What are the contraindications for Lopressor HCT. How should Lopressor HCT be administered in patients with cardiac conditions. What precautions should be taken when using Lopressor HCT in patients with specific medical conditions.

Understanding Lopressor HCT: Composition and Primary Functions

Lopressor HCT is a combination medication containing metoprolol tartrate and hydrochlorothiazide. This pharmaceutical blend is primarily used to treat hypertension and various cardiovascular conditions. But is Lopressor a diuretic? While metoprolol tartrate is a beta-blocker, hydrochlorothiazide is indeed a diuretic component of this medication.

The Dual Action of Lopressor HCT

Metoprolol tartrate, as a beta-blocker, works by slowing the heart rate and reducing the workload on the heart. Hydrochlorothiazide, the diuretic component, helps the body eliminate excess water and salt. This dual-action approach makes Lopressor HCT an effective treatment for high blood pressure and related cardiovascular issues.

Contraindications: When Lopressor HCT Should Not Be Used

Certain medical conditions preclude the use of Lopressor HCT. These contraindications are crucial for patient safety and optimal treatment outcomes.

• Sinus bradycardia
• Heart block greater than first degree
• Cardiogenic shock
• Overt cardiac failure
• Sick-sinus syndrome
• Severe arterial circulatory disorders
• Hypersensitivity to Lopressor HCT, related derivatives, or any excipients
• Anuria
• Hypersensitivity to sulfamide-derived drugs

Patients with these conditions should not use Lopressor HCT due to potential adverse effects and increased health risks.

Administering Lopressor HCT in Cardiac Conditions

For patients with hypertension and congestive heart failure controlled by digitalis and diuretics, Lopressor HCT should be administered with caution. How should healthcare providers approach treatment in patients without a history of cardiac failure? At the first sign of impending cardiac failure, digitalis and/or a diuretic should be administered. If cardiac failure persists, Lopressor HCT should be discontinued.

Ischemic Heart Disease Considerations

Abrupt cessation of Lopressor HCT therapy can exacerbate angina pectoris and potentially lead to myocardial infarction. Even in the absence of these conditions, Lopressor HCT should never be withdrawn abruptly. Gradual tapering under medical supervision is essential for patient safety.

Precautions for Specific Medical Conditions

Several medical conditions require special consideration when using Lopressor HCT:

Bronchospastic Disease

Patients with bronchospastic disease should generally not receive beta-blocker therapy, including Lopressor HCT. However, in selective instances, a physician may prescribe Lopressor HCT for these patients under close monitoring.

Diabetes Management

Diabetic patients should use Lopressor HCT with caution. Why is extra care needed for diabetic patients? The medication may mask tachycardia occurring with hypoglycemia, potentially complicating diabetes management.

Pheochromocytoma Treatment

For patients with pheochromocytoma, Lopressor HCT should only be used in combination with an alpha-blocker, and only after the alpha-blocker has been initiated. This approach helps manage the complex hormonal interactions associated with pheochromocytoma.

Thyrotoxicosis Management

Patients at risk of developing thyrotoxicosis require careful management when using Lopressor HCT. Abrupt withdrawal of beta blockade should be avoided to prevent thyroid storm or thyrotoxic crisis.

Hydrochlorothiazide-Specific Precautions

The hydrochlorothiazide component of Lopressor HCT requires additional precautions:

• Use with caution in severe renal disease
• Monitor closely in cases of impaired hepatic function or progressive liver disease
• Be aware of potential interactions with other antihypertensive drugs
• Watch for acute transient myopia and acute angle-closure glaucoma, especially in patients with a history of sulfonamide or penicillin allergy

Monitoring and Managing Side Effects

Patients taking Lopressor HCT should be monitored for various side effects and potential complications:

Fluid and Electrolyte Balance

Regular monitoring of fluid and electrolyte balance is crucial, particularly for patients prone to hypokalemia or those with severe cirrhosis. In some cases, water restriction or salt administration may be necessary, especially in hot weather conditions.

Metabolic Effects

Thiazides can cause hyperuricemia and may unmask latent diabetes. How do these metabolic effects impact patient care? Healthcare providers should monitor uric acid levels and glucose tolerance in patients taking Lopressor HCT, adjusting treatment as necessary.

Drug Interactions and Special Considerations

Lopressor HCT can interact with various medications, necessitating careful consideration and potential dosage adjustments:

Interactions with Other Cardiovascular Medications

Catecholamine-depleting drugs, such as reserpine, may have an additive effect when given with Lopressor HCT. Similarly, the combination of digitalis glycosides and beta-blockers can increase the risk of bradycardia. Healthcare providers should carefully monitor patients taking these combinations.

Anaphylactic Reactions

Patients with a history of severe anaphylactic reactions to allergens may be more reactive to repeated challenges while taking Lopressor HCT. These patients may also be unresponsive to standard doses of epinephrine used to treat allergic reactions.

CYP2D6 Enzyme Interactions

Caution is advised when using Lopressor HCT concurrently with potent inhibitors of the CYP2D6 enzyme. These inhibitors can increase plasma concentrations of metoprolol, potentially enhancing its effects and side effects.

Patient Education and Adherence

Proper patient education is crucial for the safe and effective use of Lopressor HCT:

• Take the medication regularly and continuously, as directed
• Take with or immediately following meals
• If a dose is missed, take only the next scheduled dose (do not double up)
• Do not discontinue Lopressor HCT without consulting a healthcare provider
• Avoid operating machinery or engaging in tasks requiring alertness until the response to the medication is determined
• Contact a healthcare provider if breathing difficulties occur
• Inform healthcare providers, including dentists, about Lopressor HCT use before any surgical procedures

Adherence to these guidelines helps ensure optimal treatment outcomes and minimizes the risk of adverse effects.

Long-Term Management and Follow-Up

Long-term use of Lopressor HCT requires ongoing management and regular follow-up:

Regular Health Assessments

Patients should undergo regular health assessments to monitor blood pressure, heart rate, and overall cardiovascular health. These check-ups allow healthcare providers to adjust dosages or treatment plans as needed.

Monitoring for Potential Complications

Long-term use of Lopressor HCT may require monitoring for potential complications such as electrolyte imbalances, renal function changes, and metabolic effects. Regular blood tests and clinical evaluations can help identify and address these issues promptly.

Lifestyle Modifications

In addition to medication, patients should be encouraged to adopt lifestyle modifications that support cardiovascular health. These may include:

• Maintaining a healthy diet low in sodium and rich in fruits, vegetables, and whole grains
• Engaging in regular physical activity as approved by their healthcare provider
• Managing stress through relaxation techniques or counseling
• Limiting alcohol consumption and quitting smoking

These lifestyle changes can complement the effects of Lopressor HCT and improve overall treatment outcomes.

Special Populations and Considerations

Certain patient populations require special consideration when using Lopressor HCT:

Elderly Patients

Elderly patients may be more sensitive to the effects of Lopressor HCT. Dosage adjustments and closer monitoring may be necessary to avoid adverse effects such as orthostatic hypotension or electrolyte imbalances.

Pregnant and Breastfeeding Women

The use of Lopressor HCT during pregnancy and breastfeeding should be carefully evaluated. While beta-blockers are sometimes used in pregnancy for certain conditions, the risks and benefits must be carefully weighed. Hydrochlorothiazide can pass into breast milk and may affect milk production.

Patients with Renal Impairment

For patients with renal impairment, dosage adjustments may be necessary. The hydrochlorothiazide component of Lopressor HCT is primarily eliminated by the kidneys, and its effectiveness may be reduced in patients with decreased renal function.

Alternative Treatment Options

While Lopressor HCT is effective for many patients, alternative treatment options may be considered in certain situations:

Monotherapy Options

In some cases, using metoprolol or hydrochlorothiazide alone may be sufficient to manage hypertension. This approach can help minimize potential side effects associated with combination therapy.

Other Antihypertensive Combinations

Various other antihypertensive combinations are available, including ACE inhibitors with diuretics or angiotensin receptor blockers with calcium channel blockers. The choice of medication depends on individual patient factors and comorbidities.

Non-Pharmacological Approaches

For some patients, non-pharmacological approaches may be sufficient to manage mild hypertension. These can include dietary changes, weight loss, increased physical activity, and stress management techniques.

Future Directions and Research

The field of hypertension management continues to evolve, with ongoing research into new treatment modalities and refinements of existing therapies:

Personalized Medicine Approaches

Advances in pharmacogenomics may lead to more personalized approaches to hypertension treatment, allowing healthcare providers to select medications based on an individual’s genetic profile.

Novel Drug Combinations

Research into novel drug combinations may yield new treatment options that offer improved efficacy or reduced side effect profiles compared to current therapies.

Long-Term Outcomes Studies

Ongoing long-term studies continue to evaluate the efficacy and safety of antihypertensive medications, including combination therapies like Lopressor HCT, in reducing cardiovascular morbidity and mortality.

As research progresses, treatment guidelines for hypertension and related cardiovascular conditions may evolve, potentially impacting the use of medications like Lopressor HCT in clinical practice.

Home – Lopressor HCT

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LOPRESSOR HCT^® (metoprolol tartrate and hydrochlorothiazide)

CONTRAINDICATIONS

Individuals with sinus bradycardia, heart block greater than firth degree, cardiogenic shock, overt cardiac failure, sick-sinus syndrome, and severe arterial circulatory disorders should not use Lopressor HCT^® (metoprolol tartrate and hydrochlorothiazide) Tablets.

Individuals with hypersensitivity to Lopressor HCT and related derivatives, or to any of the excipients, or hypersensitivity to any other beta blockers should not take Lopressor HCT.

Individuals with anuria or hypersensitivity to sulfamide-derived drugs should not take hydrochlorothiazide.

WARNINGS

Lopressor

Cardiac Failure: If you are hypertensive and have congestive heart failure controlled by digitalis and diuretics, Lopressor HCT should be administered cautiously.

In Patients Without a History of Cardiac Failure: At the first sign of impending cardiac failure, you should be given digitalis and/or a diuretic and, if cardiac failure continues, Lopressor HCT should be withdrawn.

Ischemic Heart Disease: Abrupt cessation of Lopressor HCT therapy can cause exacerbation of angina pectoris and in some cases, myocardial infarction. Even in the absence of angina pectoris and myocardial infarction, Lopressor HCT should never be withdrawn abruptly.

Bronchospastic Disease: IF YOU HAVE BRONCHOSPASTIC DISEASE, YOU SHOULD NOT RECEIVE ANY BETA-BLOCKER THERAPY INCLUDING LOPRESSOR HCT. IF YOU HAVE BRONCHOSPASTIC DISEASE, THERE MAY BE SELECTIVE INSTANCES WHERE YOUR DOCTOR MAY PRESCRIBE LOPRESSOR HCT.

Major Surgery: You should NOT discontinue Lopressor HCT therapy prior to major surgery, but be sure to tell your surgeon that you are taking Lopressor HCT prior to any surgery.

Diabetes: If you have diabetes, Lopressor HCT should be taken with caution as the use of Lopressor HCT may mask tachycardia occurring with hypoglycemia.

Pheochromocytoma: If you have pheochromocytoma you should only use Lopressor HCT in combination with an alpha blocker, and only after the alpha blocker has been initiated.

Thyrotoxicosis: If your doctor thinks that you may be at risk of developing thyrotoxocosis, your doctor should manage your Lopressor HCT use carefully to avoid abrupt withdrawal of the beta blockade.

Hydrochlorothiazide

If you have severe renal disease, impaired hepatic function or progressive liver disease, you should use Lopressor HCT with caution. Similarly, thiazides may add to the action of other antihypertensive drugs.

Hydrochlorothiazide can cause acute transient myopia and acute angle-closure glaucoma, particularly for those individuals with a history of allergy to sulfonamide or penicillin.

PRECAUTIONS

Lopressor HCT should be used with caution if you have impaired hepatic function.

If you are taking Lopressor HCT, you should be observed for fluid or electrolyte imbalance, hypokalemia (especially in cases of brisk diuresis or severe cirrhosis or interference with adequate oral intake of electrolytes). Individuals with problems with low blood salt content and edema in hot weather may require water restriction, or in severe cases, salt administration. This should be monitored by your doctor.

Thiazides may also cause hyperuricemia, latent diabetes, and enhanced antihypertensive effects in postsympathectomy patients. If you have progressive renal impairment, withholding or discontinuing diuretic therapy should be considered.

Patients should take Lopressor HCT regularly and continuously, as directed, with or immediately following meals. If a dose is missed, the patient should take only the next scheduled dose (without doubling it). Patients should not discontinue Lopressor HCT without consulting their doctor.

Patients should (1) avoid operating automobiles or machinery or engaging in other tasks requiring alertness until the patients response to Lopressor HCT has been determined; (2) contact their doctor is any difficulty in breathing occurs; and (3) inform their doctor or dentist before any surgery that he or she is taking Lopressor HCT.

Drug/Drug Interactions

Lopressor:

Catecholamine-depleting drugs (e.g. reserpine) may have an additive effect when given with Lopressor HCT.

Both digitalis glycosides and beta blockers slow atrioventricular conduction and decrease heart rate, so use of both medicines together can increase the risk of bradycardia.

If you have a history of severe anaphylactic reaction to a variety of allergens and take Lopressor HCT, you may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic and you may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.

If you are taking potent inhibitors of the CYP2D6 enzyme, exercise caution and speak with your doctors about using both medicines as CYP2D6 inhibitors increase plasma concentration of Lopressor HCT. Inhibors of the CYP2D6 enzyme include certain antidepressants such as fluoxetine, paraoxetine, or bupropion; antipsychotics such as thioridazine; antiarrhythmics such as quinidine or propafenone; antiretrovirals such as ritonavir; antihistimines such as diphenhydramine; antimalarials such as hydroxychloroquine or quinidine; antifungals such as terbinafine; and medications for stomach ulcers such as cimetidine.

If you are taking Lopressor HCT and clonidine treatment at the same time, and clonidine treatment is to be discontinued, the Lopressor HCT treatment should be withdrawn several days before discontinuing clonidine.

Hydrochlorothiazide:

Hydrochlorothiazide can exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability). Hypokalemia may develop during simultaneous use of steroids or ACTH. Insulin requirements in diabetic patients may change during Loressor HCT use. Thiazides may decrease the responsiveness of the heart to norepinephrine and increase responsiveness to tubocurarine. Lithium renal clearance is reduced by thiazides. Taking some nonsteroidal anti-inflammatory agents may reduce the diuretic, natriuretic, and antihypertensive effects of thiazide.

PREGNANCY CATEGORY C

There are no adequate and well-controlled studies of Lopressor HCT in pregnant women. Lopressor HCT should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

ADVERSE REACTIONS

Fatigue or lethargy and flu syndrome, dizziness or vertigo, drowsiness or somnolence, and headache have been reported in 10% of patients. Hypokalemia has been reported in less than 10% of patients. Bradycardia has been reported in 6% of patients. Decreased exercise tolerance and dyspnea, and diarrhea; digestive disorder, dry mouth, nausea or vomiting, and constipation; edema, gout, and anorexia; blurred vision, tinnitus, and earache; and sweating, purpura, impotence, and muscle pain have been reported in 1% of patients.

To report SUSPECTED ADVERSE REACTIONS, contact Validus Pharmaceuticals, LLC at — VALIDUS (1-866-982-5438) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Lopressor HCT Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

Uses

This medication is used to treat high blood pressure (hypertension). Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. This product contains 2 medications, metoprolol and hydrochlorothiazide. Metoprolol belongs to a class of drugs known as beta blockers. It works by keeping certain natural chemicals such as epinephrine from acting on the heart and blood vessels. This effect lowers the heart rate, blood pressure, and strain on the heart. Hydrochlorothiazide is a “water pill” (diuretic) and causes your body to get rid of extra salt and water. This effect may increase the amount of urine you make when you first start the medication.

How to use Lopressor HCT Tablet

See also Warning section.

Take this medication by mouth with or right after a meal as directed by your doctor, usually 1 or 2 times daily.

If you take this drug too close to bedtime, you may need to wake up to urinate. It is best to take this medication at least 4 hours before your bedtime. Consult your doctor or pharmacist if you have questions about when to take this medication.

The dosage is based on your medical condition and response to treatment.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time(s) each day.

It may take several weeks before you get the full benefit of this medication. Keep taking this medication even if you feel well. Most people with high blood pressure do not feel sick.

If you also take certain drugs to lower your cholesterol (bile acid-binding resins such as cholestyramine or colestipol), take this product at least 4 hours before or at least 4 to 6 hours after these medications.

Tell your doctor if your condition does not get better or if it gets worse (your blood pressure readings remain high or increase).

Side Effects

See also Warning and Precautions sections.

Dizziness, lightheadedness, drowsiness, headache, slow heartbeat, tiredness, or diarrhea may occur. Some people may have decreased sexual ability. If any of these effects last or get worse, tell your doctor or pharmacist promptly.

To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

This product may reduce blood flow to your hands and feet, causing them to feel cold. Smoking may worsen this effect. Dress warmly and avoid tobacco use.

Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

The hydrochlorothiazide in this product may cause your body to lose too much water and salt (dehydration). Tell your doctor promptly if you notice any symptoms of dehydration, such as unusual dry mouth/thirst, fast heartbeat, dizziness/lightheadedness, muscle cramps/weakness, confusion, fainting, seizures.

Tell your doctor right away if you have any serious side effects, including: very slow/irregular heartbeat, mental/mood changes (such as depression, mood swings), toe/joint pain, trouble breathing, blue fingers/toes, decrease in vision, eye pain, signs of kidney problems (such as change in the amount of urine).

Although this medication may be used to treat heart failure, some people may rarely develop new or worsening symptoms of heart failure. Tell your doctor right away if you experience any of these serious side effects: shortness of breath, swelling ankles/feet, unusual tiredness, unusual/sudden weight gain.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US – Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Precautions

Before taking this product, tell your doctor or pharmacist if you are allergic to metoprolol or hydrochlorothiazide; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: certain types of heart rhythm problems (such as a slow heartbeat, second- or third-degree atrioventricular block, sick sinus syndrome), blood circulation problems (such as Raynaud’s disease, peripheral vascular disease), breathing problems (such as asthma, chronic bronchitis, emphysema), liver disease, kidney disease (such as anuria), lupus, serious allergic reactions including those needing treatment with epinephrine, gout, a certain muscle/nerve disease (myasthenia gravis), skin cancer.

This drug may make you dizzy or drowsy. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).

Severe sweating, diarrhea, or vomiting can increase the risk for dehydration. Drink plenty of fluids while taking this medication unless your doctor directs you otherwise. Report prolonged diarrhea or vomiting to your doctor.

This medication may reduce the potassium levels in your blood. Ask your doctor about adding potassium to your diet. Your doctor may prescribe a potassium supplement.

This product may prevent the fast/pounding heartbeat you would usually feel when your blood sugar level falls too low (hypoglycemia). The risk is higher if you have diabetes, or are vomiting, fasting, or not eating regularly. Other symptoms of low blood sugar level, such as dizziness and sweating, are not affected by this drug.

If you have diabetes, this product may make it harder to control your blood sugar levels. Check your blood sugar levels regularly as directed by your doctor. Tell your doctor right away if you have symptoms of high blood sugar such as increased thirst/urination. Your doctor may need to adjust your diabetes medication, exercise program, or diet.

This medication may make you more sensitive to the sun. It may also increase your risk for skin cancer, especially if you take it for a long time. Limit your time in the sun. Avoid tanning booths and sunlamps. Use sunscreen and wear protective clothing when outdoors. Tell your doctor right away if you get sunburned, have skin blisters/redness, or notice new or changed moles/skin lesions.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Older adults may be more sensitive to the side effects of this drug, especially dizziness.

During pregnancy, this medication should be used only when clearly needed. It may harm an unborn baby. Discuss the risks and benefits with your doctor.

Metoprolol and hydrochlorothiazide pass into breast milk, but are unlikely to harm a nursing infant. Consult your doctor before breast-feeding.

Interactions

See also How to Use section.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.

Some products that may interact with this drug are: dofetilide, fingolimod, lithium.

Other medications can affect the removal of metoprolol from your body, which may affect how this product works. Examples include lumefantrine, propafenone, quinidine, SSRI antidepressants (such as fluoxetine, paroxetine), St. John’s wort, among others.

Some products have ingredients that could raise your heart rate or blood pressure or worsen your heart failure. Tell your pharmacist what products you are using, and ask how to use them safely (especially cough-and-cold products, diet aids, or NSAIDs such as ibuprofen/naproxen).

This product may interfere with certain lab tests (including parathyroid, tyramine, and phentolamine), possibly causing false test results. Make sure lab personnel and all your doctors know you use this drug.

Does Lopressor HCT Tablet interact with other drugs you are taking?

Enter your medication into the WebMD interaction checker

Overdose

If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe dizziness, fainting, very slow heartbeat, trouble breathing.

Do not share this medication with others.

Talk with your doctor about making changes to your lifestyle that may help this medication work better (such as stress reduction programs, exercise, and dietary changes).

Lab and/or medical tests (including kidney/liver function, blood mineral levels such as potassium, skin exams) should be done while you are taking this medication. Keep all medical and lab appointments. Consult your doctor for more details.

Check your blood pressure and pulse (heart rate) regularly while taking this medication. Learn how to check your own blood pressure and pulse at home, and share the results with your doctor.

If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

Selected from data included with permission and copyrighted by First Databank, Inc. This copyrighted material has been downloaded from a licensed data provider and is not for distribution, except as may be authorized by the applicable terms of use.

CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.

Antihypertensive drugs

In addition, ACE inhibitors, by reducing the conversion of angiotensin I to angiotensin II, lead to an increase in the content of angiotensin I in the blood and tissues.
The accumulation of angiotensin I contributes to its increased conversion into angiotensin-(1-7), which has a vasodilating and natriuretic effect.
Thus, the antihypertensive effect of ACE inhibitors is associated both with a decrease in the formation of vasoconstrictor substances (angiotensin II, as well as norepinephrine, arginine-vasopressin, endothelin-1), and with an increase in the formation or decrease in the breakdown of vasodilating substances (bradykinin, angiotensin-(1- 7), nitric oxide, prostaglandins).

A total of four ACE inhibitors (captopril, libenzapril, lisinopril and cenonapril) have direct biological activity.
All other known ACE inhibitors are themselves inactive substances, or prodrugs.
Only after absorption in the gastrointestinal tract, as a result of hydrolysis, they turn into active diacid metabolites, for example, enalapril turns into enalaprilat, fosinopril into fosinoprilat, etc.
Thus, all ACE inhibitors can be divided into two groups: 1) active dosage forms and 2) prodrugs.
Class 1 . Lipophilic drugs
• Captopril (Capoten)
Class II . Lipophilic prodiganism
• Subclass IIa – drugs with predominantly renal elimination (more than 60%): Benazepril (Lotenzin), Quinapril (Akkuper) Perindopril (Premino A, Hypernik, Perinprings, Prevent) Cylazapril (Inchibais, Caloside) Enalapril, Enalaprise, Zofenoprilay (Zofenoprilate, Zophenopril (zerois. Cardis )
• Subclass IIB – drugs with two main routes of elimination: moexipril (moex), ramipril (tritace, amprilan, chartil, dilaprel), fosinopril (monopril)
• Subclass IIC – drugs with predominantly hepatic elimination (more than 60%): spirapril (quadropril), trandolapril (hopten)
Class III . Hydrophilic preparations
Lisinopril (Irumed, Diroton, Dapril, Lysigamma, Sinopril) – a drug with high nephro- and cardioprotective properties
The most pronounced antihypertensive effect of ACE inhibitors is exerted on patients with increased activity of the renin-angiotensin-aldosterone system.
But ACE inhibitors cannot completely suppress the excess activity of the RAAS, because up to 70-80% of angiotensin II is synthesized in organs and tissues without the participation of ACE with the help of other enzymes (chymase, cathepsin, etc.), and in the treatment of ACE inhibitors, the synthesis of angiotensin II can switch from the ACE-dependent pathway to the chymase pathway.
This explains the possibility of the phenomenon of “escape” of the antihypertensive effect in the treatment of ACE inhibitors, especially against the background of a high-salt diet, and serves as a rationale for the use of drugs that suppress the activity of angiotensin II, regardless of the route of its formation.

According to the duration of the antihypertensive effect, ACE inhibitors can be divided into three groups:

1. Short-acting drugs that must be administered 2 or 3 times a day (for example, captopril).
2. Intermediate-acting drugs that need to be taken at least twice a day (zofenopril and enalapril).
3. Long-acting drugs that in most cases provide round-the-clock control of blood pressure levels when taken once a day (quinapril, lisinopril, perindopril, ramipril, spirapril, trandolapril, fosinopril, etc.).

ACE inhibitors are generally well tolerated by patients.
White men tolerate long-term ACE inhibitor therapy much better than white women, as well as blacks and Chinese.
• Side effects associated with the use of ACE inhibitors: specific and non-specific.

Specific
• Impaired renal function during treatment with ACE inhibitors is more common in patients with overt or latent kidney disease, including bilateral renal artery disease.
• Severe hyperkalemia (> 5.5 mEq/L) is uncommon with ACE inhibitors in patients with normal renal function (0%-6%).
• In addition to renal failure, concomitant use of potassium salts, potassium-sparing diuretics (amiloride, spironolactone, triamterene) and nonsteroidal anti-inflammatory drugs (indomethacin, diclofenac, sulindac) are considered risk factors for the development of hyperkalemia in patients receiving ACE inhibitors.
• On the other hand, the combined use of loop and thiazide diuretics significantly reduces the risk of hyperkalemia during treatment with ACE inhibitors.
• Dry cough, according to the literature, occurs with an incidence of 1 to 48% during treatment with ACE inhibitors.
• The incidence of cough during treatment with ACE inhibitors is highly dependent on gender and race.
• For example, ACE inhibitor-associated cough is significantly more common in women than in men (approximately 7:3 ratio).
• Non-smokers have about twice the cough frequency as smokers.
• Perindopril and fosinopril have been observed to be less likely to cause dry cough than captopril, lisinopril and enalapril.
• Angioedema (Quincke’s edema) is also a common side effect of ACE inhibitors.
• It occurs much less frequently than dry cough – in 0.1-0.5% of cases, however, angioedema, unlike cough, can pose an immediate threat to the life of patients.
Non-specific side effects of ACE inhibitors include taste disturbances, leukopenia (neuropenia), skin rashes, dyspeptic disorders, as well as isolated cases of kidney and liver damage and anemia.

Contraindications
The use of ACE inhibitors as antihypertensive drugs is not recommended for bilateral renal artery stenosis, arterial stenosis of the only functioning kidney, severe renal failure (serum creatinine level above 300 µmol/l or 3.5 mg/dl), severe hyperkalemia (above 5.5 mmol / l), during pregnancy and in childhood, as well as with individual hypersensitivity to this group of drugs (dry cough or angioedema in history).

With great caution, ACE inhibitors should be used in patients with obliterating atherosclerosis of the arteries of the lower extremities (due to the frequent combination of atherosclerotic lesions of the peripheral and renal arteries), widespread atherosclerosis with lesions of the coronary and carotid arteries, moderate renal failure, moderate hyperkalemia (from 5 to 5.5 meq / l), chronic active hepatitis or cirrhosis of the liver, as well as in women of childbearing age (taking into account the possible adverse effects of drugs on the intrauterine development of the fetus).

4. Angiotensin II receptor antagonists (AT1 receptor blockers)
In the action of AII on blood vessels, two mechanisms are distinguished – pressor and depressor.
The pressor mechanism is mediated by the influence of AII on type 1 receptors and leads to vasoconstriction, sodium and fluid retention, increased sympathetic activity, decreased vagal tone, cell proliferation, and a positive inotropic effect.
The depressant effect of AII is realized through stimulation of type 2 receptors, which leads to vasodilation, especially pronounced in the vessels of the brain and kidneys, natriuretic effect, antiproliferative effect, activation of kininogen, release of nitric oxide and prostaglandin I2.

A more effective and specific approach to inhibition of excessive activity of the renin-angiotensin system in HT is provided by a class of drugs – angiotensin II receptor blockers (ARBs) or AT1-angiotensin receptor blockers (sartans)
Sartans have a number of important advantages over ACE inhibitors
Bo- First, AT1-angiotensin receptor blockers are more effective than ACE inhibitors in suppressing the cardiovascular effects of activation of the renin-angiotensin system.
If ACE inhibitors act on only one of the pathways for the formation of angiotensin II, AT1-angiotensin receptor blockers act as angiotensin II antagonists, regardless of how angiotensin II was formed.
Therefore, AT1-angiotensin receptor blockers provide a more complete and more selective blockade of the renin-angiotensin system.

Secondly, the action of sartans is more specific than the action of ACE inhibitors.
Due to the lack of effect on the bradykinin-kallikrein-kinin system, the main distinguishing feature of ARBs was high safety and a small number of side effects comparable to placebo. The absence of cough and a negligible number of allergic reactions are the absolute advantages of sartans over ACE inhibitors.
The direct mechanism of the antihypertensive action of AT1-angiotensin receptor blockers is associated with a weakening of the effects of angiotensin II (and angiotensin III), which are mediated by AT1-angiotensin receptors.
In addition, blockade of angiotensin II receptors leads to a decrease in aldosterone secretion, a decrease in the reabsorption of sodium and water in the proximal segment of the renal tubules.
Sartans block only AT1 receptors while maintaining the ability of circulating AT II to interact with AT2 receptors, which is accompanied by vasodilation, antiproliferation and promotes additional organoprotective effects, and this, in turn, inhibits the progression of the disease.
By blocking AT1 receptors, AT1-angiotensin blockers reduce arterial vasoconstriction caused by angiotensin II (and angiotensin III), reduce increased hydraulic pressure in the renal glomeruli, and also reduce the secretion of aldosterone, arginine-vasopressin, endothelin-1 and norepinephrine.
With long-term use, AT1-angiotensin receptor blockers weaken the proliferative effects of angiotensin II on cardiomyocytes and smooth muscle cells of the vascular wall, as well as mesangial cells and fibroblasts.

• Losartan (Cozaar, Lorista, Lozap, Blocktran)
• Valsartan (Diovan, Valsakor, Valz)
• Irbesartan (Aprovel)
• Candesartan (Atakand) 900 03 • Eprosartan (Teveten)
• Telmisartan (Micardis)
• Olmesartan (benicar, cardosal)
• Azilsartan medoxomil (edarbi)
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• Prodrugs
Prodrugs include:
• Losartan – hepatic metabolism, only 14% converted to active metabolite,
• Candesartan, olmesartan and azilsartan – hydrolysis in the gastrointestinal tract.

Sartans have a large evidence base for cerebroprotection, nephroprotection and a reduction in the risk of cardiovascular complications.
A large number of controlled studies have shown their ability not only to slow down the rate of development and progression of target organ damage (decrease in left ventricular hypertrophy, decrease in the severity of microalbuminuria and proteinuria, slowing down the rate of decline in kidney function, cerebroprotection), but also to prevent organ damage.
• One of the important drug-specific aspects of the use of sartans is the reduction in the incidence of type 2 diabetes mellitus. 2010), high doses of losartan (RENAAL, 2001; RASS, 2009).
• For three drugs – losartan, valsartan and candesartan – CHF is registered as an indication for use.
At the same time, CHF is a contraindication for prescribing telmisartan
• In patients at high and very high risk of developing CV events, telmisartan is indicated even with high normal blood pressure. Among all ARBs, only telmisartan has been shown to reduce the incidence of all CV events with excellent treatment tolerance.
• Telmisartan has the longest half-life (more than 20 hours) among all sartans, which allows patients from the “non-dipper” group to move to the prognostically more favorable “dipper” group, with a minimal risk of increasing blood pressure in the early morning hours and a reduced risk of developing stroke.
• Telmisartan reduces LVH more effectively than other antihypertensive drugs
• Nephroprotection
• Reduces insulin resistance

Telmisartan not only improved anthropometric parameters, but also reduced the number and volume of body fat
When comparing Telmi sartans with other sartans were found to be beneficial in lowering triglycerides and increase in HDL level
Uricosuric effect
Decreased activity of RAAS and SNS

Azilsartan (Edarbi)
Experimental studies have shown that Edarbi® binds to angiotensin receptors more strongly than other ARBs (olmesartan, telmisartan, valsartan).
This explains the faster, longer and more pronounced antihypertensive effect of the drug
Olmesartan has not only good antihypertensive efficacy, the ability to reduce arterial stiffness, improve the function of the vascular endothelium, but also has cerebroprotective properties.
This allows us to recommend the drug primarily for the treatment of elderly patients with hypertension, for whom the task of maintaining cognitive functions is one of the priorities
In the olmesartan group, normalization of blood pressure was achieved in 75.4% of patients, in the treatment with perindopril – in 57.5%

5. α1-adrenergic receptor blockers
α-adrenergic receptor blockers represent a fairly large and heterogeneous group of drugs that have been used since the early 1960s to treat various forms of arterial hypertension.

Classification of α-adrenergic receptor blockers
α-Adrenergic receptor blockers are divided into two main groups:

1. non-selective and
2. α1-selective.

Non-selective (phentolamine) weaken the effects of catecholamines on both a1- and a2-adrenergic receptors, selective – selectively inhibit the effects of catecholamines on a1-adrenergic receptors of blood vessels and other organs and tissues.
• Prazosin – pratsiol, minipress, adverzuten,
• doxazosin – kamiren, cardura, tonocardin, artesin, doxaprostan)
• terazosin – cornam, setegis (BPH)
• tamsulosin – omnic (BPH)
hypertensive drugs that are not formally classified as group of a-blockers.
Thus, a1-adrenoblocking action was found in two b-blockers (carvedilol and proxodolol)

Extravascular effects of a1-blockers are of great clinical importance.
It has been established that selective blockers of a1-adrenergic receptors can improve the lipid composition of the blood – they significantly reduce the content of total cholesterol in the blood due to its atherogenic fraction – LDL cholesterol and at the same time increase HDL levels. The content of triglycerides also decreases during treatment with a1-blockers.
The effect of a1-blockers on blood lipid composition is especially pronounced in patients with atherogenic dyslipidemias

a1-blockers significantly increase the sensitivity of tissues to the action of insulin. Doxazosin, for example, causes a small but statistically significant decrease in basal glucose (by 7 mg/dl, or 5%) and insulin (by 14 mmol/l, or 17%) in hypertensive patients.
Two clinical studies have shown that a1-blockers (in particular, doxazosin) inhibit platelet aggregation

The predominance of a1-adrenergic receptors in the smooth muscles of the prostate and bladder neck served as the basis for the use of prazosin, and then other a1-blockers in patients with benign prostatic hyperplasia.

The tendency to orthostatic reactions, which is often found in the elderly and patients with diabetic neuropathy, is a contraindication for the use of a1-blockers.
By lowering blood pressure, a1-blockers cause reflex activation of the sympathetic nervous system, which is manifested by tachycardia.
Therefore, a1-blockers should not be used in patients with coronary artery disease with exertional angina without the simultaneous appointment of b-blockers, which prevent the occurrence of reflex tachycardia.

6. Central sympatholytics
Hyperactivity of the SNS is one of the main mechanisms for increasing blood pressure and a poor prognostic sign in patients with hypertension.
Approximately 30% of patients with hypertension have hyperactivity of the SNS, which is manifested not only by an increase in blood pressure, but also by tachycardia, an increase in cardiac output, renal vasoconstriction, fluid retention, and insulin resistance
reserpine
• 2nd generation – clonidine (clophelin, hemiton)
• 3rd generation (imidazoline receptor agonists) – moxonidine (cint, physiotens, moxogamma), rilmenidine (albarel)
According to modern concepts, the antihypertensive effect of moxonidine and rilmenidine is based on agonism against I1-imidazoline receptors of neurons located in the ventrolateral nuclei of the medulla oblongata.
By attenuating SNS hyperactivity, these I1-imidazoline receptor agonists reduce blood pressure and decrease heart rate.

Moxonidine reduces the activity of SNS and thus leads to a decrease in blood pressure.
An important advantage of moxonidine is a positive effect on carbohydrate and lipid metabolism. Moxonidine increases the sensitivity of tissues to insulin by improving the insulin-dependent mechanism of glucose transport into cells, reduces the level of insulin, leptin and glucose in the blood, reduces the content of triglycerides and free fatty acids, increases the level of HDL cholesterol.
In overweight patients, moxonidine results in weight loss (MERSY).
Moxonidine has an organoprotective effect: reduces LVH, improves diastolic function of the heart, cognitive functions of the brain, reduces MAU.
Moxonidine may be indicated for the treatment of hypertension in patients with MS or type 2 diabetes in combination with ACE inhibitors or ARBs, calcium antagonists.

Moxonidine and rilmenidine are contraindicated :
• severe mental depression,
• Sinus bradycardia (HR less than 50 per minute),
• Sick sinus syndrome,
• II-III degree atrioventricular block,
• Severe liver disease,
• Severe kidney failure.
Due to lack of clinical experience, it is recommended that moxonidine and rilmenidine should not be given to women during pregnancy and breastfeeding.

7. Renin inhibitors
Aliskiren (Rasilez) – direct renin inhibitor
Renin secretion by the kidneys and activation of the RAAS occurs with a decrease in BCC and renal blood flow through a feedback mechanism.
Renin acts on angiotensinogen, resulting in the formation of an inactive decapeptide – angiotensin I (ATI), which, with the help of ACE and, partially, without its participation, is converted into the active octapeptide angiotensin II (ATII).
ATII reduces renin secretion by a negative feedback mechanism. Drugs that inhibit the RAAS (including renin inhibitors) suppress negative feedback, leading to a compensatory increase in plasma renin concentration.

Treatment with ACE inhibitors and angiotensin II receptor antagonists also increases plasma renin activity, which is directly associated with an increased risk of cardiovascular disease in both patients with normal blood pressure and in patients with arterial hypertension.
When using aliskiren as a monotherapy and in combination with other antihypertensive agents, negative feedback suppression is neutralized, resulting in a decrease in plasma renin activity (in patients with arterial hypertension by an average of 50-80%), as well as ATI and ATII levels
In patients with arterial hypertension, when using Rasilez at a dose of 150 and 300 mg 1 time / day, there is a dose-dependent prolonged decrease in both systolic and diastolic blood pressure for 24 hours, including the early morning hours.
After 2 weeks of taking the drug, there is a decrease in blood pressure by 85-90% of the maximum, the hypotensive effect remains at the achieved level during long-term (up to 1 year) use.
After discontinuation of treatment with Rasilez, there is a gradual return of blood pressure to the initial level within a few weeks, without the development of a withdrawal syndrome and an increase in plasma renin activity.
4 weeks after discontinuation of Rasilez, blood pressure remains significantly lower compared to placebo.

When using the drug for the first time, there is no hypotensive reaction (effect of the first dose) and a reflex increase in heart rate in response to vasodilation.
When using Rasilez as monotherapy and in combination with other antihypertensive drugs, an excessive decrease in blood pressure is observed in 0.1% and 1% of cases, respectively.
Combination therapy with Rasilez with ACE inhibitors, angiotensin II receptor antagonists, calcium channel blockers and diuretics is well tolerated by patients and allows to achieve an additional reduction in blood pressure.

Contraindications
• Severe renal dysfunction (serum creatinine >150 µmol/l for women and >177 µmol/l for men and/or glomerular filtration rate < 30 ml/min).
• Nephrotic syndrome.
• Renovascular hypertension.
• Regular hemodialysis.
• Severe hepatic impairment
• Children and adolescents under 18 years of age.
• Hypersensitivity to the components of the drug.
• With caution, the drug should be prescribed to patients with unilateral or bilateral renal artery stenosis or stenosis of the artery of a single kidney, diabetes mellitus, reduced BCC, hyponatremia, hyperkalemia, or patients after kidney transplantation. The safety of using Rasilez in patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney has not been established.

Side effects
• Rasilez has been evaluated for safety in more than 7800 patients.
• When using the drug at a dose of up to 300 mg, the overall frequency of adverse reactions was similar to that when using placebo. Adverse reactions were generally mild, transient, and rarely required discontinuation of drug therapy. Diarrhea was most frequently observed in patients treated with Rasilez.
• When using the drug, there was no increase in the incidence of dry cough, characteristic of ACE inhibitors. The incidence of dry cough during treatment with Rasilez (0.9%) was similar to that of placebo (0.6%).
• From the digestive tract: often – diarrhea.
• Dermatological reactions: sometimes – skin rash.
• On the part of laboratory parameters: rarely – against the background of monotherapy, a slight decrease in the concentration of hemoglobin and hematocrit was observed (on average by 0.05 mmol / l and 0.16%, respectively), which did not require discontinuation of treatment (a decrease in the concentration of hemoglobin and hematocrit is also observed with the use of other drugs, affecting the RAAS, in particular ACE inhibitors and angiotensin II receptor antagonists), a slight increase in serum potassium concentration (0.9% compared to 0.6% when taking placebo).
• No clinically significant changes in total cholesterol, HDL, and fasting triglycerides, glucose, or uric acid were observed.
• Allergic reactions: in some cases – angioedema.

Combination therapy
• Use two drugs for initial therapy if BP is 20/10 mmHg above target. Art. (i.e. > 160/100 mmHg for patients with uncomplicated hypertension or > 150/90 mmHg Art. for people with diabetes and other comorbidities).
• Treatment of patients with grade 1 hypertension is often advisable to start with monotherapy.
• However, recent evidence suggests that the benefits of initial combination therapy may extend to patients with grade 1 hypertension.

Adverse events of antihypertensive drugs and how to manage them

What drugs can cause hearing loss

The word ototoxicity comes from the fusion of two Greek words – otos (ear) + toxikon (toxin, poison). The negative effect of ototoxic drugs is manifested in most cases by a destructive effect on the hair cells of the inner ear. Such exposure can lead to hearing impairment, sensations of noise and ringing in the ears.

Moreover, this negative effect sometimes appears while taking drugs (acute manifestation), and sometimes – after months and even years (delayed action). Children and the elderly are more likely to suffer from such exposure. But the worst thing is that in some cases the prognosis for the restoration of impaired functions turns out to be unfavorable.

Prescribe ototoxic drugs if there is no other choice – the drug is vital and has no alternatives. It is especially not recommended to prescribe such drugs to women during pregnancy and lactation, the elderly, patients with kidney disease and diabetes, and those who have established hearing problems.

The intake of ototoxic drugs must be carried out under the supervision of an audiologist and an otolaryngologist.

So which drugs can cause hearing loss?

This list will help you minimize your risks.

Antibiotics

Many groups of antibiotics have ototoxic properties.

Aminoglycosides

It can be difficult to stop using these drugs. They are used to treat pneumonia, tuberculosis, sinusitis and nosocomial infections:

• streptomycin, kanamycin, neomycin;
• erythromycin, gentamicin, sisomycin, tobramycin, netilmicin, rifampicin, florimycin;
• amikacin, ristomycin;
• isepamycin, azithromycin.

The most toxic are neomycin, gentamicin and amikacin, the least toxic is erythromycin.

The risk of hearing problems increases if the aminoglycoside is taken for more than 10 days, when taking 2 or more drugs at the same time, and also when taken with diuretics.

Aminoglycosides cross the placenta, thereby increasing the risk of having a baby with deafness. They also penetrate the blood through the skin, so even in the form of ointments they have an ototoxic effect.

Ibuprofen, indomethacin, naproxen and diclofenac sodium are also drugs that affect hearing. When you stop taking these medications, usually the toxic effect disappears.

Tetracyclines

Minocycline and minolexin cause hearing and vestibular disorders.

Polymyxins

Polymyxin B sulfate and Polydex – drops that are used in otolaryngology. May cause deafness.

Glycopeptides

Vancomycin and teicomycin cause hearing impairment.

Polypeptides

The antibiotic histomycin adversely affects the auditory nerve, causing irreversible hearing loss.

Diuretics

Loop diuretics are often prescribed for kidney disease, high blood pressure and heart failure. They cause an imbalance of sodium and potassium in the fluid that fills the cochlea of ​​the inner ear:

• Furosemide (Lasix),
• ethacrynic acid,
• bumetanide and bufenox.

Hearing problems usually disappear when diuretics are stopped.

Anti-inflammatory

Aspirin and preparations containing it interfere with the conduction of hair cell membranes, thereby complicating the conduction of sound. This effect is observed only with long-term use of 5-8 tablets per day.

Cardiac

Some drugs used to treat arrhythmias, angina pectoris, high blood pressure and thyrotoxicosis have the side effect of ototoxicity. Lidocaine, metoprolol, celiprolol, tambokor, lopressor, procainamide, propanolol have a particularly negative effect on hearing.

Hydroxychloroquine

The antimalarial and anti-inflammatory drug hydroxychloroquine was used in some countries in 2020 as a treatment for COVID-19. However, its effectiveness has not been proven.

One of the side effects of taking hydroxychloroquine can be temporary hearing loss.

Antimicrobials

Furadonin, which is used to treat cystitis and pyelonephritis, is very toxic and is contraindicated in people with hearing problems.

Chemotherapy drugs

Cisplatin, carboplatin and oxaliplatin, some of the best (today’s) platinum-based antitumor drugs, are very ototoxic. Vincristine, vinblastine, methotrexate and cyclophosphamide have the same properties.

Antidepressants

Most antidepressants and tranquilizers are ototoxic, including Xanax, Tranxen, Librium, Flurazepam, Prozepam, Midazolam, Doral, Temazepam, Oxazepam, Triazolam, Bupropion, Carbamazepine, Doxepin, Norpramine, Tofranil , molidone, phenelzine, vivactil etc.

Contraceptives and drugs for medical termination of pregnancy

Many contraceptives can cause blood clots in the vessels of the inner ear. For their level of negative impact on hearing, carefully read the instructions for the drug.

Miropristone, misoprostone, mifepristone, etc. – medicines for medical termination of pregnancy, very ototoxic. After taking them, it is recommended to conceive a child no earlier than six months later.