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Chapter 1: Pharmacodynamics

Pindolol and some other β adrenergic receptor antagonists have an additional property that is referred to as intrinsic sympathomimetic activity (ISA). This additional property indicates these agents are

a. full agonists.

b. inverse agonists.

c. partial agonists.

d. neutral antagonists.

e. noncompetitive antagonists.

Answer is c. Several β blockers (eg, pindolol, acebutolol, bucindolol) activate β receptors partially in the absence of catecholamines; however, the intrinsic activities of these drugs are less than that of a full agonist such as isoproterenol, epinephrine, or norepinephrine. Thus these are partial agonists and are said to have intrinsic sympathomimetic activity. Substantial sympathomimetic activity would be counterproductive to the response desired from a β antagonist; however, slight residual activity may, for example, prevent profound bradycardia or negative inotropy in a resting heart. The potential clinical advantage of this property, however, is unclear and may be disadvantageous in the context of secondary prevention of myocardial infarction.

Although only limited data are available, β blockers with slight partial agonist activity may produce smaller reductions in resting heart rate and blood pressure. Hence, such drugs may be preferred as antihypertensive agents in individuals with diminished cardiac reserve or a propensity for bradycardia.

Nonetheless, the clinical significance of partial agonism has not been substantially demonstrated in controlled trials but may be of importance in individual patients. Agents such as pindolol block exercise-induced increases in heart rate and cardiac output (see Chapters 15 and 16).

A 28-year-old woman is brought to the emergency department after overdosing on oxycodone, an opiate analgesic. She is unconscious and barely breathing when she arrives at the hospital, but revives and is breathing normally within 2 minutes after receiving an injection of naloxone. After about an hour, she requires another dose of naloxone as the symptoms of opiate overdose begin to redevelop. Naloxone is likely acting as a

a. strong stimulant that counteracts the CNS-depressant effects of the opiate.

b. diuretic that increases renal excretion of the opiate.

c. drug that stimulates respiratory centers in the brain.

d. competitive antagonist of opioid receptors.

e. noncompetitive antagonist of opioid receptors.

Answer is d. Naloxone is a competitive antagonist of various opioid receptors (see Chapter 10). Opioid antagonists, particularly naloxone, have an established use in the treatment of opioid-induced toxicity, especially respiratory depression. Its specificity is such that reversal by this agent is virtually diagnostic for the contribution ...

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