Lisinopril
Encyclopedia
Lisinopril is a drug of the angiotensin-converting enzyme (ACE) inhibitor
class that is primarily used in treatment of hypertension
, congestive heart failure
, and heart attacks
and also in preventing renal
and retina
l complications of diabetes
. Its indications, contraindications and side effects are as those for all ACE inhibitor
s. 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 a long half-life
and tissue penetration, and is not metabolized
by the liver.
, congestive heart failure
, acute myocardial infarction, and diabetic nephropathy
.
. 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).
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.
There are no data on the excretion of lisinopril into human milk. The manufacturer recommends that 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.
-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
.
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 intersubject 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.
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.
ACE inhibitor
ACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...
class that is primarily used in treatment of hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
, and heart attacks
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
and also in preventing renal
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
and retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
l complications of diabetes
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
. Its indications, contraindications and side effects are as those for all ACE inhibitor
ACE inhibitor
ACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...
s. It has been compared with omapatrilat
Omapatrilat
Omapatrilat is a novel antihypertensive agent that inhibits both neutral endopeptidase and angiotensin converting enzyme . NEP inhibition results in elevated natriuretic peptide levels, promoting natriuresis, diuresis, vasodilation, and reductions in preload and ventricular remodeling.This drug...
, which is of similar function.
Historically, lisinopril was the third ACE inhibitor (after captopril
Captopril
Captopril is an angiotensin-converting enzyme inhibitor used for the treatment of hypertension and some types of congestive heart failure. Captopril was the first ACE inhibitor developed and was considered a breakthrough both because of its novel mechanism of action and also because of the...
and enalapril
Enalapril
Enalapril is an angiotensin converting enzyme inhibitor used in the treatment of hypertension and some types of chronic heart failure. ACE raises blood pressure by constricting blood vessels. ACE inhibitors like enalapril prevent this effect. Enalapril has been shown to lower the death rate in...
) 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
Hydrophile
A hydrophile, from the Greek "water" and φιλια "love," is a molecule or other molecular entity that is attracted to, and tends to be dissolved by water. A hydrophilic molecule or portion of a molecule is one that has a tendency to interact with or be dissolved by, water and other polar substances...
, has a long half-life
Half-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...
and tissue penetration, and is not metabolized
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
by the liver.
Medical uses
Lisinopril is typically used for the treatment of hypertensionHypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
, acute myocardial infarction, and diabetic nephropathy
Diabetic nephropathy
Diabetic nephropathy , also known as Kimmelstiel-Wilson syndrome, or nodular diabetic glomerulosclerosis and intercapillary glomerulonephritis, is a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli. It is characterized by nephrotic syndrome and diffuse...
.
In special populations
In those 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.Formulation
Its long half-life allows for once-a-day dosing, which aids with complianceCompliance (medicine)
In medicine, compliance describes the degree to which a patient correctly follows medical advice...
. 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).
Adverse effects
Side effects, some or all of which are serious and require immediate medical attention, include:- Chills, signs of infectionInfectionAn infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
- Dark urine, decreased urination (oliguriaOliguriaOliguria is the low output of urine, It is clinically classified as an output below 300-500ml/day. The decreased output of urine may be a sign of dehydration, renal failure, hypovolemic shock, HHNS Hyperosmolar Hyperglycemic Nonketotic Syndrome, multiple organ dysfunction syndrome, urinary...
) - Difficulty swallowing or breathing (signs of angioedemaAngioedemaAngioedema or Quincke's edema is the rapid swelling of the dermis, subcutaneous tissue, mucosa and submucosal tissues. It is very similar to urticaria, but urticaria, commonly known as hives, occurs in the upper dermis...
), allergic reaction (anaphylaxisAnaphylaxisAnaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
) - Hoarseness
- Itching
- Yellowing of skin or eyes (jaundiceJaundiceJaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
) - Abdominal pain, bloating, vomiting
- Chest pain or tightness, dizziness, lightheadedness, fainting (syncopeSyncope (medicine)Syncope , the medical term for fainting, is precisely defined as a transient loss of consciousness and postural tone characterized by rapid onset, short duration, and spontaneous recovery due to global cerebral hypoperfusion that most often results from hypotension.Many forms of syncope are...
) - 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
Hyperkalemia
Hyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated...
. 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.
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 the use of ACE inhibitors during the second and third trimesters of pregnancy. If the patient becomes pregnant, lisinopril should be discontinued as soon as possible. Lisinopril is considered contraindicated during pregnancy.There are no data on the excretion of lisinopril into human milk. The manufacturer recommends that 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.
Pharmacology
Lisinopril is the lysineLysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
-analog of enalapril
Enalapril
Enalapril is an angiotensin converting enzyme inhibitor used in the treatment of hypertension and some types of chronic heart failure. ACE raises blood pressure by constricting blood vessels. ACE inhibitors like enalapril prevent this effect. Enalapril has been shown to lower the death rate in...
. Unlike other ACE inhibitors, lisinopril is not a prodrug
Prodrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
and is excreted unchanged in the urine. In cases of overdosage
Effective dose
Effective dose may refer to:*Effective dose the dose of pharmacologic agent which will have a therapeutic effect in some fraction of the population receiving the drug...
, it can be removed from circulation by dialysis
Dialysis
In medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
.
Pharmacokinetics and metabolism
For 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 intersubject 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.
Brand names
Lisinopril was developed by Merck & Co.Merck & Co.
Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...
and is marketed worldwide as Prinivil or Tensopril and by AstraZeneca
AstraZeneca
AstraZeneca plc is a global pharmaceutical and biologics company headquartered in London, United Kingdom. It is the world's seventh-largest pharmaceutical company measured by revenues and has operations in over 100 countries...
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
Functional analog
Functional analogs , are compounds that have similar physical, chemical, biochemical, or pharmacological properties. An example of a functional analog is morphine and heroin. Functional analogs are not necessarily also structural analogs with a similar chemical structure...
and structural analog of a peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
derived from the venom of the jararaca, a Brazilian pit viper (Bothrops jararaca
Bothrops jararaca
Bothrops jararaca is a venomous pit viper species found in southern Brazil, Paraguay and northern Argentina. The species name is derived from the Tupi words yarará and ca, which means "large snake." Within its range it is often abundant and is an important cause of snakebite...
). Lisinopril can also be used in conjunction with the diuretic
Diuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
Hydrochlorothiazide
Hydrochlorothiazide
Hydrochlorothiazide, abbreviated HCTZ, HCT, or HZT, is a first-line diuretic drug of the thiazide class that acts by inhibiting the kidneys' ability to retain water. This reduces the volume of the blood, decreasing blood return to the heart and thus cardiac output and, by other mechanisms, is...
and drugs which combine these two medications are available under the brand names Prinzide and Zestoretic.