Thiethylperazine

Thiethylperazine is a Dopamine antagonist belonging to Antipsychotic agent.

Thiethylperazine is a drug used for the treatment of nausea and vomiting.

Thiethylperazine absorbed well from the gastrointestinal tract. The bioavailability is approximately 60-80%. Time to peak plasma concentration is about 1-3 hours (perphenazine); 2-4 hours (7-hydroxyperphenazine). Thiethylperazine widely distributed. It crosses the placenta. Thiethylperazine extensively metabolised in the liver via sulfoxidation, hydroxylation, dealkylation, and glucuronidation mainly by CYP2D6 isoenzyme to N-dealkylated perphenazine, perphenazine sulfoxide, and 7-hydroxyperphenazine (active). Undergoes some first-pass metabolism. Excreted via urine (approx 70%, mainly as metabolites); faeces (approx 5%). Elimination half-life: 9-12 hours (perphenazine); 10-19 hours (7-hydroxyperphenazine).

Thiethylperazine shows common side effects like Diarrhea, stomach pain, change in ability to taste food, headache, sore throat, vaginal itching and/or discharge.

Thiethylperazine is available in the form of Oral tablet, Injectable solution, and suppositories.

Thiethylperazine is available in India, Malaysia, France, Russia, Singapore and Japan.

Thiethylperazine is an Antipsychotic agent belonging to the class Dopamine antagonist.

Thiethylperazine is an antagonist at types 1, 2, and 4 dopamine receptors, 5-HT receptor types 2A and 2C, muscarinic receptors 1 through 5, alpha(1)-receptors, and histamine H1-receptors. Thiethylperazine antipsychotic effect is due to antagonism at dopamine and serotonin type 2 receptors, with greater activity at serotonin 5-HT2 receptors than at dopamine type-2 receptors. This may explain the lack of extrapyramidal effects. Thiethylperazine does not appear to block dopamine within the tubero-infundibular tract, explaining the lower incidence of hyperprolactinemia than with typical antipsychotic agents or risperidone. Antagonism at muscarinic receptors, H1-receptors, and alpha(1)-receptors also occurs with thiethylperazine.

The Data of Onset and Duration of action of Thiethylperazine clinically not established.

The Tmax was found to be approximately 1-4 hours.

Thiethylperazine is available in the form of Oral tablet, Injectable solution, and suppositories.

Thiethylperazine is a dopamine antagonist that is particularly useful in treating nausea and vomiting associated with anesthesia, mildly emetic cancer chemotherapy agents, radiation therapy, and toxins. This piperazine phenothiazine does not prevent vertigo or motion sickness.

Thiethylperazine is a Dopamine antagonist belonging to Antipsychotic agent.

Trimethylpyridine blocks postsynaptic dopamine 2 (D2) receptors in the medullary chemoreceptor trigger zone (CTZ), thereby decreasing stimulation of the vomiting center in the brain. Peripherally, trimethylpyridine blocks the vagus nerve in the gastrointestinal tract. In addition, this agent also shows antagonistic activities mediated through muscarinic receptors, H1-receptors, and alpha(1)-receptors.

Thiethylperazine is approved for use in the following clinical indications

• For the relief of nausea and vomiting

Thiethylperazine is a phenothiazine medicine. It is used to treat nausea and vomiting.

• For nausea and vomiting:

For oral dosage form (tablets):

Adults: 10 milligrams (mg) one to three times a day.

Children: Use and dose must be concerned.

For injection dosage form:

Adults: 10 mg one to three times a day, injected into a muscle.

Children: Use and dose must be concerned.

For rectal dosage form (suppositories):

Adults: 10 mg one to three times a day.

Children: Use and dose must be concerned.

Thiethylperazine is available in various strengths as 10mg and 10mg/2ml.

Thiethylperazine is available in the form of Oral tablet, Injectable solution, and suppositories.

Thiethylperazine is contraindicated in patients with

• Who have demonstrated a hypersensitivity reaction (e.g., blood dyscrasias, jaundice) to phenothiazines.
• Because severe hypotension has been reported after the intravenous administration of phenothiazines, this route of administration is contraindicated.

• Abnormal movements such as extrapyramidal symptoms

(E.P.S.)(e.g., dystonia, torticollis, dysphasia, oculogyric crises, akathisia) have occurred. Convulsions have also been reported. The varied symptom complex is more likely to occur in young adults and children. Extrapyramidal effects must be treated by reduction of dosage or cessation of medication.

• Thiethylperazine tablets contain FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible individuals. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.
• Use in patients with bone marrow depression only when potential benefits outweigh risks.
• Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex, has been reported in association with phenothiazine drugs. Clinical manifestations include: hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability.
• The extrapyramidal symptoms which can occur secondary to thiethylperazine may be confused with the central nervous system signs of an undiagnosed primary disease responsible for the vomiting, e.g., Reye’s Syndrome or other encephalopathy. The use of thiethylperazine and other potential hepatotoxins should be avoided in children and adolescents whose signs and symptoms suggest Reye’s Syndrome.
• Phenothiazine drugs may cause elevated prolactin levels that persist during chronic administration. Since approximately one-third of human breast cancers are prolactin-dependent in vitro, this elevation is of potential importance if phenothiazine drug administration is contemplated in a patient with a previously-detected breast cancer. Neither clinical nor epidemiologic studies to date, however, have shown an association between the chronic administration of phenothiazine drugs and mammary tumorigenesis.
• Postoperative Nausea and Vomiting

When used in the treatment of nausea and/or vomiting associated with anesthesia and surgery, it is recommended that thiethylperazine should be administered by deep intramuscular injection at or shortly before the termination of anesthesia.

Information is not available concerning the excretion of thiethylperazine in the milk of nursing mothers. As a general rule, nursing should not be undertaken while the patient is on a drug, since many drugs are excreted in human milk.

Thiethylperazine is contraindicated in pregnancy.

• Common

Pseudo parkinsonism, dystonia, akathisia), anticholinergic effects (e.g. blurred vision, xerostomia, constipation, urinary retention), esophageal dysmotility and aspiration, postural hypotension, motor and sensory instability causing falls; liver damage (prolonged use), elevated prolactin levels, photosensitivity, ocular effects (e.g. pigmentary retinopathy, lenticular and corneal deposits), impaired core body temperature regulation.

Phenothiazines are capable of potentiating CNS depressants (e.g., barbiturates, anesthetics, opiates, alcohol, etc.) as well as atropine and phosphorous insecticides.

The common side effects of Thiethylperazine include the following

• Common side effects

Dizziness, constipation, lightheadedness, drowsiness, dry mouth, nose and throat, fainting, fever, headache, ringing or buzzing in ears, and skin rash.

• Rare side effects

Hives, difficulty breathing, swelling of your face, lips, tongue, or throat, abdominal pain, muscle or joint pain, blurred vision, change in color vision, difficulty in seeing at night, confusion, seizures, difficulty speaking or swelling, fast heartbeat, fever, chills, inability to move your eyes, lip smacking or puckering, loss of balance, mask-like face, muscle spasms in the face, neck, and back, nausea, vomiting, diarrhea, nightmares, nosebleeds, puffy cheeks, yellowing of the skin or eyes (jaundice),weakness in the arms and legs, unusual tiredness, rapid or fine, worm-like movements of the tongue, shuffling walk, itching, sore throat, stiffness of the arms or legs, unusual bleeding, easy bruising, unusual excitement, nervous ness, restlessness, and irritability.

• Pregnancy

Pregnancy Category

Thiethylperazine is contraindicated in pregnancy.

• Nursing Mothers

Information is not available concerning the excretion of thiethylperazine in the milk of nursing mothers. As a general rule, nursing should not be undertaken while the patient is on a drug, since many drugs are excreted in human milk.

• Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Manifestations of acute over dosage of thiethylperazine can be expected to reflect the CNS effects of the drug and include extrapyramidal symptoms (E.P.S), confusion and convulsions with reduced or absent reflexes, respiratory depression and hypotension. If the patient is conscious, vomiting should be induced mechanically or with emetics. Gastric lavage should be employed utilizing concurrently a cuffed endotracheal t.b. if the patient is unconscious to prevent aspiration and pulmonary complications. Maintenance of adequate pulmonary ventilation is essential. The use of pressor agents intravenously may be necessary to combat hypotension. The administration of epinephrine should be avoided since phenothiazines may induce a reversed epinephrine effect. The most suitable vasoconstrictive agents are norepinephrine and phenylephrine. Fluids should be administered intravenously to encourage diuresis.

• Pharmacodynamic

Thiethylperazine, an atypical antipsychotic agent, is used to treat both negative and positive symptoms of schizophrenia, acute mania with bipolar disorder, agitation, and psychotic symptoms in dementia. Future uses may include the treatment of obsessive-compulsive disorder and severe behavioral disorders in autism. Structurally and pharmacologically similar to clozapine, Thiethylperazine binds to alpha (1), dopamine, histamine H1, muscarinic, and serotonin type 2 (5-HT2) receptors.

• Pharmacokinetics

Absorption

Thiethylperazine absorbed well from the gastrointestinal tract. The bioavailability is approximately 60-80%. Time to peak plasma concentration is about 1-3 hours (perphenazine); 2-4 hours (7-hydroxyperphenazine).

Distribution

Thiethylperazine widely distributed. It crosses the placenta.

Metabolism and Excretion

Thiethylperazine extensively metabolised in the liver via sulfoxidation, hydroxylation, dealkylation, and glucuronidation mainly by CYP2D6 isoenzyme to N-dealkylated perphenazine, perphenazine sulfoxide, and 7-hydroxyperphenazine (active). Undergoes some first-pass metabolism. Excreted via urine (approx 70%, mainly as metabolites); faeces (approx 5%). Elimination half-life: 9-12 hours (perphenazine); 10-19 hours (7-hydroxyperphenazine).

• https://www.drugs.com/cons/thiethylperazine.html#dosage
• https://go.drugbank.com/drugs/DB00372
• https://pubchem.ncbi.nlm.nih.gov/compound/Thiethylperazine-maleate#section=Structures
• https://www.drugs.com/cons/thiethylperazine.html