Nausea phenothiazines

Stimulation of dopamine (D2) receptors in the CTZ leads to nausea and vomiting (Fig. 17-1). Phenothiazine antiemetics... 

Phenothiazines are most useful in patients with simple nausea and vomiting. 

Q82 Buccastem consists of prochlorperazine, a phenothiazine derivative, v/hich is presented as tablets that are to be placed high betv/een the upper lip and gum and allov/ed to dissolve there. It may be used in the treatment of nausea and vomiting associated v/ith migraine, as absorption from the stomach, v/hich is usually delayed in migraine, is avoided. 

Domperidone is used in combination with antiparkinsonian drugs to counteract the nausea and vomiting caused by the latter. Since it does not readily cross the blood-brain barrier, it is not associated with extra-pyramidal effects and is less likely to cause dystonia than metoclopromide and phenothiazines. 

Phenothiazines have a diverse use in medicine. They are primarily used as antipsy-chotics. Despite the fact that they do not cure the disease, they reduce psychotic symptoms to a point where the patient is provided with a better sense of reality. Phenothiazines are sometimes used for relieving severe anxiety, especially in panic attacks caused by dependence on amphetamines or lycergic acid diethylamide (LSD). Phenothiazines are used for alleviating behavioral problems in children that do not respond to treatment of other agents. Phenothiazines are sometimes used during the preoperational period because they relieve anxiety, control nausea, hiccups, diarrhea, and also cause muscle relaxation. 

Chlorpromazine is the prototype molecule of the series of substituted phenothiazine psychotherapeutic compounds. Chlorpromazine is used for the symptomatic management of schizophrenia and active acute psychoses. The drug is also used for the prevention and treatment of nausea and vomiting, and for the relief of restlessness and apprehension before surgery [1,2]. 

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 A phenothiazine that acts as an antihistamine, antiemetic, and CNS-antipsychotiC typical hypnotic. As an antihistamine, inhibits histamine at histamine receptor sites. As an antiemetic, diminishes vestibular stimulation, depresses labyrinthine function, and acts on the chemoreceptor trigger zone. As a sedative-hypnotic, produces CNS depression by decreasing stimulation to the brainstem reticular formation. Therapeutic Effect Prevents allergic responses mediated by histamine, such as rhinitis, urticaria, and pruritus. Prevents and relieves nausea and vomiting. Pharmacokinetics ... 

Mechanism of Action A piperazine phenothiazine that acts centrally to block dopamine receptors in chemoreceptor trigger zone in central nervous system (CNS). Tiicr-apeutic Effect Relieves nausea and vomiting. 

The pharmacology of all these neuroleptics is extremely complex. Briefly, phenoth-iazines and related drugs have a calming effect on psychotic patients, without producing excessive sedation. Other central effects include the important antiemetic effect in disease-, drug-, or radiation-induced nausea, but not so much in motion sickness. Butyrophenones are more effective antiemetics than phenothiazines and also potentiate the activity of anesthetics. 

When levodopa is given without a peripheral decarboxylase inhibitor, anorexia and nausea and vomiting occur in about 80% of patients. These adverse effects can be minimized by taking the drug in divided doses, with or immediately after meals, and by increasing the total daily dose very slowly antacids taken 30-60 minutes before levodopa may also be beneficial. The vomiting has been attributed to stimulation of the chemoreceptor trigger zone located in the brain stem but outside the blood-brain barrier. Fortunately, tolerance to this emetic effect develops in many patients. Antiemetics such as phenothiazines should be avoided because they reduce the antiparkinsonism effects of levodopa and may exacerbate the disease. 

DFOA has been examined for ability to inhibit chronic inflammation. In a preliminary study with rheumatoid patients, intramuscular DFOA (1 g) produced an abrupt rise in haemoglobin, a response which was taken to indicate suppression of inflammation77. Under this regime no ill effects were observed but this was not the case where rheumatoid patients received 3 g d 1 for 5 days each week over 1 to 3 weeks78. Out of seven patients ocular abnormalities were induced in four of them but subsided on termination of DFOA treatment. Further complications of DFOA therapy were observed with two patients who lapsed into unconsciousness for up to 72 hours when they were placed upon a course of treatment with phenothiazine, a treatment initiated to suppress DFOA-induced nausea. 

Emesis. BA receptor blocking agents suppress nausea and vomiting. Phenothiazines, such as chlorpromazine and prochlorperazine, are usually employed. Their action is probably mediated via blockade of BA receptors in the chemoreceptor trigger zone of the medulla oblongata. 

The incidence of opioid-induced nausea and vomiting is markedly increased in ambulatory patients. If narcotic analgesic therapy must be continued, nausea and vomiting can be treated with hydroxyzine or a phenothiazine antiemetic. 

Nausea and vomiting often develop in patients with rheumatoid arthritis after 4—12 days of treatment with deferoxamine, presumably as a result of chelation of iron from the central nervous system (37). Two patients who took the phenothiazine derivative prochlorperazine during treatment of rheumatoid arthritis with deferoxamine lost consciousness for 48-72 hours, possibly because this combination of drugs removed essential iron from the nervous system (38). 

A number of the antihistamines, particularly the phenothi-azines and aminoalkyl ethers, have antiemetic actions and thus may be u.seful in the treatment of nausea, vomiting, and motion sickness. Also, those agents that produce pronounced. sedation have application as nonpiescription sleeping aids." - "Several of the phenothiazines have limited u.se in Parkinson-like syndromes as a result of their ability to block central muscarinic receptors." -And. a number of antihistamines, including promethazine, pyrilamine. tri-pelennamine and diphenhydramine, display local anesthetic activity that may be therapeutically useful. ... 

Phenothiazines are used to treat psychosis including schizophrenia violent, agitated, disturbed behavior and manic phase of bipolar disorder. Other uses include treatment of pain, headache, hiccups, acute severe anxiety, idiopathic dystonia, withdrawal, taste disorders, leishmaniasis, alleviation of nausea and vomiting, and acute intermittent porphyria. Phenothiazines permit smoother induction of anesthesia, potentiate anesthetic agents, and allow treatment of behavioral symptoms secondary to Alzheimer s disease and senile dementia. Some phenothiazines exert an antipruritic effect and are useful for the treatment of neurodermatitis and pruriginous eczema, and may relieve psychogenic itching. 

Indications Psychotic disorders, nausea and vomiting Category Antipsychotic, phenothiazine Half-life 9 hours... 

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