PROMETHAZINE

Absorption

A 25mg dose of intramuscular promethazine reaches a Cmax of 22ng/mL. Intravenous promethazine reaches a Cmax of 10.0ng/mL, with a Tmax of 4-10h, and an AUC of 14,466ng*h/mL. Oral promethazine is only 25% bioavailable due to first pass metabolism. Oral promethazine reaches a Cmax of 2.4-18.0ng/mL, with a Tmax of 1.5-3h, and an AUC of 11,511ng*h/mL.

Toxicity

The intraperitoneal LD50 in rats is 170mg/kg and in mice is 160mg/kg. The subcutaneous LD50 in rats is 400mg/kg and in mice is 240mg/kg. The oral LD50 in mice is 255mg/kg.
Patients experiencing an overdose of promethazine may present with mild central nervous system and cardiovascular depression, hypotension, respiratory depression, unconciousness, hyperreflexia, hypertonia, ataxia, athetosis, extensor-plantar reflexes, convulsions, dry mouth, flushing, gastrointestinal symptoms, and fixed, dilated pupils. Treat overdoses with symptomatic and supportive treatment, which may include activated charcoal, sodium sulfate, magnesium sulfate, controlled ventilation, diazepam, intravenous fluids, vasopressors, norepinephrine, phenylephrine, anticholinergic antiparkinsonian agents, diphenhydramine, barbiturates, or oxygen.

Description

As a derivative of phenothiazine, promethazine is structurally and pharmacologically similar to chlorpromazine. It exhibits strong antihistamine activity as well as expressed action on the CNS. It potentiates action of sedative and analgesic drugs.

Description

Promethazine is a first-generation H1 receptor antagonist antihistamine and antiemetic medication. It is a prescription drug in the United States, but is available over the counter in the United Kingdom, Switzerland, and many other countries.

The Uses of PROMETHAZINE

Promethazine is used for treating allergic illnesses such as hives, serum disease, hay fever, dermatosis, and also for rheumatism with expressed allergic components, for allergic complications caused by antibiotics and other medicinal drugs, and for enhancing action of analgesics and local anesthetics. Synonyms of this drug are allergen, phenergan, pipolphen, prothazine, and others.

The Uses of PROMETHAZINE

Anti-emetic; antihistaminic.

The Uses of PROMETHAZINE

Promethazine is used in preparation of antibodies having inhibitory activities to IL-36R signaling triggered by agonistic ligands and application to prevention and therapies of cancers and autoimmune diseases.

Background

Promethazine, originally known as 3,277 R.P., is an N-dimethylaminopropyl derivative of phenothiazine that was developed in France in 1946. Promethazine antagonizes a variety of receptors, allowing it to be used for a number of indications including allergic reactions, pain, sedation, nausea, and vomiting.
Promethazine was granted FDA approval before 29 March 1951.

Indications

Promethazine tablets and suppositories are indicated to treat rhinitis, allergic conjunctivitis, allergic reactions to blood or plasma, dermographism, anaphylactic reactions, sedation, nausea, vomiting, pain, motion sickness, and allergic skin reactions. Promethazine cough syrup with phenylephrine and codeine is indicated to relieve cough and upper respiratory symptoms, and nasal congestion associated with allergy or the common cold.

Definition

ChEBI: A tertiary amine that is a substituted phenothiazine in which the ring nitrogen at position 10 is attached to C-3 of an N,N-dimethylpropan-2-amine moiety.

brand name

Phenergan (Wyeth).

World Health Organization (WHO)

Introduced in 1946, promethazine, a phenothiazine derivative has a variety of pharmacological properties. At present it is mainly used as an antihistamine and anti-motion-sickness drug. Promethazine is listed in the WHO Model List of Essential Drugs.

General Description

Crystals. Melting point 60°C. Used as an antihistaminic.

Air & Water Reactions

Turns blue on prolonged exposure to air and moisture.

Reactivity Profile

PROMETHAZINE neutralizes acids in exothermic reactions to form salts plus water. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable or toxic gases may be generated in combination with strong reducing agents, such as hydrides.

Health Hazard

SYMPTOMS: Symptoms of PROMETHAZINE include leucopenia; agranulocytosis; confusion; convulsions; stupor; and it potentiates the action of central nervous system depressants.

Fire Hazard

Flash point data for PROMETHAZINE are not available, however PROMETHAZINE is probably combustible.

Pharmacokinetics

Promethazine is is a histamine H1 antagonist that can be used for it's ability to induce sedation, reduce pain, and treat allergic reactions. Promethazine's effects generally last 4-6h but can last up to 12h. Patients should be counselled regarding CNS and respiratory depression, reduce seizure threshold, and bone marrow depression.

Clinical Use

Promethazine, an early agent in the series, has many useful pharmacological affects other than being an antihistamine. It has significant antiemetic and anticholinergic properties. It also has sedative-hypnotic properties and has been used to potentiate the effects of analgesic drugs. Subsequent analogues, such as trimeprazine and methdilazine, are used as antipruritic agents in the treatment of urticaria.

Safety Profile

Poison by ingestion, intravenous, intramuscular, intraperitoneal, and subcutaneous routes. Human systemic effects by ingestion: pupillary dilation, wakefulness, hallucinations, and distorted perceptions. An experimental teratogen. Other experimental reproductive effectsHuman mutation data reported. A severe eye irritant. When heated to decomposition it emits very toxic fumes of NOx and SOx

Synthesis

Promethazine, 10-(2-dimethylaminopropyl)phenothiazine (16.1.18), is synthesized by alkylating phenothiazine with 1-dimethylamino-2-propylchloride.

Metabolism

Promethazine is predominantly metabolized to promethazine sulfoxide, and minorly to desmethylpromethazine and a hydroxy metabolite. Hydroxylation of promethazine is predominantly mediated by CYP2D6.