Promethazine antiemetic effects

Promethazine Promethazine also is indicated for preoperative, postoperative, or obstetric sedation prevention and control of nausea and vomiting associated with certain types of anesthesia and surgery an adjunct to analgesics for control of postoperative pain sedation and relief of apprehension, and to produce light sleep antiemetic effect in postoperative patients active and prophylactic treatment of motion sickness (oral and rectal only). 

Stool softeners and cathartics can be used in children, as in adults, to relieve symptoms of constipation. Nausea and vomiting generally diminish as opioid therapy is continued, but antihistamines with antiemetic effects, such as hydroxyzine or promethazine, may be helpful as adjuvants to diminish impleasant G1 symptoms. Reducing the opioid dose to minimal analgesic levels may help to limit sedation or drowsiness. Mild respiratory depression, an uncommon side effect in children, may require only that the opioid dose be reduced. 

Phenothiazines (Prototype Promethazine) Most drngs of this class are Hj antagonists and also possess considerable anticholinergic activity. Promethazine, which has prominent sedative effects, and its many congeners are nsed primarily for their antiemetic effects. 

FIGURE 81 Phenothiazine derivatives such as chlorpromazine, perphenazine, prochlorperazine, promethazine, triethylperazine, and triflupro-mazine, exert their antiemetic effects by blocking the dopamine receptors in the area postrema. 

Prometh with codeine syrup 10 mg codeine phosphate and 6.25 mg promethazine hydrochloride) Promethazine competitively antagonizes histamine at H,-receptor sites and prodnces sedative as well as antiemetic effects. Codeine stimnlates opiate receptors in the CNS in addition to cansing respiratory depression, peripheral vasodilation, inhibition of intestinal peristalsis, stimulation of the chemoreceptors that cause vomiting, increased bladder tone, and suppression of cough. They are indicated in the temporary relief of coughs and upper respiratory tract symptoms associated with allergy or the common cold. 

It is an antihistamine/decongestant/antitussive/narcotic analgesic. Promethazine competitively antagonizes histamine at Hj-receptor sites and produces sedative as well as antiemetic effects. 

Meanwhile, antagonism of dopamine D2-type receptors in the chemoreceptor trigger zone in the brainstem is responsible for beneficial antiemetic effects produced by neuroleptics. Several phenothiazines (e.g., promethazine and prochlorperazine) are marketed to exploit this pharmacological effect. 

Chlorpromazine, prochlorperazine, promethazine, methylprednisolone, lorazepam, metoclopramide, dexamethasone, or dronabinol may be used for adult patients. Around the clock dosing should be considered. The choice of specific agent should based on patient specific factors, including potential for adverse drug reactions, and cost. SSRIs are effective for breakthrough nausea and vomiting but they are not superior to the less expensive antiemetics above. 

Antagonists. Most of the so-called Hi-antihistamines also block other receptors, including M-cholinoceptors and D-receptors. Hi-antihistamines are used for the symptomatic relief of allergies (e.g., bamipine, chlorpheniramine, clemastine, dimethindene, mebhydroline pheniramine) as antiemetics (meclizine, dimenhydrinate, p. 330), as over-the-counter hypnotics (e.g., diphenhydramine, p. 222). Promethazine represents the transition to the neuroleptic phenothiazines (p. 236). Unwanted effects of most Hi-antihistamines are lassitude (impaired driving skills) and atropine-like reactions (e.g., dry mouth, constipation). At the usual therapeutic doses, astemizole, cetrizine, fexofenadine, and loratidine are practically devoid of sedative and anticholinergic effects. Hj-antihistamines (cimetidine, ranitidine, famotidine, nizatidine) inhibit gastric acid secretion, and thus are useful in the treatment of peptic ulcers. 

B. Two medicines, ipecac and apomorphine, induce vomiting. Metoclopramide is a prokinetic with antiemetic properties and therefore would have the opposite of the desired effect. Morphine is an opioid with analgesic and sedating properties. Promethazine and ondansetron are also antiemetics, not emetics. 

Hepatic adverse effects secondary to antiemetic therapy are usually asymptomatic. Metoclopramide has been reported as causing cholestasis and the formation of arteriovenous shunts in the liver [12]. The 5HTj-receptor antagonists have all been documented as occasionally causing mild increases in liver fimction tests. Cholestatic jaundice has been reported with cyclizine, prochlorperazine and promethazine, and hepatitis has been reported with cyclizine. 

Antiemetics that act on the vomiting centre have antimuscarinic (their principal mode) and anti-histaminic action (hyoscine, promethazine) they alleviate vomiting from any cause. In contrast, drugs that act on the CTZ (haloperidol, ondansetron) are effective only for vomiting mediated by stimulation of the chemoreceptors (by morphine, digoxin, cytotoxics, uraemia). The most efficacious drugs act at more than one site (Table 31.1). 

The central anticholinergic and antihistaminic effects of promethazine causing inhibition of the medullary chemoreceptor trigger zone for emesis are responsible for its antiemetic and antivertigo effects (see also Figures 73 and 81). 

Some Hj antagonists, notably dimenhydrinate and meclizine, often are of benefit in vestibular disturbances such as Meniere s disease and in other types of true vertigo. Only promethazine has usefulness in treating the nausea and vomiting subsequent to chemotherapy or radiation thercq y for malignancies however, other effective antiemetic drugs are available (see Chapter 37). 

After the identification of the effects of histamine in the early twentieth century, screening for potential histamine antagonists was carried out. The first effective antihistamine compound to be found was cyclizine, which was discovered in the 1940s (Fig. 17.4). It was effective both in treating allergy and as an antiemetic. Investigations of the phenothiazine class of compounds led to the discovery of promethazine (Fig. 17.4) which is a very effective... 

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