Lisinopril

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Lisinopril
Structural formula of lisinopril
Ball-and-stick model of the lisinopril zwitterion
Chemical structure of lisinopril
Clinical data
Pronunciation/lˈsɪnəprɪl/, ly-SIN-ə-pril
Trade namesPrinivil,[1] Zestril,[2] Qbrelis,[3] Dapril,[4] others[5]
Other names(2S)-1-[(2S)-6-amino-2-{[(1S)-1-carboxy-3-phenylpropyl]amino}hexanoyl]pyrrolidine-2-carboxylic acid
AHFS/Drugs.comMonograph
MedlinePlusa692051
License data
Pregnancy
category
Routes of
administration
Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailabilityapprox. 25%, but wide range between individuals (6 to 60%)
Protein binding0
MetabolismNone
Elimination half-life12 hours
ExcretionEliminated unchanged in urine
Identifiers
  • (2S)-1-[(2S)-6-amino-2-[[(1S)-1-carboxy-3-phenylpropyl]amino]hexanoyl]pyrrolidine-2-carboxylic acid
JSmol)
  • C1CC(N(C1)C(=O)C(CCCCN)NC(CCC2=CC=CC=C2)C(=O)O)C(=O)O
  • InChI=1S/C21H31N3O5/c22-13-5-4-9-16(19(25)24-14-6-10-18(24)21(28)29)23-17(20(26)27)12-11-15-7-2-1-3-8-15/h1-3,7-8,16-18,23H,4-6,9-14,22H2,(H,26,27)(H,28,29)/t16-,17-,18-/m0/s1 checkY
  • Key:RLAWWYSOJDYHDC-BZSNNMDCSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Lisinopril is a medication belonging to the drug class of

kidney problems in people with diabetes mellitus.[7] Lisinopril is taken orally (swallowed by mouth).[7] Full effect may take up to four weeks to occur.[7]

Common side effects include headache, dizziness, feeling tired, cough, nausea, and rash.

low blood pressure, liver problems, hyperkalemia (high blood potassium), and angioedema.[7] Use is not recommended during the entire duration of pregnancy as it may harm the baby.[7] Lisinopril works by inhibiting the renin–angiotensin–aldosterone system.[7]

Lisinopril was patented in 1978 and approved for medical use in the United States in 1987.

generic medication.[7] In 2021, it was the fourth most commonly prescribed medication in the United States, with more than 88 million prescriptions.[12][13] In July 2016, an oral solution formulation of lisinopril was approved for use in the United States.[7][14]

Medical uses

Lisinopril is typically used for the treatment of

indicated for the treatment of hypertension, adjunctive therapy for heart failure, and acute myocardial infarction.[1]

Contraindications

Lisinopril is contraindicated in people who have a history of

idiopathic) or who have diabetes and are taking aliskiren.[1]

Adverse effects

Common side effects include headache, dizziness, feeling tired, cough, nausea, and rash.

low blood pressure, liver problems, hyperkalemia, and angioedema.[7] Use is not recommended during the entire duration of pregnancy as it may harm the baby.[7]

Pregnancy and breastfeeding

Animal and human data have revealed evidence of harm to the embryo and teratogenicity associated with ACE inhibitors.[1]

Interactions

Dental care

ACE-inhibitors like lisinopril are considered to be generally safe for people undergoing routine

dental surgery is more controversial, with some dentists recommending discontinuation the morning of the procedure.[15] People may present to dental care suspicious of an infected tooth, but the swelling around the mouth may be due to lisinopril-induced angioedema, prompting emergency and medical referral.[15]

Pharmacology

Lisinopril is the lysine-analog of enalapril. Unlike other ACE inhibitors, it is not a prodrug, is not metabolized by the liver, and is excreted unchanged in the urine.[1]

Mechanism of action

Lisinopril is an

Starling forces.[17] The inhibition of the RAAS system causes an overall decrease in blood pressure.[16]

Pharmacokinetics

Absorption

Following oral administration of lisinopril, peak serum concentrations of lisinopril occur within about seven hours,[1][16] although there was a trend to a small delay in time taken to reach peak serum concentrations in acute myocardial infarction patients. The peak effect of lisinopril is about 6 hours after administration for most people.[18][19] Declining serum concentrations exhibit a prolonged terminal phase, which does not contribute to drug accumulation. This terminal phase probably represents saturable binding to ACE and is not proportional to dose. Lisinopril does not undergo metabolism and absorbed drug is excreted unchanged entirely in the urine. Based on urinary recovery, the mean extent of absorption of lisinopril is approximately 25% (reduced to 16% in people with New York Heart Association Functional Classification (NYHA) Class II–IV heart failure), with large interpatient variability (6 to 60%) at all doses tested (5 to 80 mg).[1][16] Lisinopril absorption is not affected by the presence of food in the gastrointestinal tract.[18][20][21]

Studies in rats indicate that lisinopril crosses the blood-brain barrier poorly. Multiple doses of lisinopril in rats result in little or no accumulation in brain tissue.[22]

Distribution

Lisinopril does not bind to proteins in the blood.[1][16] It does not distribute as well in people with NYHA Class II–IV heart failure.[1][16]

Elimination

Lisinopril leaves the body completely unchanged in the urine.[1][16] The half-life of lisinopril is 12 hours, and is increased in people with kidney problems.[1][16] While the plasma half-life of lisinopril has been estimated between 12 and 13 hours, the elimination half-life is much longer, at around 30 hours.[18] The full duration of action is between 24 and 30 hours.[18]

Lisinopril is the only water-soluble member of the ACE inhibitor class, and thus has no metabolism by the liver.[18]

Chemistry

Pure lisinopril powder is white to off white in color.[1] Lisinopril is soluble in water (approximately 13 mg/L at room temperature),[23] less soluble in methanol, and virtually insoluble in ethanol.[1]

History

Captopril, the first ACE inhibitor, is a functional and structural analog of a peptide derived from the venom of the jararaca, a Brazilian pit viper (Bothrops jararaca).[24] Enalapril is a derivative, designed by scientists at Merck to overcome the rash and bad taste caused by captopril.[25][26]: 12–13  Enalapril is actually a prodrug; the active metabolite is enalaprilat.[27]

The di-acid metabolite of enalapril, enalaprilat, and its lysine analogue lisinopril are potent inhibitors of angiotensin converting enzyme (ACE); they do not contain sulphydryl groups. Both drugs can be assayed by high pressure liquid chromatography and by radioimmunoassay and plasma ACE inhibition remains stable under normal storage conditions. It is therefore possible to study their pharmacokinetics as well as their pharmacodynamic effects in humans. Enalaprilat and lisinopril as well as ACE activity have been measured in blood taken during the course of two studies of the effects of these drugs on blood pressure and autonomic responsiveness.

Lisinopril is a synthetic peptide derivative of captopril.[23] Scientists at Merck created lisinopril by systematically altering each structural unit of enalaprilat, substituting various amino acids. Adding lysine at one end of the drug turned out to have strong activity and had adequate bioavailability when given orally; analogs of that compound resulted in lisinopril, which takes its name from the discovery with lysine. Merck conducted clinical trials, and the drug was approved for hypertension in 1987 and congestive heart failure in 1993.[27]

The discovery posed a problem, since sales of enalapril were strong for Merck, and the company did not want to diminish those sales. Merck ended up entering into an agreement with Zeneca under which Zeneca received the right to co-market lisinopril, and Merck received the exclusive rights to an earlier stage aldose reductase inhibitor drug candidate, a potential treatment for diabetes. Zeneca's marketing and brand name, "Zestril", turned out to be stronger than Merck's effort.[28] The drug became a blockbuster for AstraZeneca (formed in 1998), with annual sales in 1999 of $1.2B.[29]

The US patents expired in 2002.[29] Since then, lisinopril has been available under many brand names worldwide; it is also available in combination drugs with diuretic hydrochlorothiazide (as lisinopril/hydrochlorothiazide), and with calcium channel blocker amlodipine (as lisinopril/amlodipine).[5]

References

  1. ^ a b c d e f g h i j k l m n o p "Prinivil- lisinopril tablet". DailyMed. 4 November 2019. Retrieved 27 February 2020.
  2. ^ a b "Zestril- lisinopril tablet". DailyMed. 31 October 2019. Retrieved 5 August 2020.
  3. ^ a b "Qbrelis- lisinopril solution". DailyMed. 31 March 2020. Retrieved 5 August 2020.
  4. ^ "Dapril". Drugs.com. Drugsite Trust. Retrieved 13 August 2021.
  5. ^ a b "Lisinopril". Drugs.com. Retrieved 23 December 2018.
  6. ^ a b "Lisinopril Use During Pregnancy". Drugs.com. 22 October 2019. Retrieved 27 February 2020.
  7. ^ a b c d e f g h i j k l m n o p "Lisinopril Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 23 December 2018.
  8. FDA
    . Retrieved 22 October 2023.
  9. ^ "Product monograph brand safety updates". Health Canada. February 2024. Retrieved 24 March 2024.
  10. ^ "Summary of Product Characteristics (SmPC) – (emc)". Lisinopril 10mg Tablet. 13 November 2019. Archived from the original on 28 February 2020. Retrieved 27 February 2020.
  11. .
  12. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  13. ^ "Lisinopril – Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  14. ^ "Drug Approval Package: Qbrelis (lisinopril)". U.S. Food and Drug Administration (FDA). 29 July 2016. Retrieved 5 August 2020.
  15. ^
    PMID 27040293
    .
  16. ^ .
  17. .
  18. ^ .
  19. ^ "Lisinopril". Wolters Kluwer Clinical Drug Information. Wolters Kluwer. 2024.
  20. ^ "Lisinopril Tablets, USP". dailymed.nlm.nih.gov. Retrieved 16 October 2022.
  21. ^ "Lisinopril: Package Insert / Prescribing Information". Drugs.com. Retrieved 16 October 2022.
  22. PMID 15752941
    – via Oxford Academic.
  23. ^ a b "Lisinopril". PubChem. Retrieved 6 June 2018.
  24. S2CID 1045315
    .
  25. ^ Jenny Bryan for The Pharmaceutical Journal, 17 April 2009 "From snake venom to ACE inhibitor – the discovery and rise of captopril"
  26. .
  27. ^ .
  28. .
  29. ^ a b Express Scripts. Patent expirations

Further reading