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Telmisartan

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Sponsored presentation at the Deapartment of Medicine, Assam medical College & Hospital, Kolkata

Telmisartan

  1. 1. Angiotensin Receptor Blockers:TelmisartanThe New Member<br />Dr. Tanoy Bose<br />Post Graduate Trainee<br />Department of Medicine<br />Assam Medical College<br />
  2. 2. Evolution of ARBs<br />
  3. 3. Mechanism of action<br />
  4. 4. ARB vs ACEI: The MoA<br />
  5. 5. Adverse Effects<br />The incidence of discontinuation of ARBs owing to adverse reactions is comparable with that of placebo. <br />Do not cause cough <br />Incidence of angioedema much less <br />Have teratogenic potential : should be discontinued before the second trimester of pregnancy. <br />Cautious in patients whose BP or renal function is highly dependent on RAAS(e.g., renal artery stenosis). <br />May cause hyperkalemia in patients with renal disease or in patients taking K+ supplements or K+-sparing diuretics. <br />Enhance the blood pressure-lowering effect of other antihypertensive drugs.<br />
  6. 6. Telmisartan: Pharmacology<br />Peak plasma levels are obtained approximately 0.5 to 1 hour after oral administration<br /> Plasma t 1/2≈ 24 hours. <br />Cleared from the circulation mainly by biliary secretion of intact drug. <br />Clearance affected by hepatic but not renal insufficiency. <br />The recommended oral dosage : 40 to 80 mg once daily<br />
  7. 7. WHY TELMISARTAN ?<br /><ul><li>Pharmacological Superiority ?
  8. 8. Additional Receptor Agonism ?
  9. 9. Insulin Sensitiser ?
  10. 10. Role in Diabetic Complications ?</li></li></ul><li>Why Telmisartan?Pharmacologic superiority!!<br />Binding affinity of ARB to AT1 receptor<br />Telmi> Olme> Cande> Valsar> Losar<br />Kakuta H, Sudoh K, Sasamatsu M, Yamagishi S. Telmisartan has the strongest binding affinity to angiotensin II type 1 receptor. Comparison with other angiotensin II type 1 receptor blockers. Int J ClinPharm Res (in press).<br /><ul><li>Could have strongest affinity to AT1
  11. 11. May have long lasting BP lowering effects
  12. 12. Superior cardioprotective properties</li></li></ul><li>Why Telmisartan?Additional receptor agonism!!<br />Partial agonist of peroxisomeproliferator-activated receptor-γ (PPAR- γ ) – Recent<br />Takano H, Hasegawa H, Zou Y, Komuro I. Pleiotropic actions of PPAR gamma activators thiazolidinediones in cardiovascular diseases. CurrPharm Des 2004; 10: 2779-86.<br /><ul><li>Induced PPAR- γ activity in AT1 receptor-deficient cell models : independent of its AT1 receptor blocking actions</li></ul>Schupp M, Janke J, Clasen R, Unger T, Kintscher U. Angiotensin type 1 receptor blockers induce peroxisomeproliferator-activated receptor-gamma activity. Circulation 2004; 109: 2054-57<br /><ul><li>PPAR- γ activity influences
  13. 13. The gene expression involved in CHO & lipid metabolism.
  14. 14. Improve insulin resistance in diabetic patients.
  15. 15. Exert antiinflammatory, anti-oxidative and anti-proliferative effects on vascular wall cells.
  16. 16. ↓↓ the risks for atherosclerosis.
  17. 17. May become a promising ‘cardiometabolicsartan’, that targets both diabetes and CVD in hypertensive patients</li></li></ul><li>Why Telmisartan?Insulin sensitiser!!<br />In vitro : Augmented glucose transporter isoform 4 expression and 2-deoxy glucose uptake both in basal and insulin-stimulated state of adipocytes.<br />Fujimoto M, Masuzaki H, Tanaka T, et al . An angiotensin II AT1 receptor antagonist, telmisartan augments glucose uptake and GLUT4 protein expression in 3T3L-1 adipocytes. FEBS Lett 2004; 576: 492-7<br />In animal study : Significant attenuation of weight gain and reduced glucose, insulin, and triglyceride levels in rats fed a high-fat, high-carbohydrate diet, compared with treatments of losartan, another type of ARB .<br />Benson SC, Pershadsingh HA, Ho CI, et al. Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPAR gamma-modulating activity. Hypertension 2004; 43: 993-1002<br />Some recent papers: Insulin-sensitizing effects of telmisartan in hypertensive patients<br />Miura Y, Yamamoto N, Tsunekawa S, et al. Replacement of valsartan and candesartan by telmisartan in hypertensive patients with diabetes. Diabetes Care 2005; 28, 757-8.<br />
  18. 18. Why Telmisartan?Diabetic complications!!<br />Blockade of upregulation of VEGF mRNA & destimulation of ROS in retinal pericytes : Promising Rx strategy for early Rx of DM retinopathy<br />Yamagishi S, Amano S, Inagaki Y, et al. Angiotensin II-type 1 receptor interaction upregulates vascular endothelial growth factor messenger RNA levels in retinal pericytes through intracellular reactive oxygen species generation. Drugs Exp Clin Res 2003; 29: 75-80.<br /><ul><li>Complete Blockade of Receptor –AGE (RAGE) protein expression in Retinal endothelial cells : Novel beneficial effect on Diabetic vascular complications</li></ul>Yamagishi S, Takeuchi M, Matsui T, et al. Angiotensin II augments advanced glycation end product-induced pericyte apoptosis through RAGE overexpression. FEBS Lett (DOI: 10.1016/j.febslet. 2005.06.058).<br />
  19. 19. To Conclude<br />The experimental animal as well as hypothetical models need to be reinforced by well conducted multicentricrandomised trials.<br />The aforementioned actions and probable advantages bear a high risk of getting derecognised in human trials.<br />Needless to mention that a unique future lies with this drug considering its pleiotropism especially when the management of diabetes and related complication is in question.<br />
  20. 20. THANK YOU<br />

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