Telmisartan

Telmisartan, sold under the brand name Micardis among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease.[1] It is a reasonable initial treatment for high blood pressure.[1] It is taken by mouth.[1] Versions are available as the combination[2] telmisartan/hydrochlorothiazide and telmisartan/amlodipine.[1]

Telmisartan
Clinical data
Pronunciation/tɛlmɪˈsɑːrtən/
Trade namesMicardis, Actavis, others
AHFS/Drugs.comMonograph
MedlinePlusa601249
License data
Pregnancy
category
  • AU: D
Routes of
administration		By mouth
Drug classAngiotensin II receptor antagonist
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
  • EU: RX-only
Pharmacokinetic data
Bioavailability42–100%
Protein binding>99.5%
MetabolismMinimal liver (glucuronidation)
Elimination half-life24 hours
ExcretionFeces 97%
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.149.347
Chemical and physical data
FormulaC33H30N4O2
Molar mass514.629 g·mol−1
3D model (JSmol)
  (verify)

Common side effects include upper respiratory tract infections, diarrhea, and back pain.[1] Serious side effects may include kidney problems, low blood pressure, and angioedema.[1] Use in pregnancy may harm the baby and use when breastfeeding is not recommended.[3] It is an angiotensin II receptor antagonist and works by blocking the effects of angiotensin II.[1]

Telmisartan was patented in 1991 and came into medical use in 1999.[4] It is available as a generic medication.[5] In 2017, it was the 249th most commonly prescribed medication in the United States, with more than one million prescriptions.[6][7]

Medical uses

Telmisartan is used to treat high blood pressure, heart failure, and diabetic kidney disease.[1] It is a reasonable initial treatment for high blood pressure.[1][8]: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.[9] 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.[9]

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.[10]

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 RAS, telmisartan acts as a selective modulator 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).[11]

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.[12] Telmisartan activates PPAR-δ receptors in several tissues.[13][14][15][16]

Also, Telmisartan has a PPARγ agonist activity.[8]:171

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.[10] It has the longest half-life of any ARB (24 hours)[17][11] and the largest volume of distribution among ARBs (500 liters).[18][19] Less than 3% of telmisartan is inactivated by glucuronidation in the liver, and over 97% is eliminated in unchanged form via bile and faeces.[1][10]

History
See also: Discovery and development of angiotensin receptor blockers

Society and culture

Telmisartan is available as a generic medication.[5]

References
  1. "Telmisartan Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 3 March 2019.
  2. Golwala, Dharmesh. "Article | Formulation and Evaluation of Mouth Dissolving Tablets of Telmisartan | Inventi Journals Pvt.Ltd". inventi.in. Retrieved 2020-07-18.
  3. "Telmisartan Pregnancy and Breastfeeding Warnings". Drugs.com. Retrieved 3 March 2019.
  4. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 471. ISBN 9783527607495.
  5. British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 178. ISBN 9780857113382.
  6. "The Top 300 of 2020". ClinCalc. Retrieved 11 April 2020.
  7. "Telmisartan - Drug Usage Statistics". ClinCalc. Retrieved 11 April 2020.
  8. Opie LH, Gersh BJ (2009). Drugs for the heart (seventh ed.). Saunders. ISBN 978-1-4160-6158-8.
  9. Drugs.com: Micardis
  10. Haberfeld, H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
  11. 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.
  12. 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): 608–10. doi:10.1519/JSC.0b013e31824301b6. PMID 22130396.
  13. 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.
  14. 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): 1572–81. doi:10.1111/j.1582-4934.2010.01085.x. PMC 3823201. PMID 20477906.
  15. 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): 869–79. doi:10.1161/HYPERTENSIONAHA.109.143958. PMID 20176998.
  16. 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): 762–74. doi:10.2337/db12-0570. PMC 3581229. PMID 23238297.
  17. Pritor prescribing information
  18. Department of Pharmacokinetics and Drug Metabolism, Biberach an der Riss, Boehringer Ingelheim Pharma KG, Biberach, Germany (July 2000). "Pharmacokinetics of orally and intravenously administered telmisartan in healthy young and elderly volunteers and in hypertensive patients" (PDF). Journal of International Medical Research. Retrieved 18 January 2014.CS1 maint: multiple names: authors list (link)
  19. 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.

Further reading
  • "Telmisartan". Drug Information Portal. U.S. National Library of Medicine.
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