Chlorthalidone – StatPearls – NCBI Bookshelf

Continuing Education Activity

Chlorthalidone is a medication used in the management and treatment of hypertension. It is in the thiazide-like diuretics class of drugs. This activity reviews chlorthalidone’s indications, action, and contraindications as a valuable agent in managing hypertension, edema, and calcium nephrolithiasis. This activity will highlight the mechanism of action, adverse event profile, and pharmacokinetics of chlorthalidone. Identifying these properties is essential for interprofessional team members to manage patients with hypertension effectively.

Objectives:

• Identify the mechanism of action of chlorthalidone.

• Describe the potential adverse effects of chlorthalidone.

• Outline appropriate monitoring for patients on therapy with chlorthalidone.

• Summarize interprofessional team strategies for improving care coordination and communication to advance proper chlorthalidone administration and verify medication allergies.

Access free multiple choice questions on this topic.

Indications

Chlorthalidone is a thiazide-like sulfonamide-derived diuretic that has been FDA approved since 1960 to manage hypertension.[1] Chlorthalidone is a first-line agent for the treatment of hypertension.[2] This medication is utilized both as an isolated agent and in combination with other antihypertensive drugs, including beta-blockers or clonidine.

It is also used in the treatment of edema.[3] The utility for edema comes in multiple settings, including congestive heart failure, hepatic cirrhosis, corticosteroid therapy, as well as renal dysfunction, including chronic renal failure, nephrotic syndrome, and acute glomerular nephritis.[3] Chlorthalidone should also be considered in the treatment of calcium nephrolithiasis, Meniere disease, and diabetes insipidus, although it does not have FDA approval to treat these conditions.[4][5] Chlorthalidone treats these conditions by antagonizing sodium chloride co-transporter in the distal convoluted tubule (DCT) in the loop of Henle. [6] 

Chlorthalidone’s first indication was as an antihypertensive agent. It is effective in the management of blood pressure by decreasing intravascular volume through promoted diuresis. Per the 2017 guideline for the prevention, detection, evaluation, and management of high blood pressure, chlorthalidone can be used as a first-line age in the setting of hypertension when there are no contraindications or contributory comorbidities.[7] However, patients with cerebrovascular disease, advanced chronic kidney disease, diabetes, and heart failure treatment would preferably receive therapy with angiotensin-converting enzyme inhibiting medication (ACE-I). These guidelines suggest that dihydropyridine calcium channel blockers and thiazide-like diuretics are the preferred agents in the absence of comorbidities because of better cardiovascular outcomes, specifically the reduced risk of heart failure and cerebral vascular accident.[8]

Of note, the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack) trial compared other first-line antihypertensives such as calcium channel blockers and angiotensin-converting-enzyme-inhibitors(ACE-I) against chlorthalidone. ALLHAT concluded that thiazide-like diuretics should be considered in the first-line treatment in hypertensive patients as chlorthalidone had less association with stroke than ACE-I and less association with heart failure compared to calcium channel blockers. The results of this study were attributed to the earlier and more significant decrease in blood pressure, specifically systolic, from chlorthalidone compared to lisinopril and amlodipine.[8]

Thiazide-like Medication Versus Thiazide-type Diuretics

Thiazide-type medications, most commonly hydrochlorothiazide (HCTZ), have been around longer than thiazide-like antihypertensives and were previously utilized more substantially. However, multiple studies have shown a preference for thiazide-like medications over their original counterparts. A 2015 systematic review showed that chlorthalidone alleviated hypertensive burden by about 5.1 mmHg of systolic blood pressure than HCTZ, finding chlorthalidone more potent than HCTZ. [9] 

In addition to potency, studies have demonstrated that chlorthalidone holds a longer duration of action than HCTZ, 24 hours with chlorthalidone versus 6 to 12 hours with HCTZ. This increased duration of action allows for the increased flexibility of dosing.[9] A study has shown that as a result of this longer duration of action that chlorthalidone is 1.5 to 2.0 times more efficacious at lowering systolic blood pressure than HCTZ (comparative antihypertensive effects between hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure.)[10] 

Cardiovascular Outcomes

With consideration of any antihypertensive medication, the effect of cardiovascular outcomes is of the highest priority. The ALLHAT trial showed a decreased risk of heart failure exacerbation and cerebral vascular accidents compared to amlodipine and lisinopril, respectively.[8][11] Additionally, a meta-analysis in 2012, including over 100000 patients, concluded that chlorthalidone and thiazide-like diuretics lowered the risk of heart failure by twenty-one percent and cardiovascular events by twelve percent. In comparison, thiazide-type HCTZ did not show improved outcomes compared to placebo.[8]

Mechanism of Action

Chlorthalidone exerts its therapeutic action by antagonizing sodium-chloride symporter in the distal convoluted tubule of the nephron. It is similar to a thiazide diuretic in its mechanism of action, although it has a mildly altered chemical structure. Both thiazide and thiazide-like diuretics contain a sulfonamide group that also works to inhibit carbonic anhydrase and its antagonistic action at the distal convoluted tubule.[9]

Chlorthalidone inhibits sodium reabsorption at the level of the distal convoluted tubule and thus chloride via inhibition of the Na/Cl symporter. By removing sodium reabsorption at this location, the distal convoluted tubule of the nephron retains a higher sodium content. This lack of reabsorption alters the osmotic gradient and shifts fluid distribution from the outside of the tubule to the inside of the tubule. The increased osmotic load from its increased sodium concentration leads to elevated intratubular volume, thus promoting its diuretic effect.  The increased excretion of sodium and extracellular fluid decreases intravascular water and solute concentration. By lowering the intravascular volume and osmotic gradient, the patient has reduced hydrostatic pressure leading to a clinical reduction in blood pressure.

Administration

Chlorthalidone is available solely as an oral medication.

Strength: 25 mg, 50 mg

Hypertension: starting from 12.5 to 25 mg daily, maximum dose: 100 mg daily

Heart failure: starting from 12.5 mg or 25 mg daily, maximum dose: 100 mg daily 

Generalized edema: starting from 50 g or 100 mg daily, maximum dose: 200 mg daily

Calcium nephrolithiasis: 25 mg/daily

The age of the patient is also an essential consideration while determining the dose. The geriatric population (i.e., over 65 years) should receive lower dosing of chlorthalidone, starting with 6.25 mg to 12.5 mg daily and titrated slowly, as mentioned above.

Chlorthalidone is available solely as an oral medication. Chlorthalidone comes in pills of 25 mg and 50 mg, which can be split for adequate dosing. Dosing regimens vary depending on clinical indication. For the treatment of heart failure, guidelines recommend dosing start at 12.5 mg or 25 mg daily and can be titrated up to 100 mg daily as necessary. For generalized edema, dosing begins with 50 to 100 mg daily and can be titrated to a maximum of 200 mg daily. As outlined above, chlorthalidone can also be utilized to manage calcium nephrolithiasis, which is generalized administered at 25 mg/daily. The age of the patient is also an essential consideration while determining the dose. The geriatric population, patients older than 65 years of age, should receive lower dosing of chlorthalidone, starting with 6.25 to 12.5 mg titrated to a maximum of 25mg/daily. Diuretic medication, such as chlorthalidone, is a Beers criteria medication and should be used cautiously.[12]

Adverse Effects

Significant adverse effects are electrolyte derangement (hypokalemia, hyponatremia, etc. ), hypersensitivity reaction, and precipitation of acute gout attacks. 

The adverse effects of chlorthalidone span across most organ systems to differing degrees and manifestations. Of significance, as a result of promoted diuresis and altering of nephron physiology, electrolyte derangement is a commonly reported adverse effect of this medication. Most commonly, chlorthalidone includes hypokalemia but may also cause hyponatremia or hypochloremia. These known derangements make monitoring serum electrolytes essential for patients receiving chlorthalidone periodically throughout hypertensive management. 

Reported side effects (per the Food and Drug Administration):

• Gastrointestinal side effects: anorexia, stomach irritation, nausea, emesis, cramping, loose stools, constipation, and pancreatitis.

• Neurologic reactions: paresthesias, dizziness, and headaches

• Hematologic reactions: aplastic anemia, leukopenia, agranulocytosis, and thrombocytopenia.

• Cardiovascular reaction: orthostatic hypotension

• Dermatologic reactions: purpura, photosensitivity, rash, urticaria, necrotizing angiitis (cutaneous vasculitis), Lyell syndrome (toxic epidermal necrolysis).

• Other adverse reactions: hyperglycemia, glycosuria, hyperuricemia, muscle spasm, weakness, restlessness, impotence

Contraindications

Absolute Contraindications

• Hypersensitivity to chlorthalidone

• Hypersensitivity to the sulfonamides-derived medications

• Significant electrolyte derangement (severe hypokalemia, severe hyponatremia)

• Anuria

Relative Contraindication

• Advanced chronic kidney disease

• Orthostatic hypotension

• Syncope

• Geriatric population (age greater than 65 due to risk of hyponatremia)

• Pregnancy

• Hypercalcemia

• Severe hyperuricemia or gout

Monitoring

The following items require periodic monitoring when the patients take chlorthalidone.  

• Serum electrolytes: Serum sodium, potassium, chloride, and calcium levels should be checked periodically.[13] 

• Fluid status and Blood pressure: All patients taking chlorthalidone require observation for dryness of mouth, thirst, lethargy, hypotension, oliguria, tachycardia, palpitations, and gastrointestinal disturbances, such as nausea and vomiting. Chlorthalidone is a diuretic, so an inappropriately high dose can cause severe volume depletion.  

• Magnesium level: It can increase the urinary excretion of magnesium and may result in hypomagnesemia.

• Uric acid level: Hyperuricemia may occur, or frank gout may be precipitated in certain patients receiving chlorthalidone.

• Serum glucose level: serum glucose may increase with chronic use. 

There is insufficient research performed to check teratogenicity, but chlorthalidone should be used during pregnancy only if absolutely necessary.  

Toxicity

Symptoms of acute overdosage:

• Nausea

• Weakness

• Dizziness (due to severe hypotension)

• Electrolyte disturbances (such as hypokalemia, hyponatremia, and hypomagnesemia)

Treatment of acute overdosage:

• No specific antidote is available

• Gastric lavage

• Supportive management includes intravenous dextrose or normal saline for hypotension, intravenous potassium chloride for severe hypokalemia

Enhancing Healthcare Team Outcomes

As a sulfonamide-derived medication, the prescribing clinician needs to review relevant allergies when prescribing chlorthalidone. An interprofessional team approach, including clinicians (MDs, DOs, NPs, PAs), specialists, mid-level practitioners, nurses, and pharmacists, can help to maintain updated allergies. A review of allergies can start upon reception by asking patients to review their previous chart and update relevant sections, including allergies. While in a hospital setting, it can be prompted before administration by the nurse. In a pharmacy setting, the pharmacist can inquire before the dispersal of the medication. Additionally, EMR now allows an additional barrier with risk-advisory when prescribing medication to which patients are allergic.[14] 

In addition to allergies, clinicians, nurses, and pharmacists are responsible for counseling the patient, verifying dosing, and monitoring for adverse events. Pharmacists must also perform medication reconciliation to preclude any possible drug-drug interactions and notify the other interprofessional healthcare team members when concerns arise.

Updating the type of adverse reaction occurring with the allergy is vital to avoid and characterize the true allergy. Deciphering whether a true allergy or previous side-effect from a medication is crucial as it changes therapeutic options for the patient.[14] [Level 3] The interprofessional paradigm will contribute to positive patient outcomes when using chlorthalidone. [Level 5]

Review Questions

• Access free multiple choice questions on this topic.

• Comment on this article.

References

1.

HOLLANDER W, WILKINS RW. Chlorothiazide: a new type of drug for the treatment of arterial hypertension. BMQ. 1957 Sep;8(3):69-75. [PubMed: 13471453]

2.

Thanikgaivasan V. Letter – Diuretics in primary hypertension – Reloaded. Indian Heart J. 2017 Mar-Apr;69(2):284. [PMC free article: PMC5414989] [PubMed: 28460781]

3.

Akbari P, Khorasani-Zadeh A. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Jan 23, 2023. Thiazide Diuretics. [PubMed: 30422513]

4.

Roush GC, Abdelfattah R, Song S, Ernst ME, Sica DA, Kostis JB. Hydrochlorothiazide vs chlorthalidone, indapamide, and potassium-sparing/hydrochlorothiazide diuretics for reducing left ventricular hypertrophy: A systematic review and meta-analysis. J Clin Hypertens (Greenwich). 2018 Oct;20(10):1507-1515. [PMC free article: PMC8030834] [PubMed: 30251403]

5.

Riley M, Hernandez AK, Kuznia AL. High Blood Pressure in Children and Adolescents. Am Fam Physician. 2018 Oct 15;98(8):486-494. [PubMed: 30277729]

6.

Greger R, Lohrmann E, Schlatter E. Action of diuretics at the cellular level. Clin Nephrol. 1992;38 Suppl 1:S64-8. [PubMed: 1338305]

7.

Zhou Y, Jia L, Lu B, Gu G, Hu H, Zhang Z, Bai L, Cui W. Updated hypertension prevalence, awareness, and control rates based on the 2017ACC/AHA high blood pressure guideline. J Clin Hypertens (Greenwich). 2019 Jun;21(6):758-765. [PMC free article: PMC8030613] [PubMed: 31131983]

8.

Dewland TA, Soliman EZ, Davis BR, Magnani JW, Yamal JM, Piller LB, Haywood LJ, Alonso A, Albert CM, Marcus GM., Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Collaborative Research Group. Effect of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) on Conduction System Disease. JAMA Intern Med. 2016 Aug 01;176(8):1085-92. [PubMed: 27367818]

9.

Dineva S, Uzunova K, Pavlova V, Filipova E, Kalinov K, Vekov T. Comparative efficacy and safety of chlorthalidone and hydrochlorothiazide-meta-analysis. J Hum Hypertens. 2019 Nov;33(11):766-774. [PMC free article: PMC6892412] [PubMed: 31595024]

10.

Pareek AK, Messerli FH, Chandurkar NB, Dharmadhikari SK, Godbole AV, Kshirsagar PP, Agarwal MA, Sharma KH, Mathur SL, Kumbla MM. Efficacy of Low-Dose Chlorthalidone and Hydrochlorothiazide as Assessed by 24-h Ambulatory Blood Pressure Monitoring. J Am Coll Cardiol. 2016 Feb 02;67(4):379-389. [PubMed: 26821625]

11.

Roush GC, Holford TR, Guddati AK. Chlorthalidone compared with hydrochlorothiazide in reducing cardiovascular events: systematic review and network meta-analyses. Hypertension. 2012 Jun;59(6):1110-7. [PubMed: 22526259]

12.

By the 2019 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2019 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019 Apr;67(4):674-694. [PubMed: 30693946]

13.

Cooney D, Milfred-LaForest S, Rahman M. Diuretics for hypertension: Hydrochlorothiazide or chlorthalidone? Cleve Clin J Med. 2015 Aug;82(8):527-33. [PubMed: 26270432]

14.

Hsieh TC, Kuperman GJ, Jaggi T, Hojnowski-Diaz P, Fiskio J, Williams DH, Bates DW, Gandhi TK. Characteristics and consequences of drug allergy alert overrides in a computerized physician order entry system. J Am Med Inform Assoc. 2004 Nov-Dec;11(6):482-91. [PMC free article: PMC524628] [PubMed: 15298998]

Disclosure: Connor Kerndt declares no relevant financial relationships with ineligible companies.

Disclosure: Jayesh Patel declares no relevant financial relationships with ineligible companies.

Which diuretics are safe and effective for patients with a sulfa allergy?

Clinical Inquiries

By

Author and Disclosure Information

References

1. Strom BL, Schinnar R, Apter AJ, et al. Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. N Engl J Med 2003;349:1628-1635.

2. Lee AG, Anerson R, Kardon RH, Wall M. Presumed “sulfa allergy” in patients with intracranial hypertension treated with acetazolamide or furosemide: Cross-reactivity, myth or reality? Am J Ophthalmol 2004;138:114-118.

3. Johnson KK, Green DL, Rife JP, Limon L. Sulfonamide cross-reactivity: fact or fiction? Ann Pharmacother 2005;39:290-301.

4. Knowles S, Shapiro L, Shear NH. Should celecoxib be contraindicated in patients who are allergic to sulfonamides? Drug Safe 2001;24:239-247.

5. Furosemide Tablets, USP. Physicians’ Desk Reference. 61st ed. Montvale, NJ: Thomson; 2007:2155.

6. Dyazide. Physicians’ Desk Reference. 61st ed. Montvale, NJ: Thomson; 2007:1424.

EVIDENCE-BASED ANSWER

Diuretics that do not contain a sulfonamide group (eg, amiloride hydrochloride, eplerenone, ethacrynic acid, spironolactone, and triamterene) are safe for patients with an allergy to sulfa. The evidence is contradictory as to whether a history of allergy to sulfonamide antibiotics increases the risk of subsequent allergic reactions to commonly used sulfonamide-containing diuretics (eg, carbonic anhydrase inhibitors, loop diuretics, and thiazides) (strength of recommendation: C, based on case series and poor quality case-control and cohort studies).

Clinical commentary

Are all sulfa drugs created equal?
Brian Crownover, MD, FAAFP
96 MDG Family Medicine Residency, Eglin Air Force Base, Fla

Historical bromides commonly fall by the wayside as better evidence becomes available. Who would have thought 15 years ago that we would be promoting beta-blockers for patients with congestive heart failure?

Likewise, with closer inspection, we have learned that not all sulfa drugs are created equal. The stereospecificity due to the absence of aromatic amines in common diuretics means they are safe for patients with known sulfa antibiotic allergies. Given that diuretics are older agents and off-patent, with no company to take up their cause, no one has been willing to challenge outdated package insert warnings.

As clinicians who regularly work without a net, we are accustomed to prescribing medications in less than ideal circumstances. Thankfully, reasonable evidence is available to support what many of us are already doing—using cheap thiazides for patients despite a history of sulfa allergy.

Evidence summary

Little research has been performed on sulfonamide antibiotic and sulfonamide diuretic allergic cross-reactivity. What we do know is that there are 2 classes of sulfonamides—those with an aromatic amine (the antimicrobial sulfonamides) and those without (eg, the diuretics acetazolamide, furosemide, hydrochlorothiazide, and indapamide). Hypersensitivity reactions occur when the aromatic amine group is oxidized into hydroxylamine metabolites by the liver. Sulfonamides that do not contain this aromatic amine group undergo different metabolic pathways, suggesting that allergic reactions that do occur in this group are not due to cross-reactivity in sulfa-allergic patients. But that point is far from settled by the research.

On one side, a large cohort study shows some cross-reactivity

A large retrospective cohort study using Britain’s General Practice Research Database identified 20,226 patients seen from 1987 through March 1999 who were prescribed a systemic sulfonamide antibiotic, and then at least 60 days later received a nonantibiotic sulfonamide (eg, thiazide diuretic, furosemide, oral hypoglycemic).¹ Researchers reviewed records to determine whether patients described as having an allergic reaction to a sulfonamide antibiotic were at increased risk of having a subsequent allergic reaction to a sulfonamide nonantibiotic.

Patients were identified as being allergic using both narrow definitions (anaphylaxis, bronchospasm, urticaria, laryngospasm, or angioedema) and broad ones. As only 18 patients out of the 20,226 patients were reported as having an allergic reaction using the narrow definition, analysis was based on the broad definition. Added to the broad category were asthma, eczema, and other “adverse” drug effects that were not specified by the author.

Using this broad definition, researchers identified allergies to sulfonamide antibiotics in 969 patients. Of this group, 96 patients (9.9%) had a subsequent reaction to a sulfonamide nonantibiotic, which included drugs from the loop and thiazide diuretic classes (including bumetanide, chlorothiazide, furosemide, hydrochlorothiazide, indapamide, and torsemide). It was unclear if any patients taking a carbonic anhydrase inhibitor experienced an allergic reaction. For comparison purposes, of the 19,257 patients who were not identified as having an allergy to a sulfonamide antibiotic, again using the broad definition, 315 (1.6%), had a subsequent allergic reaction to a sulfonamide nonantibiotic, for an unadjusted odds ratio of 6.6 (95% confidence interval [CI], 5.2–8.4).

When the results were adjusted for age, sex, history of asthma, use of medications for asthma or corticosteroids, the adjusted odds ratio for individuals experiencing an allergy to a nonantibiotic sulfonamide in those persons with a history of allergy to a sulfonamide antibiotic was 2. 8 (95 % CI, 2.1–3.7). Of note, the adjusted odds ratio for the occurrence of a penicillin allergy in a patient with a history of sulfonamide antibiotic allergy was significantly higher at 3.9 (95% CI, 3.5–4.3).

Some limitations of the study included uncertainty of cause and effect of prescribed medications and subsequent reactions, possible inconsistency of physician diagnosis and coding, and lack of precision in the diagnosis of allergic reactions. There is also the possibility of “suspicion bias,” where patients with a history of allergies may be more closely monitored for subsequent reactions than nonallergic patients.

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instruction, use, analogues of the drug, composition, indications, contraindications, side effects in the reference book of medicines from UNIAN

The use of Chlorthalidone

Chlortalidone – composition and form of release of the drug

Chlortalidone: how to take the drug

Chlortalidone – contraindications, side effects

Chlorthalidone’s analogs

Chlorthalidone is a long-acting oral diuretic with antihypertensive activity.

Application of Chlorthalidone

Indications.

Treatment of hypertension, essential or nephrogenic, or isolated systolic hypertension.

Treatment of stable, chronic mild to moderate heart failure (NYHA functional class II or III).

Treatment of edema.

Chlorthalidone – composition and formulation of the drug

Composition:

active ingredient: chlortalidone;

1 tablet contains 25 mg or 50 mg of chlorthalidone;

excipients: microcrystalline cellulose, pregelatinized starch, quinoline yellow (E104), sodium starch glycolate, anhydrous colloidal silicon dioxide, stearic acid.

Dosage form. Pills.

Chlorthalidone: how to take the drug

Dosage and administration.

Arterial hypertension.

Monotherapy. For the treatment of hypertension, the recommended starting dose of chlorthalidone for adults is 25 mg daily. This is sufficient to cause the maximum hypotensive effect in most patients. If a decrease in blood pressure does not occur at a dose of 25 mg / day, it can be increased to 50 mg / day. If additional antihypertensive therapy is used, increasing the dose of the drug to more than 50 mg increases metabolic complications and rarely has a therapeutic effect.

Combination therapy. If combination therapy is needed for the treatment of arterial hypertension, the dosage can be adjusted, first of all, when using each drug separately.

Stable chronic heart failure (NYHA functional class II or III).

The recommended starting dose is 25 to 50 mg/day, in severe cases the dose may be increased to 100 to 200 mg/day. The usual maintenance dose is the lowest effective dose, eg 25 to 50 mg daily or every other day. If the response is insufficient, digitalis preparations and/or ACE inhibitors may be added.

Children. The drug is not used in children.

Chlortalidone – contraindications, side effects

Contraindications.

• Hypersensitivity to chlorthalidone or other drugs derived from sulfonamides.
• Anuria.
• Severe hepatic or renal insufficiency (creatinine clearance <30 ml/min).
• Refractory hypokalemia, hypercalcemia and hyponatremia.
• Symptomatic hyperuricemia (history of gout or uric acid stones).
• Hypertension during pregnancy.
• Untreated Addison’s disease.
• Lithium concomitant therapy.
• Children’s age.
• Pregnancy, lactation period.
• Intoxication with cardiac glycoside preparations.

Adverse reactions.

From the digestive tract: anorexia, nausea, vomiting, spasms, diarrhea, constipation, jaundice, pancreatitis.

From the side of the nervous system: dizziness, vertigo, paresthesia, headache, xanthopsia.

From the side of the blood system: leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia, eosinophilia.

Skin: purpura, photosensitivity, rash, urticaria, necrotizing angiitis vasculitis (cutaneous vasculitis), Lyell’s syndrome (toxic epidermal necrolysis).

From the side of the cardiovascular system: orthostatic hypotension, which may be aggravated by alcohol, barbiturates or drugs. Very rarely, cardiac arrhythmias can occur.

From the hepatobiliary system: hypokalemia, hypopatremia, hypomagnesemia, hyperglycemia, hyperuricemia, elevated blood lipids, glucosuria and hypochloremic alkalosis.

Chlorthalidone analogues

Dichlor

Source: State Register of Medicines of Ukraine. The instruction is published with abbreviations for reference only. Before use, consult your doctor and carefully read the instructions. Self-medication can be harmful to your health.

Chlorthalidone | is… What is chlorthalidone?

Chlorthalidone (oxodoline, hygroton) is a diuretic thiazide-like drug used both as a separate active substance and as part of combined drugs.

Randomized study of the drug was conducted within the framework of ALLHAT, THOMS, the All-Russian multicenter study VOSTOK.

Suppresses active reabsorption of Na ⁺ , mainly in the peripheral renal tubules (cortical segment of the loop of Henle), increasing the excretion of Na ⁺ , Cl ⁻ and water. The excretion of K ⁺ and Mg ²⁺ through the kidneys increases, while the excretion of Ca ²⁺ decreases. It causes a slight decrease in blood pressure, the severity of the hypotensive effect gradually increases and manifests itself in full 2-4 weeks after the start of therapy. At the beginning of therapy causes a significant decrease in the volume of extracellular fluid, BCC and IOC; however, after several weeks of use, these indicators return to levels close to the original. Like thiazide diuretics, it causes a decrease in polyuria in patients with renal diabetes insipidus. The onset of action is 2-4 hours after ingestion, the maximum effect is 12 hours later, the duration of action is 2-3 days.

Indications: chronic heart failure stage II, arterial hypertension, cirrhosis of the liver with portal hypertension, nephrosis, nephritis, late preeclampsia (nephropathy, edema, eclampsia), fluid retention against the background of premenstrual syndrome, diabetes insipidus, dysproteinemic edema, obesity. With prolonged use, as well as with its simultaneous use with cardiac glycosides, glucocorticosteroids, ACTH, in order to prevent hypokalemia, it is recommended to prescribe potassium preparations (contraindicated when taking ACE inhibitors) or potassium-sparing diuretics (half dose of veroshpiron 12.5 instead of 25 with simultaneous administration of ACE inhibitors and chlorthalidone).

Contraindications: Hypersensitivity (including to sulfonamide derivatives, which include thiazide diuretics), hypokalemia, acute renal failure (anuria), hepatic coma, acute hepatitis, diabetes mellitus (severe forms), gout, lactation. With caution in renal and / or liver failure, allergic reactions, bronchial asthma, systemic lupus erythematosus. Side effects: From the digestive system: nausea, vomiting, gastrospasm, constipation or diarrhea, intrahepatic cholestasis, jaundice, pancreatitis. From the nervous system: dizziness, paresthesia, asthenia (excessive fatigue or weakness), disorientation, apathy, From the senses: xanthopsia, visual impairment. On the part of the hematopoietic organs: thrombocytopenia, leukopenia, agranulocytosis, eosinophilia, aplastic anemia. From the cardiovascular system: orthostatic hypotension (may increase under the influence of ethanol, anesthetics and sedative drugs), arrhythmia (due to hypokalemia). Laboratory indicators: hypokalemia, hyponatremia (including accompanied by neurological symptoms – nausea), hypomagnesemia, hypochloremic alkalosis, hypercalcemia, hyperuricemia (gout), hyperglycemia, glucosuria, hyperlipidemia. Allergic reactions: urticaria, photosensitivity. Other: muscle spasm, decreased potency. Overdose symptoms: dizziness, nausea, drowsiness, hypovolemia, excessive decrease in blood pressure, arrhythmia, convulsions. Treatment: gastric lavage, oral administration of activated charcoal; symptomatic therapy (including intravenous administration of saline solutions to restore the electrolyte balance of the blood).

Dosage and administration: Inside. With long-term therapy, it is recommended to prescribe the lowest effective dose sufficient to maintain the optimal effect, especially in elderly patients. With a mild degree of arterial hypertension – 25 mg 1 time per day or 50 mg 3 times a week; if necessary, it is possible to increase the dose to 50 mg / day. With edematous syndrome, the initial dose is 100-120 mg every other day; in severe cases – 100-120 mg / day for the first few days (doses above 120 mg usually do not cause an increase in the diuretic effect), then it is necessary to switch to a maintenance dose – 100-50-25 mg / day 3 times a week. Renal diabetes insipidus (in adults): initial dose – 100 mg 2 times a day, maintenance dose – 50 mg per day. The average daily dose for children is 2 mg/kg.

Special instructions: During the period of treatment, it is necessary to periodically determine blood electrolytes, especially in patients taking digitalis preparations. It is not recommended to prescribe a very strict salt-free diet to patients. If signs of hypokalemia appear (myasthenia gravis, rhythm disturbances) or if patients have an additional possibility of K + loss (with vomiting, diarrhea, malnutrition, liver cirrhosis, hyperaldosteronism, ACTH therapy, GCS), K + replacement therapy is indicated. In patients with hyperlipidemia, serum lipids should be constantly monitored (in case of an increase in their concentration, therapy should be discontinued). While taking thiazide diuretics, an exacerbation of SLE was noted. Although no such effects have been observed with chlorthalidone, caution should be exercised when prescribing it to patients with SLE.

Interaction: Increases the concentration of Li + in the blood (in the case when Li + causes polyuria, chlorthalidone may not have a diuretic, but an antidiuretic effect) and therefore increases the risk of intoxication with Li + drugs. (Chlorthalidone, like thiazide diuretics, is used for diabetes insipidus, including patients who are prescribed lithium.) Enhances the effect of curare-like muscle relaxants and antihypertensive drugs (including guanethidine, methyldopa, ACE inhibitors, beta-blockers, vasodilators, calcium antagonists, MAO inhibitors). Against the background of taking cardiac glycosides, it can aggravate rhythm disturbances resulting from digitalis intoxication.