Session 7 - Diuretics Flashcards
Define diuresis
• Increased formation of urine by the kidney
Define diuretics
• Block reabsorption of Na+ and therefore water by the kidney
Give three main types of diuretics
- Loop diuretics
- Thiazide diuretics
- K+ sparing diuretics and aldosterone antagonists
How do loop diuretics work?
- Acts on TAL of the loop of henle
- Block Na-K-2Cl
- Causes excretion of 10-25% of filtered Na+ ions (segments downstream also have limited capacity to reabsorb water, increasing diuresis)
Name two loop diuretics
- Furosemide
* Bumetanide
What do Thiazide diuretics do?
- Act on early DCT
- Block Na-Cl co-transporter
- Inhibits only 5% of Na+ reabsorption
Give a thiazide diuretic
• Bendroflumethiazide
Where do K+ sparing diuretics and aldosterone antagonists work?
- Late DCT and collecting duct
- Reduce ENaC reabsorption of sodium
- Inhibit 2% Na+ reabsorption
Why are K+ sparing diuretics named thus?
Reduce the loss of K+ and can produce life threatening hyperkalaemia
Give an example of a K+ sparing diuretic
• Amiloride
Give an example of an aldosterone antagonist
• Spironolactone
Give overall dangers of diuretics
- Hyper/hypokalaemia
* RAAS activation
Outline the negatives of using K+ sparing diuretics/Aldosterone Antagonists
• Reduce loss of K+ and may produce life threatening hyperkalaemia
Give a negative effect of loop diuretics
• Reduces calcium absorption, inducing urinary excretion
Patient may become hypocalcaemi
What do loop and thiazide diuretics do?
• Increase the loss of potassium in the urine
Hypokalaemia
Outline how loop and thiazide diuretics cause hypokalaemia
- Block Na+ and H20 reabsorption in LoH or early DCT
- Increase Na+ and H20 delivery to late DT + CD
- Increase Na+ absorption by principle cells/Faster flow rate of filtrate so K+ washed away faster
- Favourable electrical gradient for K+ excretion/Low K+ concentration in lumen
How do K+ sparing diuretics cause hyperkalaemia?
- Block epithelial Na+ channels
- Reduce Na+ reabsorption
- Reduce potassium loss in urine
- Hyperkalaemia
How do aldosterone antagonists cause hyperkalaemia?
- Block of action of aldosterone
- Reduce activity of Na/K+ ATPase & epithelial Na+ channels
- Reduce Na+ reabsorption
- Reduce potassium loss in urine
- Hyperkalaemia
What do all diuretics do?
- Reduce ECF volume so activate RAAS
* This increases aldosterone secretion, increase Na+ reabsorption and K+ secretion, contributing to hypokalaemia
List negative effects which come about as a result of diuretics use and abuse
- Hypokalaemia
- Hyperkalaemia
- RAAS activation
- Hypovolaemia
- Hyponatraemia
- Increased uric acid levels in blood
- Metabolic effects
What is hypovolaemia?
• Decreased ECF volume due to excessive loss of Na+ and water
What 3 things must be done to avoid hypovolaemia?
- Monitor weight
- Look for signs of dehydration
- Check BP
What is hyponatraemia?
• Decreased sodium in blood
Multiple symptoms, including nausea, vomiting, headache and confusion
What do increased uric acid levels in blood cause?
Gout
What are two negative metabolic effect of diuretic use?
- Glucose intolerance
* Increased LDL levels
What is a carbonic anhydrase inhibitor?
• Diuretic which acts in PCT by inhibitng enzyme carbonic anhydrase to interfere with Na+ and HCO3- reabsorption
Why is carbonic anhydrase no longer used a diuretic?
• HCO3- loss leads to metabolic acidosis
Give six conditions diuretics used to treat
- Conditions with ECF expansion and Oedema
- Acute pulmonary oedema
- Hypertension
- Hypercalcaemia
- Cerebral oedema (Osmotic diuretics)
- Glaucoma (carbonic anydrase)
Give four conditions which involve ECF expansion and oedema
- Congestive heart failure
- Nephrotic syndrome
- Kidney failure
- Ascites and oedema due to liver cirrhosis
What is acute pulmonary oedema usually due to?
• Left heart failure
What is pulmonary oedema treated with?
• Loop diuretics
What is hypertension treated with?
- Thiazide diuretics
* Spironolactone in primary hyperaldosteronism (Conn’s syndrome)
How is hypercalcaemia treated?
• Loop diuretics promote Ca2+ excretion in loop of henle
Give three substances with diuretic actions
- Alcohol - Inhibits ADH release
- Coffee - Increased GFR, decreased Na+ reabsorption
- Lithium - Inhibits ADH action on collection ducts
What is diuresis expressed as in the form of a symptom?
• Polyuria
Give four causes of polyuria that are non drink related
• Diabetes mellitus
○ Glucose in filtrate -> Osmotic diuresis
• Central diabetes insipidus
○ Decreased ADH release from posterior pituitary -> Diuresis
• Nephrogenic diabetes insipidus
○ Poor response of collecting ducts to ADH -> Diuresis
• Psychogenic polydypsia
○ Increased intake of fluid
