Page 296 - Basic _ Clinical Pharmacology ( PDFDrive )

282 SECTION IV Drugs with Important Actions on Smooth Muscle

General structure Ethers or ethanolamine derivative

CH 3
CH O CH 2 CH 2 N
X Y C C N
CH 3
X is: C or N
Y is: C, O, or omitted Diphenhydramine or dimenhydrinate

Alkylamine derivative Piperidine derivative

CI CH 3 OH
CH CH 2 CH 2 N C
CH 3
N
Chlorpheniramine N OH CH 3
CH 2 CH 2 CH 2 CH C COOH

CH 3
Fexofenadine

FIGURE 16–1 General structure of H 1 -antagonist drugs and examples of the major subgroups. Subgroup names are based on the shaded
moieties.

these agents, but histamine-stimulated gastric acid secretion and doxylamine (in Bendectin), were used widely in the past in the
the stimulation of the heart are unaffected. treatment of nausea and vomiting of pregnancy (see below). Although
The first-generation H -receptor antagonists have many actions Bendectin was withdrawn in 1983, a similar formulation, combining
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in addition to blockade of the actions of histamine. The large doxylamine and pyridoxine (Diclegis), was approved by the US Food
number of these actions probably results from the similarity of the and Drug Administration (FDA) in 2013.
general structure (Figure 16–1) to the structure of drugs that have
effects at muscarinic cholinoceptor, α adrenoceptor, serotonin, 3. Antiparkinsonism effects—Some of the H antagonists,
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and local anesthetic receptor sites. Some of these actions are of especially diphenhydramine, have significant acute suppressant
therapeutic value and some are undesirable. effects on the extrapyramidal symptoms associated with certain
antipsychotic drugs. This drug is given parenterally for acute
1. Sedation—A common effect of first-generation H antagonists dystonic reactions to antipsychotics.
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is sedation, but the intensity of this effect varies among chemical
subgroups (Table 16–2) and among patients as well. The effect is 4. Antimuscarinic actions—Many first-generation agents,
sufficiently prominent with some agents to make them useful as especially those of the ethanolamine and ethylenediamine sub-
“sleep aids” (see Chapter 63) and unsuitable for daytime use. The groups, have significant atropine-like effects on peripheral mus-
effect resembles that of some antimuscarinic drugs and is considered carinic receptors. This action may be responsible for some of the
very different from the disinhibited sedation produced by sedative- (uncertain) benefits reported for nonallergic rhinorrhea but may
hypnotic drugs. Compulsive use has not been reported. At ordinary also cause urinary retention and blurred vision.
dosages, children occasionally (and adults rarely) manifest excitation
rather than sedation. At very high toxic dose levels, marked stimu- 5. Adrenoceptor-blocking actions—Alpha-receptor-blocking
lation, agitation, and even seizures may precede coma. Second- effects can be demonstrated for many H antagonists, especially
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generation H antagonists have little or no sedative or stimulant those in the phenothiazine subgroup, eg, promethazine. This
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actions. These drugs (or their active metabolites) also have far fewer action may cause orthostatic hypotension in susceptible indi-
autonomic effects than the first-generation antihistamines. viduals. Beta-receptor blockade is not significant.
2. Antinausea and antiemetic actions—Several first-generation 6. Serotonin-blocking actions—Strong blocking effects at
H antagonists have significant activity in preventing motion sick- serotonin receptors have been demonstrated for some first-
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ness (Table 16–2). They are less effective against an episode of generation H antagonists, notably cyproheptadine. This drug
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motion sickness already present. Certain H antagonists, notably is promoted as an antiserotonin agent and is discussed with that
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