Does chlorthalidone contain sulfa? Is cross-reactivity a concern with sulfa-containing medications? Get the facts about chlorthalidone’s mechanism of action, adverse effects, and patient monitoring.

Chlorthalidone: A Sulfa-Containing Medication for Hypertension and Beyond

Chlorthalidone is a sulfa-containing, thiazide-like diuretic that has been FDA-approved since 1960 for the management of hypertension. It is considered a first-line agent for treating high blood pressure and is also used to treat edema associated with various medical conditions. Chlorthalidone works by antagonizing the sodium chloride co-transporter in the distal convoluted tubule, leading to increased diuresis and volume depletion.

Chlorthalidone vs. Hydrochlorothiazide (HCTZ): A Closer Look

While thiazide-type diuretics like HCTZ have been around longer, multiple studies have shown a preference for thiazide-like medications like chlorthalidone. Chlorthalidone has been found to be more potent, lowering systolic blood pressure by approximately 5.1 mmHg more than HCTZ. Additionally, chlorthalidone has a longer duration of action, allowing for increased dosing flexibility compared to HCTZ.

Indications and Uses of Chlorthalidone

In addition to its primary indication for hypertension, chlorthalidone is also used to treat edema associated with various medical conditions, including congestive heart failure, hepatic cirrhosis, corticosteroid therapy, and renal dysfunction. It may also be considered for the treatment of calcium nephrolithiasis, Meniere’s disease, and diabetes insipidus, although it does not have FDA approval for these uses.

Chlorthalidone and Cardiovascular Outcomes

The ALLHAT trial compared chlorthalidone to other first-line antihypertensive agents, such as calcium channel blockers and ACE inhibitors. The results of this study showed that thiazide-like diuretics, like chlorthalidone, should be considered first-line for hypertension management, as they were associated with a lower risk of stroke and heart failure compared to the other medications studied.

Adverse Effects and Monitoring of Chlorthalidone

As a sulfa-containing medication, chlorthalidone may pose a risk of cross-reactivity in patients with sulfa allergies. Healthcare providers should thoroughly assess patient medication allergies before prescribing chlorthalidone. Additionally, patients on chlorthalidone therapy require monitoring for potential adverse effects, such as electrolyte imbalances, hypotension, and metabolic abnormalities.

Interprofessional Collaboration for Optimal Chlorthalidone Use

Effective management of patients on chlorthalidone requires an interprofessional team approach. Healthcare providers should work together to ensure proper medication administration, monitor for adverse effects, and communicate any concerns or changes in the patient’s condition to advance optimal patient outcomes.

Key Takeaways

• Chlorthalidone is a sulfa-containing, thiazide-like diuretic used for hypertension, edema, and other conditions.
• Chlorthalidone is more potent and has a longer duration of action compared to thiazide-type diuretics like hydrochlorothiazide.
• Chlorthalidone has shown improved cardiovascular outcomes compared to other first-line antihypertensive agents.
• Patients on chlorthalidone require monitoring for potential adverse effects, and healthcare providers should be aware of the risk of cross-reactivity in patients with sulfa allergies.
• Interprofessional collaboration is key to ensure optimal administration and management of chlorthalidone therapy.

Does chlorthalidone contain sulfa? Yes, chlorthalidone is a sulfa-containing medication. Is cross-reactivity a concern with sulfa-containing medications? Yes, patients with sulfa allergies may be at risk of cross-reactivity when taking chlorthalidone, so healthcare providers should thoroughly assess medication allergies before prescribing this medication.

How does chlorthalidone work? Chlorthalidone is a thiazide-like diuretic that antagonizes the sodium chloride co-transporter in the distal convoluted tubule, leading to increased diuresis and volume depletion.

What are the potential adverse effects of chlorthalidone? Patients on chlorthalidone therapy may experience adverse effects such as electrolyte imbalances, hypotension, and metabolic abnormalities. Healthcare providers should monitor patients closely for these potential adverse events.

How can an interprofessional team approach improve chlorthalidone management? Effective management of patients on chlorthalidone requires collaboration between healthcare providers, including physicians, pharmacists, and nurses, to ensure proper medication administration, monitor for adverse effects, and communicate any concerns or changes in the patient’s condition.

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

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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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Diuretics in a pharmacy: classification, application, and what a pharmacist needs to know

Diuretics are a small but complex pharmacological group of drugs: no more than a dozen active substances. At the same time, diuretics are widely used in clinical practice and are often bought at a pharmacy. When drugs of this group are prescribed, how they differ, and whether they can be used for weight loss, read our article.

Why diuretics are needed

The general property of diuretics to increase the excretion of Na ions from the body, and hence water with urine, is used in the treatment of edema of various origins, but not only.

Various pharmacological effects of diuretics:

1. Antihypertensive: diuretics reduce blood volume and may affect vascular tone. Therefore, the main scope of diuretics is cardiovascular diseases: hypertension and heart failure with edematous syndrome .
2. Decongestant: diuretics are actively used in acute and chronic renal failure, ascites on the background of liver cirrhosis.
3. Detoxification. Diuretics, especially loop and osmotic, are used to accelerate the elimination of water-soluble xenobiotics in case of poisoning.
4. Specific effects of acetazolamide. Known effects of acetazolamide in glaucoma, intracranial pressure, altitude sickness, some types of epilepsy.
5. Other non-trivial effects. Among the unusual indications: the treatment of lung obstruction for loop diuretics, the use of acetazolamide for cerebellar ataxia, sleep apnea syndrome, psychosis. There is a high anti-inflammatory activity of furosemide and hydrochlorothiazide, the latter can be used in the treatment of diabetes insipidus.

Classification of diuretics. Table

Diuretic drugs are heterogeneous in their chemical structure, strength, speed and duration of the main diuretic action, which largely depend on the point of application. The table shows the classification depending on the locus of action and the observed diuretic effect.

Brief characteristics of the representatives of groups

Acetazolamide has limited use due to a weak and unstable diuretic effect, intensive excretion of potassium and bicarbonates, and rapidly developing tolerance. It is used to reduce intraocular and intracranial pressure, in some forms of small seizures of epilepsy, to prevent altitude sickness. Inhibits carbonic anhydrase of the ciliary body, resulting in reduced production of aqueous humor in the anterior chamber of the eye; reduces the production of cerebrospinal fluid.

Osmotic diuretics mannitol and urea are administered by intravenous drip in a hospital setting. The main indication: the removal of cerebral edema.

Thiazide diuretics hydrochlorothiazide and chlorthalidone have a moderate diuretic effect and a high ability to lower blood pressure. Long-term action allows them to be widely used in the treatment of hypertension and edematous syndrome. These drugs are preferred in patients with osteoporosis because they delay calcium excretion . These diuretics are characterized by a dose ceiling , above which there is no increase in the diuretic effect, therefore, they are not suitable for removing severe edema. In addition, thiazides remove potassium most of all. The result of therapy with these drugs depends on the state of the kidneys: with a decrease in their function, the clinical effect weakens.

Thiazide drugs directly affect the pancreatic islets by interfering with insulin secretion. There is a certain pathogenetic relationship between hyperglycemia and hypokalemia, since potassium ions stimulate insulin secretion. Thus, thiazide diuretics should not be given to diabetic patients, and potassium supplements may be used to correct this side effect.

The thiazide-like indapamide has a too mild diuretic effect, so it is not used as a decongestant. Its action is based on its ability to cause dilatation of peripheral vessels , therefore the main indication for the use of indapamide is the correction of elevated blood pressure. Therapeutic dosages prescribed for hypertension do not lead to an increase in diuresis. Taking the drug is not accompanied by electrolyte disturbances and kidney function does not affect its effectiveness.

Loop diuretics ascending loop of Henle are two drugs that differ primarily in the speed of action.

Furosemide is a short-acting, potent loop diuretic with a dose-dependent effect . The higher the dosage of the drug, the stronger the excretion of urine. The main indication is the removal of pronounced edema, acute heart failure, the removal of a hypertensive crisis. With the use of furosemide, especially in large doses, daily, the development of tolerance and the phenomenon of rebound (a sharp decrease in diuresis after cancellation when using large doses) is possible. Furosemide has side effects in the form of electrolyte shifts and ototoxicity .

Torasemide is a long-acting diuretic, comparable in strength to furosemide. The main difference from furosemide, in addition to long-term action, will also be the absence of electrolyte shifts and ototoxicity. It is used for edematous syndrome of various origins and arterial hypertension.

Loop diuretics can be used effectively in patients with poor kidney function. They remove calcium from the body, which is unfavorable for osteoporosis. The drugs of this group also delay the secretion of uric acid, thereby causing the phenomena of hyperuricemia. This is especially important to consider in patients with gout.

Clopamid is a loop diuretic with a different site of application in the loop of Henle. Average in strength, with a long-term developing, persistent hypotensive effect. It is used only in Normatens, indications: to reduce pressure in combination with reserpine and dihydroergocristine.

Potassium-sparing diuretics are most often used in combination with loop and thiazide diuretics to enhance the diuretic effect and reduce K losses.0026 Triampur compositum . They are used to treat edema and hypertension. The combination of spironolactone and cardiac glycosides can enhance the effect of cardiac glycosides, reduce their dose and at the same time prevent hypokalemia during their use.

Aldosterone blockers spironolactone and its derivative eplerenone have found particular use in groups of patients with chronic heart failure and postinfarction left ventricular systolic dysfunction. This is due to the fact that patients with CHF have increased secretion of aldosterone, which negatively affects the cardiovascular system. Spironolactone and more selective eplerenone can increase survival in this group of patients.

Aldosterone blockers, as having a steroid structure, can cause hormonal changes: gynecomastia may occur in men; in women – masculinization and menstrual irregularities.

In the treatment of potassium-sparing diuretics, it is critical to control the level of potassium in people with severe CHF, since hyperkalemia can be fatal. Combinations with drugs that cause hyperkalemia (potassium preparations, other potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, heparin) are dangerous.

Why only a doctor should prescribe diuretics, and why they cannot be used independently

Pathologies that require diuretics are serious, and only a doctor can prescribe therapy, taking into account all the features of pharmacology and the patient’s condition. The doctor prescribes them in the absence of contraindications, especially in CHF in cases where the patient has a positive sodium balance (that is, the amount of sodium taken with food exceeds its excretion). Both the drug and the dose are selected by the doctor individually for each specific case.

Therefore, diuretics should only be sold according to their indications and prescription!

All diuretics are prescription drugs, but they are often purchased over the counter for weight loss purposes, as well as for athletes to quickly lose weight or eliminate illegal supplements in the urine. In these cases, diuretics are used in large doses, which increases the chance of side effects. Medicines of this group are capable of causing a large number of undesirable reactions, which those who want to “penetrate” do not know about, but which the pharmacist knows about. Side effects primarily relate to water-electrolyte homeostasis, acid-base balance, metabolism of carbohydrates and lipids, phosphates and uric acid. There are also specific types of side effects, for example, endocrine disorders in the treatment with spironolactone, ototoxicity – when using loop diuretics. One of the classic side effects of diuretics is hypokalemia, which can be manifested by muscle cramps, palpitations, and muscle weakness. With hypokalemia, changes in the electrocardiogram occur and the risk of ischemic stroke increases. However, this is far from the only side effect of diuretics. The table shows the main significant side effects of diuretics.

The use of diuretics as a means of losing weight is dangerous. Diuretics in athletes may adversely affect maximum exercise capacity and duration of sustained submaximal exercise. Dehydration adversely affects the cardiovascular and thermoregulatory systems of the body during exercise. In the course of pharmacological counseling, the pharmacist must not only find out to whom and why the drug is being purchased, but also to learn about the huge potential harm of self-prescribing.

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  instructions, use, analogues of the drug, composition, indications, contraindications, side effects in the UNIAN drug reference book

  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.

  Chlortalidone – composition and formulation of the drug

  Composition:

  active substance: 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 nervous system: dizziness, vertigo, paresthesia, headache, xanthopsia.

  On the part 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).