List drug type, site, mechanism, indications, side effects…
Site 1 Diuretic: Carbonic anhydrase inhibitor, acts on proximal tubule. Decreases sodium-bicarbonate reabsorption in the proximal tubule, which results in more H+ and K+ ion excretion in the distal tubule. Can cause hypochloremic metabolic acidosis because of increased bicarbonate and K+ excretion (bicarbonate isn’t recycled, leads to systemic acidosis).
Indications: glaucoma (decrease intraocular pressure), short term urinary alkalinization (excrete acid toxicants, dissolve some types of urinary crystals). Not good for long-term use because waning effect.
Side effects: calcium phosphate stones due to side effects of increased bicarb.
Carbonic anhydrase inhibitor actions
decrease sodium bicarb reabsorption in the proximal renal tubule and reduce formation of some transcellular fluids (aqueous humor)
not for long-term use
can lead to systemic acidosis
Loop Diuretics actions
Block Na/K/Cl cotransport in thick ascending limb of Henle’s loop
example is Furosemide
List mechanism of action, type of drug
“Loop” Diuretic: Acts on site 2. Block NKCC2 transport proteins which inhibits Na/K/Cl cotransport in the thick ascneding limb of Henle’s loop (counter-current exchange mechanism)
Increase Na+ delivery to the distal tubule, which can only partially resorb it, resulting in lots of the Na in the urine. Additionally decreases K+ recycling, reducing lumen electropositivity and reabsorption of Ca2+ and Mg2+ ions.
Net effect is hypertonic urine with lots of Na+, Cl-, K+, Mg++ and H+ in lots of water
route of administration, metabolism, site of action
given PO or parenterally
half undergoes phase 2 glucuronidation, half is excreted unchanged in urine
exhibits plasma protein binding, secreted into nephron
(renal and one non-renal one in horses)
edema (rapidly decrease ECF volume), acute renal failure (increase urine flow and K+ excretion), toxicant ingestion (accelerate excretion), hyperkalemia, hypercalcemia, hyperthyroidism (I- secretion)
Also reduces exercise-induced pulmonary hemorrahage by decreasing blood volume
Furosemide in dogs
broad dose range, decrease BP, excrete NaCl and can possibly cause hypoglycemia
Furosemide in cats
narrow dose range, greatly decrease blood pressure, possible reversible otoxicitiy.
Furosemide adverse effects
hypokalemic metabolic alkalosis due to excretion of lots of K+ and H+
hypomagnesemia and hypocalcemia, dehydration, dilutional hyponatermia, ototoxicity leading to hearing loos esp if given with ototoxic drugs
Loop Diuretic drug interactions
NSAIDS- compete for transport into tubule
Glucocorticoids- enhance K+ depletion
Digitalis- hypokalemia increases activity and risk arrythmias
type, site, mechanism
Thiazide diuretic, acts on site 3 in early distal tubule to decrease salt reabsorption, Na + ends up being secreted.
Net effect is increased excretion of Na+, Cl-, K+, Mg++, H+ and water, and long-term increased Ca++ reabsorption.
Most NaCl and water is reaborbed before the early distal tubule so they are less effective.
type, site, mechanism, metabolism, elimination
Site 4 action, one of the K+ sparing diuretics
Directly blocks epithelial Na+ channels in principal cells of the late distal tubule and collecting duct, not dependent on aldosterone like spironolactone
short-term effects on normal K+ excretion
secreted into the proximal tubule, undergoes hepatic biotransformation to be converted to active metabolites, eliminated into urine, bind to plasma proteins
Acts on site 4 as a K+ sparing diuretic
Antagonist of mineralocorticoid receptors and inhibits aldosterone-mediated induction of epithelail Na+ channels decreasing distal Na+ reaborption
Dependent on presence of aldosterone
Decrease K+ excretion
Indications and contraindications of site 4 diuretics (spironolactone and triamterene)
Indications: hypokalemia, edema secondary to hyperaldosteronism
Contraindications: hyperkalemia or hyperkalemic metabolic acidosis, disease states that mask K+ balance
Can be combined with a site 2 or 3 diuretic for natriuretic effects
Inhibits water reaborption (proximal convoluted tubule, descending tubule, and collecting duct) and disrupts renal counter-current exchange, net effect is increasing water excretion
Given IV and filtered at glomerulus with no reaborption, no metabolism, excreted in urine
Indications and Contraindications of Mannitol use
Indications: acute renal failure, toxicant elimination, cerebral edema, glaucoma, etc.
Contraindications: edematous states liek CHF or overexpansion of blood volume, pre-existing dehydration