Dipyridamole - Cardiovascular Poisons

Dipyridamole

While dipyridamole has no role in congestive heart failure, it is being discussed here for the sake of convenience. Dipyridamole is a coronary vasodilator. It is an antithrombotic agent most often used to modify platelet function. It is also used intrave-nously as a non-nitrate coronary vasodilator for non-invasive stress thallium cardiac imaging.

Uses

·              Long-term prevention of coronary insufficiency.

·              For coronary dilatation, and to improve collateral circula-tion following myocardial infarction.

·              For inhibition of platelet aggregation.

Toxicokinetics

·              Dipyridamole is well absorbed orally, and peak plasma concen-trations are achieved in 70 to 75 minutes. Oral absorption is from 30 to 70% of the dose ingested. It is extensively protein-bound (99%), and the volume of distribution is approximately 2 L/kg. After undergoing an enterohepatic recirculation, dipyridamole is mainly excreted in the faeces. 86 to 92% of the dose is recovered in the faeces. Elimination half-life is 10 to 16 hours.

Mode of Action

Dipyridamole acts by inhibiting adenosine transport with consequent accumulation in plasma, inhibiting cyclic AMP and phosphodiesterase, and stimulating prostaglandin I₂ synthesis.

Adverse Effects

·              Gastrointestinal disturbances, headache, vertigo, facial flushing, and skin rash are common.

·              In some cases there may be significant hypotension.

·              Intravenous use can cause cardiac arrhythmias and wors-ening of angina.

·              Intravenous dipyridamole can induce severe bronchospasm in asthmatic patients.

·              Allergic reactions are rare, but have occurred.

Drug Interactions

·              Dipyridamole can be combined with aspirin in the preven-tion of thromboembolic phenomena.

·              It potentiates the effects of oral anticoagulants and anti- arrhythmic agents.

·              Heparin given concomitantly can induce bleeding.Aminophylline may reverse its vasodilating effect.

Toxic (Clinical) Features

Symptoms and signs of overdose include headache, facial flushing, drowsiness, weakness, fainting, nausea with GI distress, hypotension, and brady- or tachycardia. Fatalities are rare. Angina has been reported as a side effect and may occur following overdose in patients with underlying myocardial ischaemia.

Treatment

Blood pressure should be monitored for at least 3 to 4 hours. Patients with uderlying cardiac disease or a history of asthma may require more intensive monitoring.

·      Activated charcoal may be beneficial.

·      Haemodialysis and haemoperfusion are ineffective, since dipyridamole is highly protein-bound.

Supportive measures:

o     Atropine for bradycardia.

o     Anginal symptoms usually respond to sublingual nitro-glycerine therapy. If this is ineffective, IV theophylline can be tried.

o     Severe chest pain following dipyridamole administra-tion responds to aminophylline and anti-anginal medi-cation. Thrombolysis may be required.

o     For hypotension: Infuse 10 to 20 ml/kg of isotonic fluid and place in Trendelenburg position. If hypoten-sion persists, administer dopamine or noradrenaline. Consider central venous pressure monitoring to guide further fluid therapy.

o     Dipyridamole produces vasodilation via inhibition of adenosine reuptake, leading to accumulation in plasma and tissues. Adenosine-mediated adverse effects, such as bronchoconstriction and angina, can be reversed with intravenous aminophylline administration.