3 - Diuretics and Kidney Failure Drugs Flashcards
What are the four broad functions of the kidney?
- Regulatory: fluid, acid, electrolyte
- Excretory: waste and drugs
- Endocrine: renin, EPO, prostaglandins
- Metabolism: Vit D, insulin, morphine, paracetamol
What are the seven different types of diuretic drugs acting on the kidney?
- Carbonic anhydrase inhibitors
- Osmotic diuretics
- Loop diuretics
- Thiazides
- K+ sparing diuretics
- Aldosterone antagonists
- ADH Antagonists
- (SGLT2 inhibitors)
What are the definitions of the following:
- Diuretic
- Natriuretic
- Aquaretic
How do carbonic anhydrase inhibitors work and what are their side effects?
- Sodium bicarbonate diuresis
- Stops bicarb being broken down by blocked CA enzyme so cannot be absorbed
- Hypokalemic metabolic acidosis as loss of bicarb and upregulation of ENaC and therefore ROMK in the distal tubules
- Not used as diuretics anymore as fast tolerance, more like glaucome
How do osmotic agents work as diuretic, what are some side effects and an example of this kind of drug?
- Mannitol: used in ITU setting to relieve raised ICP
- Filtered at glomerulus
- Increase osmotic gradient throughout nephron
- Excessive water loss
- Hypernatraemia as so much H2O loss and little Na loss
How can SGLT2 inhibitors work as diuretics?
Originally an antidiabetic but the loss of Na by blocking SGLT2 means it also acts as a diuretic
What are the actions of loop diuretics, some side effects and some examples?
- Bumetanide and Furosemide
- Inhibit NCCK transporter in thick ascending limb so less Na and Cl aborsbed
- Leads to loss of Ca and Mg as they need ROMK to be absorbed
- Hypokalemic metabolic alkalosis as upregulation of ENac further down
What are the actions of thiazides and what are some side effects?
- Inhibits NaCl reabsorption in DCT at NaCl channel
- Promotes Ca reabsorption due to increase use of NCX
- Hypokalaemia due to upregulation of ENaC in CD
- Hyperuricaemia
- Hypercalcaemia
How does spironolactone act as a diuretic and what are some side effects of the use of this?
- Aldosterone receptor antagonist so inhibits Na+ retention (Na-K ATPase / Na+ flux) in collecting duct
- Blunts K+ and H+ secretion so can give with other diuretics that cause hypokalaemia
- Androgenic cross-reactivity (gynacomastia)
Where does aldosterone act in the kidney?
- Aldosterone increases expression of ENaC and Na/K/ATPase in principal cells of the collecting duct
- Spironolactone is the aldosterone receptor antagonist
How do ADH antagonists work?
- ADH antagonists (aquaretics) reduce concentrating ability of urine in collecting ducts by blocking V2 receptor
- Tolvaptan: treats hyponatraemia and prevents cyst enlargment in APCKD as no AQP inserted
- Lithium: used to treat bipolar but also inhibits ADH action so get poyuric and dehydrated
Where do ADH antagonists act?
Aquaretics act on principal cells of the collecting duct
Where do each of the main diuretics act in the nephron?
- CA inhibitors: PCT
- Osmotic diuretics: all over but mainly PCT
- Loop diuretics: thick ascending
- Thiazides: late DCT
- K+ sparing diuretics: DCT and CD
- Aldosterone antagonists: CD
- ADH Antagonists: CD
- (SGLT2 inhibitors): PCT
How do alcohol and caffeine have a diuretic action?
Caffiene act on adenosine receptors which cause vasodilation and therefore increased blood flow to the kidney
In general what are the side effects that can occur with diuretics?
- Hypovolaemia and hypotension leading to AKI
- Electrolyte disturbances
- Metabolic disturbances
- Anaphylaxis (mainly loops)
What are some specific side effects for the following diuretics:
- Thiazides
- Spironolactone
- Furosemide
- Bumetanide
- Thiazides: Gout (increased uric acid absorption), hyperglycaemia, erectile dysfunction, increased LDL, hypercalcaemia
- Spironolactone: hyperkalaemia, impotence, painful gynaecomastia
- Furosemide: ototoxicity, alkalosis (due to loss of K+ and Cl-), increased LDL, gout
Bumetanide: gout
What are some drug drug interactions with loop diuretics?
- Aminoglycosides: can cause ototoxicity and nephrotoxicity
- Digoxin: hypokalaemia so increased digoxin binding and toxicitity
- Steroids: risk of hypoK
- Lithium: reduced levels of Lithium
Don’t use in severe hypoK and hypoNa or renal failure
What are some drug drug interactions with thiazides?
Alcohol
Amlodipine
- Digoxin: hypok can increase digoxin binding and toxicity
- Beta blockers: hyperglycaemia, hyperlipidaemia, hyperuricaemia
- Steroids: risk of hypoK
- Lithium: lithium toxicity
- Carbamazepine: risk of hypoNa
Don’t use in hyponatraemia, hypercalcaemia, addison’s
What are some drug drug interactions of Amiloride ? (K+ sparing drugs)
ACEi can increase hyperkalaemia so cardiac problems
ARBs
Other K+ sparing drugs (spirinolactone)
What are some drug drug interactions of Aldosterone antagonists (K+ sparing drugs)
Alcohol
Amiloride (K+ sparing)
ACEi
ARBs
What are some uses of diuretics?
- Hypertension: thiazides (vasodilation as well as diuresis) and spironolactone
- Heart failure: Loops, spironolactone (non diuretic benefits)
- Decompensated Liver Disease: spironolactone and loops
- Nephrotic syndrome: loops (big doses), thiazides, K+ sparing or K supplements
- CKD: loops and thiazide like as alkolosis and kalliuretic effects are beneficial, avoid K+ sparing!
What factors are needed for diuretic delivery to renal tubule and therefore if any of these factors are damaged due to a disease, a higher dose of diuretic will be needed?
- No gut oedema as this can stop absorption of oral diuretic
- Blood flow to PCT must be in tact
- PCT must be functioning to allow diuretic (e.g furosemide) over
- Thick ascending limb must be intact to response to diuretic (furosemide)
When prescribing a diuretic, what should recommend to the patient?
- Lower your salt intake!!
What is refractory oedema and how do we treat it?
- Peripheral oedema that does not respond to dietary sodium restriction and diuretic treatment including loop diuretic, caused by underlying cardiac or pulmonary condition
⇒ Check salt intake
⇒ IV furosemide (if gut oedema likely)
⇒ Find minimum effective dose
⇒ Give repeated bolus or infusion (short t1/2)
How do we treat gestational hypertension?
- Carefully monitored centrally acting adrenergic and dopaminergic inhibitors
- Limit evidence on what is safe to use as pregnant people often not involved in RCTs
Describe the relationship between diuretic drugs and kidney function in terms of adverse reactions
What are some nephrotoxic drugs?
- Aminoglycosides e.g gentamicin
- Vancomycin (IV only)
- Aciclovir
- NSAIDs
Identify four drugs which can exacerbate renal dysfunction.
- ACE-Inhibitors
- Diuretics
- NSAIDs
- Metformin
What are the three steps involved in managing hyperkalaemia?
⇒ Identify a cause
⇒ ECG
⇒ Treatment:
⇒ Protect the heart → calcium gluconate
⇒ Lower serum K+ → insulin / dextrose
⇒ Remove K+ from body → calcium resonium
Which diuretics have the most electrolyte disturbances?
- Thiazides as acting at DCT and will alter the countercurrent mechanism
What are the following syndromes:
- Bartter’s
- Gitelman’s
- Liddle’s
- Bartter’s: blockage of NCCK, like giving furosemide
- Gitelman’s: NaCl in DCT blocked so like giving thiazie diuretic
- Liddle’s: ENaC constantly stuck on so hypertension, whereas the others are hypotension
What are the main side effects and uses for each type of diuretic?
Diuretic effectiveness is affected by heart and kidney function
What physiological issue occurs when prescribing diuretics?
Hormonal systems like RAAS wil be activated to restore blood volume so may just get rebound oedema for a few days when you remove diuretics as the hormones have compensated to restore sodium balance
What is a common ADR of furosemide?
- Increased LDL cholesterol
What is used to treat hypertension in pregnancy?
- Labetalol as ACEi cannot be used during pregnancy and ARBs cannot be used during lactation
- Lowers sympathetic tone and reduces HR
How do ACEi lower blood pressure apart from acting on the RAAS system?
Stop the breakdown of bradykinin causing vasodilation
