dipyridamole

Brand: Persantine, Aggrenox (combined with aspirin)

Beers Criteria Prototype: aspirin
Drug Class: antiplatelet agent
Drug Family: antiplatelet
Subclass: phosphodiesterase inhibitor / adenosine uptake inhibitor
Organ Systems: cardiovascular

Mechanism of Action

Inhibits platelet phosphodiesterase, elevating intracellular cAMP and reducing platelet aggregation; also blocks adenosine reuptake, increasing plasma adenosine levels that stimulate platelet A2 receptors to further raise cAMP; vasodilatory properties used in pharmacologic stress testing.

phosphodiesterase (PDE)adenosine reuptake transporterplatelet cAMP

Indications

  • prevention of stroke and TIA (combined with aspirin as Aggrenox)
  • pharmacologic cardiac stress testing (IV formulation)
  • prosthetic heart valve thromboprophylaxis (with warfarin)

Contraindications

  • hypersensitivity to dipyridamole
  • asthma or COPD (relative contraindication for IV stress testing due to bronchospasm risk)

Adverse Effects

Common

  • headache
  • flushing
  • dizziness
  • GI upset
  • hypotension

Serious

  • angina exacerbation (IV)
  • bronchospasm (IV)
  • severe hypotension with IV use

Pharmacokinetics (ADME)

Absorption oral bioavailability approximately 37-66%; food does not significantly affect absorption
Distribution widely distributed; Vd approximately 92 L; crosses placenta
Metabolism hepatic conjugation to glucuronide; primarily enterohepatic cycling
Excretion fecal via bile (>95%); minimal renal excretion
Half-life 10-12 hours
Onset oral: 1-2 hours; IV: minutes
Peak 75 minutes (oral)
Duration 24 hours
Protein Binding 99%
Vd approximately 92 L

Drug Interactions

Drug / Agent Mechanism Severity
adenosine dipyridamole blocks adenosine deaminase and reuptake; dramatically increases adenosine levels — reduce adenosine dose major
theophylline theophylline competitively reverses dipyridamole's effect on adenosine; use as antidote for IV dipyridamole stress-induced bronchospasm moderate
anticoagulants/antiplatelet agents additive bleeding risk moderate

Nursing Considerations

  1. For IV pharmacologic stress testing, monitor ECG continuously; have theophylline 100-200 mg IV available as a reversal agent for bronchospasm or severe hypotension.
  2. Oral Aggrenox (dipyridamole/aspirin) should be swallowed whole without crushing; counsel patients that headache is common and usually resolves within one week of therapy.
  3. Assess for active asthma or COPD before IV dipyridamole stress testing; these are relative contraindications due to adenosine-mediated bronchospasm risk.
  4. Monitor blood pressure during IV administration; hypotension may occur and is usually transient but can be significant in patients with hemodynamic instability.

Clinical Pearls

  • IV dipyridamole induces coronary steal by causing maximal vasodilation in normal vessels while diseased arteries cannot dilate further — reduced flow in stenotic areas creates perfusion defects visible on nuclear imaging.
  • Theophylline is the specific reversal agent for IV dipyridamole adverse effects (bronchospasm, severe chest pain, hypotension) and should always be readily available when performing pharmacologic stress testing.

Safety Profile

Pregnancy generally-safe
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required