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{{Infobox drug |Verifiedfields = changed|Watchedfields = changed|caption = Chemical structure of lisinopril|verifiedrevid = 432833853|IUPAC_name = N²-[(1S)-1-carboxy-3-phenylpropyl]-L-lysyl-L-proline|image = Lisinopril Structural Formulae V.2.svg|alt = Structural formula of lisinopril|image2 = Lisinopril zwitterion 3D ball.png|alt2 = Ball-and-stick model of the lisinopril zwitterion |pronounce = /laɪˈsɪnəprɪl/, ly-SIN-ə-pril|tradename = Prinivil, Tensopril, Zestril, Hipril|Drugs.com = Monograph|MedlinePlus = a692051|pregnancy_category = C (1st trimester) / D (2nd and 3rd trimester)^[1]|legal_status = Rx-only|routes_of_administration = Oral |bioavailability = approx. 25%, but wide range between individuals (6 to 60%)|protein_bound = 0|metabolism = None|elimination_half-life = 12 hours|excretion = Eliminated unchanged in urine |IUPHAR_ligand = 6360|CAS_number = 83915-83-7|ChemSpiderID_Ref = ^Y|ChemSpiderID = 4514933|ATC_prefix = C09|ATC_suffix = AA03|ATC_supplemental = |ChEBI_Ref = ^N|ChEBI = 43755|PubChem = 5362119|DrugBank_Ref = ^Y|DrugBank = APRD00560|KEGG_Ref = ^Y|KEGG = D00362|ChEMBL_Ref = ^Y|ChEMBL = 1237|synonyms = (2S)-1-[(2S)-6-amino-2-{[(1S)-1-carboxy-3-phenylpropyl]amino}hexanoyl]pyrrolidine-2-carboxylic acid|UNII_Ref = ^N|UNII = 7Q3P4BS2FD|PDB_ligand = LPR |C = 21|H = 31|N = 3|O = 5|molecular_weight = 405.488 g/mol|smiles = O=C(O)[C@H]2N(C(=O)[C@@H](N[C@H](C(=O)O)CCc1ccccc1)CCCCN)CCC2|InChIKey = RLAWWYSOJDYHDC-BZSNNMDCBR|InChI = 1/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|StdInChI_Ref = ^Y|StdInChI = 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|StdInChIKey_Ref = ^Y|StdInChIKey = RLAWWYSOJDYHDC-BZSNNMDCSA-N}} Lisinopril is a drug of the angiotensin-converting enzyme (ACE) inhibitor class used primarily in treatment of hypertension, congestive heart failure, and heart attacks, and in preventing renal and retinal complications of diabetes. Its indications, contraindications, and side effects are as those for all ACE inhibitors.

Lisinopril was the third ACE inhibitor (after captopril and enalapril) and was introduced into therapy in the early 1990s.^[2] A number of properties distinguish it from other ACE inhibitors: It is hydrophilic, has a long half-life and tissue penetration, and is not metabolized by the liver.

Medical uses

Lisinopril is typically used for the treatment of hypertension, congestive heart failure, acute myocardial infarction, and diabetic nephropathy.^[1]

Contraindications

History of angioedema (hereditary or idiopathic)^[3]
Hypersensitivity reaction to lisinopril or any of other components found in its formulation^[3]
Concomitant use of aliskiren-containing drugs in patients with diabetes^[3]

Combination of aliskiren and lisinopril is contraindicated in patients with diabetes, and should be avoided in those with creatinine clearance less than 60ml/min. This combination may heighten the hyperkalemic, hypotensive, and nephrotoxic effects of lisinopril (and other ACE inhibitors). Therefore, serum potassium, blood pressure, and serum creatinine should be carefully monitored for all patients on this combination.

Adverse effects

Side effects, incidence differs depending on which disease state the patient is being treated for.^[4]

Patients taking Lisinopril for the treatment of Hypertension may experience the following side effects:

Headache (3.8%)
Dizziness (3.5%)
Cough (2.5%)
Difficulty swallowing or breathing (signs of angioedema), allergic reaction (anaphylaxis)
Hyperkalemia (2.2% in adult clinical trials)
Fatigue (1% or more)
Diarrhea (1% or more)
Stevens–Johnson syndrome (1% or more)

Patients taking Lisinopril for the treatment of Acute Myocardial Infarction may experience the following side effects:

Hypotension (5.3%)
Renal Dysfunction (1.3%)

Patients taking Lisinopril for the treatment of Heart Failure may experience the following side effects:

Hypotension (3.8%)
Dizziness (12-19%)
Chest pain (2.1%)
Fainting (5-7%)
Hyperkalemia (4.8% in adult clinical trials)
Difficulty swallowing or breathing (signs of angioedema), allergic reaction (anaphylaxis)
Fatigue (1% or more)
Diarrhea (1% or more)
Stevens–Johnson syndrome (1% or more)

Special populations

Kidney impairment

The dose must be adjusted in those with poor kidney function. These adjustments are based on the patient's creatinine clearance and are only required when it is 30mL/min or below. Since lisinopril is dialysable, dosing changes must also be considered for patients on dialysis.^[4]

Pregnancy and breastfeeding

Lisinopril has been assigned to pregnancy category D by the FDA. Animal and human data have revealed evidence of embryolethality and teratogenicity associated with ACE inhibitors. No controlled data in human pregnancy are available. Congenital malformations have been reported with the use of ACE inhibitors during the first trimester of pregnancy, while fetal and neonatal toxicity, death, and congenital anomalies have been reported with their use during the second and third trimesters of pregnancy. The Zestril brand manufacturer states, "When pregnancy is detected, discontinue Zestril as soon as possible."^[4]

The manufacturer recommends mothers should not breastfeed while taking this medication because of the lack of safety data that currently exists.^[4]

Pharmacology

Lisinopril is the lysine-analog of enalapril. Unlike other ACE inhibitors, it is not a prodrug and is excreted unchanged in the urine. In cases of overdosage, it can be removed from circulation by dialysis.^[5]

Pharmacokinetics and metabolism

For adult patients, following oral administration of lisinopril, peak serum concentrations occur within about seven hours, although a trend to a small delay in time taken to reach peak serum concentrations in acute myocardial infarction patients was seen. Declining serum concentrations exhibit a prolonged terminal phase that does not contribute to drug accumulation. This terminal phase probably represents saturable binding to ACE and is not proportional to dose. Lisinopril does not appear to be bound to other serum proteins.

Lisinopril does not undergo metabolism and is excreted unchanged entirely in the urine. Based on urinary recovery, the mean extent of its absorption is approximately 25%, with large intersubject variability (6–60%) at all doses tested (5–80 mg). Lisinopril absorption is not influenced by the presence of food in the gastrointestinal tract. In patients with stable NYHA class II-IV congestive heart failure, its absolute bioavailability is reduced to about 16%, and the volume of distribution appears to be slightly smaller than that in normal subjects.

The oral bioavailability of lisinopril in patients with acute myocardial infarction is similar to that in healthy volunteers. Upon multiple dosing, it exhibits an effective half-life of accumulation of 12 hours.

Impaired renal function decreases elimination of lisinopril, which is excreted principally through the kidneys, but this decrease becomes clinically important only when the glomerular filtration rate is below 30 ml/min. Above this rate, the elimination half-life is little-changed. With greater impairment, however, peak and trough levels increase, time to peak concentration increases, and time to attain steady state is prolonged. Older patients, on average, have higher (around doubled) blood levels and area under the plasma concentration time curve than younger patients.

Brand names

Lisinopril was developed by Merck & Co., and is marketed worldwide as Prinivil or Tensopril, and by AstraZeneca as Zestril. In India, it is marketed by Micro Labs as Hipril. In the United States, a generic version is available. Like other ACE inhibitors, it is a synthetic functional and structural analog of a peptide derived from the venom of the jararaca, a Brazilian pit viper (Bothrops jararaca).^[6] Lisinopril can also be used in conjunction with the diuretic hydrochlorothiazide, and drugs that combine these two medications are available under the brand names Prinzide and Zestoretic.

References

^ ^a ^b "Lisinopril". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.
^ Patchett A, Harris E, Tristram E, Wyvratt M, Wu M, Taub D, Peterson E, Ikeler T, ten Broeke J, Payne L, Ondeyka D, Thorsett E, Greenlee W, Lohr N, Hoffsommer R, Joshua H, Ruyle W, Rothrock J, Aster S, Maycock A, Robinson F, Hirschmann R, Sweet C, Ulm E, Gross D, Vassil T, Stone C (1980). "A new class of angiotensin-converting enzyme inhibitors". Nature. 288 (5788): 280–3. doi:10.1038/288280a0. PMID 6253826.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ ^a ^b ^c Product Information: ZESTRIL(R) oral tablet, lisinopril oral tablet. AstraZeneca Pharmaceuticals LP, Wilmington, DE, 2005.
^ ^a ^b ^c ^d ""Zestril (Lisinopril) Package Insert". Astrazeneca. Retrieved 3 November 2015" (PDF).
^ AstraZeneca. "ZESTRIL (lisinopril) product insert" (PDF). accessdata.fda.gov. Retrieved 15 October 2011.
^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)

External links

This is a user sandbox of SelfieChamps 29. A user sandbox is a subpage of the user's user page. It serves as a testing spot and page development space for the user and is not an encyclopedia article.

Category:Cephalosporin antibiotics Category:Thiazoles Category:Oximes Category:Acetate esters

[AHFS-1] "Lisinopril". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.

[2] Patchett A, Harris E, Tristram E, Wyvratt M, Wu M, Taub D, Peterson E, Ikeler T, ten Broeke J, Payne L, Ondeyka D, Thorsett E, Greenlee W, Lohr N, Hoffsommer R, Joshua H, Ruyle W, Rothrock J, Aster S, Maycock A, Robinson F, Hirschmann R, Sweet C, Ulm E, Gross D, Vassil T, Stone C (1980). "A new class of angiotensin-converting enzyme inhibitors". Nature. 288 (5788): 280–3. doi:10.1038/288280a0. PMID 6253826.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[Product_Information_2005-3] Product Information: ZESTRIL(R) oral tablet, lisinopril oral tablet. AstraZeneca Pharmaceuticals LP, Wilmington, DE, 2005.

[:0-4] ""Zestril (Lisinopril) Package Insert". Astrazeneca. Retrieved 3 November 2015" (PDF).

[urlwww.accessdata.fda.gov-5] AstraZeneca. "ZESTRIL (lisinopril) product insert" (PDF). accessdata.fda.gov. Retrieved 15 October 2011.

[pmid15003987-6] 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)

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v t e Antihypertensive drugs acting on the renin–angiotensin system (C09)
ACE inhibitors ("-pril")	Sulfhydryl-containing: Captopril Rentiapril Zofenopril (+nebivolol) Dicarboxylate-containing: Enalapril^# (+lercanidipine, +nitrendipine) Benazepril (+amlodipine, +pimobendan) Cilazapril Delapril (+manidipine) Imidapril Lisinopril (+amlodipine, +HCT) Moexipril Perindopril (+amlodipine, +bisoprolol, +indapamide, +amlodipine and indapamide, +bisoprolol and amlodipine, +bisoprolol, amlodipine, and indapamide) Quinapril (+HCT) Ramipril (+amlodipine, +amlodipine and HCT, +bisoprolol, +felodipine) Spirapril Temocapril Trandolapril (+verapamil) Phosphonate-containing: Ceronapril Fosinopril (+HCT) Other/ungrouped: Alacepril
AIIRAs ("-sartan")	Azilsartan Candesartan (+amlodipine, +amlodipine and HCT) Eprosartan Fimasartan Irbesartan (+amlodipine, +amlodipine and HCT, +HCT) Losartan (+amlodipine, +HCT) Olmesartan (+amlodipine, +amlodipine and HCT, +HCT) Tasosartan^§ Telmisartan (+amlodipine, +amlodipine and HCT, +HCT) Valsartan (+aliskiren, +amlodipine, +amlodipine and HCT, +HCT, +lercanidipine, +nebivolol, +sacubitril)
Renin inhibitors ("-kiren")	Aliskiren (+amlodipine, +HCT, +amlodipine and HCT) Remikiren^§
Dual ACE/NEP inhibitors	Gemopatrilat Ilepatril Omapatrilat Sampatrilat
Neprilysin inhibitors	Sacubitril (+valsartan)
Other	Sparsentan
^#WHO-EM ^‡Withdrawn from market Clinical trials: ^†Phase III ^§Never to phase III