What is the effect of promethazine on blood pressure?

From the Guidelines

Promethazine can cause a decrease in blood pressure, particularly when administered intravenously or in high doses, due to its alpha-adrenergic blocking properties. This effect is evident within 5 minutes of intravenous administration, with a duration of action of 4-6 hours and a plasma half-life of 9-16 hours 1. The usual dose of promethazine is 12.5-25 mg intravenously, infused slowly to minimize the risk of hypotension.

When considering the impact of promethazine on blood pressure, it is essential to note that the medication has a strong-adrenergic inhibitory effect and blocks postsynaptic dopaminergic receptors in the brain. Additionally, promethazine is a competitive histamine H-receptor antagonist, which can also influence blood pressure.

Key points to consider:

• Promethazine can cause hypotension, especially in high doses or when administered intravenously
• The medication has alpha-adrenergic blocking properties, leading to vasodilation and potential decreases in blood pressure
• Patients with existing cardiovascular conditions, the elderly, or those taking other medications that lower blood pressure should use promethazine with caution
• Monitoring blood pressure and reporting any significant changes or symptoms, such as dizziness or lightheadedness, to a healthcare provider is crucial when taking promethazine 1.

In clinical practice, it is vital to weigh the benefits and risks of promethazine, considering its potential effects on blood pressure, particularly in vulnerable populations. By understanding the medication's pharmacology and taking necessary precautions, healthcare providers can minimize the risk of adverse effects and ensure the safe use of promethazine.

From the FDA Drug Label

OVERDOSAGE Signs and symptoms of overdosage with promethazine HCl range from mild depression of the central nervous system and cardiovascular system to profound hypotension, respiratory depression, unconsciousness, and sudden death. The treatment of choice for resulting hypotension is administration of intravenous fluids, accompanied by repositioning if indicated. In the event that vasopressors are considered for the management of severe hypotension which does not respond to intravenous fluids and repositioning, the administration of norepinephrine or phenylephrine should be considered EPINEPHRINE SHOULD NOT BE USED, since its use in patients with partial adrenergic blockade may further lower the blood pressure.

Promethazine can cause hypotension as a sign of overdosage. The treatment for this condition involves administration of intravenous fluids and vasopressors such as norepinephrine or phenylephrine if necessary. It is also important to note that epinephrine should not be used as it may further lower blood pressure in patients with partial adrenergic blockade 2.

From the Research

Promethazine and Blood Pressure

• Promethazine can significantly increase the incidence of orthostatic hypotension, even when combined with midodrine 3.
• The inhibition of sympathetic responses by promethazine may underlie the increased orthostatic hypotension, likely via enhancement of the inhibitive effects of GABA 3.
• Promethazine also appears to inhibit responses of the renin-angiotensin system during orthostatic challenge 3.
• In a study, supine to upright decreases in systolic pressure were greater with promethazine alone than control, midodrine alone, or both drugs 3.
• Cardiac output fell more with promethazine alone than with no drug or with midodrine plus promethazine 3.

Orthostatic Hypotension and Alpha-Adrenergic Blockers

• Alpha1-adrenergic-blocking drugs can reduce blood pressure, but may also cause orthostatic hypotension, particularly when a patient is volume-contracted 4.
• The use of alpha1-adrenergic blockers can trigger renal Na+ retention, leading to volume expansion and attenuation of their blood pressure-lowering effect 4.
• Midodrine, a peripheral alpha-adrenergic agonist, can be effective in treating orthostatic hypotension due to autonomic failure, but only in patients with significant preservation of autonomic reflexes 5.

Blood Pressure Regulation

• Alpha1-adrenergic blockers are most effective in reducing blood pressure in patients in the upright position, reducing systolic and diastolic pressures by 8%-10% 4.
• The acute hypotensive effects of beta-adrenergic blocking drugs with alpha-blocking activity are attributable only partially to the alpha-adrenergic blocking effect 6.
• Orthostatic tolerance can be evaluated using a standardized test, such as the Schellong test, to assess the efficacy of antihypertensive therapy 7.