuptake
•MAOIs block enzymatic destruction

2. Physiological action questions: Many of these questions involve actions of epinephrine in the presence of either an alpha or beta blocker, such as:
•”Epinephrine reversal”: in the presence of an alpha blocker (usually they give prazosin, but drug such as chlorpromazine may also be given) epi causes decrease in blood pressure rather than increase because beta mediated vasodilation predominates
•vagal reflex: injection of a pressor dose of NE may result in decreased heart rate due to activation of baroreceptors which
stimulate vagal reflex to reduce heart rate. Vagal reflex is blocked by atropine.

Thus you must be familiar with the effects of alpha or beta receptor stimulation or block. The most important ones to remember are:
•Alpha-1 receptor stimulation: vasoconstriction, urinary retention, mydriasis
•beta receptor stimulation: increased heart rate (B1), bronchodilation (B2), vasodilation (B2)
•Alpha-1 block: vasodilation
•beta block: decreased heart rate (B1), bronchoconstriction (B2)

3. They usually throw in a question regarding the use of levodopa in the treatment of Parkinson’s: remember, Parkinson’s is a result of DA deficiency in brain. Remedy is to increase DA in brain. Injected DA doesn’t cross BBB, but levodopa, a precursor to DA does cross BBB. Carbidopa is given with levodopa to block dopa decarboxylase activity in periphery, which in the absence of carbidopa, converts the levodopa to DA in the periphery, decreasing the amount of levodopa that ends up in the brain. You also need to remember that levodopa is sympathomimetic, and will produce sympathetic stimulation in the periphery. Development of abnormal facial movement, nausea and vomiting, cardiac arrhythmias, and mental disturbances are all associated with levodopa therapy.

Okay, here’s a quick review of the effects of adrenergic stimulation:
Alpha-1 agonists: increased smooth muscle tone, so vasoconstriction leading to increased blood pressure
Alpha-2 agonists: given orally they cause hypotension by reducing sympathetic outflow from the CNS
Beta-1 stimulation: increased cardiac rate and force of contraction, thus positive inotropic and chronotropic actions
Beta-2 agonists: dilation of skeletal muscle blood vessels and bronchi or relaxation of bronchiolar smooth muscle

Or to organize it another way:
Eye: mydriasis or relaxation of cilary muscle
Heart: acceleration, increased contractility
Vascular smooth muscle: vasoconstriction
Skeletal muscle vessels: relaxation or dilation Bronchiolar smooth muscle: relaxation/bronchodilation Sweat glands: sweating