ACE-I

アンジオテンシン変換酵素阻害薬

WordNet

1. a serve that the receiver is unable to reach
2. one of four playing cards in a deck having a single pip on its face
3. serve an ace against (someone)
4. someone who is dazzlingly skilled in any field (同)adept, champion, sensation, maven, mavin, virtuoso, genius, hotshot, star, superstar, whiz, whizz, wizard, wiz
5. of the highest quality; "an ace reporter"; "a crack shot"; "a first-rate golfer"; "a super party"; "played top-notch tennis"; "an athlete in tiptop condition"; "she is absolutely tops" (同)A-one, crack, first-rate, super, tiptop, topnotch, top-notch, tops
6. play (a hole) in one stroke
7. score an ace against; "He aced his opponents"
8. the 9th letter of the Roman alphabet (同)i
9. the 1st letter of the Roman alphabet (同)a
10. the blood group whose red cells carry the A antigen (同)type_A, group A

PrepTutorEJDIC

1. 『私は』私が
2. iodineの化学記号
3. answer / ampere

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2018/02/16 03:14:04」(JST)

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Not to be confused with Acetylcholinesterase inhibitor.

Angiotensin-converting-enzyme inhibitor
Drug class
Captopril, the first synthetic ACE inhibitor
Class identifiers
Use	Hypertension
ATC code	C09A
Biological target	Angiotensin-converting enzyme
Clinical data
Drugs.com	Drug Classes
Consumer Reports	Best Buy Drugs
WebMD	MedicineNet  RxList
External links
MeSH	D000806
In Wikidata

An angiotensin-converting-enzyme inhibitor (ACE inhibitor) is a pharmaceutical drug used primarily for the treatment of hypertension (elevated blood pressure) and congestive heart failure.

This group of drugs causes relaxation of blood vessels as well as a decrease in blood volume, which leads to lower blood pressure and decreased oxygen demand from the heart. They inhibit the angiotensin-converting enzyme, an important component of the renin–angiotensin system.

Frequently prescribed ACE inhibitors include benazepril, zofenopril, perindopril, trandolapril, captopril, enalapril, lisinopril, and ramipril.

Medical use

ACE inhibitors were initially approved for the treatment of hypertension and can be used alone or in combination with other anti-hypertensive medications. Later, they were found useful for other cardiovascular and kidney diseases including:

• Acute myocardial infarction (heart attack)
• Cardiac failure (left ventricular systolic dysfunction)
• Kidney complications of diabetes mellitus (diabetic nephropathy)

In treating heart disease, ACE inhibitors are not first line treatment usually used with other medications, especially if the patient has diabetes. There are fixed-dose combination drugs, such as ACE inhibitor and thiazide combinations. ACE inhibitors have also been used in chronic kidney failure and kidney involvement in systemic sclerosis (hardening of tissues, as scleroderma renal crisis). In those with stable coronary artery disease, but no heart failure, benefits are similar to other usual treatments.

In 2012, there was a meta-analysis published in the BMJ that described the protective role of ACE inhibitors in risk of pneumonia when compared to ARBs. The authors found a decrease risk in patients with previous stroke (54% Risk Reduction), with heart failure (37% Risk Reduction), and of Asian descent (43% Risk Reduction vs 54% Risk Reduction in non-Asian population). However, no reduced pneumonia related mortality was observed.

Other

ACE inhibitors may also be used to help decrease excessive water consumption in people with schizophrenia resulting in psychogenic polydipsia. A double-blind, placebo-controlled trial showed that when used for this purpose, enalapril lead to decreased consumption (determined by urine output and osmality) in 60% of people; the same effect has been demonstrated in other ACE inhibitors.

Mechanism of action

ACE inhibitors reduce the activity of the renin-angiotensin-aldosterone system (RAAS) as the primary etiologic (causal) event in the development of hypertension in people with diabetes mellitus, as part of the insulin-resistance syndrome or as a manifestation of renal disease.

Renin-angiotensin-aldosterone system

Main article: Renin–angiotensin system

Renin-angiotensin-aldosterone system

Renin-angiotensin-aldosterone system is a major blood pressure regulating mechanism. Markers of electrolyte and water imbalance in the body such as hypotension, low distal tubule sodium concentration, decreased blood volume and high sympathetic tone trigger the release of the enzyme renin from the cells of juxtaglomerular apparatus in the kidney. Renin activates a circulating liver derived prohormone angiotensinogen by proteolytic cleavage of all but its first ten amino acid residues known as angiotensin I. ACE (Angiotensin converting enzyme) then removes a further two residues, converting angiotensin I into angiotensin II. ACE is found in the pulmonary circulation and in the endothelium of many blood vessels. The system increases blood pressure by increasing the amount of salt and water the body retains, although angiotensin is also very good at causing the blood vessels to tighten (a potent vasoconstrictor).

Effects

ACE inhibitors block the conversion of Angiotensin I (ATI) to Angiotensin II (ATII). They thereby lower arteriolar resistance and increase venous capacity; decrease cardiac output, cardiac index, stroke work, and volume; lower resistance in blood vessels in the kidneys; and lead to increased natriuresis (excretion of sodium in the urine). Renin increases in concentration in the blood as a result of negative feedback of conversion of ATI to ATII. ATI increases for the same reason; ATII and aldosterone decrease. Bradykinin increases because of less inactivation by ACE.

Under normal conditions, angiotensin II has these effects:

• Vasoconstriction (narrowing of blood vessels) and vascular smooth muscle hypertrophy (enlargement) induced by ATII may lead to increased blood pressure and hypertension. Further, constriction of the efferent arterioles of the kidney leads to increased perfusion pressure in the glomeruli.
• It contributes to ventricular remodeling and ventricular hypertrophy of the heart through stimulation of the proto-oncogenes c-fos, c-jun, c-myc, transforming growth factor beta (TGF-B), through fibrogenesis and apoptosis (programmed cell death).
• Stimulation by ATII of the adrenal cortex to release aldosterone, a hormone that acts on kidney tubules, causes sodium and chloride ions retention and potassium excretion. Sodium is a "water-holding" ion, so water is also retained, which leads to increased blood volume, hence an increase in blood pressure.
• Stimulation of the posterior pituitary to release vasopressin (antidiuretic hormone, ADH) also acts on the kidneys to increase water retention. If ADH production is excessive in heart failure, Na⁺ level in the plasma may fall (hyponatremia), and this is a sign of increased risk of death in heart failure patients.
• A decrease renal protein kinase C

With ACE inhibitor use, the production of ATII is decreased, which prevents aldosterone release from the adrenal cortex. This allows the kidney to excrete sodium ions along with obligate water, and retain potassium ions. This decreases blood volume, leading to decreased blood pressure.

Epidemiological and clinical studies have shown ACE inhibitors reduce the progress of diabetic nephropathy independently from their blood pressure-lowering effect. This action of ACE inhibitors is used in the prevention of diabetic renal failure.

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, and prophylaxis of cardiovascular events) is justified, because it improves clinical outcomes independently 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.).

ACE inhibitors have also been shown to cause a central enhancement of parasympathetic nervous system activity in healthy volunteers and patients with heart failure. This action may reduce the prevalence of malignant cardiac arrhythmias, and the reduction in sudden death reported in large clinical trials. ACE Inhibitors also reduce plasma norepinephrine levels, and its resulting vasoconstriction effects, in heart failure patients, thus breaking the vicious circles of sympathetic and renin angiotensin system activation, which sustains the downward spiral in cardiac function in congestive heart failure

The ACE inhibitor enalapril has also been shown to reduce cardiac cachexia in patients with chronic heart failure. Cachexia is a poor prognostic sign in patients with chronic heart failure. ACE inhibitors are under early investigation for the treatment of frailty and muscle wasting (sarcopenia) in elderly patients without heart failure.

Adverse effects

Common adverse drug reactions include: hypotension, cough, hyperkalemia, headache, dizziness, fatigue, nausea, and renal impairment. ACE inhibitors might increase inflammation-related pain, perhaps mediated by the buildup of bradykinin that accompanies ACE inhibition.

The main adverse effects of ACE inhibition can be understood from their pharmacological action. The other reported adverse effects are hepatotoxicity and effect on the fetus. Renal impairment is a significant potential adverse effect of all ACE inhibitors that directly follows from their mechanism of action. Patients starting on an ACE inhibitor usually have a modest reduction in glomerular filtration rate (GFR) that stabilizes after several days. However, the decrease may be significant in conditions of decreased renal perfusion, such as renal artery stenosis, heart failure, polycystic kidney disease, or volume depletion. In these patients, maintenance of GFR depends on angiotensin-II-dependent efferent vasomotor tone. Therefore, renal function should be closely monitored over the first few days after initiation of treatment with ACE inhibitor in patients with decreased renal perfusion. A moderate reduction in renal function, no greater than 30% rise in serum creatinine, that is stabilized after a week of treatment is deemed acceptable as part of the therapeutic effect, providing the residual renal function is sufficient. This is especially a problem if the patient is concomitantly taking an NSAID and a diuretic. When the three drugs are taken together, the risk of developing renal failure is significantly increased.

Hyperkalemia (high concentration of potassium in the blood) is another possible complication of treatment with an ACE inhibitor due to its effect on aldosterone. Suppression of angiotensin II leads to a decrease in aldosterone levels. Since aldosterone is responsible for increasing the excretion of potassium, ACE inhibitors can cause retention of potassium. Some people, however, can continue to lose potassium while on an ACE inhibitor. Hyperkalemia may decrease the velocity of impulse conduction in the nerves and muscles, including cardiac tissues. This leads to cardiac dysfunction and neuromuscular consequences, such as muscle weakness, paresthesia, nausea, diarrhea, and others. Close monitoring of potassium levels is required in patients receiving treatment with ACE inhibitors who are at risk of hyperkalemia.

Another possible adverse effect specific for ACE inhibitors, but not for other RAAS blockers, is an increase in bradykinin level. Elevated bradykinin level due to ACE inhibition can be a cause of dry cough, angioedema and/or rash, hypotension, and inflammation-related pain.

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 has been disputed. Patients who experience this cough are often switched to angiotensin II receptor antagonists.

Some patients develop angioedema due to increased bradykinin levels. A genetic predisposition may exist toward this adverse effect in patients who degrade bradykinin more slowly than average.

Rash and taste disturbances, infrequent with most ACE inhibitors, are more prevalent in captopril, and this 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.

A severe rare allergic reaction can affect the bowel wall and secondarily cause abdominal pain.

Adverse hematologic effects

Hematologic effects, such as neutropenia, agranulocytosis and other blood dyscrasias, have occurred during therapy with ACE inhibitors, especially in patients with additional risk factors (see Warnings). Patients should be advised to report symptoms such as sore throat or fever to their physician.

In pregnant women, ACE inhibitors taken during all the trimesters have been reported to cause congenital malformations, stillbirths, and neonatal deaths. Commonly reported fetal abnormalities include hypotension, renal dysplasia, anuria/oliguria, oligohydramnios, intrauterine growth retardation, pulmonary hypoplasia, patent ductus arteriosus, and incomplete ossification of the skull. Overall, about half of newborns exposed to ACE inhibitors are adversely affected.

Overdose

Symptoms and Treatment: There are few reports of ACE inhibitor overdose in the literature. The most likely manifestations are hypotension, which may be severe, hyperkalemia, hyponatremia and renal impairment with metabolic acidosis. Treatment should be mainly symptomatic and supportive, with volume expansion using normal saline to correct hypotension and improve renal function, and gastric lavage followed by activated charcoal and a cathartic to prevent further absorption of the drug. Captopril, enalapril, lisinopril and perindopril are known to be removable by hemodialysis.

Contraindications and precautions

The ACE inhibitors are contraindicated in patients with:

• Previous angioedema associated with ACE inhibitor therapy
• Hypersensitivity to ACE inhibitors

ACE inhibitors should be used with caution in patients with:

• Impaired renal function
• Aortic valve stenosis or cardiac outflow obstruction
• Hypovolemia or dehydration
• Hemodialysis with high-flux polyacrylonitrile membranes

ACE inhibitors are ADEC pregnancy category D, and should be avoided in women who are likely to become pregnant. In the U.S., ACE inhibitors must be labeled with a boxed warning concerning the risk of birth defects when taken during the second and third trimester. Their use in the first trimester is also associated with a risk of major congenital malformations, particularly affecting the cardiovascular and central nervous systems.

A combination of ACE inhibitor with other drugs may increase effects of these drugs, but also the risk of adverse effects. The commonly reported adverse effects of drug combination with ACE are acute renal failure, hypotension, and hyperkalemia. The drugs interacting with ACE inhibitor should be prescribed with caution. Special attention should be given to combinations of ACE inhibitor with other RAAS blockers, diuretics (especially potassium-sparing diuretics), NSAIDs, anticoagulants, cyclosporine, DPP-4 inhibitors, and potassium supplements.

Potassium supplementation should be used with caution and under medical supervision owing to the hyperkalemic effect of ACE inhibitors.

Examples

ACE inhibitors are easily identifiable by their common suffix, '-pril'. 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

Dicarboxylate-containing agents

This is the largest group, including:

• Enalapril (Vasotec/Renitec/Berlipril/Enap/Enalapril Profarma)
• Ramipril (Altace/Prilace/Ramace/Ramiwin/Triatec/Tritace)
• Quinapril (Accupril)
• Perindopril (Coversyl/Aceon/Perindo)
• Lisinopril (Listril/Lopril/Novatec/Prinivil/Zestril, Lisidigal)
• Benazepril (Lotensin)
• Imidapril (Tanatril)
• Trandolapril (Mavik/Odrik/Gopten)
• Cilazapril (Inhibace)

Phosphonate-containing agents

• Fosinopril (Fositen/Monopril) is the only member of this group

Naturally occurring

• A comprehensive resource on anti-hypertensive peptides is available in form of a database. It contains around 1700 unique antihypertensive peptides
• Arfalasin (HOE 409) is angiotensin antagonist. U.S. Patent 4,013,791

Dairy products

• Casokinins and lactokinins, breakdown products of casein and whey, occur naturally after ingestion of milk products, especially cultured milk. Their role in blood pressure control is uncertain.
• The lactotripeptides Val-Pro-Pro and Ile-Pro-Pro produced by the probiotic Lactobacillus helveticus or derived from casein have been shown to have ACE-inhibiting and antihypertensive functions. In one study, L. helveticus PR4 was isolated from Italian cheeses.

Comparative information

All ACE inhibitors have similar antihypertensive efficacy when equivalent doses are administered. The main differences lie with captopril, the first ACE inhibitor. Captopril has a shorter duration of action and an increased incidence of adverse effects. It is also the only ACE inhibitor capable of passing through the blood–brain barrier, although the significance of this characteristic has not been shown to have any positive clinical effects.

In a large clinical study, one of the agents in the ACE inhibitor class, ramipril (Altace), demonstrated an ability to reduce the mortality rates of patients suffering from a myocardial infarction, and to slow the subsequent development of heart failure. This finding was made after it was discovered that regular use of ramipril reduced mortality rates even in test subjects not having suffered from hypertension.

Some believe ramipril's additional benefits may be shared by some or all drugs in the ACE-inhibitor class. However, ramipril currently remains the only ACE inhibitor for which such effects are actually evidence-based.

A meta-analysis confirmed that ACE inhibitors are effective and certainly the first-line choice in hypertension treatment. This meta-analysis was based on 20 trials and a cohort of 158,998 patients, of whom 91% were hypertensive. ACE inhibitors were used as the active treatment in seven trials (n=76,615) and angiotensin receptor blocker (ARB) in 13 trials (n=82,383). ACE inhibitors were associated with a statistically significant 10% mortality reduction: (HR 0.90; 95% CI, 0.84–0.97; P=0.004). In contrast, no significant mortality reduction was observed with ARB treatment (HR 0.99; 95% CI, 0.94–1.04; P=0.683). Analysis of mortality reduction by different ACE inhibitors showed that perindopril-based regimens are associated with a statistically significant 13% all-cause mortality reduction. Taking into account the broad spectrum of the hypertensive population, one might expect that an effective treatment with ACE inhibitors, in particular with perindopril, would result in an important gain of lives saved.

ACE inhibitor equivalent doses in hypertension

The ACE inhibitors have different strengths with different starting dosages. Dosage should be adjusted according to the clinical response.

ACE inhibitors dosages for hypertension
			Dosage
Note: bid = two times a day, tid = three times a day, d = daily Drug dosages from Drug Lookup, Epocrates Online.
Name	Equivalent daily dose		Start	Usual	Maximum
Benazepril	10 mg		10 mg	20–40 mg	80 mg
Captopril	50 mg (25 mg bid)		12.5–25 mg bid-tid	25–50 mg bid-tid	450 mg/d
Enalapril	5 mg		5 mg	10–40 mg	40 mg
Fosinopril	10 mg		10 mg	20–40 mg	80 mg
Lisinopril	10 mg		10 mg	10–40 mg	80 mg
Moexipril	7.5 mg		7.5 mg	7.5–30 mg	30 mg
Perindopril	4 mg		4 mg	4–8 mg	16 mg
Quinapril	10 mg		10 mg	20–80 mg	80 mg
Ramipril	2.5 mg		2.5 mg	2.5–20 mg	20 mg
Trandolapril	2 mg		1 mg	2–4 mg	8 mg

Angiotensin II receptor antagonists

ACE inhibitors possess many common characteristics with another class of cardiovascular drugs, 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 blockage is dose-dependent, so angiotensin II receptor antagonists may be useful because they act to prevent the action of angiotensin II at the AT₁ receptor, leaving AT₂ receptor unblocked; the latter may have consequences needing further study.

Use in combination

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 this combination of pharmacologic agents may be advantageous in the treatment of essential hypertension, chronic heart failure, and nephropathy. However, the more recent ONTARGET study showed no benefit of combining the agents and more adverse events. While statistically significant results have been obtained for its role in treating hypertension, clinical significance may be lacking. There are warnings about the combination of ACE inhibitors with ARBs.

Patients with heart failure may benefit from the combination in terms of reducing morbidity and ventricular remodeling.

The most compelling evidence for the treatment of nephropathy has been found: This combination therapy partially reversed the proteinuria and also exhibited a renoprotective effect in patients afflicted with diabetic nephropathy, and pediatric IgA nephropathy.

History

Main article: ACE inhibitors drug design

The first step in the development of ACE inhibitors was the discovery of ACE in plasma by Leonard T. Skeggs and his colleagues in 1956. Brazilian scientist Sérgio Henrique Ferreira reported a bradykinin-potentiating factor (BPF) present in the venom of Bothrops jararaca, a South American pit viper, in 1965. Ferreira then went to John Vane's laboratory as a postdoctoral fellow with his already-isolated BPF. 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 plasma ACE is too slow to account for the conversion of angiotensin I to angiotensin II in vivo. Subsequent investigation showed rapid conversion occurs during its passage through the pulmonary circulation.

Bradykinin is rapidly inactivated in the circulating blood, and it disappears completely in a single pass through the pulmonary circulation. Angiotensin I also disappears in the pulmonary circulation because of 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. In 1970, Ng and Vane, using BPF provided by Ferreira, showed the conversion is inhibited during its passage through the pulmonary circulation.

BPFs are members of a family of peptides whose 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 as a result of 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.

Captopril was approved by the United States Food and Drug Administration in 1981. The first nonsulfhydryl-containing ACE inhibitor, enalapril, was marketed two years later. At least 12 other ACE inhibitors have since been marketed.

In 1991, Japanese scientists created the first milk-based ACE inhibitor, in the form of a fermented milk drink, using specific cultures to liberate the tripeptide isoleucine-proline-proline (IPP) from the dairy protein. Valine-proline-proline (VPP) is also liberated in this process—another milk tripeptide with a very similar chemical structure to IPP. Together, these peptides are now often referred to as lactotripeptides. In 1996, the first human study confirmed the blood pressure-lowering effect of IPP in fermented milk. Although twice the amount of VPP is needed to achieve the same ACE-inhibiting activity as the originally discovered IPP, VPP also is assumed to add to the total blood pressure lowering effect. Since the first lactotripeptides discovery, more than 20 human clinical trials have been conducted in many different countries.

See also

• Angiotensin II receptor antagonist
  • Discovery and development of angiotensin receptor blockers
• Loop diuretic, also used to treat CHF
• Renin inhibitor

External links

• AHTPDB a comprehensive platform for analysis and presentation of antihypertensive peptides. Nucleic Acids Res. November 11, 2014; doi:10.1093/nar/gku1141.
• ACE Inhibitors: Summary of Recommendations – Consumer Reports Best Buy Drugs – free public education project

UpToDate Contents

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• 1. アンギオテンシン変換酵素阻害剤およびアンギオテンシンII受容体拮抗剤の主な副作用 major side effects of angiotensin converting enzyme inhibitors and angiotensin ii receptor blockers
• 2. 肺サルコイドーシスの臨床症状および診断 clinical manifestations and diagnosis of pulmonary sarcoidosis
• 3. ACE 阻害薬誘発性血管浮腫 ace inhibitor induced angioedema
• 4. 成人の非糖尿病性慢性腎臓病患者に対する降圧療法と病状の進展 antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults
• 5. 高血圧治療におけるレニン・アンギオテンシン系阻害 renin angiotensin system inhibition in the treatment of hypertension

English Journal

• Polygenic study of endurance-associated genetic markers ACE I/D, ACTN3 Arg(R)577Ter(X), CKMM A/G NcoI and eNOS Glu(G)298Asp(T) in male Gorkha soldiers.

• Malhotra S1, Preet K1, Tomar A2, Rawat S1, Singh S1, Singh I1, Varte LR1, Chatterjee T1, Pal MS1, Sarkar S3.
• Sports medicine - open.Sports Med Open.2017 Dec;3(1):17. doi: 10.1186/s40798-017-0085-0. Epub 2017 Apr 26.
• PMID 28444615

• Production of angiotensin I converting enzyme inhibitory (ACE-I) peptides during milk fermentation and their role in reducing hypertension.

• Rai AK1, Sanjukta S1, Jeyaram K2.
• Critical reviews in food science and nutrition.Crit Rev Food Sci Nutr.2017 Sep 2;57(13):2789-2800. doi: 10.1080/10408398.2015.1068736.
• PMID 26463100

• Implications of ACE (I/D) Gene Variants to the Genetic Susceptibility of Coronary Artery Disease in Asian Indians.

• Bhatti GK1, Bhatti JS2, Vijayvergiya R3, Singh B1,4.
• Indian journal of clinical biochemistry : IJCB.Indian J Clin Biochem.2017 Jun;32(2):163-170. doi: 10.1007/s12291-016-0588-3. Epub 2016 Jul 13.
• PMID 28428690

Japanese Journal

• 急性腎障害を来した III 型 Bartter 症候群の 1 例

• 杉浦 紀香,多代 篤史,藤浦 直子,山森 一輝,宮地 悠江,柴田 元博
• 日本小児腎臓病学会雑誌, 2021
• … 経験した．1 歳 1 か月の女児，生後 9 か月時に偶発的に低 Na，低 K 血症，代謝性アルカローシス，成長障害を指摘され，尿細管機能異常症を疑われカリウム製剤とアンジオテンシン変換酵素阻害薬(ACE-I)の投与が行われていた．感冒時に低 K 血症等の電解質異常悪化のため入院を繰り返し，1 歳 1 か月時にはインフルエンザ感染に伴う経口摂取不良を契機に AKI と高 K 血症を来して入院し補液と電解質 …
• NAID 130007988060

• Impact of left ventricular ejection fraction on the effect of renin-angiotensin system blockers after an episode of acute heart failure: From the KCHF Registry

• Yoshikawa Yusuke,Tamaki Yodo,Morimoto Takeshi,Yaku Hidenori,Yamamoto Erika,Inuzuka Yasutaka,Ozasa Neiko,Kitai Takeshi,Nagao Kazuya,Sato Yukihito,Kondo Hirokazu,Tamura Toshihiro,Nakagawa Yoshihisa,Kuwahara Koichiro,Kato Takao,Kimura Takeshi
• PLOS ONE 15(9), 2020-09
• … Objective: This observational study aimed to examine the prognostic association of angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin receptor blockers (ARB) in different left ventricular ejection fraction (LVEF) categories. …
• NAID 120006954100

• ARB/ACE阻害薬

• 辛島 裕士
• 日本臨床麻酔学会誌 40(7), 634-641, 2020
• … <p>ARB/ACE阻害薬は，降圧作用と臓器保護作用を併せ持ち，特にさまざまな臓器障害を伴う高血圧治療において積極的使用が勧められている．周術期においては，ARB/ACE阻害薬を術当日も服薬させると，麻酔下では昇圧薬不応性の低血圧をきたすことがあり，術前には中止すべきであるとの考え方がある．しかし一方で，臓器保護の観点から継続した方が良いとの考え方もあり，結論は出ていない． …
• NAID 130007959694

Related Pictures

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★リンクテーブル★

リンク元	「プレガバリン」
関連記事	「I」「AC」「A」「ACEs」「Id」

「プレガバリン」

　　[★]

英

pregabalin

商

リリカ

関

プレギャバリン

効能又は効果

• 末梢性神経障害性疼痛、神経障害性疼痛
• 線維筋痛症に伴う疼痛

用量

• 極量は450ないし600mg
• 排泄経路は尿中なので用量は腎機能に注意して設定する。

神経障害性疼痛

• クレアチニンクリアランス（mL/min）：≧60

• 1日投与量：150～600mg
• 初期用量：1回75mg1日2回
• 維持量：1回150mg1日2回
• 最高投与量：1回300mg1日2回

• クレアチニンクリアランス（mL/min）：≧30-＜60

• 1日投与量：75～300mg
• 初期用量：1回25mg1日3回又は1回75mg1日1回
• 維持量：1回50mg1日3回又は1回75mg1日2回
• 最高投与量：1回100mg1日3回又は1回150mg1日2回

• クレアチニンクリアランス（mL/min）：≧15-＜30

• 1日投与量：25～150mg
• 初期用量：1回25mg1日1回もしくは2回又は1回50mg1日1回
• 維持量：1回75mg1日1回
• 最高投与量：1回75mg1日2回又は1回150mg1日1回

• クレアチニンクリアランス（mL/min）：＜15

• 1日投与量：25～75mg
• 初期用量：1回25mg1日1回
• 維持量：1回25又は50mg1日1回
• 最高投与量：1回75mg1日1回

• クレアチニンクリアランス（mL/min）：血液透析後の補充用量注）

• 初期用量：25又は50mg
• 維持量：50又は75mg
• 最高投与量：100又は150mg

注：2日に1回、本剤投与6時間後から4時間血液透析を実施した場合のシミュレーション結果に基づく。

線維筋痛症に伴う疼痛

• クレアチニンクリアランス（mL/min）：≧60

• 1日投与量：150～450mg
• 初期用量：1回75mg1日2回
• 維持量：1回150mg1日2回
• 維持量（最高投与量）：1回225mg1日2回

• クレアチニンクリアランス（mL/min）：≧30-＜60

• 1日投与量：75～225mg
• 初期用量：1回25mg1日3回又は1回75mg1日1回
• 維持量：1回50mg1日3回又は1回75mg1日2回
• 維持量（最高投与量）：1回75mg1日3回

• クレアチニンクリアランス（mL/min）：≧15-＜30

• 1日投与量：25～150mg
• 初期用量：1回25mg1日1回もしくは2回又は1回50mg1日1回
• 維持量：1回75mg1日1回
• 維持量（最高投与量）：1回100もしくは125mg1日1回又は1回75mg1日2回

• クレアチニンクリアランス（mL/min）：＜15

• 1日投与量：25～75mg
• 初期用量：1回25mg1日1回
• 維持量：1回25又は50mg1日1回
• 維持量（最高投与量）：1回50又は75mg1日1回

• クレアチニンクリアランス（mL/min）：血液透析後の補充用量注）

• 初期用量：25又は50mg
• 維持量：50又は75mg
• 維持量（最高投与量）：75又は100mg

注：2日に1回、本剤投与6時間後から4時間血液透析を実施した場合のシミュレーション結果に基づく。

併用注意

• 中枢神経抑制薬：オピオイド系鎮痛薬
• オキシコドン、ロラゼパム、アルコール
• 血管浮腫を引き起こす薬剤(ACE-I等)
• 末梢性浮腫を引き起こす薬剤(チアゾリジン系薬剤等)

作用機序

• プレガバリンは中枢神経系において電位依存性カルシウムチャネルの機能に対し補助的な役割をなすα2δサブユニットと結合することによりカルシウム流入を抑制し、グルタミン酸等の神経伝達物質遊離を抑制することが示唆されている

ADME

代謝

• プレガバリンはほとんど代謝をうけない(添付文書リリカ)

排泄

• 尿中排泄率は83.9～97.7%(添付文書リリカ)

添付文書

• リリカカプセル25mg／リリカカプセル75mg／リリカカプセル150mg

http://www.info.pmda.go.jp/go/pack/1190017M1028_1_02/

「I」

　　[★]

• イソロイシン isoleucine
• イノシン inosine
• 阻害剤 inhibitor
• iodine
• ヨード iodide
• I因子 factor I

　 　 　

「AC」

　　[★]

• アデニル酸シクラーゼ
• 前交連 anterior commissure
• 腹囲 abdominal circumference

「A」

　　[★]

• アデニン adenine
• アデノシン adenosine
• アラニン alanine

　 　 　

「ACEs」

　　[★] アンジオテンシン変換酵素阻害薬 angiotensin-converting enzyme inhibitors

「Id」

　　[★]

• イディオタイプ idiotype idiotypic
• inhibitor of DNA binding