Diuretics Flashcards
What are the physiological functions of the kidney?
REEM
Regulatory
- Fluid balance
- Acid-base balance
- Electrolyte balance
Excretory
- Waste products
- Drug elimination
- Glomerular filtration
- Tubular secretion
Endocrine
- Renin-angiotensin-aldosterone
- Erythropoietin
- Prostaglandins
Metabolism
- Vitamin D
- Polypeptides
- Insulin
- PTH
What are some drugs acting on the renal tubules?
Carbonic anhydrase inhibitors Osmotic Diuretics Loop Diuretics Thiazides Potassium sparing diuretics Aldosterone antagonists ADH antagonists
Tell me about Acetazolamide/Dorzolamide.
Carbonic anhydrase inhibitor
Acts on the PCT
Leads to excretion of sodium, potassium and some phosphates
Used for some eye conditions, sickness, and benign intracranial hypertension
Tell me about Osmotic agents (mannitol)
Used for cerebral oedema (used to be)
Causes osmotic effect within the renal tubule
Works throughout the tubule
PCT, loop and CD
Causes significant water loss
ADRs
sodium retention
Tell me about loop agents
Furosemide
Bumetanide
Used in heart failure and fluid overload
Inhibit sodium chloride reabsorption
Works on the thick ascending limb of the loop of Henley
Half life of 2 hours
duration of action is about 6 hours
ADRs
Can lead to potassium loss
Can lose Mg and Ca2+
Key difference between furosemide and bumetanide is that bumetanide has a better oral bioavailability
Tell me about thiazides
Bendroflumethiazide
They cause salt and chloride loss
Calcium reabsorption
Less diuretic effect
Works on the DCT
But BP lowering effect is greater
Suspected different effect of thiazide
ADRs
Hypercalcaemia
Low sodium and chloride
Tell me about aldosterone antagonists
Spironolactone
Eplerenone
Inhibits Na retention (Na+/K+ATPase / Na+ flux)
Blunt K+ and H+ secretion
Acts on CD
ADRs
Can lead to potassium retention
Spironolactone ADRs
Androgenic cross-reactivity
Can lead to gynaecomastia
Long half life - 18 hours
Once a day drug
Tell me about ADH antagonists
Lithium (Used in bipolar)
Demeclocycline (Antibiotic)
Reduces concentrating ability of urine in collecting ducts
Acts on CD
Name some other drugs with diuretic activity.
Digoxin (used for AF (sometimes heart failure))
- Inhibits tubular Na/K-ATPase
Amiloride (often used with furosemide)
- Inhibits Na channels in DCT/CD
- K+ sparing
What are some generic adverse drug reaction of diuretics?
Anaphylaxis/rash etc.
Hypovolaemia and hypotension leading to acute renal failure
Electrolyte Disturbance
Metabolic Abnormalities
Name specific ADRs of thiazide, spironolactone, furosemide and bumetanide.
Thiazides
- Gout
- Erectile dysfunction
Spironolactone
- Hyperkalaemia
- Painful gynaecomastia
Furosemide
- Ototoxicity (rare)
Bumetanide
- Myalgia
Tell me about some important diuretic drug interactions and their consequences.
K+-sparing diuretics + ACE inhibitors
Increased Hyperkalaemia which can lead to cardiac problems
Loop diuretics + Aminoglycosides
Ototoxicity and nephrotoxicity
Thiazide and Loop D. + Digoxin
Hypokalaemia leads to increased digoxin binding and toxicity
Thiazide and Loop D. + Steroids
Increased risk of hypokalaemia
Thiazide Diuretics + Beta-Blockers
Hyperglycaemia, hyperlipidaemia, hyperuricemia
Thiazide Diuretics + Carbamazepine
Increased risk of hyponatraemia
How can diuretic resistance occur?
Incomplete treatment of primary disorder
Continuation of high Na+ intake
Patient non-compliance
Poor absorption (with an oedematous gut)
Volume depletion decreases filtration of diuretics
Volume depletion increase serum aldosterone which enhances Na+ reabsorption
NSAIDs - can reduce renal blood flow
What are some major indications for diuretic use?
Heart failure
Hypertension
Decompensated liver disease
How are diuretics used in heart failure?
Loop diuretics
Thiazide diuretics (normally an add on)
(Spironolactone - non-diuretic benefits)
ACE inhibitors/ANG II antagonists
Beta-blockers
How are diuretics used in hypertension?
Thiazide diuretics (Thiazide-like diuretics)
Spironolactone
(loop diuretics)
ACE inhibitors/Ang II antagonists
Beta blockers
What diuretics are used in decompensated liver disease?
Spironolactone
Loop diuretics
What are potentially nephrotoxic drugs?
ACA inhibitors Aminoglycosides (gentamicin) Penicillins Cyclosporin A Metformin NSAIDs Many more
There is a double whammy if renal function is already impaired.
What are some key facts about prescribing in chronic renal failure?
Avoid nephrotoxins if possible
Reduce dosages in line with GFR if metabolism or eliminated via the kidneys
Monitor renal function and drug levels
Hyperkalaemia is more likely
Uraemic patients have greater tendency to bleed
Why is special care needed when prescribing in the elderly?
Renal function is over-estimated as creatinine is dependant on body mass
Start low
Titrate cautiously
Polypharmacy more likely to be present
How do you manage hyperkalaemia?
Identify cause ECG Treatment: - Calcium gluconate - Insulin/Dextrose - Calcium resonium - Sodium bicarbonate - (Salbutamol)
