Carbonic anhydrase inhibitors

Osmotic agents

Loop agents

Potassium-sparing diuretics

ADH antagonists

Increase renal plasma flow -> increased glomerular filtration rate

Increase solute/fluid excretion from glomerular filtrate

Acetazolamide

Sulfonamide group

Well absorbed orally, effect within 30 mins, max at 2 hrs, effect 12 hrs

Elimination by secretion in proximal tubule

Inhibition of CA -> loss of bicarb -> hyperchloremic metabolic acidosis

Increased urine volume, urine osmolality, pH, K+

Decreased NH3

Dorzolamide

Brinzolamide

Topically active carbonic anhydrase inhibitors

Treats glaucoma

Decreases production of aqueous humor

Glaucoma

Acute mountain sickness - acidosis stabilizes deoxyhemoglobin

To correct metabolic alkalosis or alkalinize urine

Anticonvulsant

Rare: paresthesia, somnolence

Allergic reactions can occur in those with sulfonamide allergies because they have a sulfa group

Because they causes acidosis, can only be used for 2-3 days

May cause renal wasting

Patients with hepatic cirrhosis

Decrease in ammonium --> hepatic encephalopathy

Act in proximal tubule and descending limb

Not metabolized - filtered by glomerulus w/in 60 mins

Will cause osmotic diarrhea if given orally

Increase urine volume and flow rates -> decrease sodium Na reabsorption, may cause hypernatremia

Increase water excretion in preference to sodium excretion

Reduce total body water, reduce intracellular volume

Osmotic diuretic

Used to reduce increased intracranial pressure

Sometimes used to increase renal filtration of toxins

Prolonged use is not advised

Extracellular volume expansion into extracellular compartments prior to diuresis causes hyponatremia

May complicate CHF, produce pulmonary edema, cause headahche, nausea, or vomiting

Dehydration and hypernatremia may occur after diuresis, may alter serum electrolytes

Furosemide

Bumetanide

Ethacrynic acid

Torsemide

Most effective diuretic: selectively inhibits NaCl reabsorption in the TAL by stopping NKCC transport system

Rapidly absorbed, eliminated by renal secretion + glomerular filtration

Increase Mg and Ca excretion, COX2 (and prostaglandin) expression

(Need to avoid NSAIDs)

Furosemide

Loop diuretic

Sulfonamide derivative

Orally active (2-3 hours)

Relieves pulmonary congestion, reduces left ventricular filling pressure in CHF

Loop diuretic

Sulfonamide derivative

Loop diuretic

Phenoxyacetic acid derivative with adjacent ketone and methylene group

Relieves pulmonary congestion, reduces left ventricular filling pressure in CHF

Loop diuretic

Well absorbed orally - available in 1 hr

Effects for 4 to 6 hours

Acute pulmonary edema

Acute hypercalcemia

Hyperkalemia

Acute renal failure

Anion (bromide, fluoride, iodide) overdose

Hypokalemic metabolic acidosis

Ototoxicity - usually reversible

Hyperuricemia - can precipitate gout

Hypomagnesmia

Allergic reaction - usually reversible with withdrawal

Impaired carb tolerance - hyperglycemia

Dehydration, hyponatremia, hypercalcemia

Inhibit NaCl transport in luminal distal convoluted tubule

Enhance Ca reabsorption in DCT

Depedent on renal prostaglandin production (no NSAIDs)

Some members have some carbonic anhydrase activity

Ring structure + unsubstituted sulfonamide group

Orally absorbed

Thiazide diuretic

Slowly orally absorbed because less lipid soluble - long action, give in high dose

Thiazide diuretic

Excreted primarily by biliary system, but enough cleared by kidney

Secreted by organic acid secretory system

Competes with uric acid secretion

Hypertension

Heart failure

Nephrolithiasis - due to idiopathic hypercalciuria

Nephrogenic diabetes insipidus

Hypokalemia

Metabolic acidosis

Hyperuricemia

Hyperlipidemia - increase serum cholesterol, LDL

Hyponatremia

Allergic reaction to sulfonamide

Weakness, fatigability, paresthesia

Antagonize effect of aldosterone at CCT and late distal tubule - reduce Na absorption and K secretion

Enhances K secretion by increasing expression/transport of Na/K ATPase and ENaC Na channels

Synthetic steroid - directly antagonizes mineralcorticoid receptors and prevents translocation of receptor to nucleus

Inactivation in the liver

Depends on renal prostaglandin production - no NSAIDs

Direct pharmacological antagonism of mineralcorticoid receptor

Greater selectivity for aldosterone receptor than spirolactone - indicated for tx of HTN

Metabolized in liver, renal excretion

Inhibit sodium flux through ENaC ion channel in the luminal membrane

Metabolized

Shorter half life than amiloride

Depend on renal prostaglandin production

Inhibition of sodium flux through ENaC ion channel in luminal membrane

Excreted unchanged in urine

Hyperkalemia

High angiotensin II

Renalvascular hypertension

Mineralcorticoid excess - Conn's syndrome, ectopic ACTH production (adrenal tumor)

Secondary aldosteronism - heart failure, hepatic cirrhosis, nephrotic syndrome

Hyperkalemia

Hyperchloremic metabolic acidosis - inhibit H+ secretion

Gynecomastia - synthetic steroid

Acute renal failure - drug interaction with triamterene and indomethacin

Kidney stones - triamterene 

Vaptans- only conivaptan approved by FDA

ADH antagonist, diuretic

IV infusion for inhospital treatment of euvolemic hyponatremia

Non selective antagonist of V1a and V2 receptors

SIADH

Other ADH elevation

If treatment by volume increase not possible

Nephrogenic diabetes insipidus

Renal failure

Tremulousness, mental obtundation, cardiotoxicity, thyroid dysfunction, leukocytosis