Antiemetics anticholinergics

Pharmacoiogy Cyclizine and meclizine have antiemetic, anticholinergic, and antihistaminic properties. 

Meclizine (25 to 50 mg 1 hour prior to travel) is indicated in prevention and treatment of nausea, vomiting, and dizziness of motion sickness. Meclizine has antiemetic, anticholinergic, and antihistaminic properties. It reduces the sensitivity of the labyrinthine apparatus. The action may be mediated through neuronal pathways to the vomiting center (VC), from the chemoreceptor trigger zone (CTZ), peripheral nerve pathways, or other CNS centers (see also Figure 73). 

The antiemetics and antivertigo drug may have additive effects when used with alcohol and other CNS depressants such as sedatives, hypnotics, antianxiety drugp, opiates, and antidepressants. There may be additive anticholinergic effects (see Chap. 25) when administered with drag s that have anticholinergic activity such as the antihistamines, antidepressants, pheno-thiazines, and disopyramide The antacids decrease absorption of the antiemetics. 

Tropane alkaloids, long known to have anticholinergic, antiemetic, parasympatholytic, anesthetic, and many other actions, have been featured in an extremely wide number of pharmacological reports. The section Pharmacology in Chemical Abstracts (Vols. 90-105) lists over 600 articles. To deal in an adequate way with these articles would go far beyond the scope of the present chapter, and interested readers are referred to Chemical Abstracts. Many of the same articles are mentioned in Periodical Reports (9a-9h). Only a few papers (vide infra) will receive comment here. 

Antiemetic drugs from the antihistaminic-anticholinergic category may be appropriate in the treatment of simple symptomatology. 

Medications for symptomatic relief from vertigo consist of antiemetics, benzodiazepines and antihistamines. They are all mostly aimed at the psychological consequences of dizziness and can all have highly unfavourable side effects, for example, sedation, anticholinergic effects and insomnia. The psychological consequences of dizziness in elderly should rather be treated with information about the condition, supportive help actions and increased social activities, than with drugs. 

A combined administration of metoclopramide and anticholinergic agent to reduce dystonic reactions of metoclopramide, did not diminish antiemetic efficacy in dogs [117], Thus, the inhibitory effect on GI smooth muscle by cholinergic blockade had no significant impact on antiemetic activity of metoclopramide. 

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. 

Antihistamine Sedative effects Antihistaminic activity Anticholinergic activity Antiemetic effects... 

In anesthesia drugs from several groups are used as premedication. Pre-anesthetic medication can decrease the anesthetic doses which otherwise would be required to induce anesthesia and so decrease the risk for adverse effects. Pre-anesthetic medication will increase the rate of induction of anesthesia and can reduce pre-operative pain and anxiety. Drugs include benzodiazepines for sedation and their muscle relaxant properties, opiates for pain relieve and anticholinergics or histamine Hi receptor antagonists against nausea and vomiting. Neuroleptics are also used as premedication for their antiemetic effects. 

Hydroxyzine hydrochloride Atarax, Vistarit) is the antihistamine with the greatest use in the treatment of anxiety. It is often used to reduce the anxiety that is associated with anesthesia and surgery. It also produces sedation, dries mucous membranes (via an anticholinergic mechanism), and has antiemetic activity. A more extensive discussion of the pharmacology of the Hj-receptor antagonists is found in Chapter 38. 

Mechanism of Action An alkylamine that competes with histamine at histaminic receptor sites. Inhibits central acetylcholine. Therapeutic Effect Results in anticholinergic, antipruritic, antitussive, antiemetic effects. Produces antidyskinetic, sedative effect. 

Mechanism of Action A phenothiazine that blocks dopamine neurotransmission at postsynaptic dopamine receptor sites. Possesses strong anticholinergic, sedative, and antiemetic effects moderate extrapyramidal effects and slight antihistamine action. Therapeutic Effect Relieves nausea and vomiting improves psychotic conditions controls intractable hiccups and porphyria. 

Mechanism of Action An ethanolamine that competitively blocks the effects of histamine at peripheral Hi-receptor sites. Therapeutic Effect Produces anticholinergic, antipruritic, antitussive, antiemetic, antidyskinetic, and sedative effects. Pharmacokinetics ... 

Mechanism of Action A phenothiazine that antagonizes dopamine neurotransmission at synapses by blocking postsynaptic dopaminergic receptors in the brain. Therapeutic Effect Decreases psychotic behavior. Also produces weak anticholinergic, sedative, and antiemetic effects and strong extrapyramidal effects. Pharmacokinetics Erratic absorption. Protein binding greater than 90%. Metabolized in liver. Excreted in urine. Half-life 33 hr. 

Mechanism of Action A phenothiazine derivative that blocks dopamine at postsynap-tic receptor sites. Possesses strong extrapyramidal and antiemetic effects and weak anticholinergic and sedative effects. Therapeutic Effect Suppresses behavioral response in psychosis reduces locomotor activity and aggressiveness. Pharmacokinetics Readily absorbed following PO administration. Protein binding 90%-99%. Metabolized in liver. Excreted in urine. Half-life 24 hr. 

Promethazine (50 mg IM), an antihistaminic with sedative, antiemetic and anticholinergic properties is generally used in children as it causes little respiratory depression. 

Droperidol and hydroxyzine (25-50 mg IM) is sometime used for their antiemetic activity. Hydroxyzine has antianxiety, antihistaminic and anticholinergic properties also. 

It is antihistaminic agent having antiemetic, sedative, anticholinergic and local anaesthetic property. Used in anxiety, pruritus and dermatoses as an adjunct therapy in acute/ chronic alcoholism. 

Dronabinol (Marinof) [C-ll] [Anriemeric, Appetite Stimulant/ Antivertigo] Uses N/V associated w/ CA chemo appetite stimulation Action Antiemetic 4- V center in the medulla Dose Adults Peds. Antiemetic 5-15 mg/m2/dose q4-6h PRN Adults. Appetite stimulant 2.5 mg PO before lunch dinner max 20 mg/d Caution [C, ] Contra Hx schizophrenia, sesame oil hypersensitivity Disp Caps SE Drowsiness, dizziness, anxiety, mood change, hallucinations, depersonalization, orthostatic 4- BP, tach Interactions T Effects W/ anticholinergics, CNS depressants, EtOH 4- effects of theophylline EMS Use caution w/ sympathomimetics, can T hypertension and tach use caution w/ anticholinergics and antihistamines, can T tach concurrent EtOH use can T CNS depression this is a principal psychoactive substance present in marijuana OD May cause extreme psychiatric effects (anxiety, mood changes and depersonalization) keep pt in a quiet environment and provide reassurance activated charcoal may be effective... 

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