Dipyridamole, introduced in the early 1960s, was initially developed as a coronary vasodilator and anti-anginal agent, though its effectiveness in treating angina was limited. In 1961, the FDA approved it for preventing thromboembolic events in patients with prosthetic heart valves, typically in combination with anticoagulants. Its mechanism of action involves inhibiting phosphodiesterase (PDE) enzymes and blocking adenosine uptake into platelets and endothelial cells. This increases cyclic AMP and cGMP levels, raises extracellular adenosine, and leads to vasodilation and inhibition of platelet aggregation. As an antiplatelet and vasodilator, dipyridamole helps prevent blood clots and reduces the risk of stroke and other thromboembolic complications. It is also used in pharmacologic stress testing to aid in the diagnosis of coronary artery disease. By increasing extracellular adenosine, it activates platelet A₂-receptors, elevates cAMP, and inhibits platelet aggregation, while its weak PDE inhibition contributes to vascular smooth muscle relaxation and vasodilation.
BRAND NAMES
Dipyridamole is marketed under several brand names.
Common ones include Persantine® and Aggrenox® (combined with aspirin).
Aggrenox® is mainly used for stroke prevention.
Different brands may have immediate or sustained-release formulations.
Brand choice can depend on clinical use and patient tolerance.
MECHANISM OF ACTION
Dipyridamole works as both an antiplatelet agent and a vasodilator. It inhibits phosphodiesterase (PDE) enzymes, which increases intracellular cAMP and cGMP levels. Additionally, it blocks the uptake of adenosine into platelets, endothelial cells, and red blood cells, raising extracellular adenosine levels. This extracellular adenosine stimulates platelet A₂-receptors, leading to inhibition of platelet aggregation. The drug also relaxes vascular smooth muscle, causing vasodilation and improving blood flow.
PHARMACOKINETICS:
Absorption
Dipyridamole is well absorbed orally, reaching peak plasma levels in 1–2 hours. Its bioavailability is 37–66% due to first-pass metabolism. High-fat meals may reduce absorption of immediate-release forms. Sustained-release formulations provide more consistent plasma levels over time.
Distribution
Dipyridamole is widely distributed throughout the body.
It is highly protein-bound (~99%), mainly to plasma albumin.
Volume of distribution is approximately 0.5 L/kg.
Metabolism
Dipyridamole is primarily metabolized in the liver, mainly through conjugation processes. Only a small portion of the drug remains unchanged in the bloodstream. Liver function can influence the rate of metabolism and overall drug levels. The resulting metabolites are generally inactive and are eventually excreted by the kidneys.
Excretion
Most dipyridamole and its metabolites are excreted in the urine, with renal elimination accounting for about 90% of the drug. Fecal excretion is minimal. The oral elimination half-life is approximately 10–12 hours, while sustained-release formulations may have a slightly longer half-life, allowing for less frequent dosing.
PHARMACODYNAMICS
Dipyridamole exerts its effects by preventing platelet aggregation and promoting vasodilation. The antiplatelet action occurs through increased cAMP and extracellular adenosine, which inhibit platelet activation. Its vasodilatory effect relaxes vascular smooth muscle, enhancing coronary and systemic blood flow. These combined actions make it useful both for preventing thromboembolic events and for pharmacologic stress testing in patients with suspected coronary artery disease. Peak pharmacodynamic effects are usually observed 1–2 hours after oral administration.
ADMINISTRATION
Dipyridamole can be administered orally in tablet or extended-release capsule forms and intravenously for pharmacologic stress testing. Oral doses are typically divided 2–4 times daily, depending on the formulation and indication. Timing with meals may influence the absorption of immediate-release forms. For stroke prevention or thromboembolic prophylaxis, consistent dosing is essential. Intravenous administration is carefully monitored during stress tests to evaluate coronary artery function safely.
DOSAGE AND STRENGTH
Immediate-release dipyridamole tablets are usually given at 25–75 mg, three to four times daily. Sustained-release formulations are often prescribed at 200 mg, two to four times daily. Aggrenox®, the combination of dipyridamole 200 mg with aspirin 25 mg, is taken twice daily for stroke prevention. IV doses for pharmacologic stress testing are typically 0.57 mg/kg administered over four minutes. Dosage is adjusted based on clinical indication, patient age, and tolerance.
DRUG INTERACTIONS
Dipyridamole can interact with other medications, particularly those affecting bleeding risk. Co-administration with anticoagulants or other antiplatelet agents may increase the likelihood of bleeding. Vasodilators may enhance hypotensive effects, while caffeine and theophylline can reduce dipyridamole’s efficacy. Adenosine use alongside dipyridamole can potentiate cardiovascular effects. Careful monitoring is required in patients taking multiple cardiac or antithrombotic medications.
FOOD INTERACTIONS
High-fat meals may reduce the absorption of immediate-release dipyridamole tablets, potentially lowering effectiveness. Caffeine should be avoided during pharmacologic stress testing because it can antagonize the drug’s vasodilatory effects. Aside from these considerations, there are no strict dietary restrictions. Maintaining consistent meal patterns helps achieve stable drug levels. Awareness of food interactions is particularly important for accurate diagnostic testing and stroke prevention.
CONTRAINDICATIONS
Dipyridamole should not be used in patients with hypersensitivity to the drug. It is contraindicated in severe coronary artery disease with unstable angina and in patients who recently experienced a myocardial infarction when using IV forms. Severe hypotension is also a contraindication due to the vasodilatory effects. Careful evaluation is necessary to avoid exacerbating cardiac or vascular complications. Screening patients for these conditions ensures safe and effective use.
SIDE EFFECTS
Common side effects: headache, dizziness, flushing, hypotension.
Gastrointestinal effects: nausea, diarrhea, abdominal discomfort.
Less common effects: palpitations, mild chest pain.
Most side effects are mild and often resolve with dose adjustment or discontinuation.
Monitoring for adverse effects is important to ensure patient safety and guide therapy adjustments.
OVER DOSE
Overdose of dipyridamole can cause severe hypotension, tachycardia, arrhythmias, headache, dizziness, and flushing. Management is primarily supportive, including IV fluids and cardiovascular monitoring. There is no specific antidote for dipyridamole overdose. Prompt recognition and treatment are critical to prevent serious complications. Supportive care focuses on stabilizing blood pressure and heart function.
TOXICITY
Dipyridamole has a relatively low toxicity profile under normal dosing conditions. Excessive doses may increase the risk of hypotension and bleeding. Severe toxicity is rare, and long-term organ damage is uncommon. Management of toxicity is symptomatic, focusing on cardiovascular support and monitoring. Overall, the drug is considered safe when used appropriately for its indicated purposes.
