dipyridamole (Persantine)

Introduction

Tradename: Persantine.

Indications

• adjunct to coumadin in prevention of thromboembolic complications of cardiac valve replacement
• used for platelet aggregation inhibition in other disorders
  • transient ischemic attack
• used as diagnostic agent in myocardial perfusion scintigraphy (Persantine stress test) to evaluate coronary artery disease in patients unable to exercise
• adjunct to aspirin (Aggrenox) for secondary prevention in patients with cardiovascular disease
• inferior to warfarin for treatment of hypercoagulability

Contraindications

• bronchospasm, severe asthma
• hypotension
• sick sinus syndrome
• AV block (high degree)

pregnancy category = b

safety in lactation = ?

Dosage

• 75-100 mg PO TID-QID
• ECG stress testing: 0.57 mg/kg over 4 minutes

Tabs: 25, 50, 75 mg.

Injection: 5 mg/mL (2 mL)

Antidote: aminophylline 100 mg IV.

Pharmacokinetics

• incompletely absorbed from the GI tract
• highly bound to plasma proteins, primarily albumin
• 1/2life is 10-12 hours
• metabolized by the liver
• excreted in the bile

elimination via liver

1/2life = 8-10 hours

Adverse effects

• oral
  • dizziness
  • headache
  • abdominal discomfort - diarrhea (common)
  • rash
• intravenous
  • ventricular fibrillation
  • actue myocardial infarction
  • transient cerebral ischemia
  • chest pain
  • flushing
  • leg cramps
  • dyspepsia
  • tachycardia
  • anxiety
  • neutropenia
  • headache
  • bronchospasm
• uncommon (< 1%)
  • syncope
  • vasodilation
  • hypertonia
  • rhinitis
  • edema
  • allergic reaction

• drug adverse effects of antiplatelet agents
• drug adverse effects of antithrombotic agent(s)
• drug adverse effects of antihypertensive agents

Drug interactions

• may increase risk of bleeding when administered with heparin
• theophylline & aminophylline antagonize effects of dipyridamole

• drug interaction(s) of anti-platelet agents with SSRIs
• drug interaction(s) of antiplatelet agents with proton pump inhibitors
• drug interaction(s) of warfarin with antiplatelet agents
• drug interaction(s) of NSAIDs & antihypertensives

Mechanism of action

• dipyridamole dilates normal coronary arteries, but has little effect on stenotic vessels
• inhibition of platelet aggregation
• inhibition of erythrocyte uptake & metabolism of adenosine by inhibiting adenosine deaminase
• inhibition of platelet phosphodiesterase leading to an increased in platelet cAMP
• may stimulate release of prostacyclin or PG2

More general terms

• antiplatelet agent
• vasodilator agent

Additional terms

• myocardial perfusion & viability scintigraphy

Component of

• aspirin/dipyridamole (Aggrenox)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3108