pharmacology Flashcards
drugs that act on the kidneys
diuretics (of several classes)
vasopressin (ADH) receptor agonists and antagonists
inhibitors of sodium-glucose co-transporter 2 (SGLT2)
uricosiroc drugs
drugs used in renal failure
drugs that alter the pH of urine
diuretics summarized function
increase urine flow (by inhibiting the reabsorption of electrolytes at various sites in nephron)
enhance excretion of salt and water in conditions where an increase in the volume
how does oedema occur
imbalance between the rate of formation and absorption of interstitial fluid
disease that produce oedema
disease states that increase Pc or decrease πp
nephrotic syndrome
congestive heart failure
hepatic cirrhosis with ascites
what sodium reabsorption occurs in the proximal convoluted tubule
Na+ (passive Cl- absorption)
Na/H exchange (blocked by carbonic anhydrase inhibitors)
sodium reabsorption in the thick ascending limb of the loop of henle
Na+/K+/2Cl- co transport (blocked by loop diuretics)
sodium reabsorption in the earl distal convoluted tubule
Na+/H+ exchange (blocked by carbonic anhydrase inhibitors)
Na+/Cl- co transport (blocked by thiazide diuretics)
sodium reabsorption in the collecting tubule and duct
Na/K+ exchange (blocked by potassium-sparing diuretics)
where is the sire of action of most diuretics
apical membrane of tubular cells
pharmacodynamics of loop diuretics
inhibit the Na+/k+/2Cl transporter by binding to the CL- site and:
- decrease the tonicity of the interstitium of the medulla
- prevent dilution of the filtrate in the thick ascening limb
- increase excretion Ca2+ and Mg2+
most common loop diuretics
furosemide and bumetanide
clinical indications of loop diuretics
to reduce salt and water overload associated with: - acute pulmonary oedema - chronic heart failure - chronic kidney failure - hepatic cirrhosis with ascites - nephrotic syndrome to increase urine volume in acute kidney failure treat hypertension
contraindication of loop diuretics
sever hypovolaemia
dehydration
adverse effects of loop diuretics
hypokalaemia metabolic alkalosis hypocalcaemia hypovolaemia and hypotension hyperuricaemia
main thiazide duiretics
bendroflumethiazide chlortalidone (thoazide like)
pharmacodynamics of thiazide diuretics
inhibit the Na+/Cl- carrier by binding the Cl- site and:
- prevent the dilution of filtrate in the early distal tubule
- increase the load of Na delivered to the collecting tubules
increase reabsorption of Ca2+
clinical indications of thiazide diuretics
mild heart failure hypertension (indapamide) severe resistant oedema renal stone disease nephrogenic diabetes insipidus
adverse effects of thiazide diuretics
hypokalaemia metabolic alkalosis hypovolaemia and hypotension hypomagnaesmia hyperuricaemia- gout
why can loop and thiazide diuretics cause hypokalaemia
because loop and thiazide diuretics increase sodium delivery to the collecting ducts which increases potassium loss
mechanism of action of potassium sparing diuretics
act to prevent sodium reabsorption in the collecting tubule by either binding ENaCs (amiloride, triamterene) or by inhibiting aldosterone receptors (spironolactone, eplerenone)
clinical uses or potassium sparing diuretics
in combination with other diuretics to prevent potassium loss
heart failure
mechanism of action of osmotic diuretics
enter nephron by glomerular filtration but not reabsorbed
increase osmolality of filtrate which decreases water reabsoprtion in the parts of the nephron which are highly permeable to water
clinical use of osmotic diuretics
used in the prevention of acute hypovolaemic renal failure to maintain urine flow
in urgent treatment of acutely raised intracranial and intraocular pressure (does so by increasing plasma osmolality)
mechanism of action of inhibitors of carbonic anhydrase
increase excretion of HCO3- with Na+,K+ and H20-alkaline diuresis and metabolic acidosis
clinical use of carbonic anhydrase
no longer have a role as diuretic agents but are used in
glaucoma and following eye surgery (to reduce intraocular pressure by suppressing formation of aqueous humour)
prophylaxis of altitude sickness
some forms of infantile epilepsy
describe the utility of agonists of vasopressin receptors in neurogenic diabetes insipidus
treated with desmopressin (synthetic analogue of vasopressin with V2 receptor selectivity)
describe the utility of antagonists of vasopressin receptors in hypervolaemic hyponatraemia
blockage of V2 receptors causes excretion of water without accompanying Na+ and thus raises plasma Na+ concentration
describe the role of renal prostaglandins in kidney function
vasodilate and increase renal blood flow and GFR in response to isschaemia, mechanical trauma, angiotensin II, ADH and bradykinin
importance of renal prostaglandins when renal blood flow is compromised
important under conditions of vasoconstriction, or decreased effective arterial blood flow, where they cause compensatory vasodilation
examples of osmotic diuretics
mannitol
examples of carbonic anhydrase inhibitors
acetazolamide
major prostaglandins synthesised by the kidney are
PGE2- medulla
PGI2- glomeruli
both act as vasodilators
