Diuretics-Thiazide diuretics

Name of the Thiazide diuretics Drugs

• Chlorthalidone
• Metolazone
• Indapamide

1.Chlorthalidone

Mechanism of Action

Reduces muscle spasm by inhibiting multisynaptic reflex arcs at the level of the spinal cord and subcortical areas of the brain that are active in producing and maintaining skeletal muscle spasm.

Pharmacokinetics

• Bioavailability: 65%
• Peak plasma time: 1.5-6 hr
• Protein bound: 75%
• Metabolized in liver
• Half-life: Normal renal function, 40-60 hr; anuria, 81 hr
• Excretion: Urine (50-65%), feces

Administration

Know that dosages above 25 mg/day are likely to increase potassium excretion without further increasing sodium excretion or reducing blood pressure.

Contraindications

• Hypersensitivity to drug, other thiazides, sulfonamides, or tartrazine
• Renal decompensation

Precautions:

• Renal or severe hepatic disease, abnormal glucose tolerance, gout, systemic lupus erythematosus, hyperparathyroidism, bipolar disorder
• Elderly patients
• Pregnant or breastfeeding patients.

Adverse reactions

• CNS: dizziness, vertigo, drowsiness, lethargy, confusion, headache, insomnia, nervousness, paraesthesia, asterixis, nystagmus, encephalopathy
• CV: hypotension, ECG changes, chest pain, arrhythmias, thrombophlebitis
• GI: nausea, vomiting, cramping, anorexia, pancreatitis
• GU: polyuria, nocturia, erectile dysfunction, loss of libido
• Hematologic: blood dyscrasias
• Metabolic: gout attack, dehydration, hyperglycaemias, hypokalaemia, hypocalcaemia, hypomagnesemia, hyponatremia, hypophosphatemia, hyperuricemia, hyperlipidaemia, hyperchloremic alkalosis
• Musculoskeletal: muscle cramps, muscle spasms
• Skin: flushing, photosensitivity, hives, rash, exfoliative dermatitis, toxic epidermal necrolysis
• Other: fever, weight loss, hypersensitivity reactions

Patient monitoring

• Closely monitor patient with renal insufficiency.
• Assess for signs and symptoms of hematologic disorders.
• Monitor CBC with white cell differential and serum uric acid and electrolyte levels.
• Assess for signs and symptoms of hypersensitivity reactions, especially dermatitis.
• Watch for fluid and electrolyte imbalances.

Patient teaching

• Instruct patient to consume a lowsodium diet containing plenty of potassium-rich foods and beverages (such as bananas, green leafy vegetables, and citrus juice).
• Caution patient to avoid driving and other hazardous activities until he knows whether drug makes him dizzy or affects concentration and alertness.
• Tell patient with diabetes to check urine or blood glucose level frequently.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.

Nursing Considerations

•  If needed, crush chlorzoxazone tablets and mix with food or liquid for easier swallowing.
• Assess patients, especially those who have a history of allergies, for evidence of hypersensitivity, such as rash, hives, and itching
• Ensure adequate rest and provide other pain-relief measures as needed.
• Institute safety measures to prevent falls or injury (such as raising bed rails and assisting with ambulation) until drug’s full CNS effects are known.

2.Metolazone

Mechanism of Action

Promotes renal excretion of water and sodium by inhibiting their reabsorption in distal convoluted tubules. The resulting reduction in plasma and extracellular fluid volume reduces blood pressure. Metolazone also helps reduce blood pressure by decreasing peripheral vascular resistance.

Pharmacokinetics

• Bioavailability: 40-65%
• Peak plasma time: Zaroxolyn, 8 hr
• Protein bound: 95%
• Minimally metabolized; site of metabolism unspecified
• Half-life: 20 hr
• Excretion: Urine (80%), bile (10%)

Administration

• Give in morning to avoid frequent nighttime urination.
• Discontinue drug before parathyroid function tests are performed.
• Be aware that metolazone is the only thiazide-like diuretic that may cause diuresis in patients with glomerular filtration rates below 20 ml/minute.

Contraindications

• Hypersensitivity to drug
• Hepatic coma or precoma
• Anuria

Precautions:

• Severe hepatic or renal impairment, gout, hyperparathyroidism, glucose tolerance abnormalities, fluid or electrolyte imbalances, bipolar disorders
• Elderly patients
• Pregnant or breastfeeding patients
• Children (safety not established).

Adverse reactions

• CNS: drowsiness, lethargy, vertigo, paresthesia, weakness, headache, fatigue
• CV: chest pain, hypotension, palpitations, venous thrombosis, arrhythmias
• GI: nausea, vomiting, bloating, cramping, anorexia, pancreatitis
• GU: polyuria, nocturia, erectile dysfunction, decreased libido Hematologic: aplastic anemia, leukopenia, agranulocytosis Hepatic: hepatitis
• Metabolic: dehydration, hypercalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, hypovolemia, hyperglycemia, hyperuricemia, hypokalemia, hypochloremic alkalosis
• Musculoskeletal: muscle cramps
• Skin: photosensitivity, rashes
• Other: chills

Patient monitoring

• Monitor baseline and periodic electrolyte, blood urea nitrogen, glucose, and uric acid levels.
• Evaluate blood pressure regularly.
• Watch for signs and symptoms of hypokalemia, which may necessitate potassium supplements, potassiumrich diet, or potassium-sparing diuretic. Hypokalemia is particularly dangerous to patients who are on digitalis or have had ventricular arrhythmias.
• Assess patient for fluid and electrolyte imbalances.

Patient teaching

• Advise patient to take in morning to avoid frequent nighttime urination.
• Tell patient he may take with food or milk to prevent GI upset.
• Instruct patient to report muscle pain, weakness, or cramps; nausea; vomiting; diarrhoea; dizziness; restlessness; excessive thirst; fatigue; drowsiness; increased pulse; or irregular heartbeats.
• Inform patient that drug may cause gout attacks. Advise him to report sudden joint pain.
• Instruct patient to use sunscreen and protective clothing to avoid photosensitivity.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, herbs, and behaviours mentioned above.

Nursing Considerations

• Anticipate giving metolazone with a loop diuretic if patient responds poorly to loop diuretic alone.
• To monitor drug’s diuretic effect, measure fluid intake and output and daily weight.
• If response to 1 mg of Mykrox is inadequate, expect to add another drug rather than increase dosage.
• Monitor blood chemistry test results and assess for evidence of hypochloremia, hypokalemia, and, possibly, mild metabolic alkalosis.
• Monitor serum calcium and uric acid levels, especially if patient has a history of gout or renal calculi. Metolazone may slightly increase calcium reabsorption and decrease uric acid excretion.

3.Indapamide

Mechanism of Action

Acts mainly on distal convoluted tubules, where it enhances excretion of sodium, chloride, and water by inhibiting sodium ion movement across renal tubules. The resulting decrease in plasma and extracellular fluid volume decreases peripheral vascular resistance and reduces blood pressure. This thiazide diuretic also may cause arterial vasodilation by blocking calcium channels in smooth-muscle cells.

Pharmacokinetics

• Half-Life: 14-25 hr
• Peak Plasma Time: 2 hr
• Bioavailability: 93%
• Protein Bound: 71-79%
• Metabolism: Liver
• Excretion: Urine (70% with 7% unchanged), feces (23%)

Administration

• Administer with food or milk to reduce GI upset.
• Give early in day to avoid nocturia

Contraindications

• Hypersensitivity to drug, other thiazide-like drugs, or tartrazine
• Anuria

Precautions:

• Renal or severe hepatic impairment, ascites, fluid or electrolyte imbalances, gout, systemic lupus erythematosus impaired glucose tolerance, hyperparathyroidism, bipolar disorder
• Pregnant or breastfeeding patients.

Adverse reactions

• CNS: dizziness, light-headedness, headache, restlessness, insomnia, lethargy, fatigue, drowsiness, asthenia, depression, anxiety, nervousness, paresthesia, irritability, agitation
• CV: orthostatic hypotension, palpitations, premature ventricular contractions, arrhythmias
• EENT: blurred vision, rhinorrhea
• GI: nausea, vomiting, diarrhea, constipation, bloating, epigastric distress, gastric irritation, abdominal pain or cramps, dry mouth, anorexia
• GU: nocturia, polyuria, glycosuria, erectile dysfunction
• Metabolic: dehydration, gout, hyperglycaemia, hypokalaemia, hypocalcaemia, hypomagnesemia, hyponatremia, hypovolemia, hypophosphatemia, hyperuricemia, hypochloraemia alkalosis
• Musculoskeletal: muscle cramps and spasms
• Skin: flushing, rash, urticaria, pruritus, photosensitivity, cutaneous vasculitis, necrotizing vasculitis
• Other: weight loss

Patient monitoring

• Assess for signs and symptoms of hypokalemia, including ventricular arrhythmias, muscle weakness, and cramping.
• Monitor BUN, creatinine, and electrolyte levels.
• Assess daily weight and fluid intake and output.
• Monitor blood pressure response to drug.
• Watch for signs and symptoms of orthostatic hypotension.

Patient teaching

• Advise patient to consume potassium-rich foods, such as oranges, bananas, potatoes, and spinach.
• Instruct patient to move slowly when sitting up or standing, to avoid dizziness from sudden blood pressure decrease.
• Tell patient to weigh himself daily on same scale at same time of day while wearing similar clothing. Instruct him to report gain of more than 2 lb (0.9 kg) in 1 day or 5 lb (2.2 kg) in 1 week.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviour’s mentioned above.

Nursing Considerations

• Administer indapamide with food or milk to reduce adverse GI reactions.
• Give drug early in the day to avoid nocturia.
• Weigh patient daily, and monitor fluid intake and output, blood pressure, and serum electrolyte levels, especially in elderly women, because severe hyponatremia and hypokalaemia may occur. Hypokalaemia also commonly occurs in patients taking diuretics. Report electrolyte abnormalities, and expect to provide corrective measures, as prescribed.
• Monitor BUN and serum creatinine levels regularly, as appropriate.
• If muscle cramps and weakness develop from hypokalaemia, expect prescriber to order potassium supplement or potassium sparing diuretic.
• When managing hypertension, expect therapeutic response to indapamide to take several weeks.

REFERENCES

1. Robert Kizior, Keith Hodgson, Saunders Nursing Drug handbook,1st edition 2024, Elsevier Publications. ISBN-9780443116070
2. McGraw Hill- Drug Handbook, Seventh Edition, 2013, McGraw Hill Education Publications,9780071799430.
3. April Hazard, Cynthia Sanoski, Davi’s Drug Guide for Nurses -Sixteenth Edition 2019, FA Davis Company Publications,9780803669451.
4. Jones and Bartlet, Pharmacology for Nurses, Second Edition, 2020, Jones and Bartlet Learning Publications, ISBN 9781284141986.
5. Nursebro.com, Search – Nursebro

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