Transcription
Hi everyone, today in this video let us discuss about pentoxifylline. What is this drug, pentoxifylline? This drug is one of the hemorheological agents; that means this drug changes the rheological properties of the blood. Particularly, this drug modifies the viscosity of the blood, which increases the blood flow and reduces the blood clotting process. That's why this drug can reduce the vascular disease associated with excessive blood clotting.
And pentoxifylline is one of the methyl xanthines, having the structure like this. We know well-known methyl xanthines, caffeine, which is widely used everyday; similarly, theophylline, theobromine—all these are methyl xanthines. But among this category, pentoxifylline is one of the drugs which is used to change the blood viscosity, and this medication is particularly used in the treatment of peripheral vascular disease. So in those people who are having the reduced blood flow and increased risk of clotting, pentoxifylline can be given in order to increase the blood flow by changing blood viscosity; that's why it is called a hemorheological agent.
So today in this video, we are going to see how this drug acts, what are the important precautions, side effects, dosage, and chemical structure; all these things we will discuss in this video. First of all, let us see how this drug acts. As we have discussed earlier, pentoxifylline mainly reduces the blood viscosity. One of its main actions is to increase the ATP levels, and when these ATP levels are increased within the vascular cells as well as in the erythrocytes, it can reduce their attachment to the blood vessels as well as it can reduce their aggregation. So when these erythrocytes are not aggregated and attached to the blood vessels, the viscosity of the blood can be reduced, and the blood flow can be improved.
Similarly, another factor for reduction of blood flow is the formation of fibrin mesh. Fibrinogen is one of the precursors which can be converted into fibrin meshwork, which can reduce the blood flow by forming a dense clot within the intima of the blood vessel. This fibrin is generally formed when there is a tissue damage, but in few of the people with any risk factors for increased coagulation cascade or in those people with elevated levels of cholesterol, this fibrin formation is more enhanced, resulting in decreased blood flow. In such conditions, again pentoxifylline can inhibit the conversion of fibrinogen into the fibrin so that it can reduce the formation of clots within the intima of the blood vessel. Similarly, another action of pentoxifylline is to increase the fibrinolysis, so it can dissolve the already formed clots, thereby it can further improve the blood flow. All these factors combinedly produce a decrease in the viscosity of the blood, which increases the blood flow; that's why pentoxifylline can be given in the people with peripheral vascular disease.
Apart from these actions, we can also observe another action of pentoxifylline within the vascular smooth muscle. Cyclic AMP plays an important role; this cyclic AMP can be metabolized to AMP by one of the metabolic enzymes, phosphodiesterase. By the action of phosphodiesterase enzyme, the cyclic AMP levels are reduced within the blood vessels. Now pentoxifylline can block this phosphodiesterase enzyme activity so that it can increase the cyclic AMP levels. When these cyclic AMP levels are increased, it can produce vasodilation. In this way, pentoxifylline can also produce a vasodilatory response by inhibiting the phosphodiesterase enzyme activity. Because of this vasodilation, viscosity of the blood is reduced, and blood flow is going to be increased. But the levels of cyclic AMP can be controlled by another receptor, the adenosine A1 receptor. These adenosine A1 receptors are coupled with different subunits like alpha, beta, gamma. Now when this adenosine binds to this adenosine receptors, they are inhibitory in nature; they can reduce the activation of adenylyl cyclase. When this adenylyl cyclase is inhibited, they reduce the conversion of ATP into cyclic AMP. So cyclic AMP conversion is inhibited by the action of adenosine. Now pentoxifylline can also act as an antagonist at adenosine A1 receptors, thereby it can increase the conversion of ATP into cyclic AMP. So this increases the cyclic AMP levels, which further increases vasodilation. In this way, pentoxifylline can act by multiple mechanisms, but its main action is to increase the blood flow by reducing the viscosity of the blood. It mainly inhibits the erythrocyte aggregation and their attachment to the blood vessels, and it also improves the vasodilation and even it stimulates fibrinolysis, thereby it reduces the clot formation.
Now let us see the precautions of this drug. One of the important precautions of pentoxifylline is that this drug belongs to the chemical category of methyl xanthines. We know the different types of methyl xanthines like caffeine, theophylline, theobromine; generally these compounds are not allergic, but few of the people are hypersensitive to methyl xanthines. In such people, pentoxifylline should not be given because it can produce serious hypersensitive reactions. Similarly, the second precaution is that pentoxifylline can reduce the blood viscosity, so it is somewhat useful in the treatment of atherosclerosis, which is associated with abnormal clot formation due to excessive levels of LDL cholesterol. In such conditions, pentoxifylline can improve the blood flow; even it can also be given in the cerebrovascular disease, which are again associated with decreased cerebral blood flow. In these disorders, pentoxifylline can improve the blood flow, but at the same time this drug may increase the risk of angina, hypotension, and arrhythmia. Even this drug is useful in atherosclerosis and cerebrovascular disease, but because of these effects, pentoxifylline should be carefully used in the conditions like atherosclerosis and cerebrovascular disease. And any sudden increase in the chest pain, angina, reduction of blood pressure should be immediately monitored.
Another effect is on the warfarin. Warfarin is one of the oral anticoagulants; this drug can produce some hemorrhage; that's why the dose of warfarin should be strictly monitored. But when this warfarin is combined with pentoxifylline, the risk of hemorrhage is more pronounced because pentoxifylline can reduce clot formation as well as it can increase the blood flow. So while using with pentoxifylline, warfarin dose should be adjusted, and the risk of hemorrhage should be monitored. Similarly, few of the conditions like recent surgery, any retinal bleeding, or in the people with any peptic ulceration where the risk of bleeding is more pronounced—all these conditions are associated with increased risk of hemorrhage; again in such people, pentoxifylline can further increase the risk of hemorrhage. So before using the pentoxifylline, any of these factors should be checked.
Now let us see the side effects of this drug. The important side effects are mainly related with the gastrointestinal system; it can produce some bloating, dyspepsia, diarrhea, vomiting, abdominal discomfort. It can also produce cardiovascular as well as central side effects like chest pain, palpitations, flushing, redness of the skin because of vasodilation; even some dizziness and blurred vision can be observed with this pentoxifylline.
Now let us see the chemical nature of this drug. So this is the structure of pentoxifylline; we can clearly observe the methyl xanthine ring system. Let us give the numbering; we can start the numbering from the nitrogen, so this is 1, 2, 3, 4, 5, 6. So first we have to give the numbering to this six-membered ring system, then 7, 8, and 9. This is the common numbering system for the xanthines. This xanthine is having the methyl groups at third and seventh position, so we can write this as 3,7-dimethyl xanthine. Now at the first position it is having a long side chain; let us give the numbering: this is 1, 2, 3, 4, 5, and 6. So it is a hexyl chain with an oxo group at the fifth position, so we can write this as 1,5-oxohexyl; that is a simple name of pentoxifylline.
How is it given? This drug is available as a tablet, particularly an extended-release tablet at a dose of 400 mg, and the initial dose of the drug is started at 400 mg given three times a day. And the dose can be continued up to 8 weeks; even the effectiveness can be observed within 2 to 4 weeks of the treatment, but its usage may be continued up to 8 weeks and sometimes up to 6 months. But in few of the people where the risk of bleeding is more pronounced, then the dose may be reduced. So here the recommended dose is 400 mg three times a day; that means the total daily dose is 1200 mg. But in those people with increased risk of bleeding, the dose can be reduced to 800 mg given per day as divided doses, so 400 mg tablets can be given two times a day.
So that's all about this drug, pentoxifylline, which is a hemorheological agent. This drug reduces the blood viscosity and improves the blood flow, acting in several ways. It acts as a phosphodiesterase inhibitor; thereby it can increase the cyclic AMP levels, which increase the vasodilation, and it also increases the ATP levels within the erythrocytes, which decrease their attachment to the blood vessels and reduce their aggregation. Even it blocks the fibrin formation as well as it stimulates the fibrinolysis; thereby it can increase the dissolution of the clots. All these actions may improve the blood flow by reducing the viscosity of the blood. But hemorrhage is one of the important precautions that should be considered with this pentoxifylline, and this drug can produce few of the gastrointestinal side effects as well as cardiovascular side effects like chest pain, palpitations, central side effects like dizziness and blurred vision.
So that's all about this medication, pentoxifylline. Hope you have enjoyed this video. If you like this video, please subscribe to our channel, share this video with your friends, post your comments in the comment box. Thank you for watching this video.