Lisinopril

Lisinopril

File:Lisinopril.svg
Systematic (IUPAC) name
N2-[(1S)-1-carboxy-3-phenylpropyl]-L-lysyl-L-proline
Clinical data
Pregnancy category	D - teratogenic
Routes of administration	PO
Legal status
Legal status	℞ (Prescription only)
Pharmacokinetic data
Bioavailability	approx. 25%, but wide range between individuals (6 to 60%)
Protein binding	0
Metabolism	None
Biological half-life	12 hours
Excretion	Eliminated unchanged in Urine
Identifiers
CAS Number	83915-83-7
ATC code	C09AA03 (WHO)
PubChem	CID 5362119
DrugBank	APRD00560
ChemSpider	4514933
Synonyms	(2S)-1-[(2S)-6-amino-2-{[(1S)-1-carboxy-3-phenylpropyl]amino}hexanoyl]pyrrolidine-2-carboxylic acid
Chemical data
Formula	C21H31N3O5
Molar mass	405.488 g/mol[[]]

Lisinopril (lye-SIN-o-pril) is a drug of the angiotensin converting enzyme (ACE) inhibitor class that is primarily used in treatment of hypertension, congestive heart failure, heart attacks and also in preventing renal and retinal complications of diabetes. It has been compared with omapatrilat which is of similar function.

Historically, lisinopril was the third ACE inhibitor, after captopril and enalapril, and was introduced into therapy in the early 1990s. Lisinopril has a number of properties that distinguish it from other ACE inhibitors: it is hydrophilic, has long half-life and tissue penetration and is not metabolized by the liver.

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 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.

Pharmacology

Lisinopril is the lysine-analog of enalapril. Unlike other ACE inhibitors, lisinopril 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

Adult patients: Following oral administration of lisinopril, peak serum concentrations occur within about 7 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 absorption of lisinopril is approximately 25 percent, with large inter-subject variability (6-60 percent) at all doses tested (5-80 mg). Lisinopril absorption is not influenced by the presence of food in the gastrointestinal tract. The absolute bioavailability of lisinopril is reduced to about 16 percent 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, lisinopril 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 glomerular filtration rate, the elimination half-life is little changed. With greater impairment, however, peak and trough lisinopril 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.

Clinical use

Its indications, contraindications and side effects are as those for all ACE inhibitors. Its long half-life allows for once a day dosing which aids patient compliance. The usual daily dose in all indications ranges from 2.5 mg/day in sensitive patients to 20 mg/day in more tolerant or unresponsive subjects. Some patients have been treated with 80 mg daily and have tolerated this high dose well. Lower dosages must be used in patients with higher grade renal impairment (glomerular filtration rate (GFR) lower than 30 ml/min).

Patients whose creatinine clearance ≥10 mL/min and ≤30 mL/min (typically with a serum creatinine ≥3 mg/dL) should be given the standard 5 mg/day dosage, at first. For patients whose creatinine clearance is less than 10 mL/min, the dosage should start at 2.5 mg/day, adjusted over time according to the patient's blood pressure response.

Adverse effects

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

• Chills, infection
• Dark urine, decreased urination (oliguria)
• Difficulty swallowing or breathing (signs of angioedema), allergic reaction (anaphylaxis)
• Hoarseness
• Itching
• Rapid weight gain, stomach pain
• 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, loss of taste, nausea
• Drowsiness, headache, tiredness
• Change in mood/irrational behaviour
• Blurred vision
• Muscle cramps
• Fainting/blackouts
• Sexual dysfunction
• 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 Lisinopril, the condition may happen more on 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.

See also

• Omapatrilat

References

• Bussien JP, Waeber B, Nussberger J, Gomez HJ, Brunner HR. Once-daily lisinopril in hypertensive patients: Effect on blood pressure and the renin-angiotensin system. Curr Therap Res 1985;37:342-51.
• Lisinopril info - rx-list.com
• Goodman & Gilman's : The pharmacological basis of therapeutics, 10th. ed., 2001
• Lisinopril.com - Lisinopril information

External links

• Prescribing information for ZESTRIL
• U.S. National Library of Medicine: Drug Information Portal - Lisinopril

bg:Lisinopril uk:Лізиноприл