4.1 Diuretics and Renal Pharmacology Flashcards
What is the renal physiology mnuemonic?
Regulatory
Excretory
Endocrine
Metabolism
What are the regulatory functions of the kidney?
Fluid balance
Acid-base balance
Electrolyte balance
What are the excretory roles of the kidney?
Excretion of
- Waste products
- Drugs (glomerular filtration, tubular secretion)
What are the endocrine roles of the kidney?
Renin
Erythropoietin
Prostaglandins
1-alpha calcidol
What is the role of 1-alpha calcidol?
To hydroylate vitamin D
What is metabolised by the kidney?
Vitamin D
Polypetides - insulin
Drugs - morphine, paracetamol
Why may a diabetic present with hypoglycaemia when they have kidney damage?
Insulin is metabolised int he kidney
If they have kidney damage then insulin will stay in the body of longer
What is diuresis?
Loss of water
What word describes loss of sodium?
Natriuresis
What does aldosterone do?
Increases expression of ENaC and Na/K/ATPase in the principle cells of CD
Name two substances with diuretic action
Alcohol
Caffeine
How does alcohol act as a diuretic?
Inhibits ADH release
How does caffeine act as a diuretic?
Increase GFR
Decrease tubular Na reabsorption
Can become habituated to it
Name two ADH antagonists
Lithium
Tolvaptan
How does lithium work?
Inhibits action of ADH
Diuretic but not natriuretic
Is tolvaptan a natriuretic?
No
It is a diuretic though
What is tolvptan used to treat?
Hyponatraemia
Prevent cyst enlargement in APCKD
What are some generic adverse drug reactions to diuretics?
Anaphylaxis/photosensitivity rash Hypovolaemia and hypotension - Activates RAAS and can lead to acute kidney injury Electrolyte disturbance Metabolic abnormalities
Name some diuretics
Thiazides
Furosemide
Spironolactone
Bumetanide
Name some common specific ADRs to thiazides
Gout Hyperglycaemia Erectile dysfunction Increase LDL and TG Hypercalcaemia
Name some common specific ADRs to furosemide
Ototoxicity
Alkalosis
Increase LDL and TG
Gout
Name some common specific ADRs to spironolactone
Hyperkalaemia
Impotence
Painful gynaecomastia
Name a common specific ADR to bumetanide
Myalgia
Name some uses for diuretics
Hypertension Heart failure Decompensated liver disease Nephrotic syndrome Chronic kidney disease
Which diuretics could be used to treat hypertension?
Thiazides (also vasodilate)
Spironolactone
Loop diuretics (short duration of action so only work well in people with renal failure)
Which diuretics can be used to treat HF?
Loop diuretics
Spironolactone (Remodelling of heart)
Which drugs can be used for decompensated liver disease?
Spironolactone
Loop diuretics
Which diuretics can be used to treat nephrotic syndrome?
Large dose of loop diuretic
+/- thazides and potassium sparing diuretic/K supplements
What diuretics can be used to treat CKD?
Loop diuretics (+/- thiazides) Avoid K sparing
Why may someone with CKD need a diuretic?
Decreased GFR leads to salt and water retention
What three types of patient may have diuretic resistance?
Why?
Chronic renal failure - Less nephrons working
Nephrotic syndrome - oedematous so gut doesn’t absorb as well, low albumin
Heart failure - Less delivery to kidney
Where are diuretics absorbed?
In the gut
What do diuretics bind to in the body?
Albumin
Why may a patient develop diuretic resistance if they have acute tubular necrosis?
Diuretics are bound to albumin so can’t cross the glomerulus
Transported by OATs in proximal tubule
Proximal tubule won’t work well in acute TN
What action should be taken in refractory oedema?
Check salt intake
Give furosemide IV is gut oedema likely
Find minimum effective dose
Five repeated bolus or infusion as short half life
Why do thiazides cause hyponatraemia and hypokalaemia?
Work in cortex so dont affect medullary interstitial concentration
Block sodium reabsorption and water -> hypovolemic -> activate RAAS
But water is resorbed because there is still a hypertonic interstitium so ADH still works
What are carbonic anhydrase inhibitors used for?
Glaucoma
Altitude sickness
Why are carbonic anhydrase inhibitors not used for a diuretic?
Because the rest of the nephron would compensate
Would only end up losing bicarbonate
What are osmotic diuretics used for?
Reduce high intracerebral pressure
What are loop diuretics used for?
Oedema
Hypertension in CKD
What are thiazides used for?
Hypertension
What are potassium sparing diuretics used for e.g. amiloride?
Low potassium where diuretic required
May cause hyperkalaemia
What are aldosterone antagonists used for?
HF
Ascites
Hypertension
Hyperadrenalism - block effect of aldosterone
What are ADH antagonists used for?
Hyponatraemia
Name some potentially nephrotoxic drugs
Aminoglycosides eg gentamicin
Vancomycin IV
Aciclovir
NSAIDs
Name some drugs that can cause problems with renal dysfunction
ACE inhibitors
Diuretics
NSAIDs
What is the problem with metformin in people with renal dysfunction?
Metformin is not nephrotoxic but is acidotic
Impaired renal function can already lead to acidosis
So it is adding acidosis to already acidosis
How do NSAIDs affect renal perfusion?
Decrease GFR by stopping vasodilation of the afferent arteriole by prostaglandins
How do ACE inhibitors affect renal perfusion?
Decrease GFR by stopping AngII from vasoconstriction the efferent arteriole
What are two major risk factors for hyperkalaemia?
Increased catabolism/tissue damage
Reduced urine production
What initial ECG changes can be seen in hyperkalaemia?
Tall T waves
What on an ECG would indicate severe hyperkalaemia?
Sine waves
Outline the treatment of hyperkalaemia
1) Protect the heart - calcium gluconate
2) Lower serum K - insulin/dextrose
3) Remove K from body - Calcium resonium
