indication

For as an adjunct to coumarin anticoagulants in the prevention of postoperative thromboembolic complications of cardiac valve replacement and also used in prevention of angina.

pharmacology

Dipyridamole, a non-nitrate coronary vasodilator that also inhibits platelet aggregation, is combined with other anticoagulant drugs, such as warfarin, to prevent thrombosis in patients with valvular or vascular disorders. Dipyridamole is also used in myocardial perfusion imaging, as an antiplatelet agent, and in combination with aspirin for stroke prophylaxis.

mechanism of action

Dipyridamole likely inhibits both adenosine deaminase and phosphodiesterase, preventing the degradation of cAMP, an inhibitor of platelet function. This elevation in cAMP blocks the release of arachidonic acid from membrane phospholipids and reduces thromboxane A2 activity. Dipyridamole also directly stimulates the release of prostacyclin, which induces adenylate cyclase activity, thereby raising the intraplatelet concentration of cAMP and further inhibiting platelet aggregation.

toxicity

Hypotension, if it occurs, is likely to be of short duration, but a vasopressor drug may be used if necessary. The oral LD₅₀ in rats is greater than 6,000 mg/kg while in the dogs, the oral LD₅₀ is approximately 400 mg/kg. LD₅₀=8.4g/kg (orally in rat)

biotransformation

hepatic

absorption

70%

half life

40 minutes

route of elimination

Dipyridamole is metabolized in the liver to the glucuronic acid conjugate and excreted with the bile.

drug interactions

Adenosine: Dipyridamole may increase the effect/toxicity of adenosine.

Fludarabine: Dipyridamole may decrease the effect of fludarabine.

Ginkgo biloba: Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.

Topotecan: The p-glycoprotein inhibitor, Dipyridamole, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.

Treprostinil: The prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the antiplatelet agent, Dipyridamole. Monitor for increased bleeding during concomitant thearpy. Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.