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 rapid, and peak plasma concentrations are reached within 1 hour.
Upon entering the systemic circulation, dipyridamole demonstrates extensive plasma protein binding. Subsequent biotransformation occurs in the liver, where the molecule undergoes glucuronidation. The resulting metabolites are excreted by the kidneys. Notably, the drug has a very short half-life of only 20–30 minutes.
Mechanism of Action and Role of Adenosine
The primary mechanism responsible for coronary vasodilation relies on the accumulation of adenosine in myocardial tissues. The drug achieves this effect through two main pathways:
- Inhibition of cellular reuptake: Dipyridamole blocks the transport of endogenous adenosine into cells. As a result, adenosine remains in the extracellular space instead of entering cardiomyocytes, endothelial cells, and erythrocytes.
- Enzyme inhibition: The drug suppresses the activity of adenosine deaminase, the specific enzyme responsible for breaking down adenosine molecules.
The entire pharmacological chain works as follows: accumulation of free adenosine $\rightarrow$ potent stimulation of adenosine $A_2$ receptors $\rightarrow$ smooth muscle relaxation and dilation of coronary arteries $\rightarrow$ significant increase in myocardial oxygen delivery. As secondary yet clinically relevant properties, the drug improves myocardial microcirculation and exerts pronounced antiplatelet effects by preventing platelet aggregation.
The "Steal" Phenomenon (Hemodynamic Paradox)
A key characteristic of dipyridamole action during ischemia is the development of a hemodynamic paradox known as the "steal" phenomenon.
To understand this concept, consider the initial vascular state during ischemia. Regions distal to an atherosclerotic occlusion experience oxygen deprivation. Compensatorily, the local concentration of endogenous adenosine is already high, and the vessels are maximally dilated.
When dipyridamole enters the circulation, it induces further adenosine accumulation and vasodilation, but this occurs predominantly in non-ischemic (healthy) myocardial areas. Consequently, vascular resistance in healthy zones drops sharply. Because blood always follows the path of least resistance, blood flow is redistributed in favor of healthy tissues. As a result, perfusion to the already suffering ischemic regions paradoxically worsens.
Clinical Application and Diagnostics
Due to the high risk of the "steal" phenomenon, dipyridamole has very limited utility as a therapeutic agent for ischemic heart disease (IHD). It is strictly contraindicated in typical stable angina of effort. The only valid indication within IHD is its use exclusively in vasospastic (Prinzmetal) angina.
However, the drug's ability to redistribute coronary blood flow has found brilliant application in cardiac diagnostics. Dipyridamole is utilized in pharmacological stress tests to uncover latent forms of coronary insufficiency.
Diagnostic Procedure:
- The patient receives dipyridamole.
- Graded exercise testing (bicycle ergometry) is performed.
- Continuous ECG monitoring is conducted.
Interpretation of Results: If the patient has latent coronary atherosclerosis, dipyridamole inevitably provokes the "steal" phenomenon. This causes acute hypoxia in ischemic zones, which instantly alters the ECG with characteristic ischemic signs—specifically, ST-segment elevation.