THERAPEUTICS

Diuretics (Table 8.4)

Diuretics reduce sodium and chloride reabsorption at different sites in the nephron and thus increase urinary sodium and water loss.

Thiazide diuretics

Mechanism of action

Inhibit sodium reabsorption at beginning of distal convoluted tubule. Reduce peripheral vascular resistance (mechanism unclear).

Indications

In low doses to reduce blood pressure. At higher doses to relieve oedema in patients with mild chronic heart failure and good renal function.

Preparations and dose

Bendroflumethiazide Tablets: 2.5 mg, 5 mg.

Oral

Hypertension: 2.5 mg each morning - higher doses rarely necessary.

Oedema: initially 5-10 mg each morning.

Metolazone Tablets: 5 mg.

Oral Oedema resistant to other diuretics: start at 5 mg each morning and gradually increase if necessary to 20 mg daily in resistant oedema.

Side-effects

Postural hypotension, anorexia, diarrhoea, metabolic and electrolyte distur-bances (hypokalaemia, hyponatraemia, hypomagnesaemia, hypercalcaemia, hyperlipidaemia, hyperuricaemia and gout). May aggravate diabetes mellitus. Profound diuresis with metolazone, particularly when combined with loop diuretics. Rarely bone marrow suppression, acute pancreatitis and hyper-sensitivity reactions.

Cautions/contraindications

Contraindicated in symptomatic hyperuricaemia, severe renal and hepatic impairment, hyponatraemia, hypercalcaemia and untreated hypokalaemia.

Loop diuretics
Mechanism of action

Stimulate excretion of sodium chloride and water by blocking the sodium-potassium-chloride channel in the thick ascending limb of the loop of Henle.

Also increases venous capacitance and thus produces rapid clinical improve-ment before the diuresis in patients with acute heart failure.

Indications

Intravenously in patients with acute pulmonary oedema due to left heart failure. Orally, in patients with chronic heart failure and in patients with oedema associated with liver disease if aldosterone antagonists alone are ineffective. High doses may be needed with impaired renal function.

Preparations and dose

Furosemide Tablets: 20 mg, 40 mg, 500 mg; Oral solution: 20, 40, 50 mg/5 mL; Injection: 10 mg/mL.

Oral For oedema, initially 40 mg in the morning, increasing if necessary to 120 mg daily.

IV/IM Initially 20-50 mg; doses greater than 50 mg by i.v. infusion only; max 1.5 g daily.

Bumetanide Tablets: 1 mg, 5 mg; Injection: 500 μg/mL; Liquid 1 mg/5 mL.

(1 mg bumetanide = 40 mg furosemide (frusemide) at low doses.)

Oral Initially 1 mg (0.5 mg in the elderly) daily, increased according to response, max 5 mg daily.

IV 1-2 mg repeated after 20 minutes if necessary. Higher doses usually given as infusion over 30-60 minutes.

Side-effects

Hypokalaemia, hypomagnesaemia, hyponatraemia, urate retention causing gout, hyperglycaemia, gastrointestinal disturbance, tinnitus and deafness with rapid i.v. administration or high doses, myalgia (bumetanide at high doses). Rarely bone marrow suppression, acute pancreatitis, allergic tubulo-interstitial nephritis and other allergic reactions. Urinary retention with an enlarged prostate.

Cautions/contraindications

Untreated severe electrolyte disturbance, coma due to liver failure; renal failure due to nephrotoxic drugs or anuria.

Potassium-sparing diuretics and aldosterone antagonists

Mechanism of action

Inhibition of sodium reabsorption in the cortical collecting tubule. Amiloride and triamterene directly decrease sodium channel activity; spironolactone inhibits aldosterone. They have weak natriuretic activity.

Indications

Spironolactone is used in ascites and oedema associated with chronic liver disease and in low doses (25 mg) to improve survival in severe heart failure. Eplerenone is used in patients with heart failure following myocardial infarction and for management of fluid overload associated with chronic liver disease in patients intolerant of spironolactone due to gynaecomastia. Amiloride and triamterene in combination with loop diuretics are used as an alternative to giving potassium supplements and in resistant oedema.

Preparations and dose

Amiloride Tablets: 5 mg; Syrup 5 mg/5 mL.

Oral 5-10 mg daily. Maximum 20 mg daily if used alone.

Spironolactone Tablets: 25 mg, 50 mg, 100 mg; Suspension: 5 mg, 10 mg, 25 mg, 50 mg, 100 mg/5 mL.

Oral

Heart failure: initially 25 mg daily increased to 50 mg if necessary. Ascites in chronic liver disease: 100 mg with or without 40 mg of furo-semide, increasing gradually to a maximum of 400 mg and 160 mg, respectively.

Eplerenone Tablets: 25 mg.

Side-effects

Gastrointestinal disturbances, hyperkalaemia, hyponatraemia, gynaecom-astia (spironolactone).

Cautions/contraindications

Avoid in renal impairment and Addison's disease; co-administration with ACE inhibitors may cause hyperkalaemia.

It is preferable to prescribe thiazides and potassium-sparing diuretics separately. The use of fixed drug combinations (e.g. co-amilozide 2.5/25; amiloride hydrochloride 2.5 mg, hydrochlorothiazide 25 mg) may be justified if compliance is a problem.

Disorders of serum potassium

Potassium supplementation

Indications - potassium depletion

Oral potassium

Kay-Cee-L® Syrup: potassium chloride 7.5% (1 mmol/mL each of K+ and Cl-).

Sando-K® Effervescent tablets: potassium bicarbonate and chloride equiva-lent to potassium 470 mg (12 mmol of K+) and chloride 285 mg (8 mmol of Cl-).

Prevention of hypokalaemia: 25-50 mmol in divided doses.

Treatment of hypokalaemia: 40-100 mmol daily depending on serum potassium and severity of any continuing loss.

Intravenous potassium Inịection: 20 mmol/10 mL; Infusions 1040 mmol/L.

A variety of infusion fluids with concentrations of potassium between 10 and 40 mmol/L are available in 500 mL and 1 L size bags. Concentrations over 60 mmol/L must be infused into a large (e.g. femoral) or central vein, as high concentrations are irritant to smaller veins. Maximum rate of i.v. potassium is usually 10-20 mmol/h, although 40-100 mmol/h has been given to selected patients with paralysis or arrhythmias (with ECG monitoring).

Side-effects

Nausea and vomiting, oesophageal and small bowel ulceration with oral preparations; where appropriate, potassium-sparing diuretics are preferable. Cardiac arrhythmias and vein irritation with intravenous administration.

Cautions/contraindications

Caution in severe renal impairment and co-administration with drugs liable to raise the serum potassium, e.g. ACE inhibitors, potassium-sparing diure-tics. Oral liquid preparations should be used in preference to tablets when there is any cause for delay in transit through the gastrointestinal tract.

Ion exchange resins for potassium removal

Mechanism of action

The resin takes up potassium in the gut.

Indications

Hyperkalaemia.

Preparations and dose

Polystyrene sulphonate resins

Oral 15 g three to four times daily in water or as a paste.

By rectum as an enema: 30 g in methycellulose solution retained for 9 hours followed by irrigation to remove resin from the colon.

Side-effects

Gastrointestinal disturbance (anorexia, nausea, constipation, diarrhoea), hypercalcaemia, hypomagnesaemia, rectal ulceration and colonic necrosis following rectal administration.

Cautions/contraindications

Avoid in hypercalcaemia from any cause, caution in heart failure, hyper-tension, chronic kidney disease and oedema (due to salt loading).

Ebook Essentials of Kumar and Clark's Clinical Medicine, 5e

1. Ethics and communication

Ethics and communication

2. Infectious diseases

Infectious diseases

3. Gastroenterology and nutrition

Gastroenterology and nutrition

4. Liver, biliary tract and pancreatic disease

Liver, biliary tract and pancreatic disease
LIVER BIOCHEMISTRY AND LIVER FUNCTION TESTS
SYMPTOMS AND SIGNS OF LIVER DISEASE
JAUNDICE
HEPATITIS
NON - ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
CIRRHOSIS
COMPLICATIONS AND EFFECTS OF CIRRHOSIS
LIVER TRANSPLANTATION
TYPES OF CHRONIC LIVER DISEASE AND CIRRHOSIS
PRIMARY SCLEROSING CHOLANGITIS
BUDD - CHIARI SYNDROME
LIVER ABSCESS
LIVER DISEASE IN PREGNANCY
LIVER TUMOURS
GALLSTONES
THE PANCREAS
CARCINOMA OF THE PANCREAS
NEUROENDOCRINE TUMOURS OF THE PANCREAS

5. Haematological disease

Haematological disease
ANAEMIA
Assessment and treatment of suspected neutropenic sepsis
HAEMOLYTIC ANAEMIA
INHERITED HAEMOLYTIC ANAEMIAS
ACQUIRED HAEMOLYTIC ANAEMIA
MYELOPROLIFERATIVE DISORDERS
THE SPLEEN
BLOOD TRANSFUSION
THE WHITE CELL
HAEMOSTASIS AND THROMBOSIS
THROMBOSIS
THERAPEUTICS

6. Malignant disease

Malignant disease
MYELOABLATIVE THERAPY AND HAEMOPOIETIC STEM CELL TRANSPLANTATION
THE LYMPHOMAS
THE PARAPROTEINAEMIAS
PALLIATIVE MEDICINE AND SYMPTOM CONTROL

7. Rheumatology

Rheumatology
COMMON INVESTIGATIONS IN MUSCULOSKELETAL DISEASE
COMMON REGIONAL MUSCULOSKELETAL PROBLEMS
BACK PAIN
OSTEOARTHRITIS
INFLAMMATORY ARTHRITIS
THE SERONEGATIVE SPONDYLOARTHROPATHIES
Clinical features, Investigations
INFECTION OF JOINTS AND BONES
AUTOIMMUNE RHEUMATIC DISEASES
SYSTEMIC INFLAMMATORY VASCULITIS
DISEASES OF BONE
THERAPEUTICS

8. Water, electrolytes and acid–base balance

WATER AND ELECTROLYTE REQUIREMENTS
BODY FLUID COMPARTMENTS
REGULATION OF BODY FLUID HOMEOSTASIS
PLASMA OSMOLALITY AND DISORDERS OF SODIUM REGULATION
DISORDERS OF POTASSIUM REGULATION
DISORDERS OF MAGNESIUM REGULATION
DISORDERS OF ACID - BASE BALANCE
THERAPEUTICS

9. Renal disease

Renal disease
INVESTIGATION OF RENAL DISEASE
GLOMERULAR DISEASES
NEPHROTIC SYNDROME
URINARY TRACT INFECTION
TUBULOINTERSTITIAL NEPHRITIS
HYPERTENSION AND THE KIDNEY
RENAL CALCULI AND NEPHROCALCINOSIS
URINARY TRACT OBSTRUCTION
ACUTE RENAL FAILURE/ACUTE KIDNEY INJURY
CHRONIC KIDNEY DISEASE
RENAL REPLACEMENT THERAPY
CYSTIC RENAL DISEASE
TUMOURS OF THE KIDNEY AND GENITOURINARY TRACT
DISEASES OF THE PROSTATE GLAND
TESTICULAR TUMOUR
URINARY INCONTINENCE

10. Cardiovascular disease

COMMON PRESENTING SYMPTOMS OF HEART DISEASE
INVESTIGATIONS IN CARDIAC DISEASE
CARDIAC ARRHYTHMIAS
HEART FAILURE
ISCHAEMIC HEART DISEASE
RHEUMATIC FEVER
VALVULAR HEART DISEASE
PULMONARY HEART DISEASE
MYOCARDIAL DISEASE
CARDIOMYOPATHY
PERICARDIAL DISEASE
SYSTEMIC HYPERTENSION
ARTERIAL AND VENOUS DISEASE
ELECTRICAL CARDIOVERSION
DRUGS FOR ARRHYTHMIAS
DRUGS FOR HEART FAILURE
DRUGS AFFECTING THE RENIN - ANGIOTENSIN SYSTEM
NITRATES, CALCIUM - CHANNEL BLOCKERS AND POTASSIUM - CHANNEL ACTIVATORS

11. Respiratory disease


Respiratory disease
TUBERCULOSISnd
DIFFUSE DISEASES OF THE LUNG PARENCHYMA
OCCUPATIONAL LUNG DISEASE
CARCINOMA OF THE LUNG
DISEASES OF THE CHEST WALL AND PLEURA
DISORDERS OF THE DIAPHRAGM

12. Intensive care medicine

Intensive care medicine

13. Drug therapy, poisoning, and alcohol misuse

Drug therapy, poisoning, and alcohol misuse

14. Endocrine disease

Endocrine disease
PITUITARY HYPERSECRETION SYNDROMES
THE THYROID AXIS
MALE REPRODUCTION AND SEX
FEMALE REPRODUCTION AND SEX
THE GLUCOCORTICOID AXIS
THE THIRST AXIS
DISORDERS OF CALCIUM METABOLISM
DISORDERS OF PHOSPHATE CONCENTRATION
ENDOCRINOLOGY OF BLOOD PRESSURE CONTROL
DISORDERS OF TEMPERATURE REGULATION
THERAPEUTICS

15. Diabetes mellitus and other disorders of metabolism

DIABETES MELLITUS
DIABETIC METABOLIC EMERGENCIES
COMPLICATIONS OF DIABETES
SPECIAL SITUATIONS
HYPOGLYCAEMIA IN THE NON - DIABETIC
DISORDERS OF LIPID METABOLISM
THE PORPHYRIAS

16. The special senses

THE EAR
THE NOSE AND NASAL CAVITY
THE THROAT
THE EYE

17. Neurology

COMMON NEUROLOGICAL SYMPTOMS
COORDINATION OF MOVEMENT
THE CRANIAL NERVES
COMMON INVESTIGATIONS IN NEUROLOGICAL DISEASE
UNCONSCIOUSNESS AND COMA
STROKE AND CEREBROVASCULAR DISEASE
EPILEPSY AND LOSS OF CONSCIOUSNESS
NERVOUS SYSTEM INFECTION AND INFLAMMATION
HYDROCEPHALUS
HEADACHE, MIGRAINE AND FACIAL PAIN
SPINAL CORD DISEASE
DEGENERATIVE NEURONAL DISEASES
DISEASES OF THE PERIPHERAL NERVES
MUSCLE DISEASES
MYOTONIAS
DELIRIUM
THERAPEUTICS

18. Dermatology

Dermatology

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