Dipyridamole

Pharmacokinetics

The pharmacokinetic profile of dipyridamole has several specific features. After oral administration, the drug is absorbed in the gastrointestinal tract, specifically in the stomach and intestines. Absorption is quite active, so the maximum plasma concentration is reached within 1 hour after administration.

Upon entering the systemic circulation, dipyridamole demonstrates almost complete binding to plasma proteins. Further biotransformation takes place in the liver, where the molecule undergoes glucuronidation. The resulting metabolites are excreted by the kidneys. It is important to note that the drug has a very short half-life of only 20–30 minutes.

Mechanism of action and role of adenosine

The main mechanism responsible for coronary vasodilation is based on the accumulation of adenosine in myocardial tissues. The drug achieves this effect through two simultaneous pathways:

1. Inhibition of reuptake: dipyridamole blocks the transport of endogenous adenosine into cells. As a result, adenosine cannot penetrate cardiomyocytes, endothelial cells, and erythrocytes, remaining in the extracellular space.
2. Enzyme inhibition: the drug suppresses the activity of adenosine deaminase, a specific enzyme responsible for the degradation of adenosine molecules.

The entire chain of pharmacological effects is as follows: accumulation of free adenosine $\rightarrow$ potent stimulation of adenosine $A_2$ receptors $\rightarrow$ smooth muscle relaxation and coronary artery dilation $\rightarrow$ significant increase in myocardial oxygen delivery. As additional yet clinically significant properties, the drug improves myocardial microcirculation and exerts a prominent antiplatelet effect, preventing platelet aggregation.

Steal phenomenon (hemodynamic paradox)

A key feature of dipyridamole action during ischemia is the development of a hemodynamic paradox known as the steal phenomenon.

To understand its essence, one must examine the baseline vascular state during ischemia. In areas located distal to an atherosclerotic occlusion, oxygen deprivation occurs. In response, the concentration of endogenous adenosine is already initially high, and the vessels are maximally dilated—this is a natural compensatory reaction of the body.

When dipyridamole enters the bloodstream, it causes additional adenosine accumulation and vasodilation, but this occurs predominantly in non-ischemic (healthy) myocardial regions. As a result, vascular resistance in healthy areas drops sharply. Blood always flows along the path of least resistance, so blood flow is redistributed in favor of healthy tissues. Consequently, the blood supply to already suffering ischemic areas paradoxically worsens.

Clinical application and diagnostics

Due to the high risk of the steal phenomenon, dipyridamole has very limited use as a therapeutic agent in coronary artery disease (CAD). It is strictly contraindicated in typical stable angina pectoris. The only justified indication within CAD is the use of the drug exclusively in vasospastic angina.

However, the drug's ability to redistribute blood flow has found brilliant application in cardiological diagnostics. Dipyridamole is used in stress tests to detect latent forms of coronary insufficiency.

Diagnostic test procedure:

1. The patient takes dipyridamole.
2. Graded physical exercise is performed using bicycle ergometry.
3. Continuous ECG monitoring is carried out.

Interpretation of results: if the patient has latent coronary atherosclerosis, dipyridamole inevitably provokes the steal phenomenon. This leads to acute hypoxia in ischemic areas, which is instantly reflected on the ECG by characteristic signs of ischemia—specifically, ST-segment elevation is recorded.

Class and exam questions

What else to study on this topic

• Detailed structure and functions of adenosine A2 receptors
• Differences between vasospastic angina and stable angina
• Biochemical role of the enzyme adenosine deaminase
• Mechanisms of platelet aggregation and targets of antiplatelet agents
• Principles of performing and interpreting bicycle ergometry

Other topics in the section "Cardiovascular Drugs"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.