CPT6 - Diuretics & Renal Pharmacology Flashcards
3 drug-induced loss of urine definitions
Diuretic
Natriuretic
Aquaretic
1.) Diuretic - increased production of urine
2.) Natriuretic - loss of sodium in urine
3.) Aquaretic - loss of water w/out electrolytes
4 features of carbonic anhydrase (CA) inhibitors
Usage x2
Mechanism
Hypokalaemic Metabolic Acidosis
Side-Effects x2
1.) Usage - glaucoma and altitude sickness
- acetazolamide
2.) Mechanism - prevents HCO3- absorption in PCT
- prevents breakdown of H2CO3 in lumen
- prevents formation of H2CO3 in tubule
3.) Hypokalemic Metabolic Acidosis
- ↑Na+ delivery to CD –> ↑ENaC –> ↑ROMK
- loss of HCO3- in urine
- tolerance develops after 2-3 days
4.) Side Effects - acidosis and renal stones
3 features of osmotic agents
Usage
Mechanism
Side Effects x3
1.) Usage - reducing intracranial pressure
2.) Mechanism - osmotic agent (e.g. mannitol) in lumen causes H2O to move back into lumen via osmosis
3.) Side Effects - due to loss of water
- hypernatremia and reduced ICF
- allergic reactions are also common
6 features of SGLT2 inhibitors
Usage
Mechanism
Hyperuricemia
AA Vasoconstriction
Clinical Benefits x4
Side Effects x2
1.) Usage - diabetes
- dapagliflozin, canagliflozin
2.) Mechanism - natriuretic and diuretic
- prevents co-transport of Na-Glucose in PCT
3.) Hyperuricemia - ↑glucose –> uric acid secretion
4.) AA Vasoconstriction - ↑NaCl delivery to macula densa
- leads to a ↓GFR and ↓renin
5.) Clinical Benefits - leads to a reduction in:
- plasma glucose, body weight, BP, glomerular hyperfiltration
6.) Side Effects
- glucosuria and natriuesis
5 features of loop diuretics
Usage
Mechanism
Hypocalcemia
Hypokalaemic Metabolic Alkalosis
Side Effects x4
1.) Usage - oedema +/- hypertension in advanced CKD
- example: furosemide, bumetanide
- not given past 2pm because you don’t want patients (esp old) waking up in the middle of the night
- effective treatment is determined by a weight reduction
2.) Mechanism - blocks NKCC2 in thick ascending limb
- leads to loss of Na+ and water
3.) Hypocalcemia - due to divalent loss (Ca2+ and Mg2+)
- less activity of ROMK –> less K+ back-diffusion
- reduced Vm, driving force for cation reabsorption
4.) Hypokalaemic Metabolic Alkalosis
- ↑Na+ in CD –> ↑ENaC –> ↑ROMK
- ↑Na+ in CD –> ↑activity of NHE –> ↑H+ loss in urine
5.) Side Effects - alkalosis
- hypocalcemia and hypokalemia (see above)
- hyperuricemia: ↑urea/uric acid leads to gout
- hyperlipidemia and hyperglycaemia: ↑LDL and ↑TG
- ototoxicity
5 features of thiazide diuretics
Usage
Mechanism
Hypercalcaemia
Hypokalaemic Metabolic Alkalosis
Side Effects x8
1.) Usage - hypertension
- thiazide (bendroflumethaizide)
- thiazide-like (indapamide)
2.) Mechanism - blocks NCCT in the DCT
- causes larger electrolyte disturbance than loop diuretics because location means it doesn’t contribute to concentration gradient so doesn’t lead to increased water and salt reabsorption in collecting duct
3.) Hypercalcaemia - increased Ca2+ reabsorption
- ↓ intracellular Na+ –> ↑Ca2+ reabsorption by NCX
- Ca2+ then enters lumen via a Ca2+ uniporter (TRPV5)
- TRPV5 is also stimulated by PTH
4.) Hypokalaemic Metabolic Alkalosis
- ↑Na+ in CD –> ↑ENaC –> ↑ROMK
- ↑Na+ in CD –> ↑activity of NHE –> ↑H+ loss in urine
5.) Side Effects - ↓Na+, ↓K+, ↑Ca2+
- hyperglycaemia: increase in insulin resistance
- hyperuricemia: ↑urea/uric acid leads to gout
- hyperlipidemia: ↑LDL and ↑triglycerides
- erectile dysfunction (impotence) and arrhythmia
- bendroflumethiazide causes digoxin toxicity (vague symptoms, lethargy, colour vision deficiency)
3 features of K+ sparing diuretics
Usage (amiloride and spironolactone x4)
Mechanism x2
Side Effects x3
1.) Usage
- amiloride: patients needing diuretics but have low K+
- spironolactone: hypertension, HF, hyperadrenalism, ascites
2.) Mechanism - blocks ENaC in DCT/CD
- amiloride and triamterene block the ENaC itself
- spironolactone is an antagonist to aldosterone (MRA)
3.) Side Effects
- hyperkalemia: esp if low kidney function
- impotence, painful gynaecomastia (spironolactone)
ADH antagonists (aquaretics)
Usage x2
Mechanism x2 (tolvaptan and lithium)
Effects x3
Other Substances x2
1.) Usage - tolvaptan is used to treat hyponatraemia
- also used to prevent cyst enlargement in APCKD
2.) Mechanism - diuretics but not natriuretic
- tolvaptan is an ADH antagonist
- lithium inhibits the Gs protein (GPCR mechanism)
3.) Effects - increases serum sodium, diluted urine, decreased free water clearance
4.) Side Effects
- hypernatraemia, deranged liver function
4.) Other Substances - with diuretic action
- alcohol: inhibits ADH release
- caffeine: ↑GFR and ↓Na+ reabsorption
7 interacting drugs with diuretics
ACEi
ß-blockers
Digoxin
Steroids
Lithium x2
Carbamazepine
Aminoglycosides
1.) ACE Inhibitors - w/ K+ sparing diuretics
- increased hyperkalaemia –> cardiac problems
2.) ß-blockers - w/ thiazide diuretics
- hyperglycemia, hyperlipidemia, hyperuricemia
3.) Digoxin - w/ thiazide and loop diuretics
- hypokalaemia –> ↑digoxin binding and toxicity
4.) Steroids - w/ thiazide and loop diuretics
- increased risk of hypokalaemia
5.) Lithium - w/ thiazide and loop diuretics
- thiazides: lithium toxicity
- loop diuretics: reduced lithium levels
6.) Carbamazepine - w/ thiazide diuretics
- increased risk of hyponatremia
7.) Aminoglycosides - w/ loop diuretics
- ototoxicity and nephrotoxicity
5 uses for diuretics
Hypertension
Heart Failure
Decompensated Liver Disease
Nephrotic Syndrome
CKD
1.) Hypertension
- thiazide diuretics, spironolactone, loop diuretics
2.) Heart Failure
- loop diuretics: symptomatic treatment
- spironolactone: prognostic treatment
3.) Decompensated Liver Diseases
- spironolactone and loop diuretics
4.) Nephrotic Syndrome
- loop diuretics +/- thiazides and K+ sparing diuretics
5.) CKD - loop diuretics, avoid K+ sparing diuretics
- alkalotic effect reverses acidosis
- kalliuretic effects reverses hyperkalemia
5 causes of diuretic resistance
Gut Oedema
Albumin
Blood Flow
Nephrons
Organic Anion Transporter
1.) Gut Oedema - less absorption of oral pill
2.) Reduced Albumin - diuretic needs to bind to albumin in blood so less albumin –> less drug delivery
3.) Reduced Blood Flow - less delivery of drug
- occurs in heart failure
4.) Less Nephrons - less uptake of the diuretic
- occurs in CKD
5.) Organic Anion Transporter - moves the diuretic from the blood into the PCT epithelial cell then into lumen
- doesn’t work as well in CKD because the diuretic has to compete with other toxins
3 syndromes affecting transporters in the kidney
Bartter’s
Gitelman’s
Liddle’s
1.) Bartter’s Syndrome - no functioning NKCC2
- same effects as loop diuretics
2.) Gitelman’s Syndrome - no functioning NCCT
- same effects as thiazide diuretics
3.) Liddle’s Syndrome - overactive ENaC channel
