S3 L2 Diuretics Flashcards
(38 cards)
What are the main functions the kidney?
- Regulatory
- Fluid balance
- Acid-base balance
- Electrolyte balance - Excretory
- Waste products
- Drug elimination
→ Glomerular filtration
→ Tubular secretion - Endocrine
- Renin
- Erythropoetin
- Prostaglandins
- 1α- calcidol - Metabolism
- Vit D
- Polypeptides
→ Insulin
- Drugs
→ Morphine
→ Paracetamol
Where do different drugs act on the renal tubule?
- Carbonic anhydrase inhibitors → PCT
- Osmotic diuresis → PCT and throughout
- SGLT2 inhibitors → PCT
- Loop Diuretic → TAL
- Thiazide → DCT
- Potassium sparing diuretics → DCT and CD
- Aldosterone antagonists → CD
- ADH antagonists → CD
Define:
- Diuretics?
- Natriuretic?
- Aquaretic?
D- Increased production
N- Loss sodium in the urine
A- Loss of water without electrolytes
What do carbonic anhydrase inhibitors do?
Prevent carbonic anhydrase working Stops conversion: - CO2 + H2O ←→ H2CO3 ←→ H+ + HCO3- Loss of NaCO3 → 66% of filtered and 85% of NaHCO3 is normally reabsorbed in the proximal tubule Hypokalaemic metabolic acidosis → HCO3- excreted in urine → Enhanced Na+ delivery to the CD, taken up by ENaC, K+ excreted into urine Tolerance develops after 2-3 days
What are osmotic agents?
Mannitol
- Can’t be reabsorbed
- Increases the osmolality in the filtrate
- Draw water out of cells
- Reduced intracellular volume
- Hypernatremia risk
What are SGLT2 inhibitors?
Inhibit Na+ and glucose uptake in PCT ↑osmolality in the filtrate → water follows ↑Plasma glucose ↓Body weight ↓BP ↓Plasma uric acid ↓Glomerular hyperfiltration
How do loop diuretics work?
Inhibit the Na+/K+/2Cl- channel
- Loss of Na+ and H2O (25% of filtered reabsorbed)
- Hypokalemic metabolic alkalosis
→ Enhanced Na+ delivery to the CD, taken up by ENaC, K+ excreted into urine
- Increase Ca2+ loss
→ Normally K+ uptake and then K+ excreted, build up of +ve change forces Ca2+ and Mg2+ paracellularly
What do thiazide diuretics do?
Block Na+/Cl- cotransporter 5% of filtered reabsorbed - Loss of Na+ and H2O - Hypokalaemia metabolic alkalosis - Increased Ca2+ reabsorption as Na+/ Ca2+ exchanger works in opposite direction- more Na+ brought out of plasma into cell, Ca2+ goes into plasma so then more Ca2+ reabsorbed - hypercalcaemia
How does aldosterone work?
Increase expression of ENaC and Na+/K+ ATPase in principle cells of the collecting duct
How do amiloride and spironolactone work?
Amiloride → ENaC channel blocker (potassium sparing)
Spironolactone → aldosterone blocker → stop ↑ENaC and ↑Na+/K+ ATPase expression therefore reducing Na+ uptake
How are amiloride ad spironolactone potassium sparing?
Only affect Na+ reabsorption
Reduced the activity of the Na+/ K+ ATPase resulting in less K+ being excreted
What are ADH antagonists?
Aquaretics- no affect on Na+ just water loss
1. Tolvaptan
ADH anatogonist
Diuretic but not natriuretic
Used to treat hyponatraemia (looks like low Na+ because of ↑H2O) (and prevent cyst enlargement in APCKD)
2. Lithium
- Treat bipolar disorder
- Inhibits action of ADH
- Need to keep up with water intake to avoid dehydration
How do the ADH antagonists work?
Tolvaptan block the ADH receptors
Lithium work on G protein along the cascade
Prevents insertion of aquaporin into the collecting duct
Preventing reabsorption of water
What other substance can have an diuretic action?
Alcohol- inhibits ADH release
Caffeine- ↑GFR and ↓tubular Na+ reabsorption
What are some of the adverse reactions that diuretics can cause?
Hypovolemia and hypotension
- Activate RAAS
- → AKI (hypoperfusion)
Electrolyte disturbance (Na+, K+, Mg2+ and Ca2+)- expect aquaretic
Metabolic Abnormalities (depends on individual drug)
Anaphylaxis/ photosensitivity, rash etc… rare
What are some of the common adverse drug reactions for thiazides?
Gout → Uric acid reabsorption Hyperglycaemia Erectile dysfunction ↑LDL ↑TG Hypercalcaemia
What are some of the common adverse drug reactions for frusemide?
Ototoxicity
Alkalosis - remove the H+
↑LDL ↑TG
Gout
What are some of the common adverse drug reactions for spironolactone?
Hyperkalaemia - potassium sparing
Impotence
Painful gynaecomastia
What are some of the common adverse drug reactions for bumetanide?
Myalgia - pain or tenderness in one or more muscles of the body
How do the drug interact with each other?
ACEi and K+ sparing → hyperkalaemia - cardiac problems
Aminoglycoside + loop diuretics → ototoxicity and nephrotoxicity
Digoxin + thiazide and loop → Hypokalaemia - increased digoxin binding and toxicity
B-blockers + thiazide → hyperglycaemia, hyperlipidaemia, and hyperuricaemia
Steroids + thiazide + loop → Hypokalaemia
Lithium + thiazide + loop → Lithium toxicity (thiazides), reduced lithium levels (loop)
Carbamazepine + thiazide + loop → Increased risk of hyponatraemia
What are the uses of diuretics?
Hypertension Heart failure Decompensated liver disease Nephrotic syndrome Chronic kidney disease
What diuretics are used to treat hypertension?
Thiazide diuretics
Spironolactone → secondary hypertension, Liddle syndrome (ENaC channels are always on), inhibits aldosterone preventing expression of ENaC channels
Loop diuretic - accommodation downstream (compensated for)
(ACEi/ ARBs and B blockers also used)
How is heart failure treated?
Traditional - Loop Diuretics - Spironolactone (- ACEi/ ARB + B blockers)- not diuretics Novel - SGLT-2 inhibitors - Tolvaptan
What is secondary hyperalodersteonism?
Body trying to compensate for things that have gone wrong
Arterial ↓BP - either due to hypovolemia (trauma associated) or HF- sense hypovolemia because heart not pumping very well + blood flow is reduced but actually volume is normal or ↑
Activate RAAS and sympathetic system to ↑ Volume= fluid overload- need diuretics
