Definition of Diuretics
Definition:
Diuretics are medications that increase urine production to promote the
excretion of water and electrolytes from the kidneys.
Example
Story:
In the 1920s, diuretics like "mercurial diuretics" were used, but
they were toxic. The discovery of safer alternatives revolutionized treatment
for conditions like edema and hypertension.
Classification of Diuretics
Primary
Classes:
- Carbonic Anhydrase
Inhibitors (e.g., Acetazolamide)
- Loop Diuretics (e.g., Frusemide)
- Thiazide Diuretics (e.g.,
Hydrochlorothiazide)
- Potassium-Sparing Diuretics
(e.g., Spironolactone)
- Osmotic Diuretics (e.g.,
Mannitol)
Mechanism of Action Overview
General
Mechanism:
Diuretics act on specific nephron segments to modulate electrolyte and water
reabsorption.
Acetazolamide
Mechanism
of Action: Inhibits
carbonic anhydrase, reducing bicarbonate reabsorption in the proximal tubule.
Indications: Glaucoma, altitude sickness,
metabolic alkalosis.
Adverse
Effects:
Metabolic acidosis, hypokalemia, paresthesias.
Contraindications: Sulfonamide allergy, severe
liver/kidney dysfunction.
Drug
Interactions:
Potentiates salicylates and other acidic drugs.
Invention
Insight: First
synthesized in 1950 as an alternative to older, less effective treatments for
glaucoma.
Frusemide (Furosemide)
Mechanism
of Action: Inhibits
Na+/K+/2Cl- cotransporter in the thick ascending loop of Henle.
Indications: Pulmonary edema, heart failure,
hypertension, hypercalcemia.
Adverse
Effects:
Hypokalemia, ototoxicity, dehydration, metabolic alkalosis.
Contraindications: Severe electrolyte depletion,
sulfa allergy.
Drug
Interactions:
Increases toxicity of aminoglycosides and NSAIDs reduce its efficacy.
Story: Discovered in 1962, it
transformed emergency treatment of fluid overload conditions.
Hydrochlorothiazide
Mechanism
of Action: Inhibits
Na+/Cl- symporter in the distal convoluted tubule.
Indications: Hypertension, mild edema,
nephrogenic diabetes insipidus.
Adverse
Effects:
Hypokalemia, hyperglycemia, hyperlipidemia.
Contraindications: Anuria, hypersensitivity to
sulfa drugs.
Drug
Interactions:
Potentiates digoxin toxicity; efficacy reduced by NSAIDs.
Innovation
Fact:
Developed in 1958, it remains a cornerstone of hypertension therapy.
Spironolactone
Mechanism
of Action: Aldosterone
antagonist in the collecting ducts, promoting sodium excretion and potassium
retention.
Indications: Heart failure,
hyperaldosteronism, hypokalemia.
Adverse
Effects:
Gynecomastia, hyperkalemia, menstrual irregularities.
Contraindications: Hyperkalemia, Addison’s disease.
Drug
Interactions:
Potentiates hyperkalemia with ACE inhibitors or ARBs.
Historical
Note:
Introduced in the 1950s to address mineralocorticoid-related conditions.
Mannitol
Mechanism
of Action:
Osmotically active agent, increasing water excretion in the proximal tubule and
loop of Henle.
Indications: Cerebral edema, acute kidney
injury, glaucoma.
Adverse
Effects:
Electrolyte imbalance, pulmonary edema, dehydration.
Contraindications: Anuria, active intracranial
bleeding.
Drug
Interactions:
Incompatible with blood products in IV solutions.
Discovery
Story:
Identified in the 1960s, mannitol became critical in managing intracranial
pressure.
Summary Table
Presentation for Diuretics
END OF THE CHAPTER
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