Stroke
A combination of dipyridamole and aspirin (acetylsalicylic acid/dipyridamole) is FDA-approved for the secondary prevention of stroke and has a bleeding risk equal to that of aspirin use alone. Dipyridamole absorption is pH-dependent and concomitant treatment with gastric acid suppressors (such as a proton pump inhibitor) will inhibit the absorption of liquid and plain tablets. Modified release preparations are buffered and absorption is not affected.However, it is not licensed as monotherapy for stroke prophylaxis, although a Cochrane review suggested that dipyridamole may reduce the risk of further vascular events in patients presenting after cerebral ischemia.A triple therapy of aspirin, clopidogrel, and dipyridamole has been investigated, but this combination led to an increase in adverse bleeding events. Vasodilation occurs in healthy arteries, whereas stenosed arteries remain narrowed. This creates a "steal" phenomenon where the coronary blood supply will increase to the dilated healthy vessels compared to the stenosed arteries which can then be detected by clinical symptoms of chest pain, electrocardiogram and echocardiography when it causes ischemia. Flow heterogeneity (a necessary precursor to ischemia) can be detected with gamma cameras and SPECT using nuclear imaging agents such as Thallium-201, Tc99m-Tetrofosmin and Tc99m-Sestamibi. However, relative differences in perfusion do not necessarily imply any absolute decrease in blood supply in the tissue supplied by a stenosed artery. Other uses
Dipyridamole also has non-medicinal uses in a laboratory context, such as the inhibition of cardiovirus growth in cell culture. Drug interactions
Due to its action as a phosphodiesterase inhibitor, dipyridamole is likely to potentiate the effects of adenosine.
There is a risk of headaches caused by medication withdrawal or medication overuse.Zolmitriptan has a weak affinity for 5-HT 1A receptors; these receptors have implications in the development of serotonin syndrome.Following administration of cimetidine, the half-life and AUC of zolmitriptan and its active metabolites were approximately doubled (see CLINICAL PHARMACOLOGY in product pamphlet). Contraindications
Zolmitriptan is contraindicated in patients with cerebrovascular or cardiovascular disease because 5-HT 1B receptors are present in coronary arteries. Such conditions include, but are not limited to, coronary artery disease, stroke, and peripheral vascular disease.It is also contraindicated in hemiplegic migraine. Mechanism of action
Zolmitriptan is a selective 5-hydroxytryptamine 1B/1D receptor agonist with a weak affinity for the 5-HT 1A receptor subtypes. Its action on 5-HT 1B/1D receptors causes vasoconstriction in intracranial blood vessels; as well it can inhibit the release of pro-inflammatory neuropeptides from trigeminal perivascular nerve endings. It crosses the blood-brain-barrier as evidenced by the presence of radioactive [3H]-zolmitriptan labels within the cells of the trigeminal nucleus caudalis and nucleus tractus solitaries. Pharmacokinetics
Zolmitriptan has a rapid onset of action and has been detected in the brain as early as within 5 minutes of intranasal administration. On average, zolmitriptan has an oral bioavailability of 40%, a mean volume of distribution of 8.3 L/kg after oral administration, and 2.4L/kg after intravenous administration.Zolmitriptan is metabolized into three major metabolites by the human hepatic cytochrome P450 enzymes—primarily CYP1A2.