Diuretics Flashcards
What is the mechanism of action of Thiazide diuretics?
- Inhibiton of NaCl symporter
- Inhibits NaCl reabsorption in distal convuluted tubule
When are thiazide diuretics used?
-Hypertension (Used for vasodilation and diuresis)
What are the side effects of thiazide diuretics?
- Gout
- Hyperglycaemia
- Erectile Dysfunction
- Increase in LDL and Triglycerides
- Hypercalcaemia (promotion of Ca reabsorption)
- Hypokalaemia
- Hyperuricemia
- Impotence
What are the examples of Loop Diuretics?
- Furosemide
- Bumetanide
What is the mechanism of action of Loop Diuretics?
- Affects the thick ascending limb of the Loop of Henle
- Inhibits NaCl reabsorption
When are Loop Diuretics used?
- Heart failure
- Decompensated Liver Disease
- Nephrotic Syndrome
- Chronic kidney Disease (+/- thiazides sometimes as a boost)
- Oedema (+/- hypertension in advanced CKD)
(Hypertension - less used due to shorter duration of action)
What are the side effects of Furosemide?
- Ototoxicity
- Alkalosis (Blunt H+ secretion)
- Increase in LDL and triglycerides
- Gout
- Ca2+/Mg excretion
- Hypokalaemia (Blunt K+ secretion)
- Androgen cross-reactivity
- Metabolic effects
What are some side effects of Bumetanide?
- Myalgia
- Alkalosis
What is the mechanism of action of Spironolactone?
- Inhibits Na retention by antagonising aldosterone. (3Na+/2K+ and Na+reflux)
- Works via the eNaC
What are the uses of Spironolactone?
- Hypertension (primary drug for primary hyperaldosteronism)
- Decompensated Liver Disease
- Heart failure
- Ascites
- Hyperadrenalism
What are the side effects of Spironolactone?
-Hyperkalaemia
-Impotence
-Painful gynaecomastia
Don’t use in CKD
What is the mechanism of action of carbonic anhydrase inhibitors?
- Inhibits the enzyme carbonic anhydrase
- Leads to excretion of Na+, K+ and PO3
What are uses of carbonic anhydrase inhibitors?
- Glaucoma
- Altitude sickness
What are the side effects of carbonic anhydrase inhibitors?
- Metabolic Acidosis
- Hypokalaemia
- Acidosis
- Renal stone
What is the mechanism of action of osmotic diuretics (mannitol)?
- Filtered at glomerulus
- Increases osmotic gradient throughout nephron
What are the uses of osmotic diuretics?
-Reduce high intracerebral pressure
What are the side effects of osmotic diuretics?
- Excessive water loss
- Hypernatremia
- Allergic Reactions
What is the mechanism of action of lithium (ADH antagonists)?
- Inhibits action of ADH
- Diuretic but not natriuretic
Reduces concentrating ability of urine in collecting ducts
When are ADH antagonists used? (lithium, tolvaptan)
- Hyponatraemia
- Prevention of cyst enlargement in APCKD
What are the side effects of ADH antagonists?
- Hypernatremia
- Deranged liver function
What are the general side effects of diuretics?
- Anaphylaxis/Photosensitivity rash
- Hypovolaemia and hypotension (Activation of RAAS which can lead to acute kidney injury)
- Electrolyte Disturbance (Na+, K+, Mg2+, Ca2+)
- Metabolic abnormalities (depends on individual drug)
Why do some patients fail to respond to diuretics?
- Oedema of the gut so less absorption
- Heart failure so less delivery of the diuretic
- The nephrons are affected so work less well
How do you treat diuretic resistance due to oedema of the gut?
Give multiple doses to find the minimum effective dose
What are some potentially nephrotoxic drugs?
- Aminoglycosides
- Vancomycin
- Aciclovir
- NSAIDs
What are some drugs that can cause renal dysfunction?
- ACE inhibitors
- Diuretics
- NSAIDs
- Metmorfin (acidosis)
What is the mechanism of action of Tolvaptan (ADH antagonist)?
- ADH antagonist
- Diuretic and not natriuretic
Reduces concentrating ability of urine in collecting ducts
What are other substances that have diuretic action?
Alcohol – Inhibits ADH release
Caffeine – Increase in GFR and decrease tubular Na+ reabsorption
What do you have to be careful of when prescribing in patient with chronic kidney disease?
- Avoid nephrotoxins
- Dose gentamicin/vancomycin carefully with consultation of pharmacist
Which long term drugs have to be checked for alteration when diagnosed with chronic kidney dose?
- Allopurinol
- Digoxin
- Cyclosporin / Tacrolimus
- Low molecular weight heparins
Which common drugs have increased side effects with CKD?
- Morphine & other opiates
- Nitrofurantoin
- Statins
What are the risk of hyperkalaemia?
- Can cause life threatening cardiac arrhythmias
- Any ECG change is cause of immediate action
What are causes of hyperkalaemia?
- Excess intake (virtually never the only cause)
- Movement out of cells (Acidosis, Hypertonicity, Tissue damage)
- Reduced urine loss (Reduced GFR, Reduced distal delivery of Na+ (oliguric AKI, obstruction), Reduced secretion in collecting duct)
- Drugs (ACE-Inhibitors, spironolactone, NSAIDs, ENaC blockers)
What are major risk to cause hyperkalaemia?
- Increase catabolism/tissue damage
- Reduced urine production
How is hyperkalaemia management approached?
- Identify the cause
- ECG
- Treatment
What are the treatment methods?
Protect the heart - Calcium Gluconate
Lower serum K+ - Insulin/Dextrose
Remove K+ from the body - Calcium Resonium
Other drugs - Salbutamol, Sodium Bicarbonate
