Chapter 15

• Diphenhydramine is an example of a diverse group of drugs that competitively blocks H1-receptors. Many drugs with H1-receptor antagonist properties have considerable antimuscarinic, or atropine-like, activity (eg, dry mouth), or antiserotonergic activity (antiemetic).
• H2-blockers reduce the perioperative risk of aspiration pneumonia by decreasing gastric fluid volume and raising the pH of gastric contents.
• Metoclopramide increases lower esophageal sphincter tone, speeds gastric emptying, and lowers gastric fluid volume by enhancing the stimulatory effects of acetylcholine on intestinal smooth muscle.
• Ondansetron, granisetron, and dolasetron selectively block serotonin 5-HT3 receptors, with little or no effect on dopamine receptors. 5-HT3 receptors, which are located peripherally and centrally, appear to play an important role in the initiation of the vomiting reflex.
• Ketorolac is a parenterally administered nonsteroidal antiinflammatory drug that provides analgesia by inhibiting prostaglandin synthesis.
• Clonidine is a commonly used antihypertensive agent but in anesthesia it is used as an adjunct for epidural infusions in pain management. It is most useful in the management of patients with neuropathic pain who become increasingly resistant to epidural opioid infusions.
• Dexmedetomidine is a parenteral selective α2-agonist with sedative properties. It appears to be more selective for the α2-receptor than clonidine.
• Selective activation of carotid chemoreceptors by low doses of doxapram stimulates hypoxic drive, producing an increase in tidal volume and a slight increase in respiratory rate. However, doxapram is not a specific reversal agent and should not replace standard supportive therapy (ie, mechanical ventilation).
• Naloxone reverses the agonist activity associated with endogenous or exogenous opioid compounds.
• Flumazenil is useful in the reversal of benzodiazepine sedation and the treatment of benzodiazepine overdose.
• Aspiration does not necessarily result in aspiration pneumonia. The seriousness of the lung damage depends on the volume and composition of the aspirate. Patients are at risk if their gastric volume is greater than 25 mL (0.4 mL/kg) and their gastric pH is less than 2.5.

This final pharmacology chapter describes several drugs of particular interest to the anesthesiologist. Because some of these are histamine-receptor antagonists, the physiology of histamine is briefly reviewed. Diphenhydramine represents the classic antihistaminic drug. Cimetidine, ranitidine, and famotidine are helpful in the preoperative preparation of patients at risk for aspiration pneumonia. The chapter reviews other drugs (eg, metoclopramide, antacids, and proton pump inhibitors) that may be used to decrease the risk of aspiration as well as serotonin antagonists, which have proved to be potent antiemetics. The α2-adrenergic agonists clonidine and dexmedetomidine are also reviewed. The chapter concludes with a discussion of a respiratory stimulant (doxapram), an opioid antagonist (naloxone), and a benzodiazepine antagonist (flumazenil).

### Histamine Physiology

Histamine is found in the central nervous system, in the gastric mucosa, and in other peripheral tissues. It is synthesized by decarboxylation of the amino acid histidine. Histaminergic neurons are primarily located in the posterior hypothalamus but have wide projections in the brain. Histamine ...

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