Does codeine cause tachycardia, particularly in patients with pre‑existing cardiac disease, hypertension, or concomitant sympathomimetic medications?

Does Codeine Raise Heart Rate?

Codeine does not typically raise heart rate; in fact, opioids including codeine generally cause bradycardia (slowing of heart rate) rather than tachycardia. 1

Cardiovascular Effects of Opioids

Primary Cardiac Effects

• Opioids, including codeine, typically cause bradycardia and vasodilation rather than tachycardia. 1
• Most opioids have minimal direct negative effects on cardiac contractility when used at therapeutic analgesic doses. 1
• Opioid administration can lead to hypotension, orthostatic hypotension, and rarely syncope due to their vasodilatory and bradycardic effects. 1

Mechanism of Action

• Opioids exert anti-arrhythmic effects through stimulation of kappa receptors and via sympatholytic (reducing sympathetic nervous system activity) and parasympathomimetic (enhancing vagal tone) properties. 2
• Morphine and fentanyl (related opioids) increase the electrical fibrillation threshold of the ventricle, demonstrating protective rather than pro-arrhythmic effects. 2

Important Clinical Caveats

Risk of Reflex Tachycardia

• If codeine causes significant hypotension or vasodilation, reflex tachycardia may occur as a compensatory mechanism, but this is secondary to blood pressure changes rather than a direct cardiac effect. 2
• This reflex tachycardia represents the body's attempt to maintain cardiac output in response to decreased blood pressure, not a primary drug effect on heart rate. 2

Drug Interactions That May Cause Tachycardia

• When combined with ozanimod (a medication for ulcerative colitis), opioids including codeine may potentially cause hypertensive crisis due to MAO inhibition by ozanimod metabolites, which could theoretically trigger reflex tachycardia. 2
• Concomitant use of codeine with sympathomimetic medications (pseudoephedrine, phenylephrine, amphetamines) in patients taking MAO inhibitors can precipitate hypertensive crisis. 2

Combination with Other Sedatives

• Opioid administration combined with benzodiazepines can be associated with decreased cardiac function, though this typically manifests as bradycardia rather than tachycardia. 1

Patients with Pre-existing Cardiac Disease

Structural Heart Disease

• In patients with pre-existing cardiac disease, opioids remain more likely to cause bradycardia than tachycardia. 1
• Patients with heart failure or reduced ejection fraction may experience more pronounced hypotension with opioids, potentially triggering compensatory tachycardia. 1

Hypertension

• Opioids do not directly raise heart rate in hypertensive patients; they may actually provide modest blood pressure reduction through vasodilation. 1
• The primary concern in hypertensive patients is orthostatic hypotension rather than tachycardia. 1

Monitoring Recommendations

ECG Considerations

• Unlike methadone and buprenorphine, codeine does not prolong QTc interval and does not require ECG monitoring for this purpose. 1
• ECG monitoring is not routinely indicated for codeine use unless the patient develops symptomatic bradycardia or hypotension. 1

Clinical Vigilance

• Monitor for signs of excessive bradycardia, particularly in elderly patients or those on concurrent medications that slow heart rate (beta-blockers, calcium channel blockers, digoxin, clonidine). 2, 3
• Assess for orthostatic vital signs if the patient reports dizziness or lightheadedness, as this may indicate significant vasodilation requiring dose adjustment. 1

Common Pitfall to Avoid

Do not confuse anxiety-related tachycardia in patients experiencing pain with a direct drug effect of codeine. Patients in pain often have elevated heart rates from sympathetic activation; when codeine provides adequate analgesia, heart rate typically decreases as pain and anxiety resolve, not increases. 2