Telmisartan

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Telmisartan
Telmisartan.svg
Clinical data
Pronunciation /tɛlmɪˈsɑːrtən/
Trade names Micardis, others
AHFS/Drugs.com Monograph
MedlinePlus a601249
License data
Pregnancy
category
  • AU:D
Routes of
administration 		By mouth
Drug class Angiotensin II receptor antagonist
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 42–100%
Protein binding >99.5%
Metabolism Minimal liver (glucuronidation)
Elimination half-life 24 hours
Excretion Feces 97%
Identifiers
  • 2-(4-{[4-Methyl-6-(1-methyl-1H-1,3-benzodiazol-2-yl)-2-propyl-1H-1,3-benzodiazol-1-yl]methyl}phenyl)benzoic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.149.347 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C33H30N4O2
Molar mass 514.629 g·mol−1
3D model (JSmol)
  • O=C(O)c1ccccc1c2ccc(cc2)Cn3c4cc(cc(c4nc3CCC)C)c5nc6ccccc6n5C
  • InChI=1S/C33H30N4O2/c1-4-9-30-35-31-21(2)18-24(32-34-27-12-7-8-13-28(27)36(32)3)19-29(31)37(30)20-22-14-16-23(17-15-22)25-10-5-6-11-26(25)33(38)39/h5-8,10-19H,4,9,20H2,1-3H3,(H,38,39) Yes check.svgY
  • Key:RMMXLENWKUUMAY-UHFFFAOYSA-N Yes check.svgY
   (verify)

Telmisartan, sold under the brand name Micardis among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. [4] It is a reasonable initial treatment for high blood pressure. [4] It is taken by mouth. [4] Versions are available as the combination [5] telmisartan/hydrochlorothiazide, telmisartan/cilnidipine [6] and telmisartan/amlodipine. [4]

Contents

Common side effects include upper respiratory tract infections, diarrhea, and back pain. [4] Serious side effects may include kidney problems, low blood pressure, and angioedema. [4] Use in pregnancy may harm the baby and use when breastfeeding is not recommended. [7] It is an angiotensin II receptor antagonist and works by blocking the effects of angiotensin II. [4]

Telmisartan was patented in 1991 and came into medical use in 1999. [8] It is available as a generic medication. [9] In 2022, it was the 228th most commonly prescribed medication in the United States, with more than 1 million prescriptions. [10] [11]

Medical uses

Telmisartan is used to treat high blood pressure, heart failure, and diabetic kidney disease. [4] It is a reasonable initial treatment for high blood pressure. [4] [12] : 146 

Contraindications

Telmisartan is contraindicated during pregnancy. Like other drugs affecting the renin–angiotensin system (RAS), telmisartan can cause birth defects, stillbirths, and neonatal deaths. It is not known whether the drug passes into the breast milk. [13] Also it is contraindicated in bilateral renal artery stenosis in which it can cause kidney failure.

Side effects

Side effects are similar to other angiotensin II receptor antagonists and include tachycardia and bradycardia (fast or slow heartbeat), hypotension (low blood pressure) and edema (swelling of arms, legs, lips, tongue, or throat, the latter leading to breathing problems). Allergic reactions may also occur. [13]

Interactions

Due to its mechanism of action, telmisartan increases blood potassium levels. Combination with potassium preparations or potassium-sparing diuretics could cause hyperkalaemia (excessive potassium levels). Combination with NSAIDs, especially in patients with impaired kidney function, has a risk of causing (usually reversible) kidney failure. [14]

Pharmacology

Mechanism of action

Telmisartan is an angiotensin II receptor blocker that shows high affinity for the angiotensin II receptor type 1 (AT1), with a binding affinity 3000 times greater for AT1 than AT2.

In addition to blocking the renin–angiotensin system, telmisartan acts as a partial agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ), a central regulator of insulin and glucose metabolism. It is believed that telmisartan's dual mode of action may provide protective benefits against the vascular and renal damage caused by diabetes and cardiovascular disease (CVD). [15] [12] : 171  As a partial agonist, it activates the receptor by 25–30%. Clinical trials have shown that telmisartan increases insulin sensitivity, reduces cardiac fibrosis and hypertrophy, and improves endothilial function; all these effects can be attributed to its activity on PPAR-γ. [16] The kidney-protecting activity of telmisartan is attributed to both angiotensin II antagonism and improved endothelial function from PPAR-γ. [16]

Telmisartan's activity at the peroxisome proliferator-activated receptor delta (PPAR-δ) receptor has prompted speculation around its potential as a sport doping agent as an alternative to GW 501516. [17] Telmisartan activates PPAR-δ receptors in several tissues. In mice, this results in effects such as enhanced endurance. [18] [19] [20] [21] However, telmisartan does not improve the walking performance (6-minute walk distance) in people with lower extremity peripheral artery disease. [22]

Telmisartan activates PPAR-αin vitro. [23]

Pharmacokinetics

The substance is quickly but to varying degrees absorbed from the gut. The average bioavailability is about 50% (42–100%). Food intake has no clinically relevant influence on the kinetics of telmisartan. Plasma protein binding is over 99.5%, mainly to albumin and alpha-1-acid glycoprotein. [14] It has the longest half-life of any angiotensin II receptor blocker (ARB) (24 hours) [24] [15] and the largest volume of distribution among ARBs (500 liters). [25] [26] Less than 3% of telmisartan is inactivated by glucuronidation in the liver, and over 97% is eliminated in unchanged form via bile and faeces. [4] [14]

History

Society and culture

Telmisartan is available as a generic medication. [9]

Research

Telmisartan does not appear effective for slowing the growth of abdominal aortic aneurysm. [27]

Telmisartan does not cause rapid cancer growth like the PPAR-δ agonist GW 501516, but whether it causes a change in cancer rates is disputed. Short-term use is not associated with an increased incidence of cancer over other ARB drugs, according to a large 2016 analysis of UK patients. [28] A 2022 meta-analysis finds that a longer duration of taking ARBs (including telmisartan) is associated with an increase in cancer rates. Patients who have taken an ARB for more than 3 years appears 11% more likely to develop cancer. [29] A 2023 large-scale study on Lebanese patients finds that taking ARBs reduces the incidence of cancer, with greater effects on those who have taken the drug for a long time. A 2021 Korean study and a 2012 Japanese study finds similar results. [30]

Related Research Articles

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<span class="mw-page-title-main">Renin</span> Aspartic protease protein and enzyme

Renin, also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body's renin-angiotensin-aldosterone system (RAAS)—also known as the renin-angiotensin-aldosterone axis—that increases the volume of extracellular fluid and causes arterial vasoconstriction. Thus, it increases the body's mean arterial blood pressure.

<span class="mw-page-title-main">Renin–angiotensin system</span> Hormone system

The renin-angiotensin system (RAS), or renin-angiotensin-aldosterone system (RAAS), is a hormone system that regulates blood pressure, fluid, and electrolyte balance, and systemic vascular resistance.

<span class="mw-page-title-main">Peroxisome proliferator-activated receptor</span> Group of nuclear receptor proteins

In the field of molecular biology, the peroxisome proliferator–activated receptors (PPARs) are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes. PPARs play essential roles in the regulation of cellular differentiation, development, and metabolism, and tumorigenesis of higher organisms.

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<span class="mw-page-title-main">Potassium-sparing diuretic</span> Drugs that cause diuresis without causing potassium loss in the urine and leading to hyperkalemia

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References

  1. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 October 2023.
  2. ↑ "Semintra EPAR". European Medicines Agency. 28 February 2013. Retrieved 26 June 2024.
  3. ↑ "Tolura EPAR". European Medicines Agency (EMA). 4 June 2010. Retrieved 13 September 2024.
  4. 1 2 3 4 5 6 7 8 9 10 "Telmisartan Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 3 March 2019.
  5. ↑ Golwala D. "Formulation and Evaluation of Mouth Dissolving Tablets of Telmisartan". Inventi Journals. Retrieved 18 July 2020.[ permanent dead link ]
  6. ↑ "Cilacar T". Medical Dialogues. Retrieved 23 February 2021.
  7. ↑ "Telmisartan Pregnancy and Breastfeeding Warnings". Drugs.com. Retrieved 3 March 2019.
  8. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 471. ISBN   9783527607495.
  9. 1 2 British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 178. ISBN   9780857113382.
  10. ↑ "The Top 300 of 2022". ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
  11. ↑ "Telmisartan Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
  12. 1 2 Opie LH, Gersh BJ (2009). Drugs for the heart (seventh ed.). Saunders. ISBN   978-1-4160-6158-8.
  13. 1 2 Drugs.com: Micardis
  14. 1 2 3 Haberfeld, H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
  15. 1 2 Benson SC, Pershadsingh HA, Ho CI, Chittiboyina A, Desai P, Pravenec M, et al. (May 2004). "Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARgamma-modulating activity". Hypertension. 43 (5): 993–1002. doi: 10.1161/01.HYP.0000123072.34629.57 . PMID   15007034.
  16. 1 2 Ayza MA, Zewdie KA, Tesfaye BA, Gebrekirstos ST, Berhe DF (2020). "Anti-Diabetic Effect of Telmisartan Through its Partial PPARγ-Agonistic Activity". Diabetes, Metabolic Syndrome and Obesity. 13: 3627–3635. doi: 10.2147/DMSO.S265399 . PMC   7567533 . PMID   33116714.
  17. ↑ Sanchis-Gomar F, Lippi G (March 2012). "Telmisartan as metabolic modulator: a new perspective in sports doping?". Journal of Strength and Conditioning Research. 26 (3): 608–610. doi: 10.1519/JSC.0b013e31824301b6 . PMID   22130396.
  18. ↑ Cytoplasmic and Nuclear Receptors: Advances in Research and Application: 2011 Edition. ScholarlyEditions. 2012. pp. 21–. ISBN   978-1-464-93110-9 . Retrieved 2 April 2013.
  19. ↑ Feng X, Luo Z, Ma L, Ma S, Yang D, Zhao Z, et al. (July 2011). "Angiotensin II receptor blocker telmisartan enhances running endurance of skeletal muscle through activation of the PPAR-δ/AMPK pathway". Journal of Cellular and Molecular Medicine. 15 (7): 1572–1581. doi:10.1111/j.1582-4934.2010.01085.x. PMC   3823201 . PMID   20477906.
  20. ↑ He H, Yang D, Ma L, Luo Z, Ma S, Feng X, et al. (April 2010). "Telmisartan prevents weight gain and obesity through activation of peroxisome proliferator-activated receptor-delta-dependent pathways". Hypertension. 55 (4): 869–879. doi: 10.1161/HYPERTENSIONAHA.109.143958 . PMID   20176998.
  21. ↑ Li L, Luo Z, Yu H, Feng X, Wang P, Chen J, et al. (March 2013). "Telmisartan improves insulin resistance of skeletal muscle through peroxisome proliferator-activated receptor-δ activation". Diabetes. 62 (3): 762–774. doi:10.2337/db12-0570. PMC   3581229 . PMID   23238297.
  22. ↑ McDermott MM, Bazzano L, Peterson CA, Sufit R, Ferrucci L, Domanchuk K, et al. (October 2022). "Effect of Telmisartan on Walking Performance in Patients With Lower Extremity Peripheral Artery Disease: The TELEX Randomized Clinical Trial". JAMA. 328 (13): 1315–1325. doi:10.1001/jama.2022.16797. PMC   9533188 . PMID   36194220.
  23. ↑ Yin SN, Liu M, Jing DQ, Mu YM, Lu JM, Pan CY (2014). "Telmisartan increases lipoprotein lipase expression via peroxisome proliferator-activated receptor-alpha in HepG2 cells". Endocrine Research. 39 (2): 66–72. doi:10.3109/07435800.2013.828741. PMID   24067162.
  24. ↑ Pritor prescribing information
  25. ↑ Stangier J, Su CA, Roth W (2000). "Pharmacokinetics of orally and intravenously administered telmisartan in healthy young and elderly volunteers and in hypertensive patients". The Journal of International Medical Research. 28 (4): 149–167. doi:10.1177/147323000002800401. PMID   11014323. S2CID   33299699.
  26. ↑ Gosse P (September 2006). "A review of telmisartan in the treatment of hypertension: blood pressure control in the early morning hours". Vascular Health and Risk Management. 2 (3): 195–201. doi: 10.2147/vhrm.2006.2.3.195 . PMC   1993985 . PMID   17326326.
  27. ↑ Golledge J, Pinchbeck J, Tomee SM, Rowbotham SE, Singh TP, Moxon JV, et al. (December 2020). "Efficacy of Telmisartan to Slow Growth of Small Abdominal Aortic Aneurysms: A Randomized Clinical Trial". JAMA Cardiology. 5 (12): 1374–1381. doi:10.1001/jamacardio.2020.3524. PMC   7450408 . PMID   32845283.
  28. ↑ Tascilar K, Azoulay L, Dell'Aniello S, Bartels DB, Suissa S (December 2016). "The Use of Telmisartan and the Incidence of Cancer". American Journal of Hypertension. 29 (12): 1358–1365. doi:10.1093/ajh/hpw095. PMC   5863774 . PMID   27557862.
  29. ↑ Sipahi I (2022). "Risk of cancer with angiotensin-receptor blockers increases with increasing cumulative exposure: Meta-regression analysis of randomized trials". PLOS ONE. 17 (3): e0263461. doi: 10.1371/journal.pone.0263461 . PMC   8890666 . PMID   35235571.
  30. ↑ Dagher YG, El Helou S, Haifa KG, Chalhoub IG, Boulos RT, Atallah B, et al. (September 2023). "The association between angiotensin receptor blockers and lung, bladder, and colon cancer development: A 10-year multicentric retrospective Lebanese study". Medicine. 102 (36): e34901. doi:10.1097/MD.0000000000034901. PMC   10489396 . PMID   37682163.

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