Promethazine

[proh-meth-uh-zeen, -zin]

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 (brand names Phenergan, Promethegan, Romergan, Fargan, Farganesse, Prothiazine, Avomine, Atosil).

Promethazine also has strong anticholinergic and sedative effects. Previously it was used as an antipsychotic, although it is generally not administered for this purpose now; promethazine has only approximately 1/10 of the antipsychotic strength of chlorpromazine.

Chemically, promethazine hydrochloride (HCl) appears as a white to faint yellow crystaline powder which is practically odorless. Slow oxidation may occur upon prolonged exposure to air causing blue discoloration. Promethazine as the hydrochloric salt is freely soluble in water and somewhat soluble in alcohol.

Indications

As a sedative.
For preoperative sedation and to counteract postnarcotic nausea.
As antiallergic medication to combat hay fever, allergic rhinitis, etc. To treat allergic reactions it can be given alone or in combination with oral decongestants like pseudoephedrine.
As an adjunct treatment for anaphylactoid conditions (IM/IV route preferred).
Together with codeine or dextromethorphan against cough.
As a motion sickness or seasickness remedy when used with Ephedrine or Pseudoephedrine.
To combat moderate to severe morning sickness and hyperemesis gravidarum. In the UK promethazine is drug of first choice, being preferred as an older drug with which there is a greater experience of use in pregnancy (second line being metoclopramide or prochlorperazine).

Contraindications

Promethazine should not be given to children under two years of age; there is potential for fatal respiratory depression in this age group.
Hypersensitivity to phenothiazines
Closed angle glaucoma
Intoxication with alcohol or other central depressants
Severe hypotension or shock
Coma due to any reason
Severely impaired liver function
Urine hesitancy due to enlargement of the prostate gland

Mechanism of action

Promethazine is a phenothiazine derivative that competitively blocks histamine H₁ receptors without blocking the secretion of histamine.
It has sedative, anti-motion-sickness, anti-emetic, and anti-cholinergic effects
However, unlike other phenothiazines, it has no dopaminergic action due to a structural difference with other phenothiazines.

Side effects

Some common side effects include:

Blurred vision
Confusion in the elderly
Drowsiness, dizziness, fatigue, more rarely vertigo
Dry mouth
Seizures (extremely rare)
Neuroleptic malignant syndrome (extremely rare)
Respiratory depression in patients under age of 2 and in those with severely compromised pulmonal function
Constipation
Euphoria (very rare with high IV doses and/or coadministration with opioids/CNS depressants)
Restless legs

When incorrectly administered parenterally, severe reactions requiring immediate medical attention include:

Phlebitis (inflammation of a vein), potentially severe when administered intravenously
Severe tissue necrosis due to arterial or inadvertent perivascular extravasation
Gangrene
Arterial spasm / Distal vessel spasm
Thrombophlebitis
Vascular Insufficiency
Deep Vein Thrombosis
Paralysis
Paresthesia

It is recommended that Promethazine only be given through an existing intravenous set in a large vein, and diluted to concentration no greater than 25mg per ml, not to exceed a rate of administration of 25mg a min. Serious complications including those listed above have resulted from improper parenteral administration, including those requiring surgical intervention and amputation.

Laboratory examinations

All patients should have their blood pressure measured frequently. During long-term therapy, blood cell counts, liver function studies, EKG, and EEG are recommended. The intervals should be determined according to the risk profile of the patient. In high doses Promethazine can create auditory and visual hallucinations causing panic and intense fear. If mixed with alcohol less needs to be taken to get these effects therefore can really take someone by surprise.

Recreational use

Promethazine is sometimes used as a recreational drug in conjunction with codeine in prescription cough syrup. The syrup by itself contains 7% alcohol. The traditional mixture of Sprite and cough syrup with codeine, which is known as "purple drank" or "Sizzurp", is popularized in the rap world, especially in the Houston area. It is also sometimes used to counteract nausea caused by illicit opioid use.