Antipsychotics antiemetic effects

Tourette s syndrome, a heterogeneous behavioral disorder associated with motor and vocal tics of variable form and severity, can be effectively treated with haloperidol. Antipsychotics can also be employed to control disturbed behavior in senile dementia or Alzheimer s disease, since they decrease confusion, agitation, and hyperactivity. Most of these drugs also exhibit a strong antiemetic effect and can sometimes be used clinically for this purpose. 

Mechanism of Action An antipsychotic, antiemetic, and antidyskinetic agent that competitiveiy biocks postsynaptic dopamine receptors, interrupts nerve impulse movement, and increases turnover of dopamine in the brain. Has strong extrapyrami-dai and antiemetic effects weak antichoiinergic and sedative effects. Therapeutic Effect Produces tranquiiizing effect. 

Most older typical antipsychotic drugs, with the exception of thioridazine, have a strong antiemetic effect. This action is due to dopamine-receptor blockade, both centrally (in the chemoreceptor trigger zone of the medulla) and peripherally (on receptors in the stomach). Some drugs, such as prochlorperazine and benzquinamide, are promoted solely as antiemetics. 

In our 1987 review, we summarized the research and clinical experience in this area [1], Surprisingly, in spite of the enormous public interest in medical marijuana and countless articles in the daily press and magazines focused predominantly on this aspect of marijuana use, little progress has been reported on the antiemetic activity of cannabinoids in the last decade. Plasse et al. have reviewed the clinical experience gained over 7 years with dronabinol (d9-THC) in antiemetic treatment [117]. With doses of 7 mg/m2 or below, complete response was noted in 36% of the patients, 32% showed partial response and 32% showed no response. However, 65% displayed drowsiness and dizziness and 12% had dysphoric effects. Combination treatment of dronabinol with prochlorperazine (a dopamine receptor blocker widely used as an antipsychotic drug with antiemetic effects) was more effective than each drug alone [118]. 

Psychosis is caused by a dopamine (neurotransmitter) imbalance in the brain. Antipsychotic medications (dopamine antagonists) block the D2 dopamine receptors, reducing the psychotic symptoms. Some antipsychotic medications block the chemoreceptor trigger zone and vomiting (emetic) center, producing an antiemetic effect. Blocking dopamine causes the side effects of Parkinsonism (see 15.24 Parkinsonism Medication). Psychosis is treated with antipsychotic medications. Categories of antipsychotic are ... 

Perphenazine is thought to exert its antipsychotic effects by postsynaptic blockade of CNS dopamine receptors, thus inhibiting dopamine-mediated effects. The antiemetic effects of perphenazine are attributed to dopamine-receptor blockade in the medullary chemoreceptor trigger zone. Perphenazine has many other central and peripheral effects it produces both alpha and ganglionic blockade and counteracts histamine- and serotonin-mediated functions. It produces... 

Promazine (initially 50 to 150 mg IM) is indicated in the management of psychotic disorders. In addition, it has antiemetic and antivertigo properties and possesses antihista-minic actions, and hence may be used pre- or post-operatively (25 to 50 mg IM). The antiemetic effects of promazine may be due to its anticholinergic actions. Eur-thermore, promazine inhibits the medullary chemoreceptor trigger zone for emesis. The antipsychotic effects of promazine may be due in part to blockade of hyperactive dopaminergic transmission in the mesocortical and mesolimbic systems. 

Haloperidol was introduced for the treatment of psychoses in Europe in 1958 and in the United States in 1967 (Fig. 22.7). it is an effective aiternative to more famiiiar antipsychotic phenothiazine drugs and also is used for the manic phase of bipolar (manic-depressive) disorder. Haloperidol decanoate has been introduced as depot maintenance therapy. When injected every 4 to 6 weeks, the drug appears to be as effective as daily orally administered haloperidol. Other currently available (mostly in Europe) butyrophenones include the very potent spiperone (spiroperidol) as well as trifluperidol and droperidol. Droperidol, a short-acting, sedating butyrophenone, is used in anesthesia for its sedating and antiemetic effects and, sometimes, in psychiatric emergencies as a sedative-neuroleptic. Droperidol often is administered in combination with the potent narcotic analgesic fentanyl for preanesthetic sedation and anesthesia. 

Even before the identification of central 5-HTg receptors, 5-HTg receptor antagonists have been suggested to possess striking properties. To date, based on animal studies, several reports have shown that these drugs display anxiolytic, antipsychotic [see 3,4, 5,166,167], promnesic [72,169,170], antidepressant [136], antinociceptive [23, 171] and antiemetic [172, 173] properties, generally at low doses and without side-effects [4]. Confirmation of these results in human are necessary before drawing any definitive conclusion since, except for the antiemetic effects, data from clinical trials are few and generally limited to ondansetron. Critical reviews on the subject have recently been published [9, 235-238]. 

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 ... 

Prochlorperazine Maleate. 2-Chloro-10-[3-(4-methyl-l-piperazinyl)-propyl]-10 H-phenothiazine maleate [84-02-6] (Compazine) (22) is a white or pale yellow crystalline powder. It is almost completely odorless, its saturated solution is acidic to litmus, it is practically insoluble in water and ethanol, and it is slightly soluble in warm chloroform. It may be made by the synthesis described in Reference 18. Prochlorperazine maleate [84-02-6] is an effective antiemetic and tranquilizing agent. It is not particularly effective for motion sickness. Adverse reactions that may occur include extrapyramidal reactions, motor resdessness, dystonias, tardive dyskinesia, and contact dermatitis. Prochlorperazine is also a significant phenothiazine antipsychotic. 

In addition to their well-established antipsychotic properties, the neuroleptics have a number of clinically important properties that include their antiemetic and antinauseant actions, their antihistaminic effects and their ability to potentiate the actions of analgesics and general anaesthetics. 

Various neuroleptics are also used for nonpsychiatric purposes, usually in smaller doses for shorter durations. However, severe effects can sometimes develop from these limited uses. Reserpine (Serpasil) is a neuroleptic that is more often used to suppress the symptoms of tardive dyskinesia (chapter 4). Prochlorperazine (Compazine) is used as an antiemetic and rarely as a neuroleptic. If given in sufficient doses to manifest psychoactive effects, these drugs produce the same emotional indifference as the other antipsychotic drugs. 

PROPAFENONE I. ANTIARRHYTHMICS - disopyra-mide, procainamide 2. ANTIBIOTICS - macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/ dalfopristin 3. ANTICANCER AND IMMUNOMODULATING DRUGS -arsenic trioxide 4. ANTIDEPRESSANTS - TCAs, venlafaxine 5. ANTIEMETICS-dolasetron 6. ANTIFUNGALS-fluconazole, posaconazole, voriconazole 7. ANTIHISTAMINES - terfenadine, hydroxyzine, mizolastine 8. ANTI-M ALARIALS - artemether with lumefantrine, chloroquine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS - pentamidine isetionate 10. ANTIPSYCHOTICS-atypicals, phenothiazines, pimozide II. BETA-BLOCKERS - sotalol 12. BRONCHODILATORS -parenteral bronchodilators 13. CNS STIMULANTS - atomoxetine Risk of ventricular arrhythmias, particularly torsades de pointes Additive effect these drugs prolong the Q-T interval. Also, amitriptyline, clomipramine and desipramine levels may be t by propafenone. Amitriptyline and clomipramine may t propafenone levels. Propafenone and these TCAs inhibit CYP2D6-mediated metabolism of each other Avoid co-administration... 

METOCLOPRAMIDE ANTIPSYCHOTICS t risk of extrapyramidal effects Additive effect Consider using an alternative antiemetic... 

AMANTADINE 1. ANTIEMETICS-metodopramide 2. ANTIPSYCHOTICS 3. CENTRALLY ACTING ANTI HYPERTENSIVES -methyldopa 4. TETRABENAZINE 1 efficacy of amantadine Antagonism of antiparkinson s effect these drugs have extrapyramidal side-effects Use with caution avoid in patients <20 years... 

---