What medications are associated with syncope?

From the Guidelines

Medications that can cause syncope include antihypertensives, diuretics, antiarrhythmics, psychiatric medications, nitrates, alpha-blockers, opioid analgesics, anti-epileptic drugs, and medications that prolong the QT interval, and reducing or withdrawing these medications can be beneficial in selected patients with syncope. Several drug classes have been implicated in syncope, including diuretics, vasodilators, venodilators, negative chronotropes, and sedatives 1. The prevalence of medication-related syncope appears higher in older patients, who frequently have multiple comorbidities requiring treatment and are prone to polypharmacy effects 1. Some of the medications that can cause syncope are:

• Antihypertensives like beta-blockers (metoprolol, propranolol), ACE inhibitors (lisinopril, enalapril), and calcium channel blockers (amlodipine, diltiazem)
• Diuretics such as furosemide and hydrochlorothiazide
• Antiarrhythmics including amiodarone, sotalol, and flecainide
• Psychiatric medications like tricyclic antidepressants (amitriptyline), antipsychotics (haloperidol, quetiapine), and SSRIs (fluoxetine, sertraline)
• Nitrates (nitroglycerin, isosorbide) used for angina
• Alpha-blockers (tamsulosin, doxazosin) prescribed for prostate issues
• Opioid analgesics, anti-epileptic drugs, and medications that prolong the QT interval (certain antibiotics like azithromycin and fluoroquinolones) The risk of syncope increases with polypharmacy, especially in elderly patients, and syncope typically occurs when starting a new medication, increasing dosage, or combining medications with similar effects 1. Patients should be advised to rise slowly from sitting or lying positions and stay well-hydrated when taking these medications. Close supervision during adjustment of medications is frequently required because of potential worsening of preexisting supine hypertension or cardiac arrhythmias 1. Other factors to consider include frailty, HF and/or cardiac dysfunction, and the use of a large number of medications causing adverse effects because of drug-drug interactions 1.

From the FDA Drug Label

As with all alpha-blockers, prazosin hydrochloride may cause syncope with sudden loss of consciousness. Patients who experience any signs or symptoms suggesting bradycardia (pulse slowing, increased dizziness, syncope, cardiac awareness) should be advised to discontinue midodrine and should be re-evaluated.

The medications associated with syncope are:

• Prazosin: due to its excessive postural hypotensive effect, which can cause syncope with sudden loss of consciousness 2
• Midodrine: patients who experience any signs or symptoms suggesting bradycardia, including syncope, should be advised to discontinue midodrine and should be re-evaluated 3

From the Research

Medications Associated with Syncope

Medications that are associated with syncope include:

• Nitrates, which can cause symptomatic orthostatic hypotension 4
• Beta blockers, which can cause symptomatic orthostatic hypotension 4 and are also used to treat neurocardiogenic syncope 5
• Alpha 1-blockers, such as prazosin, which can cause orthostatic hypotension, especially with the first dose 6, 7
• Calcium channel blockers, such as nifedipine and verapamil, which can cause symptomatic orthostatic hypotension 4
• Centrally acting drugs, such as methyldopa, which can cause orthostatic hypotension 4, 6
• Antianginals, such as quinidine, which can cause symptomatic orthostatic hypotension 4
• Antipsychotics, such as phenothiazines, which can cause orthostatic hypotension 6
• Antidepressants, such as tricyclic antidepressants and monoamine oxidase inhibitors, which can cause orthostatic hypotension 6
• Anti-Parkinsonian drugs, which can cause orthostatic hypotension 8
• Diuretics, which can cause orthostatic hypotension, especially in the elderly 8
• ACE inhibitors, which can cause orthostatic hypotension, especially in the elderly 8

Mechanisms and Patient Characteristics

The mechanisms by which these medications cause syncope vary, but often involve orthostatic hypotension, which can be exacerbated by factors such as:

• Autonomic dysfunction 5, 6
• Age, with the elderly being more susceptible to orthostatic hypotension 6, 8
• Concomitant medical conditions, such as hypertension, heart failure, and renal impairment 7
• Polypharmacy, which can increase the risk of orthostatic hypotension 8