Types of Blood Pressure Medications

Prescription blood pressure drugs come in many classes

Many blood pressure medications, known as antihypertensives, are available by prescription to lower high blood pressure (HBP or hypertension). There are a variety of classes of high blood pressure medications and they include a number of different drugs.

Overviews of the classes of blood pressure medications

Summaries of some of the major types of commonly prescribed cardiovascular medications are provided here.

• For your information and reference, we have included generic names as well as major trade names (noted with a *) to help you identify what you may be taking. However, this information does not signify a recommendation or endorsement from the American Heart Association.
• If your prescription medication isn’t on this list, remember that your healthcare provider and pharmacist are your best sources of information.
• It’s important to discuss all of the drugs you take with your doctor and understand their desired effects and possible side effects.
• Never stop taking a medication and never change your dose or frequency without first consulting your doctor.

Patients taking ACE-i and ARBs who contract COVID-19 should continue treatment, unless otherwise advised by their physician

The classes of blood pressure medications include:

Diuretics

Diuretics help the body get rid of excess sodium (salt) and water and help control blood pressure. They are often used in combination with additional prescription therapies.

Some noted possible side effects from diuretics:

• Some of these drugs may decrease your body’s supply of the mineral potassium. Symptoms such as weakness, leg cramps or being tired may result. Eating foods containing potassium may help prevent significant potassium loss. If your doctor recommends it, you could prevent potassium loss by taking a liquid or tablet that has potassium along with the diuretic. Diuretics such as amiloride (Midamar)*, spironolactone (Aldactone)* or triamterene (Dyrenium)* are called “potassium sparing” agents. They don’t cause the body to lose potassium. They might be prescribed alone, but are usually used with another diuretic. Some of these combinations are Aldactazide*, Dyazide*, Maxzide* or Moduretic*.
• Some people suffer from attacks of gout after prolonged treatment with diuretics. This side effect isn’t common and can be managed by other treatment.
• People with diabetes may find that diuretic drugs increase their blood sugar level. A change in medication, diet, insulin or oral anti-diabetic dosage corrects this in most cases.
• Impotence may occur.

Beta-blockers

Beta-blockers reduce the heart rate, the heart’s workload and the heart’s output of blood, which lowers blood pressure.

Some noted possible side effects of beta-blockers:

• Insomnia
• Cold hands and feet
• Tiredness or depression
• Slow heartbeat
• Symptoms of asthma
• Impotence may also occur
• If you have diabetes and you’re taking insulin, have your responses to therapy monitored closely.
• If you have been prescribed beta-blockers, consult your healthcare provider prior to conception if you are considering pregnancy or if there is a chance you could become pregnant. If you discover that you are pregnant consult your healthcare provider as soon as possible to determine the safest medication for you at this time.

ACE inhibitors

Angiotensin is a chemical that causes the arteries to become narrow, especially in the kidneys but also throughout the body. ACE stands for Angiotensin-converting enzyme. ACE inhibitors help the body produce less angiotensin, which helps the blood vessels relax and open up, which, in turn, lowers blood pressure.

Some noted possible side effects of ACE inhibitors:

• Skin rash
• Loss of taste
• Chronic dry, hacking cough
• In rare instances, kidney damage
• Women who are taking ACE inhibitors or ARBs for high blood pressure should not become pregnant while on this class of drugs. If you’re taking an ACE inhibitor or an ARB and think you might be pregnant, see your doctor immediately. These drugs have been shown to be dangerous to both mother and baby during pregnancy. They can cause low blood pressure, severe kidney failure, excess potassium (hyperkalemia) and even death of the newborn.

Angiotensin II receptor blockers

These drugs block the effects of angiotensin, a chemical that causes the arteries to become narrow. Angiotensin needs a receptor- like a chemical “slot” to fit into or bind with- in order to constrict the blood vessel. ARBs block the receptors so the angiotensin fails to constrict the blood vessel. This means blood vessels stay open and blood pressure is reduced.

Some noted possible side effects of Angiotensin II receptor blockers:

• May cause occasional dizziness.
• ARBs should not be used during pregnancy. Medications that act directly on the renin-angiotensin system can cause injury or even death to a developing fetus. When pregnancy is detected, consult your healthcare professional as soon as possible.

Calcium channel blockers

This drug prevents calcium from entering the smooth muscle cells of the heart and arteries. When calcium enters these cells, it causes a stronger and harder contraction, so by decreasing the calcium, the hearts’ contraction is not as forceful. Calcium channel blockers relax and open up narrowed blood vessels, reduce heart rate and lower blood pressure.

Some noted possible side effects of calcium channel blockers:

• Palpitations
• Swollen ankles
• Constipation
• Headache
• Dizziness

Alpha blockers

These drugs reduce the arteries’ resistance, relaxing the muscle tone of the vascular walls.

Some noted possible side effects of alpha blockers:

Alpha-2 Receptor Agonists

These drugs reduce blood pressure by decreasing the activity of the sympathetic (adrenaline-producing) portion of the involuntary nervous system. Methyldopa is considered a first line antihypertensive during pregnancy because adverse effects are infrequent for the pregnant woman or the developing fetus.

Some noted possible side effects of Alpha-2 Receptor Agonists:

• Methyldopa can cause drowsiness or dizziness

Combined alpha and beta-blockers

Combined alpha and beta-blockers are used as an IV drip for those patients experiencing a hypertensive crisis. They may be prescribed for outpatient high blood pressure use if the patient is at risk for heart failure.

A noted possible side effect of combined alpha and beta-blockers:

• May cause a drop in blood pressure when you stand up

Central agonists

Central agonists also help decrease the blood vessels’ ability to tense up or contract. The central agonists follow a different nerve pathway than the alpha and beta-blockers, but accomplish the same goal of blood pressure reduction.

Some noted possible side effects of central agonists:

• Alpha methyldopa (Aldomet)* may produce a greater drop in blood pressure when you’re in an upright position (standing or walking), and it may make you feel weak or faint if the pressure has been lowered too far. This drug may also cause drowsiness or sluggishness, dryness of the mouth, fever or anemia. Male patients may experience impotence. If this side effect persists, your doctor may have to change the drug dosage or use another medication.
• Clonidine (Catapres)*, guanabenz (Wytensin)* or guanfacine (Tenex)* may produce severe dryness of the mouth, constipation or drowsiness. If you’re taking any of these drugs, don’t stop suddenly because your blood pressure may rise quickly to dangerously high levels.

Peripheral adrenergic inhibitors

These medications reduce blood pressure by blocking neurotransmitters in the brain. This blocks the smooth muscles from getting the “message” to constrict. These drugs are rarely used unless other medications don’t help.

Some noted possible side effects of peripheral adrenergic inhibitors:

• Reserpine may cause a stuffy nose, diarrhea or heartburn. These effects aren’t severe, and no treatment is required other than to change the dosage. If you have nightmares or insomnia or get depressed, tell your doctor immediately.
• Guanadrel (Hylorel)* or guanethidine (Ismelin)* may cause some diarrhea, which may persist in some people. This side effect usually becomes less of a problem if you continue treatment. These drugs reduce blood pressure more when you stand. Consequently, you may get dizzy and lightheaded and feel weak when you get out of bed in the morning or stand up suddenly. If you notice any of these reactions and if they persist for more than a minute or two, contact your doctor. He/she may instruct you to reduce or omit the next dose of the medication.
• When taking guanethidine, don’t stand in the hot sun or at a social gathering if you begin to feel faint or weak. These activities cause low blood pressure and fainting. Male patients may experience impotence. Contact your doctor if either of these side effects occurs.

Blood vessel dilators (vasodilators)

Blood vessel dilators, or vasodilators, can cause the muscle in the walls of the blood vessels (especially the arterioles) to relax, allowing the vessel to dilate (widen). This allows blood to flow through better.

Some noted possible side effects of vasodilators:

• Hydralazine (Apresoline)* may cause headaches, swelling around the eyes, heart palpitations or aches and pains in the joints. Usually none of these symptoms are severe, and most will go away after a few weeks of treatment. This drug isn’t usually used by itself.
• Minoxidil (Loniten)* is a potent drug that’s usually used only in resistant cases of severe high blood pressure. It may cause fluid retention (marked weight gain) or excessive hair growth.

† Used in severe cases or when kidney failure is present.

Univasc

Univasc

1. Home
2. Univasc

Keywords Suggestions

› Substitute for vascepa

› Univase forte enzymes

Related websites

Univasc Uses, Side Effects & Warnings

• What is Univasc? Univasc is an ACE inhibitor
• ACE stands for angiotensin converting enzyme
• Univasc is used to treat high blood pressure (hypertension).
• Univasc may also be used for purposes not listed in this medication guide.

Drugs.com   DA: 13 PA: 17 MOZ Rank: 31

Univasc (Moexipril): Uses, Dosage, Side Effects

• univasc® is indicated for treatment of patients with hypertension
• It may be used alone or in combination with thiazide diuretics
• In using univasc®, consideration should be given to the fact that another ACE inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen-vascular disease.

Rxlist.com   DA: 14 PA: 17 MOZ Rank: 33

Univasc Oral: Uses, Side Effects, Interactions, Pictures

• Moexipril is used to treat high blood pressure
• Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems
• Moexipril belongs to a class of drugs known as ACE

Webmd.com   DA: 13 PA: 40 MOZ Rank: 56

Univasc (Moexipril) Oral: Uses, Dosage & Side Effects

• Univasc is a treatment for high blood pressure that can be used alone or with other medicines
• High blood pressure brings more work to the heart and arteries

Findatopdoc.com   DA: 19 PA: 46 MOZ Rank: 69

Univasc (Moexipril) Side effects, Images, Uses, Dosage

• What is Univasc (Moexipril)? Learn about drug imprint, side effects, uses (treating), dosage, interaction, overdose, and warnings
• Drugs & Vitamins Drugs A-Z Drugs by Classification Drugs Comparison (Drug Vs
• Drug) Vitamins & Supplements Drug Interaction Checker Pill Identifier.

Rxlist.com   DA: 14 PA: 45 MOZ Rank: 64

Univasc Prices, Coupons & Savings Tips

• It is available in brand and generic versions
• Generic trandolapril is covered by most Medicare and insurance plans, but pharmacy coupons or cash prices may be lower
• The lowest GoodRx price for the most common version of generic Univasc is around $33.10, 71% off the average retail price of $117.79

Goodrx.com   DA: 14 PA: 8 MOZ Rank: 28

Medications before surgery – San Diego Orthopedic Surgeon

• Scott Hacker is a Sports Medicine Orthopedic Surgeon in San Diego, CA, Knee and Shoulder Surgeon, and Principal Investigator for Orthopedic Clinical Trials.

Drscotthacker.com   DA: 21 PA: 21 MOZ Rank: 49

Moexipril (Univasc)

• ACE stands for angiotensin converting enzyme
• Moexipril is used to treat high blood pressure (hypertension)
• Moexipril may also be used for purposes not listed in

Everydayhealth. com   DA: 22 PA: 16 MOZ Rank: 46

Univasc Medicare Coverage and Co-Pay Details

• Trandolapril is a moderately priced drug used alone or together with other medicines to treat high blood pressure (hypertension).This drug is less popular than comparable drugs
• It is available in brand and generic versions
• Generic trandolapril is covered by most Medicare and insurance plans, but pharmacy coupons or cash prices may be lower

Goodrx.com   DA: 14 PA: 26 MOZ Rank: 49

Univasc (moexipril) Uses, Side Effects, Dosage & Interactions

• ACE stands for angiotensin converting enzyme
• Moexipril is used to treat high blood pressure (hypertension)
• Moexipril may also be used for purposes not listed in this medication guide
• This is not a complete list of side effects and others may occur

Emedicinehealth.com   DA: 23 PA: 30 MOZ Rank: 63

Moexipril (Univasc)

• What is Moexipril (Univasc)? The Information about Moexipril (Univasc) contained herein is a compilation of materials available from drugs. com and simplified for the average consumer
• Moexipril also known by the brand name Univasc, is an Angiotensin-converting enzyme inhibitor or (ACE) inhibitor.

Medicalpublications.org   DA: 23 PA: 19 MOZ Rank: 53

Univasc Plus Price Comparison: Uses, Dosage, Form & Side

• Univasc Plus is a thiazide diuretic that helps prevent your body from absorbing too much salt, which can cause fluid retention
• Moexipril is in a group of drugs called ACE inhibitors
• ACE stands for angiotensin converting enzyme.

Gmedication.com   DA: 19 PA: 19 MOZ Rank: 50

Univasc Information, Side Effects, Warnings and Recalls

• univasc® is indicated for treatment of patients with hypertension
• It may be used alone or in combination with thiazide diuretics
• In using univasc®, consideration should be given to the fact that another ACE inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen-vascular disease.

Recallguide.org   DA: 19 PA: 14 MOZ Rank: 46

Univasc (moexipril) dosing, indications, interactions

• WARNING: Moexipril can cause serious (possibly fatal) harm to an unborn baby if used during pregnancy
• It is important to prevent pregnancy while taking this medication
• Consult your doctor for more details and to discuss the use of reliable forms of birth control while taking this medication.

Reference.medscape.com   DA: 22 PA: 30 MOZ Rank: 66

Univasc (UCB, Inc.): FDA Package Insert

• univasc ® is supplied as scored, coated tablets containing 7.5 mg and 15 mg of moexipril hydrochloride for oral administration
• In addition to the active ingredient, moexipril hydrochloride, the tablet core contains the following inactive ingredients: lactose, magnesium oxide, crospovidone, magnesium stearate and gelatin.

Medlibrary. org   DA: 14 PA: 23 MOZ Rank: 52

Common and Rare Side Effects for Univasc oral

List Univasc oral side effects by likelihood and severity ; Does Univasc oral interact with other medications? Should I avoid certain foods while taking Univasc oral?

Webmd.com   DA: 13 PA: 50 MOZ Rank: 79

What should I know about Univasc before taking it

• You should know that Univasc is in a class of drugs known as ACE inhibitors
• Another ACE inhibitor, captopril, has caused lowered white blood cell counts in some patients, particularly those with kidney impairment or collagen-vascular disease
• This risk has not been shown to occur with Univasc, but a connection has not been disproven, either.

Sharecare.com   DA: 17 PA: 50 MOZ Rank: 84

Can You Get a Univasc Prescription Online

• How Does Univasc Work? As an ACE inhibitor, Univasc works to block the action of angiotensin-converting enzyme (ACE)
• Univasc helps relax blood vessels, which lowers blood pressure
• The initial dosage of Univasc is usually 7. 5 mg taken once per day an hour before a meal.

Plushcare.com   DA: 13 PA: 48 MOZ Rank: 79

Univasc (moexipril hydrochloride) 7.5 mg and 15 mg Tablets

• Discuss treatment options with women planning to become pregnant
• Patients should be asked to report pregnancies to their physicians as soon as possible
• PRECAUTIONS/Pediatric Use, a new section was added: Neonates with a history of in utero exposure to Univasc:

Accessdata.fda.gov   DA: 22 PA: 50 MOZ Rank: 91

Univasc discussions (experiences, side effects, dosages

Univasc is an ACE inhibitor, and I understand that Accupril effects with the Accupril, and if so what were they? The Univasc had the tickly cough, but so many of them do, but otherwise I had no side effects at all from Univasc brand or generic after the first couple of days of my MD tried to find me something cheaper than brand

Healthboards. com   DA: 20 PA: 27 MOZ Rank: 67

RxNorm Concept ID 220675

• Univasc: Description of concept identifier: Term Type (TTY) BN: Term type in source with name and description: Term Type Name: Brand Name: Name of term type in source: Term Type Description: A proprietary name for a family of products containing a specific active ingredient
• Description of term type in source: CODE: 220675 “Most useful” source

Ndclist.com   DA: 11 PA: 20 MOZ Rank: 52

Univasc Drug Information PDR.net

The Related Drug Information Index provides comprehensive access to all drug information related to a specific drug Types of content include full prescribing information, drug summaries, Full Prescribing Information Continuing Medication Education (Full PI CME), Medication Guides, Risk Evaluation and Mitigation Strategies (REMS Summaries), REMS Continuing Medication Education (REMS CME), and

Pdr. net   DA: 11 PA: 25 MOZ Rank: 58

Univasc definition of Univasc by Medical dictionary

Univasc: Perdix (UK), Univasc Pharmacologic class: Angiotensin-converting enzyme (ACE) inhibitor Therapeutic class: Antihypertensive Pregnancy risk category C (first trimester), D (second and third trimesters) Pregnancy risk category C (first trimester), D (second and third trimesters) FDA Box Warning • When used during second or third

Medical-dictionary.thefreedictionary.com   DA: 40 PA: 8 MOZ Rank: 71

Univasc Entire Monograph

• moexipril + aliskiren contraindicated in diabetic patients; avoid combo in pts w/ CrCl 60; for all other pts, use alternative or monitor BP, potassium, renal fxn: combo may incr
• risk of hypotension, hyperkalemia, renal impairment w/o additional benefit (additive effects, dual blockade of …

Online.epocrates.com   DA: 20 PA: 31 MOZ Rank: 75

Univasc (UCB, Inc.

): FDA Package Insert, Page 2

• univasc ® is indicated for treatment of patients with hypertension
• It may be used alone or in combination with thiazide diuretics
• In using univasc ®, consideration should be given to the fact that another ACE inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen-vascular disease.

Medlibrary.org   DA: 14 PA: 30 MOZ Rank: 69

Moexipril (Univasc) Davis’s Drug Guide

• Find information on Moexipril (Univasc) in Davis’s Drug Guide including dosage, side effects, interactions, nursing implications, mechanism of action, half life, administration, and more

Drugguide.com   DA: 17 PA: 47 MOZ Rank: 90

Univasc Coupon and Discount

• Univasc is an active non sulfhydryl angiotensin-converting enzyme inhibitor, ACE, which treats congestive heart failure and hypertension
• Univasc is available in generic form as moexipril hydrochloride
• It can be taken alone or with other diuretics or antihypertensive.

Save.health   DA: 11 PA: 15 MOZ Rank: 53

Univar Solutions About Us Univar Solutions

• Univar Solutions is a global partner to our customers and suppliers for the value-added distribution of chemistry and related products and services
• We are a committed ally, with the capabilities and know-how to help their business run smoothly, and the expertise to help them anticipate, navigate and leverage meaningful growth opportunities.

Univarsolutions.com   DA: 23 PA: 9 MOZ Rank: 60

[email protected]: FDA-Approved Drugs

• UNIVASC: MOEXIPRIL HYDROCHLORIDE: 15MG **Federal Register determination that product was not discontinued or withdrawn for safety or efficacy reasons** TABLET;ORAL: Discontinued: None No: No: Approval Date(s) and History, Letters, Labels, Reviews for NDA 020312
• Original Approvals or Tentative Approvals.

Accessdata. fda.gov   DA: 22 PA: 27 MOZ Rank: 78

How to pronounce univasc HowToPronounce.com

univasc pronunciation with meanings, synonyms, antonyms, translations, sentences and more Which is the right way to pronounce the word sentar in Portuguese? SAYN-tahr

Howtopronounce.com   DA: 22 PA: 8 MOZ Rank: 60

Which statements about moexipril Univasc are true Correct

• Moexipril (Univasc) is an angiotensin-converting enzyme inhibitor that is used as an antihypertensive drug
• This drug has the effect of increasing serum lithium levels, causing lithium toxicity.

Coursehero.com   DA: 18 PA: 50 MOZ Rank: 99

How to pronounce Telmisartan, Univasc HowToPronounce.com

How to say Telmisartan, Univasc in English? Pronunciation of Telmisartan, Univasc with 1 audio pronunciation and more for Telmisartan, Univasc.

Howtopronounce.com   DA: 22 PA: 20 MOZ Rank: 74

Moexipril (Univasc) Reviews Everyday Health

• Be the first to review Moexipril (Univasc) and share your experience with other Everyday Health users
• Your contribution and support is always highly appreciated
• All reviews are completely anonymous and will not display any information about you, even if you are a registered user of Everyday Health

Reviews. everydayhealth.com   DA: 26 PA: 16 MOZ Rank: 75

Moexipril HCl Dosage & Rx Info Uses, Side Effects

• Moexipril HCl prescription and dosage sizes information for physicians and healthcare professionals
• Pharmacology, adverse reactions, warnings and side effects.

Empr.com   DA: 12 PA: 20 MOZ Rank: 66

Domain Expiry Date Updated

Expiry Date	Expiry Date	Domain Provider	Hosting Provider
Signsmithsoftx.com	255 days left	Google LLC	New Dream Network, LLC
Ebandflowyoga.com	143 days left	FastDomain Inc.	Squarespace, Inc.
Autotechnic.net	92 days left	Register.com, Inc.	Internet Brands Inc.
Nomorobo.com	63 days left	1&1 IONOS SE	Amazon Technologies Inc.
Avanse.com	7 years, 248 days left	PDR Ltd. d/b/a PublicDomainRegistry.com	Internet Service Provider
C4dco.com	237 days left	Bizcn.com, Inc.	Transferred to the RIPE region on 2018-08-27T14:42:34Z.
Mpegla.com	3 years, 323 days left	GoDaddy.com, LLC	Google LLC
Cyprusninja.com	341 days left	GoDaddy.com, LLC	Google LLC
Amycotler.com	1 year, 14 days left	Network Solutions, LLC	The Endurance International Group, Inc.
Galeriastores.com	21 days left	GoDaddy.com, LLC	GoDaddy.com, LLC

>

Top

.COM – 10,595,200+   .ORG – 1,117,549+   .EDU – 123,500+   .NET – 792,945+   .GOV – 30,232+   .US – 84,439+   . CA – 122,904+   .DE – 220,061+   .UK – 272,390+   .IT – 108,882+   .AU – 152,812+   .CO – 51,739+   .BIZ – 59,081+   .IO – 32,494+   .NL – 99,647+   .SG – 19,713+   .INFO – 81,589+   .IE – 26,934+   .ME – 25,076+   .FR – 98,576+   .EU – 61,372+   .RU – 165,043+   .PH – 9,511+   .INT – 1,166+   .IN – 87,021+   .ES – 38,035+   .CZ – 71,869+   .VN – 48,920+   .TV – 14,250+   .SITE – 9,829+   .RO – 37,484+   .PL – 44,520+   .PK – 10,373+   .MOBI – 4,464+   .LK – 5,507+   .CN – 66,137+   .CH – 66,914+   .AT – 31,992+  

Email Address Search | IP Address Blacklist Check | Hosting Providers | Domain Providers | Website Error Checker

© 2018 Site-Stats.org. All rights reserved. Email: [email protected]

Fast facts about ACE inhibitors : Nursing2021

Angiotensin-converting enzyme (ACE) inhibitors prevent the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in vasodilation, decreased systemic arterial resistance, and decreased blood pressure. In addition, ACE inhibitors decrease aldosterone production, resulting in reduced sodium and water retention; this also helps lower blood pressure.

A patient may receive ACE inhibitor therapy for one or more of these conditions:

• heart failure
• hypertension
• diabetic nephropathy
• myocardial infarction.

Adverse effects of ACE inhibitors include angioedema, persistent dry cough, altered taste, fatigue, headache, hyperkalemia, hypotension, photosensitivity, proteinuria, rash, tachycardia, and pancytopenia. Severe hypotension may occur at toxic levels.

Contraindications or cautions apply for the following:

• patients who are hypersensitive to ACE inhibitors. Avoid ACE inhibitor use.
• patients with impaired renal function or serious autoimmune disease. Use cautiously.
• patients taking other drugs known to decrease the white blood cell (WBC) count or the immune response. Use cautiously.
• women of childbearing age. A woman who’s likely to become pregnant shouldn’t take an ACE inhibitor because it could cause fetal defects or death, especially in the second or third trimester. Teach your patient to report a suspected pregnancy immediately so her health care provider can discontinue ACE inhibitor therapy and prescribe a different drug.
• breast-feeding women. Some ACE inhibitors (including benazepril, captopril, enalapril, enalaprat, and tosinopril) pass into breast milk, so instruct a woman not to breast-feed during therapy with any of these drugs.
• children. Safety and efficacy aren’t known; ACE inhibitors should be prescribed only if the potential benefit outweighs the risk.
• older adults. Lower dosages may be needed because of impaired kidney function.

Nursing considerations

• Observe your patient for adverse reactions.
• Monitor her vital signs regularly and her WBC count and serum electrolytes, especially potassium level, periodically.
• Give potassium supplements and potassium-sparing diuretics cautiously because ACE inhibitors can cause potassium retention and hyperkalemia. Warn the patient to avoid potassium-containing salt substitutes.
• Give captopril and moexipril 1 hour before meals.
• Advise your patient that therapy may cause a dry, persistent cough. Tell her to discuss this reaction, if it occurs, with her health care practitioner—it could also signal worsening heart failure.
• Teach her to rise and change positions slowly to minimize orthostatic hypotension. Urge her to report light-headedness or evidence of infection (such as a sore throat and fever) and to seek immediate medical attention if she has facial swelling or trouble breathing.
• Warn your patient to check with her health care provider before taking over-the-counter medications or herbal supplements, which may interact with her prescribed medication.
• Advise a woman of childbearing age to avoid pregnancy during therapy.

Source: Nursing Rapid-Fire Drug Facts. Lippincott Williams & Wilkins, 2004.

ACE inhibitors

• benazepril (Lotensin)
• captopril (Capoten)
• enalapril (Vasotec)
• fosinopril (Monopril)
• lisinopril (Prinivil, Zestril)
• moexipril (Univasc)
• perindopril (Aceon)
• quinapril (Accupril)
• ramipril (Altace)
• trandolapril (Mavik)

ACE Inhibitors – NephCure Kidney International ®

An ACE inhibitor (or angiotensin converting enzyme inhibitor) is a medication used primarily for the treatment of heart, blood vessel, and kidney problems.

How does an ACE inhibitor work?

ACE inhibitors prevent an enzyme in your body from producing angiotensin II, a substance that affects your cardiovascular system by narrowing your blood vessels and releasing hormones that can raise your blood pressure. This narrowing can cause high blood pressure and force your heart to work harder. ACE inhibitors also increase blood flow, which helps to decrease the amount of work your heart has to do and can help protect your kidneys from the effects of hypertension (high blood pressure).

What are the different types of ACE inhibitors?

There are many different names and brands of ACE inhibitors. Examples of ACE inhibitors include:

• Benazepril (Lotensin)
• Captopril
• Enalapril (Vasotec)
• Fosinopril
• Lisinopril (Prinivil, Zestril)
• Moexipril (Univasc)
• Perindopril (Aceon)
• Quinapril (Accupril)
• Ramipril (Altace)
• Trandolapril (Mavik)

For what conditions are ACE inhibitors used?

Doctors prescribe ACE inhibitors to prevent, treat or improve symptoms in conditions such as:

• High blood pressure
• Coronary artery disease
• Heart failure
• Diabetes
• Certain chronic kidney diseases (Primary Nephrotic Syndrome)
• Heart attacks
• Migraines

In studies, individuals with hypertension (high blood pressure), heart failure or prior heart attacks that were treated with an ACE inhibitor lived longer than patients who did not take an ACE inhibitor. However, some individuals with hypertension do not respond sufficiently to ACE inhibitors alone. In these cases, other drugs are used in combination with ACE inhibitors.

ACE inhibitors are regularly prescribed for patients diagnosed with primary (idiopathic) Nephrotic Syndrome in order to manage high blood pressure as a result of malfunctioning kidneys leading to fluid retention or overload.
Are there any differences among the different types of ACE inhibitors?

ACE inhibitors are very similar. However, they differ in how they are eliminated from the body and their doses. Some ACE inhibitors need to be converted into an active form in the body before they work. In addition, some ACE inhibitors may work more on the ACE (angiotensin converting enzyme) that is present in tissues than on ACE that is present in the blood.

The importance of this difference or whether one ACE inhibitor is better than another has not been determined. Many seem to work equally as well. Your physician will prescribe what he/she thinks will work best for your condition based on experience. Side effects may vary for different ones.

How is an ACE inhibitor administered?

ACE inhibitors are pills that you take by mouth. ACE inhibitors are usually taken once daily, and many people take them in the morning. Try to take your medications at the same time, or times, each day. Do not stop taking your medicines without talking with your doctor first.

Other important tips:

• Before taking ibuprofen (Advil, Motrin) or aspirin, talk to your doctor.
• Tell your doctor what other medicines you are taking. This includes over the counter drugs, diuretics (water pills), potassium pills, or herbal or dietary supplements.
• Do not take ACE inhibitors if you are pregnant or breastfeeding. Do not take these medicines if you are planning to become pregnant. Call your doctor if you become pregnant when you are taking these medicines.

What are the side effects of ACE inhibitors?

ACE inhibitors are well-tolerated by most individuals. Nevertheless, they are not free of side effects, and some patients should not use ACE inhibitors. You should discuss the benefits and risks of all medications with your physician.

ACE inhibitors usually are not prescribed for pregnant patients because they may cause birth defects. Individuals with bilateral (two-sided) renal artery stenosis (narrowing of blood vessels in the kidneys) may experience worsening of kidney function. People who have had a severe reaction to ACE inhibitors should avoid them.

The most common side effects are:

• Chronic cough
• Elevated blood potassium levels
• Low blood pressure
• Dizziness
• Headache
• Drowsiness
• Weakness
• Abnormal taste (metallic or salty taste)
• Rash
• It may take up to a month for coughing to subside, and if one ACE inhibitor causes a cough it is likely that the others will too.

The most serious, but rare, side effects of ACE inhibitors are:

• Kidney failure
• Allergic reactions
• Decrease in white blood cells
• Marked swelling of tissues (angioedema)

With which drugs do ACE inhibitors interact?

ACE inhibitors have few interactions with other drugs. Since ACE inhibitors may increase blood levels of potassium, the use of potassium supplements, salt substitutes (which often contain potassium), or other drugs that increase the body’s potassium may result in excessive blood potassium levels.

There have been reports that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen (Advil, Children’s Advil/Motrin, Medipren, Motrin, Nuprin, PediaCare Fever etc.), indomethacin (Indocin, Indocin-SR), and naproxen (Anaprox, Naprelan, Naprosyn, Aleve) may reduce the effects of ACE inhibitors.

ACE inhibitors also may increase the blood concentration of lithium (Eskalith) and lead to an increase in side effects from lithium.

*Note: The decision to prescribe a medication is the responsibility of your physician/primary care provider based on his/her evaluation of your condition. The above is meant for informational purposes only. Discuss this information and all information about drugs/medications with your physician before starting or stopping any medication.

Lisinopril Side Effects Can Be Lethal

How do you keep your blood pressure under control? Managing blood pressure is an important pillar for maintaining good health and reducing the risk of strokes or heart disease. Regular exercise, a diet high in healthful vegetables and fruits and ways to relax and manage stress can help. But sometimes people need blood pressure medication to get hypertension into bounds. Lisinopril is one of the most popular prescription pills for hypertension, but what about lisinopril side effects?

ACE Inhibitors for Blood Pressure Control:

Blood pressure pills are perceived as generally safe medications. ACE (angiotensin converting enzyme) inhibitors in particular are considered highly effective with few adverse reactions. We calculate that at least 100 million prescriptions are filled for ACE inhibitors each year. Here is a list of commonly prescribed ACEi drugs:

ACE Inhibitors:

• Benazepril (Lotensin)
• Captopril (Capoten)
• Enalapril (Vasotec)
• Fosinopril (Monopril)
• Lisinopril (Prinivil, Zestril)
• Moexipril (Univasc)
• Perindopril (Aceon)
• Quinapril (Accupril)
• Ramipril (Altace)
• Trandolapril (Mavik)

We have frequently written about an ACEi cough.  This lisinopril side effect drives many patients crazy because it can keep them awake at night, cause incontinence and make them miserable. This is not a minor side effect. Some people throw up because of an ACEi-induced cough. Here are just a few stories:

Wendy had no idea her BP medicine could cause a cough:

I have been coughing to the point of vomiting for the last two years. My primary said it was post nasal drip, asthma or heartburn. When none of those proved true, I called an allergist who asked me right over the phone about my BP meds. I called back my GP and he said, Oh yes, that drug causes cough too! I could have screamed!”

D. Jones had the cough from hell:

I was taking lisinopril for about three months. It was crazy. The coughing was sooooo bad I too was unable to sleep or eat. My body was hurting all over and the coughing was so bad I started gagging with violent coughing spells. My back felt like someone was stabbing me with a knife. My body almost shut down. I was not able to sleep for three days, I was having panic attacks and was unable to eat.

“My husband and daughter stayed home for three days to take care of me. On the third day my doctor was able to see me. By that time my body was so weak and my skin was pale that it was hard to get dressed (THANK GOD for a wonderful husband). I had reached out to all my family and friends and asked them to pray for me. I was thinking… am I going crazy? I was not able to stop crying maybe due to no sleep or food.

“When my doctor walked in the room she was so surprised to see how I looked. My husband was very upset my doctor just said the coughing was from lisinopril but not the other symptoms.

“I have been off Lisinopril for two weeks now. WOW!!! I feel GREAT! No back pain, very little coughing and lots of sleep.”

Lisinopril Side Effects Can Be Life Threatening:

A lisinopril cough can ruin the quality of your life. It can disrupt sleep and lead to lots of other complications. It is rarely lethal. A far more worrisome lisinopril side effect is called angioedema. It can be life threatening.

A Turkish patient died from angioedema triggered by lisinopril despite emergency treatment (Iranian Journal of Allergy, Asthma, and Immunology, Dec., 2015).

We received the following message from Gary, a visitor to this website.

“One night after taking lisinopril my lips began to swell as if I had a fever blister. Within two hours my face was extremely swollen and my throat began to feel like it was closing off my air passage. I went to the hospital and spent the night in the emergency room with an IV and other meds.

“The doctors identified that I had a reaction from the lisinopril. I still had some swelling a full 24 hours after the incident. I was told that I was lucky and that they were close to doing a tracheotomy.

“I had taken lisinopril for four years before the reaction. I would strongly advise alternative medications other than lisinopril, and recommend anyone who has been taking this for any length of time have a discussion with their physician.

“The final advice I have is that if you have a bad reaction, seek medical attention immediately.” Gary

Angioedema and Other Lisinopril Side Effects:

Angioedema is a somewhat mysterious reaction to ACE inhibitor blood pressure pills. It can happen within the first few days or weeks of starting treatment, or, as in Gary’s case, show up after years of taking the medication. There is no way to predict what will trigger such a hazardous reaction. When it happens, however, it requires emergency medical attention. If your airways close, breathing becomes impossible. That is why they were considering an emergency tracheotomy in Gary’s case.

Dee in Menifee, California had to have two tracheotomies:

I had been taking Lisinopril for 13 years. Over the last 5  years I had allergic reactions to what I thought were nuts. My left jaw would begin swelling in the middle of the night. The swelling would spread to my upper lip. The swelling would last up to 3 days.

“On Dec. 30th 2017, around 8 pm, I had a sensation in the interior of my jaw that felt like a sore throat was coming on. Around 10 pm, I felt a hard knot in my left jaw area. Around 10:30 my throat felt swollen. I drove to the nearest emergency room and waited to be seen.

“By the time I was seen, my tongue was swollen to the point that I could barely talk. They tried to intubate but my throat and tongue were too swollen. they performed a tracheotomy on me. My husband said that I was transferred to my hospital the following day where they waited for the swelling to go down to perform a second tracheotomy.

“I woke up 3 days later in intensive care not knowing what had happened. I spent a horribly uncomfortable week in the hospital and am still recovering after week 5. I may need to go back to have some cartilage repaired and some laser treatment for scar tissue removal.

“While in the ER, a nurse asked my husband if I was on lisinopril and if so, to stop taking it as she was aware of other people who had experienced the same reaction. A family member who is a nurse asked the same question and suggested we look into the side effects of taking lisinopril.

“Since then, we have spoken to two people who had been on lisinopril, one for over 20 years, and experienced the same reaction that I had. I am glad that we found out what caused the reaction. It was a frightening experience for myself and my family.”

Lisinopril Side Effects in the Digestive Tract:

Angioedema doesn’t always affect the face, tongue and neck, though. We have heard from other visitors that ACE inhibitors can also affect the belly. Here is one poignant story:

I was put on lisinopril for high blood pressure in January. That month I experienced severe stomach cramping and vomiting. I was rolling on the floor in agony. The doctor said it was most likely the flu but started me on two different antibiotics in case it was bacterial.

“A few weeks later I had another attack with severe stomach cramping and vomiting. I went to the ER, where I was given IV pain meds. A CT scan showed small intestine inflammation partially blocking off my bowel. I was sent home but returned the next day with pain that was a 10 on a 10-point scale. The doctor said that all the tests had been done and there was nothing he could do. I was sent home with pain medication.

“A few weeks later I was admitted to the hospital with increased small intestine inflammation and another blockage. I vomited and dry-heaved for 12 hours. I was released four days later with no definitive diagnosis.

“I was told most likely I had Crohn’s disease, but a colonoscopy was negative for Crohn’s. I underwent extensive tests, including endoscopy, and all were negative. None of the doctors made a connection with the drug lisinopril.

“After two months of missing work, three more ER visits and untold suffering, I found several other people who reported similar symptoms connected to lisinopril. I stopped the medication and have not had another attack. If you look on PubMed you can see reports on lisinopril and intestinal angioedema, but doctors don’t think to connect this with lisinopril because it is not listed as a common side effect.” 

Angioedema of the Abdomen:

Many physicians are aware that ACE inhibitors can cause angioedema in the lips, mouth and throat. Lisinopril side effects are not restricted to the upper airways, though. An equally serious c0mplication that often goes misdiagnosed for weeks or months involves angioedema of the abdomen (Journal of Emergency Medicine, April, 2016; GE Portuguese Journal of Gastroenterology, Dec. 2, 2015; Postgraduate Medicine, March, 2015). It too can be life threatening if the bowels become obstructed. Here is one story to help you understand the gravity of this condition:

Monique in Missouri was rushed to the hospital with abdominal angioedema:

On December 15, I had to be taken to the ER due to really bad stomach pains. The pains I felt were worse than labor pains. It felt like someone was stomping on my intestines with high heel shoes on.

“Once admitted, the doctors ran all of the tests including colonoscopy, upper GI, and different blood tests. Everything the doctors were looking for came back negative. While in the hospital they kept giving me my blood pressure med, lisinopril. My lips became swollen while I was there and I was told it was because of the test I had done earlier. I replied, ‘no something is not right,’ but they continued to say I was ok, it’s because of the test.

“I suffered in pain for a week and 2 1/2 days while lying in the hospital. The doctors could not find or figure out was going on and said ‘we feel like it would be safe to send you home.’ They then released me from the hospital with instructions, a 2 week follow up appointment and another colonoscopy and also with an added blood pressure pill to go with the lisinopril.

“Once at home I continued taking my blood pressure pills according to the doctors directions. The pain, vomiting, diarrhea and the horrible coughing, continued. I began having chest pains and shortness of breath, I thought it was because I was trying to do too much to fast.

“On January 17 my upper lip started to swell and later that night it got worse. The next day when I woke up I looked horrible. My face, upper lip and neck were swollen even more. I returned to the ER that’s when the ER Doctor said I was having an allergic reaction to the lisinopril. They began to give me steroids and other meds to stop what was going on and to keep my throat from swelling up as well. They then released me with a prescription for a 3 day steroid fix. I could have died. Feeling safe enough to send me home the first time almost cost my life.”

Taking ACE Inhibitors for Hypertension:

ACE inhibitors can be very effective medications for many people. As long as you don’t experience an unrelenting cough, breathing difficulties or severe abdominal discomfort, you may be home free. Nevertheless, it is essential to know about other lisinopril side effects. No medicine should ever be stopped without medical supervision.

Here are some other lisinopril side effects to aware of.

Lisinopril Side Effects:

• Dry cough, uncontrollable cough, nausea, vomiting
• Dizziness, excessively low blood pressure
• Kidney function changes, BUN & creatinine elevations
• Headache
• Digestive distress, diarrhea, abdominal pain
• Tiredness, fatigue, malaise
• Excessive potassium levels (requires immediate medical attention!), irregular heart rhythms, chest pain
• Elevated uric acid levels
• Sensitivity to sunlight (photosensitivity), skin rash
• Angioedema (swelling in abdomen, severe abdominal pain)
• Severe allergic reaction (anaphylaxis) requiring emergency treatment
• Toxicity to liver or pancreas
• Blood disorders
• Potential birth defects if taken during early pregnancy
• Sexual difficulties

In one case report, lisinopril caused hair loss (Journal of Pharmacy Practice, online June 6, 2016). Anyone who would like to learn more about non-drug approaches to controlling hypertension may find our Guide to Blood Pressure Treatment of interest. There is also information about other medications for dealing with blood pressure problems.

Share your own experiences below. Those who would like to learn more about ACE inhibitor cough will find this link of great interest.

When Will Doctors Pay Attention to an ACE Cough?

Revised 2/8/18

Moexipril (Moexipril): description, recipe, instruction

Moexipril

Analogues (generics, synonyms)

Moeks

Active ingredient

Moexipril (Moexiprilum)

Pharmacological group

ACE inhibitors

Recipe

International:

Rp .: Moexiprili 0.015
D. t. d. No. 10 in tab.
S. 1 tablet once a day

Russia:

Prescription form 107-1 / y

Pharmacological action

Antihypertensive, vasodilating, natriuretic, cardioprotective.
Blocks ACE, prevents the transformation of angiotensin I into angiotensin II and weakens the effects of the latter (vasoconstrictor, suppression of renin synthesis, increased secretion of aldosterone). ACE activity decreases by 80–90% within 2 hours and remains reduced by 80% within 24 hours when administered at a dose of 15 mg. It inhibits the degradation of bradykinin (an endogenous vasodilator) and increases its plasma concentration. Reduces OPSS, reduces afterload on the heart. It causes regression of hypertrophy and the processes of remodeling of the left ventricular myocardium, reduces the risk of myocardial infarction and sudden death.Normalizes lipid metabolism, slightly increases the level of potassium in plasma. Prevents angiotensin II-induced stimulation of osteoclast activity and bone resorption (prevention of osteoporosis). The antihypertensive effect appears 1 hour after administration, reaches a maximum after 3–6 hours and lasts for 1 day. With a course admission, a significant decrease in blood pressure is recorded in the first 2-4 weeks. Course use in patients with mild and moderate arterial hypertension lowers the average daily blood pressure without changing the nature of the blood pressure curve and heart rate variability, while the effect is more pronounced in the daytime.Highly effective in patients with postmenopausal hypertension. With prolonged use, it reduces the symptoms of heart failure (increases the stroke volume, reduces the systemic vascular resistance, increases exercise tolerance) and improves the quality of life. The expediency of prescribing in the early stages of myocardial infarction has been proved. It has racial specificity – in Negroids, the antihypertensive properties of moexipril are less pronounced (a population with a low level of renin prevails) and the risk of developing angioedema is increased.

Pharmacodynamics

There is no data for this section. We are currently processing information, please come back later.

Pharmacokinetics

There is no data for this section. We are currently processing information, please come back later.

Method of application

For adults:

The first dose is 3.75 mg 1 time / day, then it is used at a dose of 7.5 mg 1 time / day. If there is no effect, the dose is increased to 15 mg / day.The maximum daily dose is 30 mg. The maintenance dose is usually 7.5-15 mg / day. The daily dose should be taken 1 time / day, in exceptional cases – 2 times / day.

Readings

– Arterial hypertension.

Contraindications

– Hypersensitivity to moexipril or other ACE inhibitors
– Severe hypotension (SBP <90 mm Hg)
– Pregnancy, breastfeeding, childhood (safety and efficacy have not been determined).

Special instructions

There is no data for this section. We are currently processing information, please come back later.

Side effects

– From the side of the cardiovascular system and blood (hematopoiesis, hemostasis): hypotension, palpitations, chest pain, angina pectoris, myocardial infarction, cardiac arrhythmias, hemolytic anemia, leuko / neutropenia, agranulocytosis.
– From the nervous system and sensory organs: dizziness (4.3%), headache, syncope, cerebrovascular disorders, mood and / or sleep disorders, vision.
– From the digestive tract: decreased appetite, dry mouth, taste disturbance, nausea, dyspepsia, vomiting, abdominal pain, diarrhea (3.1%), constipation, pancreatitis, liver dysfunction (jaundice, fulminant liver necrosis with fatal outcome), change in the level of transaminases.
– Allergic reactions: rash (1.6%), urticaria, angioedema (face, lips, fingers, pharynx, larynx), photosensitivity.
– From the genitourinary system: edema, proteinuria, acute (asymptomatic) renal failure.
– From the respiratory system: cough (6.1%), pharyngitis (1.8%) and other respiratory diseases of the upper respiratory tract, rhinitis, sinusitis, bronchospasm, dyspnea.
– Others: pain syndrome – myalgia (1.3%), arthralgia, etc., gynecomastia, increased concentration of bilirubin, alkaline phosphatases, antinuclear antibody titer, creatinine, urea, uric acid, hyperkalemia, hyponatremia.

Overdose

There is no data for this section. We are currently processing information, please come back later.

Drug interactions

There is no data for this section. We are currently processing information, please come back later.

Form of issue

Finely dispersed white or almost white powder, soluble in distilled water at room temperature. Tablets (7.5 mg, 15 mg).

MOEXIPRIL (moexipril) active ingredient | 36i6.info

Moexipril is a non-sulfhydryl-containing precursor of moexiprilate, an active angiotensin-converting enzyme (ACE) inhibitor.It is used to treat high blood pressure (hypertension). Works by relaxing the blood vessels, causing them to dilate. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems.

Mechanism of action

Moexipril is a prodrug for moexiprilate, which inhibits ACE in humans and animals. The mechanism by which moexiprilate lowers blood pressure is thought to primarily inhibit ACE activity.ACE is a peptidyldipeptidase that catalyzes the conversion of the inactive decapeptide angiotensin I to the vasoconstrictor angiotensin II. Angiotensin II is a potent peripheral vasoconstrictor that also stimulates the secretion of aldosterone by the adrenal cortex and provides negative feedback on renin secretion. ACE is identical to kinase II, an enzyme that breaks down bradykinin, an endothelium-dependent vasodilator. Moexipril is approximately 1000 times more potent than moexipril in inhibiting ACE and kininase II.Inhibition of ACE leads to a decrease in the formation of angiotensin II, which leads to a decrease in vasoconstriction, an increase in plasma renin activity, and a decrease in aldosterone secretion. The latter leads to diuresis and natriuresis and a slight increase in serum potassium concentration (an average increase of about 0.25 mEq / L was observed with moexipril alone). Whether elevated levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of moexipril remains to be seen.Although the renin-angiotensin-aldosterone system is believed to be the main mechanism of moexipril in lowering blood pressure, ACE inhibitors have some effect on blood pressure even in severe hypertension with low renin content.

back to contents ↑

Absorption

Moexipril is incompletely absorbed, bioavailability as moexiprilat is about 13% compared to intravenous (IV) moexipril (both measure the metabolite of moexipril), and is markedly affected by food, which lowers C max and AUC by about 70% and 40%, respectively, after eating a low-fat breakfast or 80% and 50%, respectively, after eating a high-fat breakfast.

back to contents ↑

Protein binding

Moexiprilate is approximately 50% protein bound.

Rapidly converted to moexiprilate, an active metabolite. It is believed that carboxyesterases are required for conversion to an active metabolite and may occur in organs or tissues other than the gastrointestinal tract in which carboxyesterases occur. It is believed that the liver is one of the conversion centers, but not the main center.

back to contents ↑

Remedy

Moexiprilat undergoes renal elimination.

Half-life

The half-life of moexipril is approximately 1 hour. The half-life of moexiprilate is 2 to 9 hours.

Toxicity

No human overdose of moexipril has been reported. In cases of reports of overdose with other ACE inhibitors, hypotension was the main reported side effect. Single oral doses of 2 g / kg moexipril have been associated with significant mortality in mice.Rats, however, tolerated single oral doses up to 3 g / kg. Common side effects include cough, dizziness, diarrhea, flu syndrome, fatigue, pharyngitis, hot flashes, rashes, and myalgia.

back to contents ↑

Food Interactions

Herbs that may weaken the antihypertensive effect of moexipril: bayberry, bush, cayenne, ephedra, ginger, ginseng (American), cola and licorice.

High salt intake may weaken the antihypertensive effect of moexipril.

Moexipril can reduce the excretion of potassium. Salt substitutes containing potassium may increase the risk of hyperkalemia.

Cardiologist | New Medicine

Cardiologist – a doctor who diagnoses all diseases of the cardiovascular systems.

Clinical medicine specialist engaged in the prevention, treatment, rehabilitation, diagnosis of all diseases of the heart and blood vessels.

List of diseases of the cardiovascular system that a cardiologist treats:

– Cardiac arrhythmias,
– Arterial hypotension,
– Atherosclerosis,
– Hypertensive crises,
– Vegetative-vascular dystonia,
– Myocardial infarction,
– Ischemic (coronary) heart disease ,
– Cardialgia,
– Cardiosclerosis,
– Myocardial dystrophy,
– Circulatory failure,
– Neurocirculatory dystonia,
– Pericarditis,
– Congenital heart defects,
– Acquired heart defects,
– Heart failure,
– Vascular – Vascular crises,
– Angina pectoris (angina pectoris),
– Endocarditis.

Heart.

Complaints of stabbing in the part of the heart, aching pain and heaviness in the left side of the chest, discomfort in it, and in the left shoulder blade and left arm, palpitations, breaks in the heart, acute pain behind the sternum, shortness of breath on exertion, rare pulse – less 50 beats per minute, swelling without sitting down requires an immediate visit to a cardiologist.

– general blood test,
– general urine analysis,
– alanine aminotransferase,
– aspartate aminotransferase,
– total bilirubin,
– direct bilirubin,
– alkaline photosphase,
– gamma-glutamyltransferase,
– glucose,
– creatinine
– urea,
– total cholesterol, HDL cholesterol, with an atherogenic index calculator,
– triglycerides,
– neopterin.

– electrocardiogram of the heart (ECG, electrocardiography),
– daily cardiogram of the heart (daily monitoring of heart activity according to Holter),
– daily monitoring of blood pressure,
– echocardiography,
– diagnosis of myocardiopathies,
– genetic markers of cardiovascular diseases ( myocardial infarction, coronary heart disease, hypertension, atherosclerosis),
– markers of autoimmune myocardial damage.
– cardiac risk,
– angiography.

To keep your heart healthy for many years, you must follow several important rules:

1. Do not smoke.

2. Eat correctly and variedly (meat, fish, vegetables, fruits, cereals, whole grain bread, vegetable oils, less fat and sweets) and monitor your weight.

3. Move more, especially in nature: for example, walk at quick steps for more than 3, and preferably 5 km per day.

4. Control your blood pressure. With a stable increase or frequent drops, it is imperative to undergo an examination.

5. After 40 years, regularly check your natural cholesterol and sugar levels.

6. Drink a glass of red wine with dinner two or three times a week.

High blood pressure, also called hypertension, is a major risk factor for heart disease, kidney disease, stroke and heart failure.

What blood pressure is considered high?

Blood pressure 140/90 and above is considered elevated. This can be called hypertension.

A blood pressure level from 120/80 to 139/89 is called prehypertension. That, in fact, you do not have hypertension, but it is very likely to develop in the future, if you do not make changes in your lifestyle to keep your blood pressure level under control.

Blood pressure less than 120/80 is considered normal.

How can I prevent high blood pressure?

You have the ability to prevent high blood pressure in the following ways:
– Maintain a healthy weight.Lose weight if you are overweight.
– Increase in physical activity.
– Eating foods that are low in salt.
– Consuming healthy foods such as fruits and vegetables.
– By reducing the amount of alcoholic beverages you drink, if you drink them at all.

These guidelines also apply to the treatment of high blood pressure, although drugs are most commonly included in the treatment.

What is the relationship between blood pressure and weight?

As your body weight increases, your blood pressure rises.In addition, being overweight can increase your likelihood of developing hypertension compared to your normal weight.

More than 60% of the world’s adult population is overweight. By losing weight, you can reduce your risk of developing high blood pressure. Even a small amount of weight loss can make a big difference in the prevention and treatment of high blood pressure.

How can I reduce my weight?

To lose weight, you need to eat slightly fewer calories than you burn.But don’t go on an intense diet to see how quickly you can lose those pounds. The healthiest and most lasting weight loss occurs when you lose 250-500g in a week. By reducing the calorie content of food consumed by 500 calories / day, its quantity and increasing physical activity, you can lose about 500g per week.

Here are some tips to help you lose weight and make your debut on the road to healthy eating:

– Choose foods that are low in calories and fat.Naturally, low-calorie food choices will lower your calorie intake. But did you know that choosing low-fat foods also lowers your calorie intake?

Fat is a concentrated source of calories, so the less fatty foods you eat, the fewer calories you eat.

High-fat foods that should be avoided include butter, margarine, regular salad dressings, fatty meats, cooked poultry skins, fried foods, whole milk products such as cheese, biscuits, cakes, and fast foods.
– Choose foods rich in starch and fiber. Foods that are high in starch and fiber, such as fruits, vegetables, dried peas and beans, whole grains, noodles, rice, and bread, are excellent substitutes for fatty foods. They contain less calories than fatty foods, but they are also good sources of vitamins and minerals.
– Limit portion sizes. Keeping track of what you eat is not enough to lose weight; quantity also matters. To reduce your calorie intake, you need to limit your portion sizes.Especially try to eat smaller portions of high-calorie foods such as fatty meats and cheese. And try not to deviate from the chosen nutritional strategy, not to come back for an additional portion in a few seconds.
– Keep a food diary. Keep a record of what you eat, when and why you do it. Record whether you snack in front of the TV with some fatty foods or skip breakfast and then eat a hearty lunch. Once you become aware of your eating habits, you can set yourself the necessary goals.
– Exercise. Exercise is another important part of the weight loss process. The combination of reduced intake of fatty and high-calorie foods and exercise will allow you to lose more weight and maintain your weight for a longer time than just dietary restrictions or exercise alone. Exercise can also help lower blood pressure. Physically active people are less likely to develop hypertension than people with low physical activity.You don’t have to be a marathon runner to benefit from physical activity. Even light physical activity, if done every day, can help reduce the risk of heart disease. Try to use the stairs instead of the escalator, park further from the entrance to walk more.

How can I reduce my salt intake?

Americans eat more salt and other sodium foods than they need. Often, after a person with high blood pressure refuses to consume large amounts of salt, their blood pressure drops to normal values.

Salt restriction also prevents high blood pressure.

Some people, such as dark-skinned and elderly people, are more sensitive to the effects of sodium than others. Since it is almost impossible to predict exactly who will be sensitive to sodium, it makes sense for everyone to limit their salt intake to prevent high blood pressure.

Everyone, especially people with high blood pressure, should consume no more than 6 g of salt per day, which is the equivalent of 2,400 mg of sodium.This is about one teaspoon of salt. But remember to take into account all the salt, including that found in ready-made foods and the salt added during cooking.

You can train your taste buds to enjoy less salty foods. Here are some tips:

– Pay attention to the information on food labels that says the amount of sodium.

– Try to opt for low sodium foods more often.Look for foods that say “no sodium,” “very low sodium,” “low sodium,” “low sodium,” or “unsalted,” on cans, boxes, bottles, and bags.
– Buy fresh, frozen or canned “no salt” foods. Eat fresh poultry, fish, and lean meats more often than canned and prepared foods.
– Use herbs, spices and salt-free seasoning mixes instead of salt when cooking.
– Cook rice, noodles and hot cereals without salt. Limit your meals of plain or instant rice, pasta, and cereal mixes because they usually contain salt.
– Wash canned foods such as tuna to reduce sodium.

The Dietary Approaches to Prevention of Hypertension (DASH) study found that you can reduce your blood pressure by eating foods rich in cereals, fruits, vegetables and low-fat dairy products.

How much alcohol can I drink if I have high blood pressure?

Drinking a lot of alcohol can increase your blood pressure. It can also lead to the development of arterial hypertension. Therefore, to prevent high blood pressure, if you do drink alcohol, then limit the amount to two glasses a day.

The American Diet Guide recommends limiting alcohol consumption to one glass a day to maintain a healthy body in women with low body weight.

One glass is equivalent to:
– 50 ml of 80% whiskey or 30 ml of 100% whiskey,
– 150 ml of wine,
– 350 ml of beer (regular or light).

You may have heard that certain types of alcohol are good for the heart.

It is believed that people who drink a glass or two a day have lower blood pressure and live longer than those who consume excessive amounts of alcohol. Some people note that wine raises the level of “good” (HDL) cholesterol in the blood, which prevents the buildup of fatty plaques on the walls of the arteries.

While this opinion is possible and correct, there are other aspects: drinking too much alcohol can cause other health problems, such as those that occur in car accidents, liver and pancreas diseases, brain and heart damage, increased risk of developing oncological diseases and alcohol syndrome in the fetus. Alcohol is also high in calories. All this means that you should limit the amount of alcohol consumed.

Should I take any nutritional supplements?

Food supplements can also help prevent high blood pressure. Below is a summary of them.
– Potassium. Eating foods rich in potassium will help protect some people from high blood pressure. You may be getting enough potassium in your diet so you don’t need supplements. Many fruits, vegetables, dairy products, and fish contain sufficient amounts of potassium.
– Calcium. Populations with low calcium intake have high levels of high blood pressure. Despite all this, there is no evidence that taking calcium pills can prevent high blood pressure. It is important to get at least the recommended amount of calcium with food every day – 800-1200 mg per day for adults (pregnant and lactating women need more). Dairy products such as low-fat milk, yogurt, and cheese are good sources of calcium.

Low-fat or non-fat dairy products contain even more calcium than high-fat products.

– Magnesium. A diet low in magnesium can raise your blood pressure. But doctors do not recommend taking too much magnesium to prevent high blood pressure – the amount found in foods with a healthy diet is quite enough.

Magnesium is found in whole grains, green vegetables, nuts, seeds, dry peas and beans.

– Fish oil. Fatty fish like mackerel and salmon contain a type of fatty acid called omega-3 fatty acids. Large amounts of fish oil may help lower high blood pressure, but their role in prevention has not been clarified. It is not recommended to take fish oil capsules because high doses can cause unwanted side effects. These capsules are also high in calories and fat. Most fish, unless they are fried or cooked with added fat, are low in saturated fat and calories and can be eaten frequently.

Should I limit my caffeine intake if I’m worried about my blood pressure?

Caffeine, which is found in beverages such as coffee, tea, and soda, can cause temporary high blood pressure. In a short time, your blood pressure will return to its original values. If you are not hypersensitive to caffeine and your blood pressure is not dropping, then you should not limit your caffeine intake to prevent high blood pressure.

What medications are used to treat blood pressure?

If you have hypertension, the lifestyle changes listed above may not be enough to lower your blood pressure. Your doctor may recommend adding medications to these.

Most people with hypertension need more than one drug to lower their blood pressure. Blood pressure lowering drugs are divided into groups:

– Diuretics: Aldactone, Bumex, Demadex, Diuril, Dyrenium, Enduron, Hydrodiuril, Inspra, Lasix, Lozol, Microzide, Midamor, Mykrox, Thalitone, Zaroxolyn.
– Beta blockers: Blocadren, Coreg, Corgard, Inderal, Innopran, Kerlone, Levatol, Lopressor, Normodyne, Pindolol, Sectral, Tenormin, Toprol, Trandate, Zebeta.
– ACE inhibitors: Accupril, Aceon, Altace, Captoten, Lotensin, Mavik, Monopril, Prinivil, Univasc, Vasotec, Zestril.
– Angiotensin II receptor blockers: Atacand, Avapro, Benicar, Cozaar, Diovan, Micardis, Teveten.
– Calcium channel blockers: Adalat CC, Calan SR, Cardene, Cardizem, Covera, Procardia, Dilacor, Dynacirc, Isoptin, Norvasc, Plendil, Sular, Tiazac, Verelan.
– Alpha Blockers: Cardura, Catapres, Chlorpres, Hytrin, Minipress, Tenex.
– Vasodilators: Hydralazine, Loniten.

Clinical pharmacology of ACE inhibitors and AT1-angiotensin receptor blockers – what lessons can be learned from it | Dobrovolskiy A.V.

Introduction
Angiotensin-converting enzyme (ACE) inhibitors have been used for over 20 years and are currently among the most widely used cardiotropic drugs.Created about ten years later, AT1-angiotensin receptor blockers were for some time “in the shadow” of ACE inhibitors, but in recent years the frequency of their use in cardiological practice (primarily for the treatment of patients with arterial hypertension and chronic heart failure) has been steadily increasing. Despite the well-known differences in the mechanism of action on the renin-angiotensin-aldosterone system (RAAS), a detailed description of which is beyond the scope of this publication, ACE inhibitors and AT1-angiotensin receptor blockers have a similar effect on the cardiovascular system, have almost the same indications for use1 and often serve as an alternative to each other (for example, in case of drug intolerance).At the same time, drugs within each of these pharmacological groups, at first glance, seem to be very similar (or at least not as heterogeneous as calcium antagonists and b-blockers). The problem is further complicated by the fact that several ACE inhibitors and AT1-angiotensin receptor blockers are simultaneously present on the Russian medical market, which creates the prerequisites for frequent and often unjustified drug changes (for example, in the absence of the necessary drug in the pharmacy, the patient will be offered it with a high probability ” analog “).At the same time, there are significant differences (primarily in terms of pharmacokinetics) both between drugs within each of these groups, and between groups as a whole. Ignorance of these differences can lead to the prescription of inadequate dosages, the prescription of the wrong dosage regimen and, ultimately, to the failure to achieve the desired therapeutic effect. Finally, ACE inhibitors and AT1-angiotensin receptor blockers are often considered “safe” drugs (in contrast to the same b-blockers) and are prescribed without due regard to the patient’s concomitant physiological and pathological conditions.Accordingly, this publication, based on a comparative analysis of certain infrequently discussed aspects of the pharmacokinetics and pharmacodynamics2 of ACE inhibitors and AT1-angiotensin receptor blockers, is intended to identify the most significant, from a practical point of view, differences between individual drugs and drug groups, as well as to formulate indicative recommendations for their use in various clinical situations.

Introduction
Angiotensin-converting enzyme (ACE) inhibitors have been used for over 20 years and are currently among the most widely used cardiotropic drugs.Created about ten years later, AT1-angiotensin receptor blockers were for some time “in the shadow” of ACE inhibitors, but in recent years the frequency of their use in cardiological practice (primarily for the treatment of patients with arterial hypertension and chronic heart failure) has been steadily increasing. Despite the well-known differences in the mechanism of action on the renin-angiotensin-aldosterone system (RAAS), a detailed description of which is beyond the scope of this publication, ACE inhibitors and AT1-angiotensin receptor blockers have a similar effect on the cardiovascular system, have almost the same indications for use1 and often serve as an alternative to each other (for example, in case of drug intolerance).At the same time, drugs within each of these pharmacological groups, at first glance, seem to be very similar (or, at least, not as heterogeneous as calcium antagonists and b-blockers). The problem is further complicated by the fact that several ACE inhibitors and AT1-angiotensin receptor blockers are simultaneously present on the Russian medical market, which creates the prerequisites for frequent and often unjustified drug changes (for example, in the absence of the necessary drug in the pharmacy, the patient will be offered it with a high probability ” analog “).At the same time, there are significant differences (primarily in terms of pharmacokinetics) both between drugs within each of these groups, and between groups as a whole. Ignorance of these differences can lead to the prescription of inadequate dosages, the prescription of the wrong dosage regimen and, ultimately, to the failure to achieve the desired therapeutic effect. Finally, ACE inhibitors and AT1-angiotensin receptor blockers are often considered “safe” drugs (in contrast to the same b-blockers) and are prescribed without due regard to the patient’s concomitant physiological and pathological conditions.Accordingly, this publication, based on a comparative analysis of certain infrequently discussed aspects of the pharmacokinetics and pharmacodynamics2 of ACE inhibitors and AT1-angiotensin receptor blockers, is intended to identify the most significant, from a practical point of view, differences between individual drugs and drug groups, as well as to formulate indicative recommendations for their use in various clinical situations.
Angiotensin inhibitors –
converting enzyme
Classification of ACE inhibitors
There is currently no generally accepted classification of drugs.The classification of ACE inhibitors by their chemical structure has become widespread, according to which drugs are distinguished: 1) containing a sulfhydryl group (captopril, zofenopril), 2) containing a carboxyalkyl group (enalapril, lisinopril, quinapril, moexipril, perindopril, ramipril, trandolapril, cilazapril ) and 3) containing a phosphinyl group (fosinopril) [1], but its practical value is not great. It is believed that the presence of a sulfhydryl group in the chemical structure of captopril is responsible for the appearance of such side effects inherent only to this drug as neutropenia, loss of taste sensitivity, unpleasant taste in the mouth and proteinuria [7].
Other authors divide ACE inhibitors, depending on the physicochemical properties and metabolic characteristics, into: 1) lipophilic drugs (captopril), 2) lipophilic prodrugs with preferential excretion through the kidneys (quinapril, perindopril), 3) lipophilic prodrugs with two elimination pathways ( moexipril, ramipril, etc.) and 4) hydrophilic drugs (lisinopril) [5]. However, more essential here is the division of the considered drugs into drugs and prodrugs.Thus, among the available ACE inhibitors, only captopril and lisinopril have independent biological activity [6]. The rest of the drugs are prodrugs and acquire pharmacological activity only after de-esterification. The transformation into active diacid metabolites occurs mainly in the liver, partly in the mucous membrane of the gastrointestinal tract. The clinical significance of lipophilicity / hydrophilicity is low3. In addition, ACE inhibitors are classified according to the duration of the pharmacological action (see.below).
Pharmacokinetics of ACE inhibitors
Bioavailability
Among ACE inhibitors, the lowest bioavailability is observed in trandolapril (11%) [8], lisinopril (25-29%) [9,10], moexipril (22%) and fosinopril (32%) [1]. For other drugs, this indicator is significantly higher. Thus, the bioavailability of captopril and quinapril is approximately the same and amounts to 60–65% [11,12]. The bioavailability of enalapril among all ACE inhibitors is the highest and reaches 60–70% [13, 14].
One of the factors that determine the bioavailability of a drug is its interaction with food. It is known that food reduces the absorption of captopril by 30–40%, so the drug must be taken at least one hour before meals [11]. Similarly (no earlier than one hour before a meal), moexipril should be taken [15,16]. Other ACE inhibitors (in particular, enalapril [17], lisinopril [10] and quinapril [12]) are characterized by more stable absorption in the gastrointestinal tract and can be prescribed both before and after meals.
Protein binding
Most lipophilic ACE inhibitors in free form in blood plasma are almost not present and are bound to proteins by 80–95% (benazepril, quinapril, trandolapril, moexipril, fosinopril, zofenopril) [1]. To a small extent, they bind to proteins lisinopril (no more than 5-10%) [10], as well as perindopril (20%) and captopril (30%). Enalapril and ramipril occupy an intermediate position and are bound to blood plasma proteins by about 50-60% [1]
Half-life and duration of action
It should be noted that in ACE inhibitors there is no unambiguous parallelism between the half-life of the drug and the duration of its pharmacological action.Thus, it is known that the half-life of captopril is only from 1–2 to 6 hours [8,14]. However, with prolonged use, the concentration of the drug in the blood plasma and the duration of action increase somewhat. It is believed that due to the sulfhydryl group
captopril forms unstable compounds with endogenous thiol-containing substances (such as cysteine ​​and glutathione), which, with a decrease in the concentration of the ACE inhibitor in question, are capable of cleaving off captopril and thus are a kind of “depot” of the latter [11, 14].
The half-life of quinapril is even shorter than that of captopril, and is only 1-3 hours (on average, about two hours) [19]. However, due to its high affinity for tissue angiotensin-converting enzymes, the drug can be taken twice a day or even once [12].
The average duration of pharmacological action is typical for enalapril (half-life from 2-4 to 11 hours with prolonged use) [14,17], lisinopril (half-life of 7-13 hours) [10], fosinopril (12-15 hours) [20] and cilazapril (from 4 to 12 hours) [21-23], although according to some data the half-life of the latter may exceed 24-48 hours and reach 86 hours [1].Drugs with a long half-life include perindopril (27-40 hours) [24-26], ramipril (23-48 hours) [27], trandolapril (16-24 hours) [28] and moexipril (29-30 hours) [ 15]. All of these drugs are also characterized by a significant duration of pharmacological action.
Thus, all ACE inhibitors can be divided into: 1) short-acting drugs, which are
it is necessary to prescribe 3 times a day (captopril), 2) drugs with an average duration of action, prescribed 2 times a day (enalapril, lisinopril) and 3) long-acting drugs, which in most cases can be taken once a day (trandolapril, ramipril, perindopril, moexipril, fosinopril, quinapril) 4 [1].
At the end of this section, it should be noted that the rate of onset of the pharmacological effect in the vast majority of ACE inhibitors is low, which makes it impractical to use them in urgent situations (for example, to relieve a hypertensive crisis). The only exception is captopril, which has a rapid hypotensive effect due to its high bioavailability (the drug is found in the blood within 15 minutes and reaches its peak concentration 45-60 minutes after ingestion [11]) and the presence of its own pharmacological effect.When taken sublingually, the action of captopril develops even faster, due to which the drug can be effectively used sublingually to quickly reduce blood pressure [29].
Excretion
All ACE inhibitors are characterized by renal elimination, but only lisinopril is excreted exclusively by the kidneys and only in unchanged form [10]. The rest of the drugs are eliminated not only by the kidneys, but also by the liver; however, the proportion of hepatic excretion differs from drug to drug. Thus, enalapril [13,17] and captopril [11] are almost completely excreted by the kidneys.In addition, 60% of quinaprilat and 70% of perindoprilat (active metabolites of quinapril and perindopril, respectively) are excreted by the renal route [12,25]. In contrast, ACE inhibitors such as moexipril,
ramipril, trandolapril, fosinopril and benazepril are excreted by the kidneys and liver to approximately the same extent [8].
Drug interactions of ACE inhibitors
Due to the fact that the metabolism of ACE inhibitors occurs mainly without the participation of cytochrome P450, the drugs under consideration do not enter into clinically significant interactions with cimetidine and warfarin [10,11,17,30].There is no evidence that ACE inhibitors increase the risk of digitalis intoxication when used together with cardiac glycosides [30, 31].
Clinically significant pharmacokinetic drug interactions with ACE inhibitors are relatively few. Thus, antacids containing magnesium or aluminum hydroxide interfere with the absorption of captopril and fosinopril [11]. The excretion of captopril is impaired when it is used together with probenecid, which may be accompanied by a significant increase in the content of this ACE inhibitor in the blood plasma [11].It is also known that ACE inhibitors slow down the excretion of lithium salts from the body (especially during diuretic therapy) and can even lead to lithium intoxication [32].
Among pharmacodynamic interactions, interactions of ACE inhibitors with non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid and diuretics are of greatest clinical importance. Thus, by reducing the synthesis of prostaglandins I2 (prostacyclin) and E2, NSAIDs reduce renal blood flow, decrease glomerular filtration and cause sodium retention, thus weakening the vasodilating and natriuretic effect of ACE inhibitors and preventing the implementation of the hypotensive effect of the latter [33–35].It should be remembered that acetylsalicylic acid interacts in a similar way with ACE inhibitors, and the severity of its effect increases with increasing dose [36]. At the same time, the results of these studies show that acetylsalicylic acid in a daily dose of not more than 300–325 mg does not lead to an increase in blood pressure in patients receiving ACE inhibitors [37,38]. Indirect evidence suggests that acetylsalicylic acid can also
neutralize favorable hemodynamic changes and the positive effect of ACE inhibitors on
the survival rate of patients with chronic heart failure [39–41]; however, this question still remains open.
The interaction between ACE inhibitors and diuretics deserves special consideration. It is known that thiazide diuretics increase sodium excretion from the body, activate the RAAS and thus
potentiate the action of ACE inhibitors. On the other hand, potassium-sparing and uricosuric action
ACE inhibitors [10,17], to a certain extent weakens the potassium uretic and hyperuricemic effects of thiazide and loop diuretics. Thus, the combination of various ACE inhibitors with thiazide diuretics is considered beneficial [10,17,19,22,24,42].However, patients taking diuretics are more likely to experience renal dysfunction after starting therapy
ACE inhibitors [1].
ACE inhibitors can cause dilatation of systemic and renal arterioles, decrease the perfusion pressure in the glomeruli and, as a result, decrease the glomerular filtration rate [43]. For this reason, at the beginning of therapy with these drugs in patients with chronic heart failure receiving maintenance doses of loop diuretics, fluid retention may be observed (and this effect is more pronounced, the higher the dose of the ACE inhibitor [44]).In this regard, it is recommended to take thiazide and loop diuretics at least 2 hours before taking an ACE inhibitor [1], and also prescribe the latter, starting with low daily doses.
Potassium-sparing diuretics significantly increase the risk of developing hyperkalemia during therapy with ACE inhibitors, therefore, the combined use of these drugs should be avoided, especially for the treatment of hypertension. On the contrary, in the combination therapy of chronic heart failure, the combined use of ACE inhibitors with spironolactone is very useful [45], however, regular monitoring of the level of potassium in the blood plasma is required [46].
In conclusion, it should be noted that the combination of ACE inhibitors with calcium antagonists in the treatment of hypertension is very effective (in addition to the summation of the hypotensive action,
ACE inhibitors weaken the activation of the RAAS and the sympathoadrenal system caused by calcium channel blockers and reduce reflex tachycardia). On the contrary, the combination of ACE inhibitors with b-blockers is irrational due to the fact that drugs of both drug groups act on different levels of RAAS (as you know, the hypotensive effect of b-blockers is largely associated with inhibition of renin secretion) [1].
Application of ACE inhibitors
in special clinical situations
Chronic renal failure
Studies have shown that there is a strict linear correlation between creatinine clearance and the rate of elimination of most ACE inhibitors [47]. This applies primarily to drugs with a predominantly renal elimination pathway. So, in patients with chronic renal disease
insufficiency slows down excretion and increases serum concentration of captopril [11], lisinopril [10], enalapril [17] and quinapril [12], which requires the use of these drugs in half doses if creatinine clearance is less than 30 ml / min.Although the pharmacokinetics of perindopril in chronic renal failure is not impaired, there is an increase in the intensity and duration of inhibition of serum ACE, and therefore it is recommended to reduce the dose of the drug in patients with severe renal impairment [48].
It is believed that drugs with significant hepatic elimination are safer in chronic renal failure. In particular, it was found that the excretion of fosinopril does not slow down in case of impaired renal function [49-51]. However, in patients with moderate to severe renal impairment, it is recommended to reduce the dose of trandolapril and moexipril [16].Thus, in chronic renal failure, any ACE inhibitors should be used in doses 25–50% lower than in individuals with preserved renal function [52].
Hemodialysis
It has been established that captopril, perindopril and enalapril are eliminated from the body during hemodialysis and peritoneal dialysis. Accordingly, additional administration of these drugs may be required after extracorporeal detoxification [48]. Other ACE inhibitors (in particular, quinapril and cilazapril) are not eliminated from the body during hemodialysis [52].
Liver failure
Previously, it was assumed that in hepatic insufficiency, the biotransformation of inactive prodrugs into active metabolites may decrease5. However, in a number of studies it was found that liver dysfunction does not affect the pharmacokinetics of captopril, enalapril [17], perindopril [53] and other ACE inhibitors. At the same time, in severe liver diseases, it is recommended to reduce the doses of drugs with significant hepatic elimination (in particular, moexipril [16]).Thus, it seems that in this category of patients it is most advisable to use drugs with a renal elimination pathway (first of all, lisinopril) [8,10].
Elderly and senile age 6
The pharmacokinetics of captopril and lisinopril do not change with age [11,54]. At the same time, in the elderly, there is a slight increase in the concentration of perindopril in the blood plasma [25], which may be a reflection of a more rapid de-esterification of drugs, as well as a decrease in the rate of secretion due to an age-related decrease in renal function.In general, old age in itself is not an indication for dose reduction of ACE inhibitors, however, caution should be exercised when using high dosages of these drugs.
Pregnancy
It is known that ACE inhibitors have a pronounced fetotoxic effect, contribute to the formation of a number of fetal malformations (tubular nephropathy, hypoplasia of the lungs and kidneys, oligohydramnios, contractures of the extremities, underdevelopment of the occipital bone with encephalocele or exencephaly), and are also the cause of long-term post-anaturia [58].In this regard, the use of all ACE inhibitors is absolutely contraindicated in the II and III trimesters of pregnancy. At the same time, it was previously believed that ACE inhibitors do not have a teratogenic effect [59, 60], and therefore are relatively safe in the first trimester of pregnancy. However, in June 2006, data from a retrospective study in the United States was published, according to which, with the use of ACE inhibitors in the first trimester,
pregnancy, the risk of significant congenital defects increased 2.7 times (95% confidence interval 1.72-4.27), malformations of the cardiovascular system – 3.72 times (95% confidence interval 1.89-7.30 ), malformations of the central nervous system – 4.39 times (95% confidence interval 1.37-14.02) [61].Thus, the use of ACE inhibitors should be considered contraindicated throughout pregnancy. In addition, one should, apparently, avoid the use of ACE inhibitors in women of childbearing age who do not use effective methods of contraception, giving preference to other antihypertensive drugs [62].
AT1-angiotensin blockers
receptor
Classification of blockers
AT1-angiotensin receptors
There is no generally accepted classification of AT1-angiotensin receptor blockers.According to their chemical structure, the drugs under consideration are divided into four main groups: 1) biphenyl derivatives of tetrazole (losartan (Vasotens), irbesartan, candesartan, olmesartan, tazosartan), 2) non-phenyl derivatives of tetrazole (telmisartan), 3) non-phenyl compounds) 4) non-heterocyclic compounds (valsartan, fonsartan) [63]. In addition, these drugs can be classified according to the characteristics of binding to AT1-angiotensin receptors. Thus, some blockers bind reversibly to receptors and can be displaced from this connection by an excess of angiotensin II.Such drugs are called competitive or surmountable AT1-angiotensin receptor blockers. These include losartan (Vasotens et al.), Eprosartan, as well as tazosartan and its active metabolite enoltazosartan. Other drugs (such as valsartan, candesartan, irbesartan, telmisartan, as well as the active metabolite of losartan EXP-3174) bind to receptors irreversibly and are not displaced by an excess of angiotensin II, i.e. are noncompetitive or insurmountable blockers [64].It has now been established that the so-called insurmountable blockers of AT1 – angiotensin receptors, in fact, are also competitive, but with a very slow dissociation [65]. Thus, within the group under consideration, drugs with rapidly reversible and slowly reversible blockade should be isolated. The first subgroup consists of losartan, eprosartan and tazosartan, and the second includes all other known AT1-angiotensin receptor blockers (including the pharmacologically active metabolite of losartan) [2].
Finally, AT1-angiotensin receptor blockers can be classified depending on the presence of their own pharmacological action, as well as active metabolites. Moreover, most of the drugs in this group have their own activity (that is, they are drugs in themselves). These include losartan (Vasotens et al.), Valsartan, irbesartan, telmisartan, eprosartan, and tazosartan. At the same time, losartan (Vasotens) and tazosartan also have active metabolites (E-3174 and enoltazosartan, respectively), which are superior in their pharmacodynamic activity (E-3174) and duration of action (both metabolites) to the original drugs.Only two AT1-angiotensin receptor blockers (candesartan cilexetil and olmesartan medoxomil) are prodrugs and are converted into active substances (candesartan and olmesartan, respectively) during absorption in the gastrointestinal tract [66,67].
Pharmacokinetics of blockers
AT1-angiotensin receptors
Bioavailability
The lowest oral bioavailability is observed in eprosartan (13.1%) [68], valsartan (23-29%) [69] and olmesartan medoxomil (28.6%) [67], and the highest in irbesartan (60-85 %) [70] Other drugs occupy intermediate
position, and their bioavailability varies from 30 to 60% [63].
It should be borne in mind that food reduces the absorption of valsartan by 40–50% [63], and therefore this drug should be taken at least one hour before meals. When taking eprosartan with meals, the rate of absorption decreases, but the completeness of absorption and overall bioavailability do not change. Accordingly, eprosartan can be taken with or after meals [68]. Other AT1-angiotensin receptor blockers (in particular, losartan [71] and irbesartan [70]) can be prescribed regardless of food intake.
Protein binding
All drugs of this group are almost completely bound to blood proteins [63]. At the same time, even when using irbesartan (the drug that is least bound to protein [70]), only about 10% of the total amount of the administered dose is determined in free form.
Half-life and duration of action
Drugs with a short half-life include losartan (1.3–2.5 hours) [72], valsartan (5–7 hours) [69] and eprosartan (5–7 hours) [68].A longer half-life is characteristic of candesartan cilexetil (about 9 hours) [66] and olmesartan medoxomil (10-15 hours) [67]. The longest half-life is observed in telmisartan (16-24 hours) and irbesartan (11-20 hours) [65,70]. Accordingly, blockers of AT1-angiotensin receptors are divided by some authors into short-acting (losartan, valsartan, eprosartan) and long-acting (all others) drugs [73]. However, the relationship between the half-life and the duration of the pharmacological action is not unambiguous.In particular, losartan has an active metabolite E-3174, which is characterized by a longer half-life (6-9 hours) and a slowly reversible interaction with
angiotensin receptors [72] and due to which the drug can be taken once a day. The long-term effect of valsartan is also explained by its irresistible binding to receptors. Thus, it is believed that almost all currently existing AT1 blockers –
angiotensin receptors can be administered once a day [63] 7.
Excretion
All blockers of AT1-angiotensin receptors are characterized mainly by the hepatic pathway of elimination. In this case, valsartan, telmisartan and eprosartan are almost completely excreted from the body with bile and feces in unchanged form, and only an extremely insignificant part of them is metabolized in the liver and excreted by the kidneys [76,77]. However, a number of drugs have significant renal excretion. In particular, up to 30–40% of substance E – 3174 (active metabolite of losartan) [72], about 20% of irbesartan [70], as well as up to 30–40% of candesartan [66] and olmesartan [67] are excreted through the kidneys.
Drug Interactions
AT1-angiotensin blockers
receptor
Clinically significant pharmacokinetic interactions of AT1-angiotensin receptor blockers with other drugs are relatively few. Moreover, the number of
revealed interactions in different drugs is not the same and is in direct proportion to the intensity of their hepatic metabolism. Thus, losartan is characterized by the highest affinity for cytochrome P450-2C9 and 3A48 isoenzymes [71] and an increased likelihood of unwanted drug interactions.In particular, a significant slowdown in the transformation of losartan into E-3174 was noted when it was used together with fluconazole (an inhibitor of cytochrome P450-2C9) [80]), which may be accompanied by a weakening of the pharmacological action of this inhibitor of AT1-angiotensin receptors [81]. Similar changes can be observed with the combined use of losartan with some other drugs, in the metabolism of which the cytochrome P450-2C9 isoenzyme is involved (in particular, with phenytoin [82]). At the same time, it was found that fluvastatin, an inhibitor of cytochrome P450-2C9, essentially
alters the pharmacokinetics of losartan [83].
Erythromycin and grapefruit juice (inhibitors of cytochrome P450-3A4) also slow down the conversion
losartan in E-3174, but their effect is less pronounced compared with fluconazole [84, 85].
On the contrary, rifampicin, a nonspecific cytochrome P450 inducer, significantly accelerates the biotransformation and elimination of losartan and E-3174, which will most likely lead to a decrease in the effect of the latter when these drugs are used together [84].
It should be emphasized that for losartan (Vasotens et al.) are not characterized by clinically significant interactions with cardiotropic drugs (i.e., with drugs that are most likely to be used simultaneously with losartan). In particular, it was found that losartan does not exhibit undesirable pharmacokinetic interactions with hydrochlorothiazide, warfarin and digoxin [71,86,87].
Among other AT1-angiotensin receptor blockers, irbesartan has the highest affinity for cytochrome P450 isoenzymes [88]; however, the presence of clinically significant drug interactions with inhibitors and inducers of cytochrome has not been reported9.It was also found that irbesartan does not affect the pharmacokinetics of warfarin and digoxin, and does not interact with hydrochlorothiazide, nifedipine, simvastatin and tolbutamide [89,90].
The rest of the drugs in this group are either not metabolized at all with the participation of hepatic peroxidation systems (telmisartan, eprosartan), or have extremely low affinity for cytochrome P450 (candesartan, olmesartan, valsartan) [75,88]. Accordingly, the likelihood of interactions of these AT1 – angiotensin receptor blockers is extremely low.In particular, no interaction of eprosartan with ranitidine [68] and fluconazole [80], as well as valsartan with cimetidine [91], was revealed. In addition, all of the above drugs do not enter into clinically significant interactions with digoxin, warfarin, antacids and hypoglycemic drugs [66,67,80,92,93].
Among the pharmacodynamic interactions of AT1-angiotensin receptor blockers, the largest amount is
their interaction with diuretics is of clinical importance. Thus, thiazide diuretics increase sodium excretion from the body, activate the RAAS and thereby potentiate the action of drugs that block angiotensin II receptors [2].At the same time, AT1-angiotensin receptor blockers (like ACE inhibitors) increase the risk of renal dysfunction in patients receiving continuous diuretic therapy. It should be noted that AT1-angiotensin receptor blockers (unlike ACE inhibitors) increase potassium excretion and can lead to severe hypokalemia, especially when administered together with loop diuretics [2]. On the contrary, the combination of AT1 – angiotensin receptor blockers with spironolactone (the effectiveness of which in chronic heart failure seems to be very significant [94]) is often accompanied by the development of clinically significant hyperkalemia [95] and is possible only with regular monitoring of the level of potassium in the blood plasma [46].
It should also be noted that AT1-angiotensin receptor blockers differ significantly from ACE inhibitors in terms of their effect on uric acid secretion. Thus, losartan is the only drug that significantly increases the excretion of uric acid in hypertensive patients [96]. All other AT1-angiotensin receptor blockers have no uricosuric effect [76.97.98].
Concluding the consideration of the problem of drug interactions, it should be noted the high efficiency of the combined use of AT1-angiotensin receptor blockers with calcium antagonists in hypertension.Angiotensin II receptor blockers and b-adrenergic blockers, when used together, do not worsen each other’s pharmacokinetic parameters [99,100], but the feasibility of such a combination for the treatment of hypertension does not seem obvious [2]. As for the combined use of AT1-angiotensin receptor blockers with ACE inhibitors, despite the obvious similarity in the mechanisms of action, such a combination may be useful in the treatment of vysokorenin forms of arterial hypertension, provide an additional renoprotective effect in chronic kidney disease (in particular, in diabetic nephropathy [ 101.102]), as well as in chronic heart failure against the background of systolic dysfunction of the left ventricle [2].
The use of blockers
AT1-angiotensin receptors
in special clinical situations
Chronic renal failure (CRF)
In AT1-angiotensin receptor blockers, which have a predominantly hepatic elimination pathway, there is no correlation between creatinine clearance and the concentration of drugs in the blood plasma.
Accordingly, drugs such as valsartan and telmisartan can be used for renal failure.In moderate and severe chronic renal failure, the concentration of eprosartan in the blood plasma increases, however, taking into account the predominantly hepatic route of excretion, the use of this drug in chronic renal failure is also considered safe [77]. Great care should be taken when using AT1-angiotensin receptor blockers, which have a dual pathway of excretion. Thus, with a slight and moderate decrease in renal function, the pharmacokinetics of candesartan does not change [103], however, in severe renal failure, there is a significant increase in the concentration of the drug in the blood plasma and an increase in its half-life [104], which may require a decrease in its dose.Similarly, with a decrease in creatinine clearance, the plasma level of olmesartan increases [105]. As for losartan and irbesartan, the use of these drugs in standard dosages is safe only for mild and moderate renal failure [70,71,106], while in patients with severe chronic renal failure, these drugs should be used only in low daily doses.
Hemodialysis
Losartan and its active metabolite E-3174 [71], as well as irbesartan [106], and candesartan [104] are not eliminated from blood plasma during hemodialysis.In contrast to these drugs, eprosartan is found in the dialysate, but the fraction of the drug eliminated in this way is insignificant and there is no need for its additional administration10 [107].
Liver failure
In case of impaired liver function, drugs with a predominantly hepatic elimination pathway should be used with extreme caution. Thus, it was found that when using eprosartan in persons with moderate liver disease, the total concentration of the drug in the blood, the content of the free drug in the blood and the degree of binding to proteins do not change, but the area under the concentration-time curve for total and free eprosartan increases, respectively. by 40 and 50%, which reflects the tendency for drug accumulation and may require a decrease in its dosages [108].Somewhat safer in liver failure are drugs with double excretion. In particular, with moderate hepatic failure, there is a slight (by 20%) increase in the concentration of the drug candesartan in the blood plasma and a slight lengthening of its half-life, which do not require dose adjustment [103,109]. With an increase in hepatic
insufficiency, the renal excretion of olmesartan increases compensatory, which increases the safety of use of the drug in patients with
liver damage [105].Finally, liver failure does not alter the pharmacokinetics of irbesartan and losartan [110], so the latter can be used even in severe liver dysfunction [71]
Old age
In elderly and senile people, the pharmacokinetics of losartan and irbesartan do not change [70,71]. At the same time, an increase in the serum concentration of olmesartan and a lengthening of its half-life in patients of older age groups were noted [105]. In addition, in elderly and senile patients, the half-life of candesartan slightly increases and its maximum concentration and the area under the concentration-time curve increase by about 50%, which, however, is not accompanied by a clinically significant accumulation of the drug [111].Finally, it was found that in older age groups the bioavailability of eprosartan increases and, accordingly, its concentration in blood plasma increases, which requires caution when titrating the dosages of this drug [112].
Pregnancy
It is known that AT1-angiotensin receptor blockers (as well as ACE inhibitors) are contraindicated in the II and III trimesters of pregnancy due to the possibility of developing fetotoxic action (hypoplasia
kidney, tubular nephropathy, oligohydramnios, underdevelopment of the lungs, hypoplasia of the occipital bone, etc.) [113]. At the same time, the teratogenic effect of AT1-angiotensin receptor blockers was considered unproven until recently [114]. However, given the increased risk of having children with malformations in women who took ACE inhibitors at the beginning of pregnancy, as well as isolated clinical observations published in recent years11, the teratogenic effect of AT1-angiotensin receptor blockers seems to be very likely. Thus, the use of the drugs in question during pregnancy in general should be considered contraindicated.According to some authors, it is better not to use AT1-angiotensin receptor blockers at all in women of childbearing age (especially those who do not use reliable methods of contraception) [62].
In the event of pregnancy in a woman who initially took AT1-angiotensin receptor blockers, it is recommended to immediately discontinue these drugs, replacing them with medicines that are more harmless to the fetus, and perform an ultrasound scan to exclude malformations. The very fact of taking AT1-angiotensin receptor blockers in early pregnancy cannot 90 021
be considered an indication for its interruption [114]).Po–
apparently, the same tactics should be followed in relation to ACE inhibitors.
Conclusion
ACE inhibitors and AT1-angiotensin receptor blockers are rather heterogeneous in their pharmacokinetic and (to a lesser extent) pharmacodynamic characteristics. Knowledge of the characteristics of each of the drugs within these pharmacological groups will undoubtedly increase their effectiveness and reduce the risk of adverse effects on the patient’s body (especially with such common concomitant pathological conditions as chronic renal and hepatic failure).

Literature
1. Sidorenko B.A., Preobrazhensky D.V. Angiotensin-converting enzyme inhibitors. – M .: JSC “Informatik”, 1999 .;
2. Sidorenko B.A., Preobrazhensky D.V. AT1-angiotensin receptor blockers. M .: JSC “Informatik”, 2001
3. Blizzard V.I. Handbook of clinical pharmacology of cardiovascular drugs / ed. 2nd, rev. and add. – M .: Publishing house BINOM – SPb .: Nevsky dialect, 2002. – 926 p.
4. Belousov Yu.B., Moiseev V.C., Lepakhin V.K. Clinical pharmacology and pharmacotherapy. M, 1997; 530 p.
5. Opie LH. Angiotensin – converting enzyme inhibitors: scientific basis for clinical use. John Wiley & Sons: New York, 1992
6. Raia JJ Jr, Barone JA, Byerly WG, Angiotensin – converting enzyme inhibitors: a comparative review. DICP. 1990 May; 24 (5): 506-25.
7. Nikiforov V.S., Svistov A.S. Modern trends in the use of angiotensin-converting enzyme inhibitors in clinical practice “PHARMindex-Praktik” 2005, no.7, pp. 21-31
8. Fischler MP, Follath F. Comparative evaluation of ACE inhibitors: which differences are relevant? Schweiz Med Wochenschr. 1999 Jul 27; 129 (29-30): 1053-60
9.Noble TA Murray KM. Lisinopril: a nonsulfhydryl angiotensin – converting enzyme inhibitor. Clin Pharm. 1988 Sep; 7 (9): 659-69
10. Gomez HJ, Cirillo VJ, Moncloa F. The clinical pharmacology of lisinopril. J Cardiovasc Pharmacol. 1987; 9 Suppl 3: S27–34
11. Duchin KL, McKinstry DN, Cohen AI, Migdalof BH.Pharmacokinetics of captopril in healthy subjects and in patients with cardiovascular diseases. Clin Pharmacokinet. 1988 Apr; 14 (4): 241-59
12. Cetnarowski – Cropp AB. Quinapril: a new second – generation ACE inhibitor. DICP. 1991 May; 25 (5): 499-504
13. Vlasses PH, Larijani GE, Conner DP, et al. Enalapril, a nonsulfhydryl angiotensin – converting enzyme inhibitor. Clin Pharm. 1985 Jan – Feb; 4 (1): 27–40
14. Kubo SH, Cody RJ. Clinical pharmacokinetics of the angiotensin converting enzyme inhibitors.A review. Clin Pharmacokinet. 1985 Sep – Oct; 10 (5): 377–91
15. Cawello W, Boekens H, Waitzinger J, Miller U. Moexipril shows a long duration of action related to an extended pharmacokinetic half – life and prolonged ACE inhibition. Int J Clin Pharmacol Ther. 2002 Jan; 40 (1): 9-17
16. Song JC, White CM Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. Clin Pharmacokinet. 2002; 41 (3): 207-24
17. Gomez HJ, Cirillo VJ, Irvin JD.Enalapril: a review of human pharmacology. Drugs. 1985; 30 Suppl 1: 13-24
18. Piepho RW. Overview of the angiotensin – converting – enzyme inhibitors. Am J Health Syst Pharm. 2000 Oct 1; 57 Suppl 1: S3-7 Greenbaum R, Zucchelli P, Caspi A, et al. Comparison of the pharmacokinetics of fosinoprilat with enalaprilat and lisinopril in patients with congestive heart failure and chronic renal insufficiency. Br J Clin Pharmacol. 2000 Jan; 49 (1): 23-31
19. Plosker GL, Sorkin EM Quinapril. A reappraisal of its pharmacology and therapeutic efficacy in cardiovascular disorders.Drugs. 1994 Aug; 48 (2): 227–52
20. Ford NF, Natarajan C, Fulmor IE, et al. Invasive pharmacodynamics of fosinopril in patients with congestive heart failure. J Clin Pharmacol. 1995 Aug; 35 (8): 785-93
21. Louis WJ, Conway EL, Krum H, et al. Comparison of the pharmacokinetics and pharmacodynamics of perindopril, cilazapril and enalapril. Clin Exp Pharmacol Physiol Suppl. 1992; 19: 55-60
22. Deget F, Brogden RN. Cilazapril. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in cardiovascular disease.Drugs. 1991 May; 41 (5): 799-820
23. Belz GG, Breithaupt K, Erb K. Review of studies on the clinical pharmacodynamics of cilazapril Drugs. 1991 May; 41 (5): 799-820, J Cardiovasc Pharmacol. 1994; 24 Suppl 2: S14-9
24. Todd PA, Fitton A. Perindopril. A review of its pharmacological properties and therapeutic use in cardiovascular disorders. Drugs. 1991 Jul; 42 (1): 90-114
25. Macfadyen RJ, Lees KR, Reid JL. Perindopril. A review of its pharmacokinetics and clinical pharmacology.Drugs. 1990; 39 Suppl 1: 49–63
26. Louis WJ, Workman BS, Conway EL, et al. Single – dose and steady – state pharmacokinetics and pharmacodynamics of perindopril in hypertensive subjects. J Cardiovasc Pharmacol. 1992 Sep; 20 (3): 505-11
27. Todd PA, Benfield P. Ramipril. A review of its pharmacological properties and therapeutic efficacy in cardiovascular disorders. Drugs. 1990 Jan; 39 (1): 110-35
28. Peters DC, Noble S, Plosker GL. Trandolapril. An update of its pharmacology and therapeutic use in cardiovascular disorders.Drugs. 1998 Nov; 56 (5): 871–93
29. al – Furaih TA, McElnay JC, Elborn JS Sublingual captopril –– a pharmacokinetic and pharmacodynamic evaluation. Eur J Clin Pharmacol. 1991; 40 (4): 393-8
30. Shionoiri H. Pharmacokinetic drug interactions with ACE inhibitors. Clin Pharmacokinet. 1993 Jul; 25 (1): 20–58
31 de Mey C, Elich D, Schroeter V, et al. Captopril does not interact with the pharmacodynamics and pharmacokinetics of digitoxin in healthy man. Eur J Clin Pharmacol. 1992; 43 (4): 445-7
32.Teitelbaum M. A significant increase in lithium levels after concomitant ACE inhibitor administration. Psychosomatics. 1993 Sep – Oct; 34 (5): 450–3
33. Juhlin T, Bjorkman S, Hoglund P. Cyclooxygenase inhibition causes marked impairment of renal function in elderly subjects treated with diuretics and ACE – inhibitors.Eur J Heart Fail. 2005 Oct; 7 (6): 1049-56
34. Morgan T, Anderson A. The effect of nonsteroidal anti – inflammatory drugs on blood pressure in patients treated with different antihypertensive drugs.J Clin Hypertens (Greenwich). 2003 Jan – Feb; 5 (1): 53–7
35. Polonia J. Interaction of antihypertensive drugs with anti – inflammatory drugs. Cardiology. 1997; 88 Suppl 3: 47-51
36. Di Gennaro FP, Cingolani OH, Abbate AF, et al. High doses of aspirin reduce natriuresis in hypertensive patients treated with enalapril. Medicina (B Aires). 2004; 64 (4): 301-5
37. Nawarskas JJ, Townsend RR, Cirigliano MD, Spinler SA Effect of aspirin on blood pressure in hypertensive patients taking enalapril or losartan.Am J Hypertens. 1999 Aug; 12 (8 Pt 1): 784-9
38. Zanchetti A, Hansson L, Leonetti G, et al. Low – dose aspirin does not interfere with the blood pressure – lowering effects of antihypertensive therapy. J Hypertens. 2002 May; 20 (5): 1015–22
39. MacIntrye IM, Jhund PS, McMurray JJ. Aspirin inhibits the acute arterial and venous vasodilator response to captopril in patients with chronic heart failure. Cardiovasc Drugs Ther. 2005 Aug; 19 (4): 261-5
40. Ahmed A. Interaction between aspirin and angiotensin – converting enzyme inhibitors: should they be used together in older adults with heart failure? J Am Geriatr Soc.2002 Jul; 50 (7): 1293-6
41. Stys T, Lawson WE, Smaldone GC Does aspirin attenuate the beneficial effects of angiotensin – converting enzyme inhibition in heart failure? Arch Intern Med. 2000 May 22; 160 (10): 1409-13
42. Shionoiri H, Naruse M, Minamisawa K, et al. Fosinopril. Clinical pharmacokinetics and clinical potential. Clin Pharmacokinet. 1997 Jun; 32 (6): 460-80
43. Dzau VJ. Renal effects of angiotensin – converting enzyme inhibition in cardiac failure. Am J Kidney Dis.1987 Jul; 10 (1 Suppl 1): 74-80
44. Motwani JG, Fenwick MK, Morton JJ, Struthers AD. Furosemide-induced natriuresis is augmented by ultra-low-dose captopril but not by standard doses of captopril in chronic heart failure Circulation, Aug 1992; 86: 439 – 445
45. van Vliet AA, Donker AJ, Nauta JJ, Verheugt FW. Spironolactone in congestive heart failure refractory to high – dose loop diuretic and low – dose angiotensin – converting enzyme inhibitor. Am J Cardiol. 1993 Jan 21; 71 (3): 21A – 28A
46.Saito M, Takada M, Hirooka K, Isobe F, Yasumura Y. Serum concentration of potassium in chronic heart failure patients administered spironolactone plus furosemide and either enalapril maleate, losartan potassium or candesartan cilexetil. J Clin Pharm Ther. 2005 Dec; 30 (6): 603-10
47. Leblanc JM, Dasta JF, Pruchnicki MC, Schentag JJ Impact of disease States on the pharmacokinetics and pharmacodynamics of Angiotensin – converting enzyme inhibitors. J Clin Pharmacol. 2006 Sep; 46 (9): 968–80
48.Verpooten GA, Genissel PM, Thomas JR, De Broe ME. Single dose pharmacokinetics of perindopril and its metabolites in hypertensive patients with various degrees of renal insufficiency. Br J Clin Pharmacol. 1991 Aug; 32 (2): 187–92
49. Davis R, Coukell A, McTavish D. Fosinopril. A review of its pharmacology and clinical efficacy in the management of heart failure. Drugs. 1997 Jul; 54 (1): 103-16.
50. O’Grady P, Yee KF, Lins R, et al. Fosinopril / hydrochlorothiazide: single dose and steady – state pharmacokinetics and pharmacodynamics.Br J Clin Pharmacol. 1999 Sep; 48 (3): 375–81
51. Greenbaum R, Zucchelli P, Caspi A, et al. Comparison of the pharmacokinetics of fosinoprilat with enalaprilat and lisinopril in patients with congestive heart failure and chronic renal insufficiency. Br J Clin Pharmacol. 2000 Jan; 49 (1): 23-31
52. Hoyer J, Schulte KL, Lenz T. Clinical pharmacokinetics of angiotensin converting enzyme (ACE) inhibitors in renal failure. Clin Pharmacokinet. 1993 Mar; 24 (3): 230-54
53. Tsai HH, Lees KR, Howden CW, Reid JL.The pharmacokinetics and pharmacodynamics of perindopril in patients with hepatic cirrhosis. Br J Clin Pharmacol. 1989 Jul; 28 (1): 53-9
54. Langtry HD, Markham A. Lisinopril. A review of its pharmacology and clinical efficacy in elderly patients. Drugs Aging. 1997 Feb; 10 (2): 131–66
55. Saenz-Campos D, Bayes MC, Masana E, et al. Sex – related pharmacokinetic and pharmacodynamic variations of lisinopril. Methods Find Exp Clin Pharmacol. 1996 Oct; 18 (8): 533-8
56. Massana E, Barbanoj MJ, Moros C, et al.No sex – related pharmacokinetic and pharmacodynamic differences of captopril. Pharmacol Res. 1997 Jul; 36 (1): 41-7
57. Vree TB, Dammers E, Ulc I, et al. Lack of male – female differences in disposition and esterase hydrolysis of ramipril to ramiprilat in healthy volunteers after a single oral dose. ScientificWorldJournal. 2003 Dec 11; 3: 1332–43
58. Piper JM, Ray WA, Rosa FW. Pregnancy outcome following exposure to angiotensin – converting enzyme inhibitors. Obstet Gynecol. 1992 Sep; 80 (3 Pt 1): 429–32
59.Postmarketing surveillance for angiotensin – converting enzyme inhibitor use during the first trimester of pregnancy –– United States, Canada, and Israel, 1987–1995. MMWR Morb Mortal Wkly Rep. 1997 Mar 21; 46 (11): 240–2
60. Burrows RF, Burrows EA. Assessing the teratogenic potential of angiotensin – converting enzyme inhibitors in pregnancy. Aust N Z J Obstet Gynaecol. 1998 Aug; 38 (3): 306-11
61. Cooper WO, Hernandez-Diaz S, Arbogast PG, et al. Major congenital malformations after first – trimester exposure to ACE inhibitors.N Engl J Med. 2006 Jun 8; 354 ​​(23): 2443-51
62. Quan A, Fetopathy associated with exposure to angiotensin converting enzyme inhibitors and angiotensin receptor antagonists. Early Hum Dev. 2006 Jan; 82 (1): 23-8
63. Israili ZH. Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. J Hum Hypertens. 2000 Apr; 14 Suppl 1: S73–86
64. Timmermans PB. Pharmacological properties of angiotensin II receptor antagonists. Can J Cardiol. 1999 Nov; 15 Suppl F: 26F – 8F
65.Burnier M, Maillard M. The comparative pharmacology of angiotensin II receptor antagonists. Blood Press Suppl. 2001; 1: 6-11
66. See S, Stirling AL. Candesartan cilexetil: an angiotensin II – receptor blocker. Am J Health Syst Pharm. 2000 Apr 15; 57 (8): 739–46
67. Laeis P, Puchler K, Kirch W. The pharmacokinetic and metabolic profile of olmesartan medoxomil limits the risk of clinically relevant drug interaction. J Hypertens Suppl. 2001 Jun; 19 (1): S21–32
68. Tenero D, Martin D, Ilson B, et al.Pharmacokinetics of intravenously and orally administered eprosartan in healthy males: absolute bioavailability and effect of food. Biopharm Drug Dispos. 1998 Sep; 19 (6): 351-6
69. Flesch G, Muller P, Lloyd P. Absolute bioavailability and pharmacokinetics of valsartan, an angiotensin II receptor antagonist, in man. Eur J Clin Pharmacol. 1997; 52 (2): 115–20
70. Brunner HR. The new angiotensin II receptor antagonist, irbesartan: pharmacokinetic and pharmacodynamic considerations.Am J Hypertens. 1997 Dec; 10 (12 Pt 2): 311S – 317S
71. Sica DA, Gehr TW, Ghosh S. Clinical pharmacokinetics of losartan. Clin Pharmacokinet. 2005; 44 (8): 797-814
72. Dickstein K, Timmermans P, Segal R. Losartan: a selective angiotensin II type 1 (AT1) receptor antagonist for the treatment of heart failure. Expert Opin Investig Drugs. 1998 Nov; 7 (11): 1897-914
73. Oparil S. Newly emerging pharmacologic differences in angiotensin II receptor blockers.Am J Hypertens. 2000 Jan; 13 (1 Pt 2): 18S – 24S
74.Robins GW, Scott LJ Episartan: a review of its use in the management of hypertension. Drugs. 2005; 65 (16): 2355–77
75. Hedner T. The clinical profile of the angiotensin II receptor blocker eprosartan. J Hypertens Suppl. 2002 Jun; 20 (5): S33-8
76. Muller P, Flesch G, de Gasparo M, et al. Pharmacokinetics and pharmacodynamic effects of the angiotensin II antagonist valsartan at steady state in healthy, normotensive subjects. Eur J Clin Pharmacol. 1997; 52 (6): 441-9
77.Martin DE, Chapelsky MC, Ilson B, et al. Pharmacokinetics and protein binding of eprosartan in healthy volunteers and in patients with varying degrees of renal impairment. J Clin Pharmacol. 1998 Feb; 38 (2): 129–37
78. Yasar U, Forslund-Bergengren C, Tybring G, et al. Pharmacokinetics of losartan and its metabolite E-3174 in relation to the CYP2C9 genotype. Clin Pharmacol Ther. 2002 Jan; 71 (1): 89–98,
79. Lee CR, Pieper JA, Hinderliter AL, et al. Losartan and E3174 pharmacokinetics in cytochrome P450 2C9 * 1 / * 1, * 1 / * 2, and * 1 / * 3 individuals.Pharmacotherapy. 2003 Jun; 23 (6): 720-5
80. Kazierad DJ, Martin DE, Blum RA, et al. Effect of fluconazole on the pharmacokinetics of eprosartan and losartan in healthy male volunteers. Clin Pharmacol Ther. 1997 Oct; 62 (4): 417-25
81. Kaukonen KM, Olkkola KT, Neuvonen PJ. Fluconazole but not itraconazole decreases the metabolism of losartan to E – 3174. Eur J Clin Pharmacol. 1998 Feb; 53 (6): 445-9
82. Fischer TL, Pieper JA, Graff DW, et al. Evaluation of potential losartan – phenytoin drug interactions in healthy volunteers.Clin Pharmacol Ther. 2002 Sep; 72 (3): 238–46
83. Meadowcroft AM, Williamson KM, Patterson JH, et al. The effects of fluvastatin, a CYP2C9 inhibitor, on losartan pharmacokinetics in healthy volunteers. J Clin Pharmacol. 1999 Apr; 39 (4): 418-24
84. Williamson KM, Patterson JH, McQueen RH, et al. Effects of erythromycin or rifampin on losartan pharmacokinetics in healthy volunteers. Clin Pharmacol Ther. 1998 Mar; 63 (3): 316-23
85. Zaidenstein R, Soback S, Gips M, et al.Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers.Ther Drug Monit. 2001 Aug; 23 (4): 369-73
86. De Smet M, Schoors DF, De Meyer G, et al. Effect of multiple doses of losartan on the pharmacokinetics of single doses of digoxin in healthy volunteers. Br J Clin Pharmacol. 1995 Dec; 40 (6): 571-5
87 Kong AN, Tomasko L, Waldman SA Losartan does not affect the pharmacokinetics and pharmacodynamics of warfarin. J Clin Pharmacol.1995 Oct; 35 (10): 1008-15
88. Unger T, Kaschina E. Drug interactions with angiotensin receptor blockers: a comparison with other antihypertensives. Drug Saf. 2003; 26 (10): 707–20
89. Marino MR, Vachharajani NN. Drug interactions with irbesartan. Clin Pharmacokinet. 2001; 40 (8): 605-14
90. Mangold B, Gielsdorf W, Marino MR. Irbesartan does not affect the steady – state pharmacodynamics and pharmacokinetics of warfarin. Eur J Clin Pharmacol. 1999 Oct; 55 (8): 593-8
91.Schmidt EK, Antonin KH, Flesch G, Racine-Poon A. An interaction study with cimetidine and the new angiotensin II antagonist valsartan. Eur J Clin Pharmacol. 1998 Feb; 53 (6): 451-8
92. Martin DE, Tompson D, Boike SC, et al. Lack of effect of eprosartan on the single dose pharmacokinetics of orally administered digoxin in healthy male volunteers. Br J Clin Pharmacol. 1997 Jun; 43 (6): 661-4
93. Martin DE, DeCherney GS, Ilson BE, et al. Eprosartan, an angiotensin II receptor antagonist, does not affect the pharmacodynamics of glyburide in patients with type II diabetes mellitus.J Clin Pharmacol. 1997 Feb; 37 (2): 155-9
94. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999 Sep 2; 341 (10): 709-17
95. Juurlink DN, Mamdani MM, Lee DS, et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med. 2004 Aug 5; 351 (6): 543-51
96. Puig JG, Mateos F, Buno A, et al.Effect of eprosartan and losartan on uric acid metabolism in patients with essential hypertension. J Hypertens. 1999 Jul; 17 (7): 1033-9
97. Ilson BE, Martin DE, Boike SC, et al. The effects of eprosartan, an angiotensin II AT1 receptor antagonist, on uric acid excretion in patients with mild to moderate essential hypertension. J Clin Pharmacol. 1998 May; 38 (5): 437–41
98. Wurzner G, Gerster JC, Chiolero A, et al. Comparative effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia and gout.J Hypertens. 2001 Oct; 19 (10): 1855-60;
99. Czendlik CH, Sioufi A, Preiswerk G Pharmacokinetic and pharmacodynamic interaction of single doses of valsartan and atenolol. Eur J Clin Pharmacol. 1997; 52 (6): 451-9
100. Andrawis NS, Battle MM, Klamerus KJ, et al. A pharmacokinetic and pharmacodynamic study of the potential drug interaction between tasosartan and atenolol in patients with stage 1 and 2 essential hypertension. J Clin Pharmacol. 2000 Mar; 40 (3): 231–41
101.Rossing K, Jacobsen P, Pietraszek L, Parving HH. Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy: a randomized double – blind crossover trial. Diabetes Care. 2003 Aug; 26 (8): 2268–74
102. Fujisawa T, Ikegami H, Ono M, Combination of half doses of angiotensin type 1 receptor antagonist and angiotensin – converting enzyme inhibitor in diabetic nephropathy. Am J Hypertens. 2005 Jan; 18 (1): 13-7
103.Stoukides CA, McVoy HJ, Kaul AF. Candesartan cilexetil: an angiotensin II receptor blocker. Ann Pharmacother. 1999 Dec; 33 (12): 1287–98
104. de Zeeuw D, Remuzzi G, Kirch W. Pharmacokinetics of candesartan cilexetil in patients with renal or hepatic impairment. J Hum Hypertens. 1997 Sep; 11 Suppl 2: S37–42
105. von Bergmann K, Laeis P, Puchler K, et al. Olmesartan medoxomil: influence of age, renal and hepatic function on the pharmacokinetics of olmesartan medoxomil. J Hypertens Suppl.2001 Jun; 19 (1): S33-40
106. Sica DA, Marino MR, Hammett JL, et al. The pharmacokinetics of irbesartan in renal failure and maintenance hemodialysis. Clin Pharmacol Ther. 1997 Dec; 62 (6): 610-8
107. Kovacs SJ, Tenero DM, Martin DE, et al. Pharmacokinetics and protein binding of eprosartan in hemodialysis – dependent patients with end – stage renal disease. Pharmacotherapy. 1999 May; 19 (5): 612-9
108. Tenero D, Martin D, Chapelsky M, et al. Effect of hepatic disease on the pharmacokinetics and plasma protein binding of eprosartan.Pharmacotherapy. 1998 Jan – Feb; 18 (1): 42–50
109. Hoogkamer JF, Kleinbloesem CH, Ouwerkerk M, et al. Pharmacokinetics and safety of candesartan cilexetil in subjects with normal and impaired liver function. Eur J Clin Pharmacol. 1998 Jun; 54 (4): 341-5
110. Marino MR, Langenbacher KM, Raymond RH, et al. Pharmacokinetics and pharmacodynamics of irbesartan in patients with hepatic cirrhosis. J Clin Pharmacol.