Promethazine Does Not Cause Hypertension—It Causes Hypotension
Promethazine causes hypotension, not hypertension, due to its strong alpha-adrenergic blocking effects. This is a critical clinical distinction that should inform your prescribing decisions and patient monitoring.
Primary Cardiovascular Effect: Hypotension
- Promethazine has a strong alpha-adrenergic inhibitory effect that contributes to its sedative properties and potential hypotensive side effects 1, 2
- The hypotension risk is particularly pronounced when promethazine is administered intravenously at rapid rates 2
- To minimize hypotension risk, promethazine should be infused slowly (≤25 mg/min) when given intravenously 1
Evidence Against Hypertensive Effects
- A controlled study specifically examining promethazine's effects on autonomic cardiovascular mechanisms found no significant effect on resting arterial pressure at 3 hours and 19.5 hours post-injection of 50 mg intramuscular promethazine 3
- The same study found no effect on carotid baroreflex function or plasma catecholamine levels, indicating minimal interference with autonomic cardiovascular control 3
Clinical Context: Phenothiazines and Blood Pressure
- While phenothiazines as a drug class are not listed among agents that commonly cause hypertension in the JNC 7 guidelines 1, they are well-recognized for causing hypotension
- The one case report of a patient with promethazine-induced neuroleptic malignant syndrome who presented with "labile blood pressure" 4 represents an extreme, life-threatening complication rather than simple hypertension—this patient had hyperthermia (42.4°C), muscle rigidity, and multi-organ failure
Practical Monitoring Recommendations
- Monitor for hypotension, not hypertension, especially in the first 5 minutes after intravenous administration when clinical effects become evident 1, 2
- Be particularly vigilant when promethazine is combined with other CNS depressants (benzodiazepines, opioids) as sedative effects are enhanced 2
- Patients with pre-existing cardiovascular instability or those receiving other medications affecting blood pressure require closer monitoring 1
Common Pitfall to Avoid
Do not confuse the "labile blood pressure" seen in neuroleptic malignant syndrome (a rare, life-threatening reaction) with routine hypertension. The former is a medical emergency characterized by hyperthermia, rigidity, altered mental status, and autonomic instability 4, not a simple elevation in blood pressure.