Diuretics Flashcards
What are the important components of renal physiology?
- Regulation
- Excretion
- Endocrine
- Metabolism
What are the regulatory functions of the kidneys?
- Fluid balance
- Acid-base balance
- Electrolyte balance
What are the excretory functions of the kidney?
- Excretes waste products
- Excretes drugs
How does the kidney eliminate drugs?
- Glomerular filtration
- Tubular secretion
What are the endocrine functions of the kidney?
- Renin-angiotensin-aldosterone system
- Produces erythropoietin
- Produces prostaglandins
What produces angiotensinogen?
The liver
What happens to angiotensinogen?
It is converted to angiotensin I by renin
What happens to angiotensin I?
It is converted to angiotensin II by ACE
What is the function of angiotensin II?
- Causes an increase in aldosterone
- Causes retention of salt and water
What molecules does the kidney metabolise?
- Vitamin D
- Polypeptides - insulin, PTH
What drugs act on the renal tubules?
- Carbonic anhydrase inhibitors
- Osmotic diuretics
- Loop diuretics
- Thiazides
- Potassium sparing diuretics
- Aldosterone antagonists
- ADH antagonists
Where do acetazolamide/dorzolamide act?
On the PT
What does acetazolamide/dorzolamide lead to?
Diuresis of NaHCO3-
Give an example of an osmotic agent
Mannitol
What do osmotic agents cause?
Massive diuresis
Why do you get massive diuresis with osmotic agents?
Because they act on the whole of the nephron
What is the problem with osmotic agents such as mannitol?
You get a lot of water loss, but not much electrolyte loss, so at risk of electrolyte imbalances such as hyponatraemia
Give an example of a loop diuretic
Furosemide
Where do loop diuretics act?
On the thick ascending loop
What can loop diuretics lead to?
Electrolyte abnormalities, such as hypocalcaemia
How long is the onset of action of furosemide when given IV?
30 minutes
What is the half life of furosemide?
About 90 minutes
What is good about the relatively short half life of furosemide?
If taken in morning, doesn’t give nocturia
Where are thiazides used?
As an adjunct, e.g. in heart failure
How do thiazide diuretics cause diuresis?
They increase sodium loss, so increase water loss
Give an example of an aldosterone antagonist
Spironolactone
What conditions are aldosterone antagonists used in?
- Heart failure
- Hypertension
- Liver disease
Why does aldosterone antagonists have a long half life?
Because they are metabolised to active metabolites
What conditions are ADH antagonists used in?
Treatment of SIADH
How does digoxin act as a diuretic?
It inhibits tubular Na/K-ATPase
How does amiloride act as a diuretic?
Inhibits Na channels in DCT/CD
What effect does amiloride have on potasisum?
It is potassium sparing
Generally, what adverse drug reactions might diuretics cause?
- Anaphylaxis/rash
- Hypovolaemia and hypotension, leading to acute renal failure
- Electrolyte disturbance
- Metabolic abnormalities
What electrolyte disturbances commonly result from diuretics?
Hyponatraemia
When is there a particular risk of electrolyte disturbances?
When using diuretics in combination
What are the adverse drug reactions of thiazide diuretics?
- Gout
- Erectile dysfunction
What are the ADRs of spironolactone?
- Hyperkalaemia
- Painful gynaecomastia
What are the adverse drug reactions of spironolactone related to?
Dose
What are the adverse drug reactions of frusemide?
Ototoxicity
What are the adverse drug reactions of bumetanide?
Myalgia
What drugs do K+ sparing diuretics interact with?
ACE inhibitors
What results from interaction between K+ sparing diuretics and ACE inhibitors?
Increased hyperkalaemia leading to cardiac problems
What drugs do aminoglycosides interact with?
Loop diuretics
What might result from interaction between aminoglycosides and loop diuretics?
Ototoxicity and nephrotoxicity
What drugs do thiazide diuretics interact with?
- Digoxin
- ß-blockers
- Steroids
- Carbamazepine
What drugs do loop diuretics interact with?
- Digoxin
- Steroids
What might result from the interaction between thiazide or loop diuretics and digoxin?
Hypokalaemia, leading to increased digoxin binding and toxicity
What might result from interaction between thiazide diuretics and ß-blockers?
- Hyperglycaemia
- Hyperlipidaemia
- Hyperuricaemia
What might result from interaction between thiazide or loop diuretics and steroids?
Increased risk of hypokalaemia
What might result from the interaction between thiazide diuretics and carbamazepine?
Increased risk of hyponatraemia
What might cause diuretic resistance?
- Incomplete treatment of the primary disorder
- Continuation of high sodium intake
- Patient non-compliance
- Poor absorption
- Volume depletion
- NSAIDs
Why does volume depletion cause diuretic resistance?
- Decreases filtration of diuretics
- Increases serum aldosterone, which enhances sodium reabsorption
Why does NSAID use lead to diuretic resistance?
Can reduce renal blood flow
What are the major indications for diuretic use?
- Heart failure
- Hypertension
- Decompensated liver disease
What diuretics are used in the treatment of heart failure?
- Loop diuretics
- Thiazide diuretics
- Spironolactone, which has non diuretic benefits
Describe the nature of use of thiazide diuretics in heart failure
Add on-therapy
What do you need to be cautious of when using thiazide diuretics in heart failure?
Hypocalaemia
What diuretics are used in hypertension?
- Thiazide diuretics
- Spironolactone
- Loop diuretics
Why are diuretics required in decompensated liver disease?
Reduced protein, therefore oedematous state
What diuretics are used in decompensated liver disease?
- Spironolactone
- Loop diuretics
What are the categories of ways that drugs might reduce kidney function?
Direct or indirect toxicity
When might drugs accumulate to toxic levels?
If they are excreted through the kidneys, and renal function is impaired
What drugs are potentially nephrotoxic?
- ACE inhibitiors
- Aminoglycosides, e.g. gentamicin
- Penicillins
- Cyclosporin A
- Metformin
- NSAIDs
What impact on renal function will ACE inhibitiors have on most patients?
Up to 10% decrease before worrying
At what kidney function should you consider stopping metformin?
50%
What guidelines should be following when prescribing drugs in chronic renal failure?
- Avoid nephrotoxins if possible
- Reduce doseages in line with GFR if metabolised or eliminated via the kidneys
- Monitor renal function and drug levels
- Hyperkalaemia is more likely
- Consider bleeding, as uraemic patients have a greater tendency to bleed
What should be considered, regarding the kidneys, 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 is hyperkalaemia treated?
- Calcium gluconate
- Insulin/dextrose
- Calcium resonium
- Sodium bicarbonate
- Salbutamol