Programmed Problem Set on Agents Affecting the Autonomic Nervous System

Ladislav Volicer, M.D.,Ph.D
Professor of Pharmacology
Boston University School of Medicine

Questions or comments should be mailed to Carol Walsh

This set of questions should help you to familiarize yourself with drugs acting on the autonomic nervous system, their effects and mechanisms of action. The package is composed of two parts which are independent; each of them consists of ten items.

PART A

The dose-effect curves labeled A, B, C, D, and E below represent curves for drugs administered alone or in combination. Use these curves to help you choose the most appropriate answer for the following items.

I. Before we can consider specific agents, you have to know the basic principles governing receptor-drug interactions. Which of the following statements is true?

II. Many drugs act by affecting the activity of endogenous substances, such as neurotransmitters, autacoids, and hormones. Some of them potentiate an effect, some of them inhibit or antagonize it. There are three types of antagonists: chemical, physiological and pharmacological. Which of the following statements about an agent and its antagonist is true?

III. There are two types of pharmacological antagonists: competitive and non-competitive. A competitive antagonist interacts with the ligand-binding site on a receptor and produces a reversible or irreversible antagonism depending on the kinetics of its binding and dissociation. A non-competitive antagonist interacts with a site on the receptor other than the ligand-binding site or within the receptor signal transduction mechanism.

If you assume that some of the dose-effect curves shown above were obtained with a combination of an agonist and an antagonist, which of the following statements is true?

IV. If curve C represents the increase of motility of isolated stomach after acetylcholine was administered alone, which curve represents the effect of acetylcholine in a preparation pretreated with physostigmine?

V. If curve C represents the increased heart rate of an isolated heart after treatment with norepinephrine, which curve might represent the effect of isoproterenol in the same preparation?

VI. If curve C represents the vasoconstriction after norepinephrine was given alone, which curve represents the effect of norepinephrine in a preparation pretreated with cocaine?

VII. If curve C represents the increased heart rate of an isolated heart after norepinephrine was given alone, which curve represents the effect of norepinephrine in a preparation pretreated with phentolamine?

VIII. If curve C represents contraction of an isolated skeletal muscle after acetylcholine was administered alone, which curve represents the effect of acetylcholine in a preparation pretreated with succinylcholine?

IX. If curve C represents contraction of an isolated blood vessel after phenylephrine was administered alone, which curve represents the effect of phenylephrine in a preparation pretreated with phenoxybenzamine?

X. If curve C represents contraction of an isolated skeletal muscle after acetylcholine administration, which curve represents the effect of acetylcholine in a preparation pretreated with d-tubocurarine?

PART B

An experiment was set up to record the blood pressure and heart rate of a cat, anesthetized with pentobarbital and maintained at plane III surgical anesthesia. The right vagus nerve was isolated and separated from its central connections. A pair of stimulating electrodes was placed around the distal vagus for stimulation when desired. Both carotids were isolated in the neck (below the carotid sinus) and were readily available for occlusion when desired. Doses of different drugs were administered intravenously or the nerves were stimulated for a period of two to three seconds. Blood pressure was measured with a pressure transducer, and heart rate was recorded as increased (+) or decreased (-) with respect to the base line represented as 0.

Use the information above to answer the following questions:

XI. Which procedure or drug would induce the changes of the blood pressure and heart rate observed 3 min after the beginning of the experiment?

XII. Which drug or procedure would induce the changes of the blood pressure and heart rate observed 6 min after the beginning of the experiment?

XIII. Which of the following in the same dose would diminish and/or abolish the blood pressure changes resulting from both distal vagal nerve stimulation and carotid occlusion?

XIV. Which drug or drug combinations would induce the changes of the blood pressure and heart rate observed 12 min after the beginning of the experiment?

XV. Which drugs would induce the changes of the blood pressure and heart rate observed 15 min after the beginning of the experiment?

XVI. Which of the following could induce the changes of the blood pressure and heart rate observed 18 min after the beginning of the experiment?

XVII. Which treatment would induce the changes of the blood pressure and heart rate observed 21 min after the beginning of the experiment?

XVIII. If phenoxybenzamine were administered to the animal and the test procedures were repeated, you might expect which of the following?

XIX. Which treatment would induce the changes of the blood pressure and heart rate observed 24 minutes after the beginning of the experiment?