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Sunday, July 27, 2025

Dipyridamole


Dipyridamole is an antiplatelet and vasodilator medication primarily used to reduce the risk of thromboembolic events such as stroke or transient ischemic attacks (TIAs), particularly in patients with a history of cerebrovascular disease. It can also be employed as a coronary vasodilator during pharmacologic stress testing. Its pharmacological actions stem from its ability to inhibit adenosine uptake and phosphodiesterase enzymes in platelets, leading to increased intracellular cyclic adenosine monophosphate (cAMP) and enhanced antiplatelet effects.

Pharmacological Classification

  • Therapeutic class: Antiplatelet agent

  • Pharmacologic class: Platelet aggregation inhibitor, phosphodiesterase inhibitor, vasodilator

  • ATC code: B01AC07

  • Legal status: Prescription-only medicine (Rx)

Brand Names and Formulations

  • As monotherapy: Persantine®, Pytazen®, Dipyridamole Generic

  • In fixed-dose combination with aspirin: Aggrenox® (Dipyridamole + Aspirin)

  • Available forms:

    • Oral tablets (25 mg, 75 mg, 100 mg)

    • Extended-release capsules (200 mg)

    • IV injectable solution (for diagnostic stress testing)

Mechanism of Action

Dipyridamole works through several mechanisms to exert its antiplatelet and vasodilatory effects:

1. Antiplatelet Action

  • Inhibition of phosphodiesterase (PDE) in platelets → Increased cAMP → Reduced platelet aggregation

  • Blocks adenosine reuptake → Increased extracellular adenosine → Stimulates adenosine A2 receptors → More intracellular cAMP → Inhibits thrombus formation

2. Vasodilator Effect

  • Indirect vasodilation by increasing adenosine levels in the vascular endothelium

  • Promotes coronary blood flow, particularly useful in patients unable to perform exercise-based cardiac stress tests

The combined result is reduced platelet aggregation and improved microvascular perfusion, without significantly increasing bleeding time as seen in stronger antithrombotics like warfarin.

Indications

Approved Uses

As monotherapy (oral or IV)

  • Adjunct to oral anticoagulation in patients with mechanical heart valves to prevent thromboembolism

  • Pharmacologic stress testing in nuclear cardiology (IV form)

In combination with aspirin

  • Secondary prevention of ischemic stroke or TIAs (e.g., Aggrenox)

Off-label or less common uses

  • Pulmonary hypertension (investigational)

  • Peripheral vascular disease (symptomatic improvement in some cases)

  • Migraine prophylaxis (limited and inconsistent data)

Dosage and Administration

Adults – Stroke/TIA prevention (Aggrenox)

  • 200 mg extended-release dipyridamole + 25 mg aspirin, taken twice daily

  • Swallow capsules whole; do not crush or chew

As monotherapy (e.g., for prosthetic heart valve thromboembolism)

  • 75–100 mg oral dipyridamole four times daily (rarely used alone now)

IV Dipyridamole (diagnostic use)

  • 0.14 mg/kg/min IV over 4 minutes for stress testing

  • Total dose: ~0.56 mg/kg

Renal and hepatic impairment

  • No specific dosage adjustment guidelines, but use with caution in hepatic dysfunction due to hepatic metabolism

Contraindications

  • Hypersensitivity to dipyridamole or any component

  • Severe coronary artery disease (risk of angina or MI due to coronary steal effect)

  • Unstable angina or recent myocardial infarction

  • Hypotension (potentiates vasodilation and hypotensive episodes)

  • Active peptic ulcer or bleeding disorder (with combination therapy)

Warnings and Precautions

  • Bleeding risk increases when combined with anticoagulants or other antiplatelets

  • Use with caution in patients with hypotension or syncope

  • May worsen angina due to coronary steal phenomenon (vasodilation shunting blood away from diseased vessels)

  • Hepatic impairment may alter drug metabolism and enhance effects

  • May interfere with cardiac imaging by increasing blood flow and affecting tracer distribution

Adverse Effects

Common (1–10%)

  • Headache (most frequent, due to vasodilation)

  • Dizziness, lightheadedness

  • Flushing

  • GI disturbances: Nausea, vomiting, diarrhea

  • Fatigue, myalgia, arthralgia

Uncommon/Rare

  • Hypotension, tachycardia, palpitations

  • Exacerbation of angina pectoris

  • Allergic reactions, rash, pruritus

  • Elevated liver enzymes

  • Bronchospasm in patients with asthma

  • Thrombocytopenia or other hematologic effects (rare)

Drug Interactions

Pharmacodynamic interactions

  • Adenosine: Dipyridamole potentiates effects by blocking adenosine reuptake → avoid combining unless under supervision

  • Anticoagulants (e.g., warfarin): Increased bleeding risk

  • Antiplatelet agents (aspirin, clopidogrel): Additive effect on bleeding

  • Blood pressure-lowering medications: Enhanced hypotensive effect

  • Heparin: May increase bleeding time

Pharmacokinetic interactions

  • Dipyridamole is metabolized by the liver; no significant CYP450 interactions

  • Cholinesterase inhibitors: Dipyridamole may theoretically increase acetylcholine by adenosine potentiation, but not clinically significant

Use in Pregnancy and Lactation

Pregnancy

  • Category B (US FDA)

  • Animal studies show no teratogenic effects; however, limited human data

  • Use only if clearly needed

Breastfeeding

  • Unclear whether dipyridamole is excreted in breast milk

  • Use with caution; some authorities recommend avoiding breastfeeding within several hours of dosing

Use in Special Populations

  • Elderly: No specific dose adjustments, but increased sensitivity to hypotension or dizziness

  • Renal impairment: No adjustment needed

  • Hepatic impairment: Use with caution; drug is extensively metabolized by the liver

Comparative Insights (Without Tables)

Dipyridamole vs. Aspirin

  • Aspirin inhibits platelet aggregation by blocking COX-1 and thromboxane A2 synthesis

  • Dipyridamole increases cAMP by blocking PDE and adenosine uptake

  • Combination provides synergistic platelet inhibition and reduces stroke recurrence better than aspirin alone

  • Aspirin alone preferred in cost-sensitive settings or when dipyridamole is not tolerated

Dipyridamole vs. Clopidogrel

  • Clopidogrel inhibits P2Y12 ADP receptor on platelets

  • More potent platelet inhibition than dipyridamole

  • In the PRoFESS trial, clopidogrel and dipyridamole-aspirin had similar efficacy in stroke prevention

  • Clopidogrel causes less headache, making it preferred by some patients

Clinical Guidelines

  • NICE (UK): Recommends dipyridamole + aspirin for secondary prevention of stroke or TIA if clopidogrel not tolerated

  • AHA/ASA: Dipyridamole-aspirin combo acceptable alternative to clopidogrel

  • ESC Guidelines: Suggest dipyridamole mainly in patients at high risk of recurrent non-cardioembolic stroke

Overdose and Management

Symptoms

  • Hypotension

  • Tachycardia

  • GI discomfort

  • CNS stimulation (rare)

Management

  • Activated charcoal if early ingestion

  • Symptomatic treatment

  • Aminophylline may reverse vasodilation and hypotension due to its action as an adenosine antagonist

Patient Counseling Points

  • Take oral formulations with food to minimize stomach upset

  • Do not crush extended-release capsules

  • Headache is common and may subside with continued use

  • Rise slowly from sitting/lying to avoid dizziness

  • Report any signs of bleeding, bruising, black stools, or chest pain

  • Inform doctor before any surgical or dental procedure

  • Avoid OTC NSAIDs unless approved by physician (may increase bleeding risk)




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