Does Compazine (prochlorperazine) lower heart rate?

Does Compazine (Prochlorperazine) Lower Heart Rate?

Compazine (prochlorperazine) does not lower heart rate; in fact, it typically causes postural tachycardia (increased heart rate) as one of its primary cardiovascular effects. 1, 2

Cardiovascular Effects of Prochlorperazine

Primary Effect: Tachycardia, Not Bradycardia

• Postural tachycardia is a well-documented effect of prochlorperazine, observed consistently in pharmacokinetic studies of healthy volunteers receiving both intravenous and oral doses 1
• This tachycardia occurs as a compensatory response to the drug's alpha-adrenergic blocking properties, which cause vasodilation and potential hypotension 1
• The heart rate increase persists even with chronic dosing (25 mg twice daily for 14 days), indicating this is not merely a transient effect 1

Mechanism of Cardiovascular Effects

Prochlorperazine acts as an antagonist at multiple receptor sites that influence cardiovascular function 1:

• Alpha-adrenergic receptor blockade: This is the primary mechanism causing hypotension and reflex tachycardia 1
• Dopamine D2 receptor antagonism: Centrally acting effect that does not directly slow heart rate 1
• The drug has high plasma clearance (0.98 L/kg/h) and large volume of distribution (12.9 L/kg), contributing to its systemic cardiovascular effects 1

Clinical Evidence on Heart Rate Effects

Studies in Healthy Volunteers

• In controlled pharmacodynamic studies, postural tachycardia was consistently observed after 12.5 mg IV and 25 mg oral doses 1, 2
• Cardiovascular effects were described as "minimal" in terms of severity, but tachycardia was a reproducible finding 2
• No bradycardia (heart rate lowering) was reported in any of the pharmacokinetic studies 1, 2

Studies in Acute Myocardial Infarction

• In 16 patients with acute MI receiving 2.5 mg IV prochlorperazine for nausea/vomiting, no patient developed symptomatic hypotension, though heart rate effects were not specifically reported 3
• This suggests the drug can be used safely in cardiac patients at low doses, but does not indicate heart rate reduction 3

Comparison with Related Phenothiazines

Promethazine (Related Compound)

• Promethazine, another phenothiazine antiemetic, significantly worsens orthostatic hypotension and increases presyncope rates from 38% to 100% in tilt-table studies 4
• This occurs through inhibition of sympathetic responses and suppression of compensatory tachycardia, leading to inadequate cardiovascular compensation 4
• While promethazine may blunt reflex tachycardia, prochlorperazine's profile differs and typically causes tachycardia 1, 4

Other Phenothiazines and QT Effects

• Multiple phenothiazines including prochlorperazine carry risk of QT interval prolongation, which can lead to arrhythmias but not specifically bradycardia 5, 6
• Prochlorperazine is listed among antipsychotics that pose risk of prolonged QT interval when combined with other QT-prolonging drugs 5

Clinical Implications and Monitoring

When Prochlorperazine is Used

• Monitor for tachycardia rather than bradycardia, especially in patients with cardiovascular disease 1
• The postural tachycardia typically occurs 2-4 hours after peak plasma concentrations, not immediately 1
• Hypotension is more concerning than heart rate changes in most clinical scenarios, though symptomatic hypotension appears uncommon at standard antiemetic doses (2.5-10 mg) 3

Contraindications Related to Cardiovascular Effects

• Use with caution in patients taking other QT-prolonging medications due to additive arrhythmia risk 5, 6
• The drug should be used cautiously in patients with CNS depression or those using adrenergic blockers 6
• Avoid concurrent use with betahistine due to increased risk of orthostatic hypotension and dizziness without additional therapeutic benefit 6

Common Pitfalls to Avoid

• Do not expect prochlorperazine to slow heart rate in tachycardic patients—it will likely worsen tachycardia 1
• Do not confuse prochlorperazine's effects with beta-blockers or calcium channel blockers, which do lower heart rate; phenothiazines have opposite cardiovascular effects 5
• Be aware that chronic dosing (>14 days) leads to drug accumulation with terminal half-life extending to 18 hours, potentially intensifying cardiovascular effects 1