Diuretics Flashcards
List drugs that act on renal tubules
- Carbonic anhydrase inhibitors
- Osmotic diuretics
- Loop diuretics
- Thiazides
- Potassium sparing diuretics
- Aldosterone antagonists
- ADH antagonists
Describe the uses of carbonic anhydrase inhibitors
- Eg. Acetazolamide
- Used to treat glaucoma and altitude sickness
- Not useful at inducing diuresis, as preventing Na reabsorption in PCT will cause greater Na reabsorption downstream
Describe the ADRs of carbonic anhydrase inhibitors
- Decreasing bicarbonate reabsorption leads to metabolic acidosis
- Renal stones
Describe the use of osmotic diuretics
- Eg. Mannitol
- Used to reduce high intracerebral pressure
- Increase osmotic gradient throughout nephron to reduce water reabsorption
List the ADRs of osmotic diuretics
Allergic reactions, hypernatraemia, nausea, vomiting, dehydration
Describe the uses and mechanism of loop diuretics
- Used to treat oedema (+/- hypertension in advanced CKD)
- Mechanism
- Inhibit NaKCC in the thick ascending limb of loop of Henle to decrease Na reabsorption
- Reduces Ca and Mg reabsorption as well
- Increased Na levels in the nephron means more Na is reabsorbed in the collecting duct, leading to more K secretion causing hypokalaemia
- Decreased sodium reabsorption from loop diuretics reduces osmolarity gain in interstitium
- Means RAAS and ADH effects aren’t able to absorb as much water as osmolarity in interstitium lower
- Thiazide do not affect interstitium osmolarity
- Means RAAS and ADH effects aren’t able to absorb as much water as osmolarity in interstitium lower
Describe the ADRs for loop diuretics
- ADR for furosemide - ototoxicity, alkalosis, increase LDL, gout (increased urate), hypokalaemia
- ADR for bumetanide - myalgia, alkalosis, hypokalaemia
Describe the uses and mechanism of thiazides
- Eg. Bendroflumethiazide, indapamide
- Used to treat hypertension
- Mechanism
- Inhibits NaCl co-transporter in the distal convoluted tubule
- Promotes Ca reabsorption as K channels leak K back into the lumen, creating a positive luminal force
- Increased Na levels in the nephron means more Na is reabsorbed in the collecting duct, leading to more K secretion causing hypokalaemia
List the ADRs of thiazides
Gout, hyperglycaemia (problem for diabetics), erectile dysfunction, increase LDL, hypercalcaemia, impotence
Describe the uses and mechanism of potassium sparing drugs
- Eg. Amiloride
- Used to treat hypokalaemia where diuretic is required
- Mechanism
- Inhibits ENac in the collecting duct to reduce Na reabsorption
- Decreases K secretion leading to hyperkalaemia
List the ADRs of aldosterone antagonists
Hyperkalaemia, painful gynaecomastia (enlargement of man’s breasts)
Describe the uses and mechanism of aldosterone antagonists
- Eg. Spironolactone
- Used to treat heart failure, ascites, hypertension, hyperadrenalism
- Inhibits aldosterone effect, thus inhibiting Na retention
- Aldosterone increases expression of ENaC and Na/K ATPase in principal cells of collecting duct
- Decreases K secretion leading to hyperkalaemia
Describe the uses of ADH antagonists
- Eg. Lithium, tolvaptan
- Used to treat hyponatraemia and prevent cyst enlargement in polycystic kidney disease
- Acts as a diuretic, however not a natriuretic
List the ADRs of ADH antagonists
Hypernatraemia, deranged liver function
What are general ADR of diuretics
- Anaphylaxis, photosensitivity rash
- Hypovolaemia and hypotension
- Activates RAAS and can lead to acute kidney injury
- Electrolyte disturbance (Na, K, Mg, Ca)
- Metabolic abnormalities
List common drug drug interactions involving diuretics
- ACE inhibitors and K-sparing diuretics - increased hyperkalaemia leading to cardiac problems
- Aminoglycosides and loop diuretics - ototoxicity and nephrotoxicity
- Digoxin and thiazide/loop diuretics - hypokalaemia increases digoxin binding and toxicity (digoxin more toxic with low K)
- ß-blockers and thiazides - hyperglycaemia, hyperlipidaemia, hyperuricaemia
- Steroids and thiazide/loop diuretics - increased risk of hypokalaemia
- Lithium and thiazide/loop diuretics - lithium toxicity (thiazides), reduced lithium levels (loop)
- Carbamazepine and thiazide - increased risk of hyponatraemia
List the drugs used to treat hypertension
- Thiazide diuretics - vasodilation as well as diuresis
- Spironolactone - especially hyperaldosteronism
- (ACE inhibitors / Ang II antagonists)
- (ß-blockers)
List the drugs used to treat heart failure
- Loop diuretics - best at removing fluid
- Spironolactone - non-diuretic benefits (remodeling of heart)
- (ACE inhibitors / Ang II antagonists)
- (ß-blockers)
- May need to increase diuretic dose as drug not delivered to kidney well
List the drugs used to treat decompensated liver disease (low albumin, ascites)
- Spironolactone
- Loop diuretics
List the drugs used to treat nephrotic syndrome
- Loop diuretic - big doses needed
- +/- Thiazides
- +/- Potassium-sparing diuretics/potassium supplements
- May need to increase diuretic dose as gut swollen in nephrotic syndrome - decreased reabsorption of drug
- Give IV furosemide IV if gut oedema likely
Describe the problems of prescribing diuretics in renal failure
- Patients with CKD have decreased GFR leading to salt and water retention
- Patients given loop diuretics +/- thiazide
- Avoid giving K-sparing diuretics - patients with renal failure have reduced potassium secretion leading to hyperkalaemia
- Not all nephrons working - may need to increase dose of diuretics to achieve desired effect
- When prescribing gentamicin/vancomycin, careful with dose as nephrotoxins causes nephron dysfunction
Describe causes of hyperkalaemia
- Excess intake
- Movement out of cells - acidosis, hypertonicity, tissue (muscle) damage
- Reduced urine loss - reduced GFR, reduced distal delivery of Na, reduced secretion in collecting duct
- Drugs - RAAS inhibitors, NSAIDs, ENaC blockers
Explain the effect of hyperkalaemia on the heart
- Increase in potassium levels increases the resting membrane potential closer to threshold
- At first, this increases the excitability of the heart
- At higher concentrations, this leads to a decrease in excitability of the heart due to inactivation of sodium gated channels
Explain the effect of hypokalaemia on the heart
- In hypokalaemia, the increase in gradient between IC and EC potassium levels leads to hyperpolarisation and therefore shifting resting potential further from threshold
- However in SA and AV node, hyperpolarisation enhances the funny current and thus depolarisation frequency
- Leads to increased excitability and possible ventricular fibrillation and arrhythmias
Describe the management of hyperkalaemia
- Identify cause
- ECG
- Treatment
- Protect the heart from toxicity - calcium gluconate
- Lower serum K - insulin/dextrose, remove K from diet
- Remove K from body - calcium resonium
