 Captopril, the first ACE inhibitor ACE inhibitors, or inhibitors of Angiotensin-Converting Enzyme, are a group of pharmaceuticals that are used primarily in treatment of hypertension and congestive heart failure, in some cases as the drugs of first choice. Image File history File links molecular structure of captopril File history Legend: (cur) = this is the current file, (del) = delete this old version, (rev) = revert to this old version. ...
Image File history File links molecular structure of captopril File history Legend: (cur) = this is the current file, (del) = delete this old version, (rev) = revert to this old version. ...
Angiotensin converting enzyme Angiotensin-Converting Enzyme (ACE, EC 3. ...
Pharmacology (in Greek: pharmacon is drug, and logos is science) is the study of how chemical substances interfere with living systems. ...
For other forms of hypertension, see Hypertension (disambiguation). ...
Congestive heart failure (CHF), also called congestive cardiac failure (CCF) or just heart failure, is a condition that can result from any structural or functional cardiac disorder that impairs the ability of the heart to fill with or pump a sufficient amount of blood throughout the body. ...
Clinical use
Indications for ACE inhibitors include: In several of these indications, ACE inhibitors are used first-line as several agents in the class have been clinically shown to be superior to other classes of drugs in the reduction of morbidity and mortality. The circulatory system or cardiovascular system is the organ system which circulates blood around the body of most animals. ...
Congestive heart failure (CHF), also called congestive cardiac failure (CCF) or just heart failure, is a condition that can result from any structural or functional cardiac disorder that impairs the ability of the heart to fill with or pump a sufficient amount of blood throughout the body. ...
For other forms of hypertension, see Hypertension (disambiguation). ...
In the heart, a ventricle is a heart chamber which collects blood from an atrium (another heart chamber that is smaller than a ventricle) and pumps it out of the heart. ...
Nephropathy refers to damage to or disease of the kidney. ...
For the disease characterized by excretion of large amounts of very dilute urine, see diabetes insipidus. ...
In medicine, epidemiology and actuarial science, the term morbidity can refer to the state of being diseased (from Latin morbidus: sick, unhealthy), the degree or severity of a disease, the prevalence of a disease: the total number of cases in a particular population at a particular point in time, the...
ACE inhibitors are often combined with diuretics in the control of hypertension (usually a thiazide), when an ACE inhibitor alone proves insufficient; and in chronic heart failure (usually furosemide) for improved symptomatic control. Thus there exists, on the market, combination products combining an ACE inhibitor with a thiazide (usually hydrochlorothiazide) in a single tablet to allow easy administration by patients. This illustration shows where some types of diuretics act, and what they do. ...
Thiazides are a class of drug that promote water loss from the body ((diuretics)). They inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. ...
Furosemide (INN) or frusemide (former BAN) is a loop diuretic used in the treatment of congestive heart failure and edema. ...
Hydrochlorothiazide (Apo-Hydro®, Aquazide H®, Microzide®, Oretic®), sometimes abbreviated HCT, HCTZ, or HZT is a popular diuretic drug that acts by inhibiting the kidneys ability to retain water. ...
The renin-angiotensin-aldosterone system (RAAS) -
Main article: Renin-angiotensin system This system is activated in response to hypotension, decreased sodium concentration in the distal tubule, decreased blood volume and renal sympathetic nerve stimulation. In such a situation, the kidneys release renin which cleaves the liver derived angiotensinogen into Angiotensin I. Angiotensin I is then converted to angiotensin II via the angiotensin-converting-enzyme (ACE) in the pulmonary circulation. The system in general aims to increase blood pressure. Schematic depicting how the RAAS works. ...
Recently (2008), scientists have found that blocking this system induces the rate of metabolism. Current studies involve modifying the ACE inhibitor drugs and targeting the RAAS system, strictly for weight loss.
Effects ACE inhibitors lower arteriolar resistance and increase venous capacity; increase cardiac output and cardiac index, stroke work and volume, lower renovascular resistance, and lead to increased natriuresis (excretion of sodium in the urine). An arteriole is a small diameter blood vessel that extends and branches out from an artery and leads to capillaries. ...
Cardiac output (CO) is the volume of blood being pumped by the heart, in particular by a ventricle in a minute. ...
Cardiac index (CI) is a vasodynamic parameter that relates the cardiac output (CO) to body surface area (BSA), thus relating heart performance (HR) to the size of the individual (SV). ...
In cardiovascular physiology, stroke volume (SV) is the volume of blood ejected from a ventricle with each beat of the heart. ...
Urine is liquid waste excreted by the kidneys and eventually expelled from the body in a process known as urination. ...
For sodium in the diet, see Salt. ...
This article is about the urine of animals generally. ...
Normally, angiotensin II will have the following effects:
- vasoconstriction (narrowing of blood vessels), which may lead to increased blood pressure and hypertension
- Specifically, angiotensin II constricts the efferent arterioles of the kidney, leading to increased perfusion pressure in the glomeruli.
- Ventricular remodeling of the heart, which may lead to ventricular hypertrophy and CHF
- stimulate the adrenal cortex to release aldosterone, a hormone that acts on kidney tubules to retain sodium and chloride ions and excrete potassium. Sodium is a "water-holding" molecule, so water is also retained, which leads to increased blood volume, hence an increase in blood pressure.
- stimulate the posterior pituitary into releasing vasopressin (also known as anti-diuretic hormone (ADH)) which also acts on the kidneys to increase water retention.
With ACE inhibitor use, the effects of angiotensin II are prevented, leading to decreased blood pressure. For other forms of hypertension, see Hypertension (disambiguation). ...
The Efferent arterioles are a group of blood vessels that are part of the urinary system of many animals. ...
The kidneys are the organs that filter wastes (such as urea) from the blood and excrete them, along with water, as urine. ...
Glomerulus refers to two unrelated structures in the body, both named for their globular form. ...
This article needs to be wikified. ...
Although ventricular hypertrophy may occur in either the left or right or both ventricles of the heart , left ventricular hypertrophy (LVH) is more commonly encountered. ...
Aldosterone, is a steroid hormone (mineralocorticoid family) produced by the outer-section (zona glomerulosa) of the adrenal cortex in the adrenal gland, and acts on the kidney nephron to conserve sodium, secrete potassium,increase water retention, and increase blood pressure. ...
RNA expression pattern Orthologs Human Mouse Entrez Ensembl Uniprot Refseq Location Pubmed search Arginine vasopressin (AVP), also known as vasopressin, argipressin or antidiuretic hormone (ADH), is a hormone found in most mammals, including humans. ...
Epidemiological and clinical studies have shown that ACE inhibitors reduce the progress of diabetic nephropathy independently from their blood pressure-lowering effect[citation needed] . This action of ACE inhibitors is utilised in the prevention of diabetic renal failure. Epidemiology is the study of factors affecting the health and illness of populations, and serves as the foundation and logic of interventions made in the interest of public health and preventive medicine. ...
Diabetic nephropathy (nephropatia diabetica), also known as Kimmelstiel-Wilson syndrome and intercapillary glomerulonephritis, is a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli. ...
Renal failure or kidney failure is a situation in which the kidneys fail to function adequately. ...
ACE inhibitors have been shown to be effective for indications other than hypertension even in patients with normal blood pressure. The use of a maximum dose of ACE inhibitors in such patients (including for prevention of diabetic nephropathy, congestive heart failure, prophylaxis of cardiovascular events) is justified because it improves clinical outcomes, independent of the blood pressure lowering effect of ACE inhibitors. Such therapy, of course, requires careful and gradual titration of the dose to prevent the effects of rapidly decreasing blood pressure (dizziness, fainting, etc).
Adverse effects Common adverse drug reactions (≥1% of patients) include: hypotension, cough, hyperkalemia, headache, dizziness, fatigue, nausea, renal impairment.[1] An adverse drug reaction (abbreviated ADR) or adverse drug event (abbreviated ADE) is an expression that describes the unwanted, negative consequences associated with the use of given medications. ...
In physiology and medicine, hypotension refers to an abnormally low blood pressure. ...
Hyperkalemia is an elevated blood level (above 5. ...
A headache (cephalgia in medical terminology) is a condition of pain in the head; sometimes neck or upper back pain may also be interpreted as a headache. ...
Vertigo, a specific type of dizziness, is a major symptom of a balance disorder. ...
The word fatigue is used in everyday living to describe a range of afflictions, varying from a general state of lethargy to a specific work induced burning sensation within muscle. ...
For other uses, see Nausea (disambiguation). ...
A persistent dry cough is a relatively common adverse effect believed to be associated with the increases in bradykinin levels produced by ACE inhibitors, although the role of bradykinin in producing these symptoms remains disputed by some authors.[2] Patients who experience this cough are often switched to angiotensin II receptor antagonists. Spacefilling model of bradykinin Bradykinin is a physiologically and pharmacologically active peptide of the kinin group of proteins, consisting of nine amino acids. ...
Losartan, the first ARB Angiotensin II receptor antagonists, also known as angiotensin receptor blockers (ARBs), AT1-receptor antagonists or sartans, are a group of pharmaceuticals which modulate the renin-angiotensin-aldosterone system. ...
Rash and taste disturbances, infrequent with most ACE inhibitors, are more prevalent in captopril and is attributed to its sulfhydryl moiety. This has led to decreased use of captopril in clinical setting, although it is still used in scintigraphy of the kidney. Captopril is an Angiotensin-Converting Enzyme inhibitor (ACE inhibitor) used for the treatment of hypertension and some types of chronic heart failure. ...
Nuclear medicine is the branch of medicine that uses unsealed radioactive substances in diagnosis and therapy. ...
Renal impairment is a significant adverse effect of all ACE inhibitors. The reason for this is still unknown. Some suggest that it is associated with their effect on angiotensin II-mediated homeostatic functions such as renal blood flow. Renal blood flow may be affected by Angiotensin II because it vasoconstricts the efferent arterioles of the glomeruli of the kidney, thereby increasing glomerular filtration rate (GFR). Hence, by reducing angiotensin II levels, ACE inhibitors may reduce GFR, a marker of renal function. However this is actually untrue as whilst the efferent arteriole is more relaxed, so too is the afferent arteriole which acts to increase GFR in a compensatory manner. Specifically, ACE inhibitors can induce or exacerbate renal impairment in patients with renal artery stenosis. This is especially a problem if the patient is also concomitantly taking an NSAID and a diuretic - the so-called "triple whammy" effect - such patients are at very high risk of developing renal failure.[3] Homeostasis (from Greek: ὅμος, homos, equal; and ιστημι, histemi, to stand lit. ...
The Efferent arterioles are a group of blood vessels that are part of the urinary system of many animals. ...
Glomerulus refers to two unrelated structures in the body, both named for their globular form. ...
Glomerular filtration rate (GFR) is the volume of fluid filtered from the renal (kidney) glomerular capillaries into the Bowmans capsule per unit time. ...
In medicine (nephrology) renal function is an indication of the state of the kidney and its role in physiology. ...
Renal artery stenosis is the narrowing of the renal artery. ...
Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAIDs, are drugs with analgesic, antipyretic and anti-inflammatory effects - they reduce pain, fever and inflammation. ...
This illustration shows where some types of diuretics act, and what they do. ...
ACE inhibitors may cause hyperkalemia, because angiotensin II increases aldosterone release. Since aldosterone is responsible for increasing the excretion of potassium, ACE inhibitors ultimately cause retention of potassium. Hyperkalemia is an elevated blood level (above 5. ...
Some patients develop angioedema due to increased bradykinin levels. There appears to be a genetic predisposition towards this adverse effect in patients who degrade bradykinin slower than average.[4] Angioedema (BE: angiooedema), also known by its eponym Quinckes edema, is the rapid swelling (edema) of the skin, mucosa and submucosal tissues. ...
Mnemonic
- The first ACE-i available on market: CAPTOPRIL
C - Cough
A - Angioedema
P - Potassium (increase)
T - Taste disturbance
O - Othostatic hypotension
P - Pregnancy (contraindicated)
R - Renal failure in bilateral renal artery stenosis
IL - Idiosynatic Leukopenia
Examples ACE inhibitors can be divided into three groups based on their molecular structure:
Sulfhydryl-containing agents - Captopril (trade name Capoten), the first ACE inhibitor
- Zofenopril
Captopril is an Angiotensin-Converting Enzyme inhibitor (ACE inhibitor) used for the treatment of hypertension and some types of chronic heart failure. ...
Dicarboxylate-containing agents This is the largest group, including: Enalapril is an angiotensin converting enzyme (ACE) inhibitor used in the treatment of hypertension and some types of chronic heart failure. ...
Ramipril (marketed as Tritace or Altace) is an angiotensin-converting enzyme (ACE) inhibitor, used to treat hypertension and congestive heart failure. ...
Quinapril (or Accupril ®) is an ACE inhibitor used to control blood pressure. ...
Coversyl (perindopril) is a long-acting ACE inhibitor. ...
Lisinopril (lye-SIH-no-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. ...
Benazepril, brand name Lotensin®, is a medication used to treat high blood pressure (hypertension), congestive heart failure, and chronic renal failure. ...
Phosphonate-containing agents Fosinopril is an angiotensin converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of chronic heart failure. ...
Naturally occurring Casokinins and lactokinins are breakdown products of casein and whey that occur naturally after ingestion of milk products, especially cultured milk. Their role in blood pressure control is uncertain.[5] The tripeptides Val-Pro-Pro and Ile-Pro-Pro produced by the probiotic Lactobacillus helveticus have been show to have ACE-inhibiting and antihypertensive functions.[6] Casein (from Latin caseus cheese) is the most predominant phosphoprotein found in milk and cheese. ...
Percentages are relative to US recommendations for adults. ...
A glass of cows milk. ...
Fermented milk products, also known as cultured dairy foods, cultured dairy products, or cultured milk products, are dairy foods that have been fermented with lactic acid bacteria such as Lactobacillus, Leuconostoc, Pediococcus, Lactococcus, and Streptococcus. ...
A tripeptide is a peptide consisting of three amino acids, e. ...
Probiotics are dietary supplements containing potentially beneficial bacteria or yeasts. ...
Comparative information Comparatively, all ACE inhibitors have similar antihypertensive efficacy when equivalent doses are administered. The main point-of-difference lies with captopril, the first ACE inhibitor, which has a shorter duration of action and increased incidence of certain adverse effects (cf. captopril). Captopril is an Angiotensin-Converting Enzyme inhibitor (ACE inhibitor) used for the treatment of hypertension and some types of chronic heart failure. ...
Certain agents in the ACE inhibitor class have been proven, in large clinical studies, to reduce mortality post-myocardial infarction, prevent development of heart failure, etc. The ACE inhibitor most prominently recognized for these qualities is ramipril (Altace). Owing to the fact that ramipril has been shown to reduce mortality rates even among patient groups not suffering from hypertension, there is widespread belief that ramipril's benefits may extend beyond those of the general abilities it holds in common with other members of the ACE inhibitor class. Heart attack redirects here. ...
Contraindications and precautions The ACE inhibitors are contraindicated in patients with: ACE inhibitors should be used with caution in patients with: Angioedema (BE: angiooedema), also known by its eponym Quinckes edema, is the rapid swelling (edema) of the skin, mucosa and submucosal tissues. ...
Renal artery stenosis is the narrowing of the renal artery. ...
ACE inhibitors are ADEC Pregnancy category D, and should be avoided in women who are likely to become pregnant.[1] In the U.S., ACE inhibitors are required to be labelled with a "black box" warning concerning the risk of birth defects when taking during the second and third trimester. It has also been found that use of ACE inhibitors in the first trimester is also associated with a risk of major congenital malformations, particularly affecting the cardiovascular and central nervous systems.[7] Aortic valve stenosis (AS) is a heart condition caused by the incomplete opening of the aortic valve. ...
In physiology and medicine, hypovolemia is a state of decreased blood volume; more specifically, decrease in volume of blood plasma. ...
Dehydration (hypohydration) is the removal of water (hydro in ancient Greek) from an object. ...
In medicine, dialysis is a method for removing waste such as urea from the blood when the kidneys are incapable of this, i. ...
The Australian Drug Evaluation Committee or ADEC, is a committee that provides independent scientific advice to the Australian Government regarding therapeutic drugs. ...
The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. ...
It has been suggested that this article or section be merged with Black_Box_Warning. ...
The human gestation period of approximately 40 weeks between the time of the last menstrual cycle and delivery is traditionally divided into three periods of three months, or trimesters. ...
A congenital disorder is a medical condition that is present at birth. ...
For transport in plants, see Vascular tissue. ...
A diagram showing the CNS: 1. ...
Potassium supplementation should be used with caution and under medical supervision owing to the hyperkalaemic effect of ACE inhibitors. Hyperkalemia is an elevated blood level (above 5. ...
Angiotensin II receptor antagonists ACE inhibitors share many common characteristics with another class of cardiovascular drugs called angiotensin II receptor antagonists, which are often used when patients are intolerant of the adverse effects produced by ACE inhibitors. ACE inhibitors do not completely prevent the formation of angiotensin II, as there are other conversion pathways, and so angiotensin II receptor antagonists may be useful because they act to prevent the action of angiotensin II at the AT1 receptor. Losartan, the first ARB Angiotensin II receptor antagonists, also known as angiotensin receptor blockers (ARBs), AT1-receptor antagonists or sartans, are a group of pharmaceuticals which modulate the renin-angiotensin-aldosterone system. ...
Use in combination While counterintuitive at first glance, the combination therapy of angiotensin II receptor antagonists with ACE inhibitors may be superior to either agent alone. This combination may increase levels of bradykinin while blocking the generation of angiotensin II and its activity at the AT1 receptor. This 'dual blockade' may be more effective than using an ACE inhibitor alone, because angiotensin II can be generated via non-ACE-dependent pathways. Preliminary studies suggest that this combination of pharmacologic agents may be advantageous in the treatment of essential hypertension, chronic heart failure, and nephropathy.[8][9] However, more studies are needed to confirm these highly preliminary results. While statistically significant results have been obtained for its role in treating hypertension, clinical significance may be lacking.[10] Essential hypertension is a subtype of arterial hypertension in which no one specific etiology can be isolated as the cause of increased blood pressure. ...
Nephropathy refers to damage to or disease of the kidney. ...
Patients with heart failure may benefit from the combination in terms of reducing morbidity and ventricular remodeling.[11][12] In medicine, epidemiology and actuarial science, the term morbidity can refer to the state of being diseased (from Latin morbidus: sick, unhealthy), the degree or severity of a disease, the prevalence of a disease: the total number of cases in a particular population at a particular point in time, the...
This article needs to be wikified. ...
The most compelling evidence has been found for the treatment of nephropathy: this combination therapy partially reversed the proteinuria and also exhibited a renoprotective effect in patients afflicted with diabetic nephropathy,[8] and pediatric IgA nephropathy.[13] Proteinuria (from protein and urine) means the presence of an excess of serum proteins in the urine. ...
Diabetic nephropathy (nephropatia diabetica), also known as Kimmelstiel-Wilson syndrome and intercapillary glomerulonephritis, is a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli. ...
IgA nephropathy (also known as IgA nephritis, IgAN, Bergers disease and synpharyngitic glomerulonephritis) is a form of glomerulonephritis (inflammation of the glomeruli of the kidney). ...
History -
The first step in the development of (ACE) inhibitors was the discovery of angiotensin converting enzyme (ACE) in plasma by Leonard T. Skeggs and his colleagues in 1956. The conversion of the inactive angiotensin I to the potent angiotensin II was thought to take place in the plasma. However, in 1967, Kevin K. F. Ng and John R. Vane showed that the plasma (ACE) was too slow to account for the conversion of angiotensin I to angiotensin II in vivo. Subsequent investigation showed that rapid conversion occurs during its passage through the pulmonary circulation.[14] Blood plasma is the liquid component of blood, in which the blood cells are suspended. ...
A car from 1956 Year 1956 (MCMLVI) was a leap year starting on Sunday (link will display full calendar) of the Gregorian calendar. ...
Sir John Robert Vane (March 29, 1927 - November 19, 2004) was a British pharmacologist. ...
Bradykinin is rapidly inactivated in the circulating blood and it disappears completely in a single passage through the pulmonary circulation. Angiotensin I also disappears in the pulmonary circulation due to its conversion to angiotensin II. Furthermore, angiotensin II passes through the lungs without any loss. The inactivation of bradykinin and the conversion of angiotensin I to angiotensin II in the lungs was thought to be caused by the same enzyme.[15] In 1970, Ng and Vane using bradykinin potentiating factor (BPF) provided by Sérgio Henrique Ferreira showed that the conversion of angiotensin I to angiotensin II was inhibited during its passage through the pulmonary circulation.[16] Spacefilling model of bradykinin Bradykinin is a physiologically and pharmacologically active peptide of the kinin group of proteins, consisting of nine amino acids. ...
Sérgio Henrique Ferreira (b. ...
Bradykinin potentiating factor (BPF) is derived from the venom of the pit viper (Bothrops jararaca). It is a family of peptides and its potentiating action is linked to inhibition of bradykinin by ACE. Molecular analysis of BPF yielded a nonapeptide BPF teprotide (SQ 20,881) which showed the greatest (ACE) inhibition potency and hypotensive effect in vivo. Teprotide had limited clinical value, due to its peptide nature and lack of activity when given orally. In the early 1970s, knowledge of the structure-activity relationship required for inhibition of ACE was growing. David Cushman, Miguel Ondetti and colleagues used peptide analogues to study the structure of ACE, using carboxypeptidase A as a model. Their discoveries led to the development of captopril, the first orally-active ACE inhibitor in 1975. Binomial name Bothrops jararaca (Wied-Neuwied, 1824) Synonyms Cophias Jajaraca - Wied-Neuwied, 1824 Bothrops leucostigma - Wagler, 1824 Cophias Jararaca - Wied-Neuwied, 1824 [Cophias] Jararaca - Wied-Neuwied, 1825 C[ophias]. Jararakka - Wied-Neuwied, 1825 Cophias Jararaca - Wagler, 1830 T[rigonocephalus]. jararaca - Schlegel, 1837 Craspedocephalus brasiliensis - Günther, 1858 Crotalus Craspedocephalus Brasiliensis...
David Cushman (November 15, 1939 – August 14, 2000) was an American chemist famous for his role in the invention of captopril, the first of the ACE inhibitors used in the treatment of cardiovascular disease. ...
Miguel Ondetti (born May 14, 1930) is an American chemist famous for his role in the invention of captopril, the first of the ACE inhibitors for the treatment of cardiovascular disease. ...
Captopril is an Angiotensin-Converting Enzyme inhibitor (ACE inhibitor) used for the treatment of hypertension and some types of chronic heart failure. ...
Captopril was approved by the United States Food and Drug Administration in 1981. The first non-sulfhydryl-containing (ACE) inhibitor enalapril was marketed two years later. Since then, at least twelve other ACE inhibitors have been marketed. FDA redirects here. ...
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