Материал: 2016_Kaplan_USMLE_Step_1_Lecture_Notes_Pharmacology

Section II λ Autonomic Pharmacology

Chapter Summary

λNeurotransmission across adrenergic junctions is mediated by norepinephrine

(NE). Adrenergic effectors may act indirectly by influencing NE synthesis, monoamine oxidase (MAO) enzymes, the mobile NE pool, the NE transporter, prejunctional α-adrenoceptors, granule uptake, or release of NE, or they may act directly on the postjunctional receptor as agonists or antagonists.

λExcess NE normally subjects tyrosine hydroxylase to feedback inhibition, making this enzyme the rate-limiting step in the synthetic pathway of NE and epinephrine. Tyrosine conversion to DOPA can be inhibited by methyl-p- tyrosine, a tyrosine hydroxylase inhibitor.

λMAO inhibitors regulate presynaptic NE levels.

λAmphetamine, ephedrine, and tyramine act, in part, by releasing NE from the mobile pool (NE stored outside granules but within the neuron).

λCocaine and the tricyclic antidepressants act by inhibiting NE reuptake, which normally removes NE from the environment and makes it unavailable as a transmitter and also conserves it for future use.

λPrejunction availability of NE can also be decreased by inhibiting NE release from the granules. This can be achieved by drugs such as clonidine or

methyldopa, which are activators of the prejunctional α2-adrenoceptor; by drugs such as guanethidine, which act directly on the granules; or by drugs such as reserpine, which reduce NE levels by inhibiting granule uptake.

λTable II-3-1 summarizes the distribution and physiologic effects associated

with the activation of alpha 1 and 2, beta 1 and 2, and D1 receptors. Table II-3- 2 summarizes the mechanism through which these receptors work.

λThe major direct-acting adrenoceptor agonist drugs are described. The alpha agonist phenylephrine increases mean BP, has no effect on pulse pressure, and elicits a reflex bradycardia. Isoproterenol, a beta agonist, decreases mean BP, increases pulse pressure, and causes marked tachycardia. Cardiovascular effects of norepinephrine (NE) are similar to phenylephrine,

but it is also a cardiac β1 adrenoceptor activator. The cardiovascular effects of epinephrine (E) are betalike at low doses and alphalike at high doses.

λThe nonselective alpha blockers (phentolamine, phenoxybenzamine) are

described. The α1-selective blockers (e.g., prazosin) are used in hypertension and BPH.

λThe properties, clinical uses, and adverse effects of the nonselective beta receptor antagonist propranolol are described. A comparison of beta adrenoceptor antagonists that are cardioselective and those that have intrinsic sympathomimetic activity is made (Table II-3-3). Drugs that block both alpha and beta adrenoceptors are identified.

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Section II λ Autonomic Pharmacology

CO

TPR

BP

Resp.

resist.

X and Y are, respectively:

A. Isoproterenol and Propranolol

B. Epinephrine and Phenoxybenzamine

C. Norepinephrine and Phentolamine

D. Terbutaline and Phenylephrine

E. Acetylcholine and Hexamethonium

Figure II-4-7

HR

BP

What is drug X?

A. Hexamethonium

B. Neostigmine

C. Atropine

D. Scopolamine

E. Ipratropium

What would you expect to see if the infused drug was Neostigmine?

Figure II-4-8

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