Lisinopril

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Lisinopril
Lisinopril structure.svg
Lisinopril zwitterion 3D ball.png
Chemical structure of lisinopril
Clinical data
Pronunciation /laɪˈsɪnəprɪl/ , ly-SIN-ə-pril
Trade names Prinivil, [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.com Monograph
MedlinePlus a692051
License data
Pregnancy
category
Routes of
administration 		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability approx. 25%, but wide range between individuals (6 to 60%)
Protein binding 0
Metabolism None
Elimination half-life 12 hours
Excretion Eliminated unchanged in urine
Identifiers
  • (2S)-1-[(2S)-6-amino-2-[[(1S)-1-carboxy-3-phenylpropyl]amino]hexanoyl]pyrrolidine-2-carboxylic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard 100.071.332 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C21H31N3O5
Molar mass 405.495 g·mol−1
3D model (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 Yes check.svgY
  • Key:RLAWWYSOJDYHDC-BZSNNMDCSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Lisinopril is a medication belonging to the drug class of angiotensin-converting enzyme (ACE) inhibitors and is used to treat hypertension (high blood pressure), heart failure, and heart attacks. [7] For high blood pressure it is usually a first-line treatment. It is also used to prevent 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]

Contents

Common side effects include headache, dizziness, feeling tired, cough, nausea, and rash. [7] Serious side effects may include 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. [7] [10] It is available as a generic medication. [7] In 2021, it was the fourth most commonly prescribed medication in the United States, with more than 88 million prescriptions. [11] [12] In July 2016, an oral solution formulation of lisinopril was approved for use in the United States. [7] [13]

Medical uses

Lisinopril is typically used for the treatment of high blood pressure, congestive heart failure, and diabetic nephropathy and after acute myocardial infarction (heart attack). [7] [1] Lisinopril is part of the ACE inhibitors drug class. [1] Lisinopril is 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 angioedema (hereditary or idiopathic) or who have diabetes and are taking aliskiren. [1]

Adverse effects

Common side effects include headache, dizziness, feeling tired, cough, nausea, and rash. [7] Serious side effects may include 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 care, though the use of lisinopril prior to dental surgery is more controversial, with some dentists recommending discontinuation the morning of the procedure. [14] 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. [14]

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 ACE inhibitor, meaning it blocks the actions of angiotensin-converting enzyme (ACE) in the renin–angiotensin–aldosterone system (RAAS), preventing angiotensin I from being converted to angiotensin II. Angiotensin II is a potent direct vasoconstrictor and a stimulator of aldosterone release. Reduction in the amount of angiotensin II results in relaxation of the arterioles. Reduction in the amount of angiotensin II also reduces the release of aldosterone from the adrenal cortex, which allows the kidney to excrete sodium along with water into the urine, and increases retention of potassium ions. [15] Specifically, this process occurs in the peritubular capillaries of the kidneys in response to a change in Starling forces. [16] The inhibition of the RAAS system causes an overall decrease in blood pressure. [15]

Pharmacokinetics

Absorption

Following oral administration of lisinopril, peak serum concentrations of lisinopril occur within about seven hours, [1] [15] 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. [17] [18] 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] [15] Lisinopril absorption is not affected by the presence of food in the gastrointestinal tract. [17] [19] [20]

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. [21]

Distribution

Lisinopril does not bind to proteins in the blood. [1] [15] It does not distribute as well in people with NYHA Class II–IV heart failure. [1] [15]

Elimination

Lisinopril leaves the body completely unchanged in the urine. [1] [15] The half-life of lisinopril is 12 hours, and is increased in people with kidney problems. [1] [15] 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. [17] The full duration of action is between 24 and 30 hours. [17]

Lisinopril is the only water-soluble member of the ACE inhibitor class, and thus has no metabolism by the liver. [17]

Chemistry

Pure lisinopril powder is white to off white in color. [1] Lisinopril is soluble in water (approximately 13 mg/L at room temperature), [22] 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 ). [23] Enalapril is a derivative, designed by scientists at Merck to overcome the rash and bad taste caused by captopril. [24] [25] : 12–13  Enalapril is actually a prodrug; the active metabolite is enalaprilat. [26]

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. [22] 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. [26]

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. [27] The drug became a blockbuster for AstraZeneca (formed in 1998), with annual sales in 1999 of $1.2B. [28]

The US patents expired in 2002. [28] 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]

Related Research Articles

<span class="mw-page-title-main">ACE inhibitor</span> Class of medications used primarily to treat high blood pressure

Angiotensin-converting-enzyme inhibitors are a class of medication used primarily for the treatment of high blood pressure and heart failure. This class of medicine works by causing relaxation of blood vessels as well as a decrease in blood volume, which leads to lower blood pressure and decreased oxygen demand from the heart.

<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">Angiotensin</span> Group of peptide hormones in mammals

Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adrenal cortex to promote sodium retention by the kidneys.

<span class="mw-page-title-main">Bradykinin</span> Chemical compound

Bradykinin (BK) (Greek brady-, slow; -kinin, kīn(eîn) to move) is a peptide that promotes inflammation. It causes arterioles to dilate (enlarge) via the release of prostacyclin, nitric oxide, and endothelium-derived hyperpolarizing factor and makes veins constrict, via prostaglandin F2, thereby leading to leakage into capillary beds, due to the increased pressure in the capillaries. Bradykinin consists of nine amino acids, and is a physiologically and pharmacologically active peptide of the kinin group of proteins.

<span class="mw-page-title-main">Captopril</span> Antihypertensive drug of the ACE inhibitor class

Captopril, sold under the brand name Capoten among others, is an angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of congestive heart failure. Captopril was the first oral ACE inhibitor found for the treatment of hypertension. It does not cause fatigue as associated with beta-blockers. Due to the adverse drug event of causing hyperkalemia, as seen with most ACE Inhibitors, the medication is usually paired with a diuretic.

Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%, and can reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.

<span class="mw-page-title-main">Enalapril</span> ACE inhibitor medication

Enalapril, sold under the brand name Vasotec among others, is an ACE inhibitor medication used to treat high blood pressure, diabetic kidney disease, and heart failure. For heart failure, it is generally used with a diuretic, such as furosemide. It is given by mouth or by injection into a vein. Onset of effects are typically within an hour when taken by mouth and last for up to a day.

<span class="mw-page-title-main">Fosinopril</span> Antihypertensive drug of the ACE inhibitor class

Fosinopril is an angiotensin converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of chronic heart failure. Fosinopril is the only phosphonate-containing ACE inhibitor marketed, by Bristol-Myers Squibb under the trade name Monopril. Fosinopril is a cascading pro-drug. The special niche for the medication that differentiates it from the other members of the ACE Inhibitor drug class is that was specifically developed for the use for patients with renal impairment. This was through manipulation of the metabolism and excretion, and is seen that fifty percent of the drug is hepatobiliary cleared, which can compensate for diminished renal clearance. The remaining fifty percent is excreted in urine. It does not need dose adjustment.

<span class="mw-page-title-main">Ramipril</span> ACE inhibitor medication

Ramipril, sold under the brand name Altace among others, is an ACE inhibitor type medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It can also be used as a preventative medication in patients over 55 years old to reduce the risk of having a heart attack, stroke or cardiovascular death in patients shown to be at high risk, such as some diabetics and patients with vascular disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth.

<span class="mw-page-title-main">Quinapril</span> ACE inhibitor used in the treatment of hypertension and congestive heart failure

Quinapril, sold under the brand name Accupril by the Pfizer corporation. It a medication used to treat high blood pressure (hypertension), heart failure, and diabetic kidney disease. It is a first line treatment for high blood pressure. It is taken by mouth.

<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

Potassium-sparing diuretics refers to drugs that cause diuresis without causing potassium loss in the urine. They are typically used as an adjunct in management of hypertension, cirrhosis, and congestive heart failure. The steroidal aldosterone antagonists can also be used for treatment of primary hyperaldosteronism. Spironolactone, a steroidal aldosterone antagonist, is also used in management of female hirsutism and acne from PCOS or other causes.

<span class="mw-page-title-main">Benazepril</span> Medication used to treat high blood pressure and heart failure

Benazepril, sold under the brand name Lotensin among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combinations benazepril/hydrochlorothiazide and benazepril/amlodipine.

<span class="mw-page-title-main">Losartan</span> Blood pressure medication

Losartan, sold under the brand name Cozaar among others, is a medication used to treat high blood pressure (hypertension). It is in the angiotensin receptor blocker (ARB) family of medication, and is considered protective of the kidneys. Besides hypertension, it is also used in diabetic kidney disease, heart failure, and left ventricular enlargement. It comes as a tablet that is taken by mouth. It may be used alone or in addition to other blood pressure medication. Up to six weeks may be required for the full effects to occur.

<span class="mw-page-title-main">Valsartan</span> Angiotensin II receptor antagonist

Valsartan, sold under the brand name Diovan among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It belongs to a class of medications referred to as angiotensin II receptor blockers (ARBs). It is a reasonable initial treatment for high blood pressure. It is taken by mouth.

<span class="mw-page-title-main">Aliskiren</span> Medication

Aliskiren is the first in a class of drugs called direct renin inhibitors. It is used for essential (primary) hypertension. While used for high blood pressure, other better studied medications are typically recommended due to concerns of higher side effects and less evidence of benefit.

<span class="mw-page-title-main">Renin inhibitor</span> Compound inhibiting the activity of renin

Renin inhibitors are pharmaceutical drugs inhibiting the activity of renin that is responsible for hydrolyzing angiotensinogen to angiotensin I, which in turn reduces the formation of angiotensin II that facilitates blood pressure.

Drug-induced angioedema is a known complication of the use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II antagonists (ARBs), and Angiotensin-Neprilysin Inhibitor LCZ969. The angioedema appears to be dose dependent as it may resolve with decreased dose.

<span class="mw-page-title-main">Sacubitril/valsartan</span> Combination medication

Sacubitril/valsartan, sold under the brand name Entresto, is a fixed-dose combination medication for use in heart failure. It consists of the neprilysin inhibitor sacubitril and the angiotensin receptor blocker valsartan. The combination is sometimes described as an "angiotensin receptor-neprilysin inhibitor" (ARNi). In 2016, the American College of Cardiology/American Heart Association Task Force recommended it as a replacement for an ACE inhibitor or an angiotensin receptor blocker in people with heart failure with reduced ejection fraction.

An ACE inhibitor and thiazide combination is a drug combination used to treat hypertension. They are given by mouth. ACE inhibitors reduce the activity of angiotensin-converting enzyme (ACE) which produces angiotensin II, a hormone that constricts blood vessels. Thiazides are a class of diuretics that inhibit the thiazide receptor, thereby increasing urine production and reducing excess water and salt in the body. Several organizations recommend combination therapy for hypertension in cases of failure of a single drug to achieve target blood pressure, or even as a first line treatment for some patients.

References

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  2. 1 2 "Zestril- lisinopril tablet". DailyMed. 31 October 2019. Retrieved 5 August 2020.
  3. 1 2 "Qbrelis- lisinopril solution". DailyMed. 31 March 2020. Retrieved 5 August 2020.
  4. ↑ "Dapril". Drugs.com . Drugsite Trust. Retrieved 13 August 2021.
  5. 1 2 "Lisinopril". Drugs.com. Retrieved 23 December 2018.
  6. 1 2 "Lisinopril Use During Pregnancy". Drugs.com. 22 October 2019. Retrieved 27 February 2020.
  7. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 "Lisinopril Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 23 December 2018.
  8. ↑ "Summary of Product Characteristics (SmPC) – (emc)". Lisinopril 10mg Tablet. 13 November 2019. Archived from the original on 28 February 2020. Retrieved 27 February 2020.
  9. ↑ "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.
  10. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 467. ISBN   978-3-527-60749-5.
  11. ↑ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  12. ↑ "Lisinopril – Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  13. ↑ "Drug Approval Package: Qbrelis (lisinopril)". U.S. Food and Drug Administration (FDA). 29 July 2016. Retrieved 5 August 2020.
  14. 1 2 Weinstock RJ, Johnson MP (April 2016). "Review of Top 10 Prescribed Drugs and Their Interaction with Dental Treatment". Dental Clinics of North America. 60 (2): 421–434. doi:10.1016/j.cden.2015.11.005. PMID   27040293.
  15. 1 2 3 4 5 6 7 8 Katzung B (2012). Basic and Clinical Pharmacology. New York: McGraw Hill. pp. 175, 184–185. ISBN   978-0-07-176401-8.
  16. ↑ Reddi A (2018). "Disorders of ECF Volume: Nephrotic Syndrome". Fluid, Electrolyte and Acid-Base Disorders. Springer. ISBN   978-3-319-60167-0.
  17. 1 2 3 4 5 Khan MG (2015). "Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers". Cardiac Drug Therapy. New York: Springer. ISBN   978-1-61779-962-4.
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  21. ↑ Tan J, Ming Wang J, Leenen F (February 2005). "Inhibition of brain angiotensin-converting enzyme by peripheral administration of trandolapril versus lisinopril in Wistar rats". American Journal of Hypertension. 18 (2): 158–164. doi:10.1016/j.amjhyper.2004.09.004. PMID   15752941 – via Oxford Academic.
  22. 1 2 "Lisinopril". PubChem. Retrieved 6 June 2018.
  23. ↑ Patlak M (March 2004). "From viper's venom to drug design: treating hypertension". FASEB J. 18 (3): 421. doi: 10.1096/fj.03-1398bkt . PMID   15003987. S2CID   1045315.
  24. ↑ Jenny Bryan for The Pharmaceutical Journal, 17 April 2009 "From snake venom to ACE inhibitor – the discovery and rise of captopril"
  25. ↑ Li JJ (2013). "History of Drug Discovery". In Li JJ, Corey EJ (eds.). Drug Discovery: Practices, Processes, and Perspectives. John Wiley & Sons. ISBN   978-1-118-35446-9.
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  27. ↑ Glover DR (2016). "Merck Sharp and Dohme: lisinopril section". Vie D'or: Memoirs of a Pharmaceutical Physician. Troubador Publishing Ltd. ISBN   978-1-78589-494-7.
  28. 1 2 Express Scripts. Patent expirations

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