Promethazine is a neuroleptic (actually an antihistamine) that produces sedative, antiallergic, antiemetic, and sleep-inducing effects. It is used primarily for the treatment of agitation states.
What is promethazine?
Promethazine (chemical molecular formula: C17H20N2S) belongs to the group of phenothiazines. It is a neuroleptic, but because of its mechanism of action, it actually belongs to the antihistamines. Promethazine has little or no use as an antipsychotic, which is unusual for a neuroleptic. However, it is used as a sedative (tranquilizer). In addition, it can be used as an antiallergic and antiemetic.
Pharmacological action
Promethazine belongs to the first group of neuroleptics. It is a low-potency neuroleptic. Neuroleptics are used in the therapy of schizophrenia, for example, because they exert an antipsychotic and spedative effect. Psychoses are mainly due to the action of the neurotransmitters dopamine and serotonin. Almost all neuroleptics therefore have an inhibitory effect on the dopamine and serotonin receptors in the central nervous system by occupying them and thus acting as antagonists to weaken the effect of the two neurotransmitters. In this way, they regulate their influence on the psyche. Promethazine, however, has a different mechanism of action than most neuroleptics. Primarily, it is an antihistamine and thus blocks histamine by binding to H1 receptors as an antagonist. Histamine receptors are also located in the central nervous system. Since promethazine also binds to these, it has a sleep-promoting and sedative effect. It is therefore particularly suitable for the therapy of states of agitation. However, it is not suitable for the sole therapy of schizophrenia. The absorption of promethazine takes place in the intestine and is very rapid. However, it is subject to a high first-pass effect, resulting in relatively low bioavailability. The plasma half-life of the substance is about 10-12 hours, the highest plasma concentration is present after one and a half to three hours. The drug is metabolized by an enzyme from the cytochrome P450 group, and the resulting metabolites are not pharmacologically active. Thus, they do not exert their own effect.
Medical application and use
Promethazine is used for agitation and anxiety, restlessness, sleep disorders, and allergies. However, its use in allergies is only when concomitant sedation is desired. In addition, the drug is also used for nausea and vomiting when better tolerated antiemetics cannot be used. Promethazine is not suitable for the sole therapy of schizophrenia. The neuroleptic potency of the drug is given as 0.5. It thus belongs to the group of low-potency neuroleptics, which are mainly used for their sedative effect. From this, its unsuitability for the sole therapy of schizophrenia can be deduced. For the treatment of allergic reactions, nausea and vomiting, promethazine is not the drug of first choice because of its sedative effect. There are better-tolerated drugs that do not exert sedative and sleep-promoting effects and yet are effective against allergic reactions, nausea, and vomiting. However, if these agents are not available, cannot be administered for other reasons, or if concomitant sedation is desired, promethazine can be used for these complaints, for which it is well effective.
Risks and side effects
Promethazine can produce a number of adverse drug effects. These include dry mouth, constipation, loss of libido, confusion, dizziness, hypotension (low blood pressure), cardiac arrhythmias, headache, dyskinesias (movement disorders), akathisia (abnormal restlessness), seizures, malignant neuroleptic syndrome, and respiratory depression in young children and in patients with bronchial asthma or COPD. Promethazine should not be taken at the same time as antihypertensive drugs, sleeping pills, painkillers and alcohol, as it increases the effect of these substances.Promethazine must not be used in children under two years of age, when taking MAO inhibitors, in Reye’s syndrome, in epilepsy, impaired consciousness, hypotension, in coronary heart disease, liver dysfunction, kidney dysfunction, bronchial asthma, bronchitis, bronchiectasis, in cystic fibrosis, narrow-angle glaucoma, prostatic hyperplasia, urinary retention and in pyloro-duodenal constipation. In the elderly, it may be given only under strict indications. Promethazine is misused to enhance the central effects, e.g., the euphoric effects of opiates.