drugs which affect the kidney Flashcards
what are diuretics?
a drug that increases the excretion of both fluids and solutes
what does a natriuretic do?
increases Na+ excretion
what does a kaliuretic do?
increases K+ excretion
what are the 2 ways in which most diuretics increase excretion of Na+ and water by the kidneys?
1) they reduce reabsorption of Na+ from the filtrate
2) increase water loss is secondary to Na+ excretion
what are aquaretic agents?
new diuretics that increase urine excretion without increasing Na+ excretion
what are the 2 modes of action of diuretics?
1) direct action of the cells of the nephron
2) modification of content of the filtrate
what are the 2 major applications of diuretic agents?
1) reduce circulating fluid volume
2) removal of excess body fluid (oedema)
what are possible of side effects of diuretics due to actions they have on the kidneys?
- hypertension
- chronic heart failure
- liver cirrhosis
- renal disease
- premenstrual oedema
- toxic oedema
- increase elimination of drugs
- rapid weight loss
what are other side effects of diuretics?
- glaucoma
- epilepsy
where do carbonic anhydrases act?
proximal tubule
where do osmotic diuretics act?
proximal tubule, descending loop of Henle
where do loop diuretics act?
ascending loop of Henle
where do thiazides and thiazide-like diuretics act?
early distal tubule
what are the 2 types potassium sparing diuretics?
- aldosterone antagonists
- non-aldosterone antagonists
where do potassium sparing diuretics act?
late distal tubule, early collecting duct
what are the most effective diuretics?
loop diuretics
how do loop diuretics work?
they inhibit the Na+/K+/2Cl- transporters (NKCC2) in the thick ascending limb of the loop of Henle which reduces reabsorption of Na+, K+ and Cl-
what can a single dose of loop diuretics do to the urine volume?
increase urine volume from 200 to 1,200ml over 3 hours
what are the clinical uses of loop diuretics?
- acute pulmonary oedema
- chronic heart failure
- cirrhosis of liver
- resistance hypertension
- nephrotic syndrome
- acute kidney injury
what are the unwanted effects of loop diuretics?
- dehydration
- K+ loss leading to low plasma K+
- metabolic alkalosis
- hypokalaemia can potentiate effects of cardiac glycosides
- deafness
how does sodium-potassium exchange change due to loop diuretics?
- loop diuretics cause increased Na+ delivery to distal tubule
- this is exchanged for K+ in the DT which is excreted in the urine
- this K+ loss contributes to hypokalaemia associated with loop diuretics
how do thiazide diuretics work?
- act in the distal tubule to inhibit the apical Na+/Cl- co-transporter
- cause moderate but sustained Na+ excretion with increased water excretion
how long do thiazide diuretics work?
up to 24 hours
what are the clinical uses for thiazide diuretics?
- hypertension
- oedema
- mild heart failure
what are the unwanted effects of thiazide diuretics?
- plasma K+ depletion
- metabolic acidosis
- increased plasma uric acid: gout
- hyperglycaemia
- increased plasma cholesterol
- male impotence (reversible)
what is currently the preferred diuretic for resistance hypertension and why?
- indapamide
- lower incidence of unwanted effects
what are the symptoms of mild hypokalaemia?
fatigue, drowsiness, dizziness, muscle weakness
what are the symptoms of severe hypokalaemia?
abnormal heart rhythm, muscle paralysis, death
how do potassium sparing diuretics work?
act on distal tubules to inhibit Na+ reabsorption but K+ isn’t secreted into the distal tubule
what is spironolactone metabolised to?
canrenone
what is canrenone?
a competitive antagonist of aldosterone
how does spironolactone work?
reduces Na+ channel formation and its absorption from distal tubule
what are the clinical uses of spironolactone?
- heart failure
- oedema
what are the unwanted effects of spironolactone?
- hyperkalaemia
- metabolic acidosis
- GI upsets
- gymaecomastia, menstrual disorder, testicular atrophy
*eplernone produces less unwanted effects
how do triamterene and amiloride work?
- weak diuretic: act on distal tubule to inhibit Na+ reabsorption and decrease K+ excretion
- block luminal Na+ channel by which aldosterone produces its main effects
what are the main unwanted effects of triamterene and amiloride?
- hyperkalaemia
- metabolic acidosis
- GI upsets
- skin rashes
what are the 2 main reasons diuretics are used in combination?
1) to increase diuretic effect
2) to avoid the unwanted effects of hypokalaemia
what is the best combination of diuretics to use to avoid hypokalaemia?
use loop diuretics or thiazides with potassium sparing diuretics
what is the main example of a carbonic anhydrase inhibitor?
azetozolamide
how do carbonic anhydrase inhibitors work?
- ## blocks sodium bicarbonate reabsorption in the proximal tubule
what are carbonic anhydrase inhibitors used to treat?
- glaucoma
- epilepsy
what are the unwanted effects of carbonic anhydrase inhibitors?
- metabolic acidosis
- enhances renal stone formation
what is the main example of an osmotic diuretic?
mannitol
what are the clinical uses of osmotic diuretics?
- treatment of raised inter cranial pressure
- treatment of intraoccular pressure
- cause osmotic diarrhoea if given orally
- can treat acute renal failure
what is the unwanted effector osmotic directs?
increased plasma volume
what volume of urine does ADH usually maintain?
1.5L/day
what happens with toxicity of ADH antagonists?
1) diabetes insipidus
2) renal failure
3) Li+ can cause tremors, mental confusion, cardiotoxcicity, thyroid dysfunction and leukocytosis
4) demeclocylcine shouldn’t be used in patients with liver disease
what are the 2 non-selective agents used in potential ADH antagonists?
- lithium
- demeclocyline
how doe Xanthines work?
- produce weak diuretic effect by increasing cardiac output
- possible also some vasodilation of the glomerular afferent arteriole
- results in increased renal and glomerular blood flow which increases glomerular filtration rate and urine output
