Lisinopril

Lisinopril

Chemical structure of lisinopril
Systematic (IUPAC) name
N2-[(1S)-1-carboxy-3-phenylpropyl]-L-lysyl-L-proline
Clinical data
Trade names	Prinivil, Tensopril, Zestril, Hipril
AHFS/Drugs.com	monograph
MedlinePlus	a692051
Pregnancy cat.	C (1st trimester) / D (2nd and 3rd trimester)
Legal status	℞ Prescription only
Routes	Oral
Pharmacokinetic data
Bioavailability	approx. 25%, but wide range between individuals (6 to 60%)
Protein binding	0
Metabolism	None
Half-life	12 hours
Excretion	Eliminated unchanged in urine
Identifiers
CAS number	83915-83-7
ATC code	C09AA03
PubChem	CID 5362119
DrugBank	APRD00560
ChemSpider	4514933 Y
UNII	7Q3P4BS2FD N
KEGG	D00362 Y
ChEBI	CHEBI:43755 N
ChEMBL	CHEMBL1237 Y
Synonyms	(2S)-1-[(2S)-6-amino-2-{[(1S)-1-carboxy-3-phenylpropyl]amino}hexanoyl]pyrrolidine-2-carboxylic acid
Chemical data
Formula	C21H31N3O5
Mol. mass	405.488 g/mol
SMILES O=C(O)[C@H]2N(C(=O)[C@@H](N[C@H](C(=O)O)CCc1ccccc1)CCCCN)CCC2
InChI 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 Y Key:RLAWWYSOJDYHDC-BZSNNMDCSA-N Y
N (what is this?)  (verify)

Lisinopril (pron.: /laɪˈsɪnəprɪl/ ly-SIN-ə-pril) is a drug of the angiotensin-converting enzyme (ACE) inhibitor class primarily used in treatment of hypertension, congestive heart failure, and heart attacks, and also in preventing renal and retinal complications of diabetes. Its indications, contraindications and side effects are as those for all ACE inhibitors.

Historically, lisinopril was the third ACE inhibitor (after captopril and enalapril) and was introduced into therapy in the early 1990s. 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.

In special populations

The dose needs to be adjusted in those with poor kidney function.

Adverse effects

Side effects, some or all of which are serious and require immediate medical attention, include:

• Chills, signs of infection
• Dark urine, decreased urination (oliguria)
• Difficulty swallowing or breathing (signs of angioedema), allergic reaction (anaphylaxis)
• Hoarseness
• Itching
• Yellowing of skin or eyes (jaundice)
• Abdominal pain, bloating, vomiting
• Chest pain or tightness, dizziness, lightheadedness, fainting (syncope)
• Dry cough
• Fever
• Joint pain
• Rash
• Diarrhea, nausea
• Drowsiness, headache, tiredness
• Muscle cramps
• Fainting/blackouts
• Serious (possibly fatal) liver problems

Lisinopril causes the kidneys to retain potassium, which may lead to hyperkalemia. From a study of more than 1,000 patients who have hyperkalemia when using it, the condition may happen more in older male users.

A rare but severe allergic reaction can occur that affects the bowel wall and secondarily causes abdominal pain. This "anaphylactic" reaction is very rare and must be given immediate medical attention.

Pregnancy and breastfeeding

Lisinopril has been assigned to pregnancy category D by the FDA for use during the second and third trimesters and to category C during the first trimester. Animal and human data have revealed evidence of embryolethality and teratogenicity associated with angiotensin converting enzyme (ACE) inhibitors. There are no controlled data in human pregnancy. 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. If the patient becomes pregnant, lisinopril should be discontinued as soon as possible; it is considered contraindicated during pregnancy.

There are no data on the excretion of lisinopril into human milk. The manufacturer recommends, due to the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Lisinopril 40 mg oral tablet

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.

Pharmacokinetics and metabolism

For adult patients, following oral administration of lisinopril, peak serum concentrations occur within about seven hours, although there was a trend to a small delay in time taken to reach peak serum concentrations in acute myocardial infarction patients. 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 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. Its absolute bioavailability is reduced to about 16% in patients with stable NYHA Class II-IV congestive heart failure, 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 (approximately doubled) higher blood levels and area under the plasma concentration time curve (AUC) 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). Lisinopril can also be used in conjunction with the diuretic hydrochlorothiazide and drugs which combine these two medications are available under the brand names Prinzide and Zestoretic.

See also

• Omapatrilat

Further reading

• Fogari R, Zoppi A, Corradi L, Lazzari P, Mugellini A, Lusardi P (November 1998). "Comparative effects of lisinopril and losartan on insulin sensitivity in the treatment of non diabetic hypertensive patients". Br J Clin Pharmacol 46 (5): 467–71. doi:10.1046/j.1365-2125.1998.00811.x. PMC 1873694. PMID 9833600. 
• Bussien JP, Waeber B, Nussberger J, Gomez HJ, Brunner HR (1985). "Once-daily lisinopril in hypertensive patients: Effect on blood pressure and the renin-angiotensin system". Curr Therap Res 37: 342–51. 

External links

• Prescribing information for Zestril
• U.S. National Library of Medicine: Drug Information Portal – Lisinopril
• Lisinopril.com – Lisinopril information