Flashcards in Session 4 - Diuretics Deck (49)
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1
What are the regulatory functions of the kidneys?
Fluid balance
Acid-base balance
Electrolyte balance
2
What are the excretory functions of the kidneys?
Waste product removal
Drug elimination
Through either glomerular filtration of tubular secretion
3
What are the endocrine functions of the kidneys?
Produce the following hormones:
Renin
Erythropoietin
Prostaglandins
1-alpha calcidol
4
What are the metabolic functions of the kidneys?
Metabolise:
Vitamins D
Polypeptides (e.g. insulin)
Drugs (e.g. morphine, paracetamol)
5
What is the difference between diuresis and natriuresis?
Diuresis - loss of water
Natriuresis - loss of sodium
6
Give examples of classes of drugs that act on the renal tubules.
Carbonic anhydrase inhibitors
Osmotic diuretics
Loop diuretics
Thiazides
Potassium sparing diuretics
Aldosterone antagonists
ADH antagonists
7
What is the effect of aldosterone on the nephron?
Aldosterone increases the expression of ENaC and Na/K/ATPase in principle cells of the collecting duct. This allows more sodium uptake from the collecting duct and therefore more water uptake.
8
Give an example of an aldosterone antagonists.
Spironolactone
9
How do loop diuretics act on the nephron?
Loop diuretics inhibit the Na+/K+/2Cl- symporter in the thick ascending limb of the loop of Henle. Less sodium is reabsorbed so therefore less water is reabsorbed.
10
Gives two examples of loop diuretics.
Furosemide
Bumetanide
11
How do thiazides act on the nephron?
Thiazides inhibit the Na+/Cl- symporter in the distal tubule.
12
Give two examples of thiazides.
Bendroflumethiazide
Metolazone
13
What are the two types of potassium sparing diuretics?
Inhibitors of Epithelial Na Channels (ENaC) - Amiloride, Triamterene
Aldosterone antagonists - Spironolactone, Eplerenone
Both act on the late distal tubule and collecting duct
14
Give an example of a carbonic anhydride inhibitor. Where in the nephrons does it act?
Acetazolamide
Acts in the proximal tubule.
15
Give an example of an osmotic diuretic.
Mannitol
Acts in the proximal tubule and other sites of water absorption
16
Give two examples of other substances which have diuretic action.
Alcohol - inhibits ADH release
Caffeine - increases GFR and decreases tubular Na+ reabsorption
17
Give two examples of ADH antagonists.
Lithium - diuretic but not natriuretic. Inhibits action of ADH
Tolvaptan - diuretic but not natriuretic. Inhibits action of ADH.
18
What is Tolvaptan used to treat?
Hyponatraemia
Prevents cyst enlargement in Adult Polycystic Kidney Disease (APCKD)
19
What are the generic adverse drug reactions caused by diuretics?
Anaphylaxis/photosensitivity rash
Hypovolaemia and hypotension (activates RAS - can lead to acute kidney injury)
Electrolyte disturbances (Na+, K+, Mg2+, Ca2+)
Metabolic abnormalities (depends on individual drug)
20
What common adverse drug reactions are specific to thiazides?
Gout
Hyperglycaemia
Erectile dysfunction
Increased LDL and triglycerides
Hypercalcaemia
21
What common adverse drug reactions are specific to spironolactone?
Hyperkalaemia
Impotence
Painful gynaecomastia
22
What common adverse drug reactions are specific to furosemide?
Ototoxicity
Alkalosis
Increased LDL and triglycerides
Gout
23
What common adverse drug reaction is specific to bumetanide?
Myalgia
24
Drug interactions between ACE inhibitors and K+ sparing diuretics could lead to what problems?
Increased hyperkalaemia —> cardiac problems
25
Drug interactions between aminoglycosides and loop diuretics leads to what problems?
Ototoxicity
Nephrotoxicity
26
Drug interactions between digoxin and thiazides or loop diuretics can cause what problems?
Hypokalaemia —> increases digoxin binding and toxicity
27
Drug interactions between beta blockers and thiazides diuretics can lead to what problems?
Hyperglycaemia, hyperlipidaemia, hyperuricaemia
28
Drug interactions between steroids and thiazide or loop diuretics can lead to what problems?
Increased risk of hypokalaemia
29
Drug interactions between lithium and thiazide or loop diuretics can lead to what problems?
Lithium toxicity (thiazides)
Reduced lithium levels (loop diuretics)
30
Drug interactions between carbamazepine and thiazides can lead to what problem?
Increased risk of hyponatraemia.
31
What drugs are used to treat hypertension?
First line treatment:
ACE inhibitors/Angiotensin II antagonists
Beta-blockers
If not responding to first line treatment, add diuretic:
Thiazide (vasodilation as well as diuresis)
Spironolactone
Loop diuretics (best for hypertension in renal failure, less effective when kidney function is normal)
32
What drugs are used to treat heart failure?
Loop diuretics
Spironolactone (for its non-diuretic effects - remodelling of the heart)
ACE inhibitors/Angiotensin II antagonists
Beta-blockers
33
What diuretics are used to treat decompensated liver disease?
Spironolactone
Loop diuretics
34
What diuretics are used to treat nephrotic syndrome?
Loop diuretic (often big doses are needed)
+/- thiazides
+/- potassium-sparing diuretic / potassium supplements
35
What diuretics are used to treat chronic kidney disease?
Loop diuretic
(+/- thiazide)
Generally avoid K+ sparing diuretics
36
What dietary conditions must a patient on diuretics follow?
They must have a reduced salt diet. Too much salt intake negates the effects of the diuretic.
37
Why is furosemide given IV if gut oedema is suspected?
Patients with gut oedema do not absorb well from the gut so less furosemide would be taken up if it was given orally.
38
What is a carbonic anhydrase inhibitor used to treat?
Glaucoma
Altitude sickness
39
What are osmotic diuretics used to treat?
High intracerebral pressure
40
What are ADH antagonists used to treat?
Hyponatraemia
41
What are aldosterone antagonists used to treat?
Heart failure
Ascites
Hypertension
Hyperadrenalism
42
Give examples of drugs which are potentially nephrotoxic.
Aminoglycosides e.g. gentamicin
Vancomycin (intravenous only)
Aciclovir
NSAIDs
+ many more
43
Give examples of drugs which cause problems with renal function.
ACE-inhibitors
Diuretics
NSAIDs
Metformin
44
How do ACE-inhibitors and NSAIDs affect renal perfusion?
They override the intrinsic autoregulatory mechanisms of the nephron. E.g. NSAIDs stop prostaglandins from vasodilating the afferent arteriole and ACE-inhibitors stop angiotensin II from vasoconstricting the efferent arteriole.
45
What guidelines should be followed when prescribing to patients with chronic kidney disease?
Avoid nephrotoxins
If gentamicin/vancomycin required, dose very carefully in consultation with pharmacist.
Check with pharmacist whether any existing drugs need dose altering.
The side effects of some common drugs are increased with renal disease due to the accumulation of metabolites (e.g. morphine, nitrofuratoin, statins)
46
What are the possible causes of hyperkalaemia?
Excess intake (virtually never the only cause)
Movement of potassium out of cells:
- acidosis
- hypertonicity
- tissue (especially muscle) damage
Reduced urine loss:
- reduced GFR
- reduced distal delivery of Na+ (oliguric AKD, obstruction)
- reduced secretion in collecting duct
Drugs:
- RAAS inhibitors (ACE-inhibitors, spironolactone), NSAIDs, ENaC blockers (trimethoprim, amiloride)
47
Hyperkalaemia can result in what?
Life threatening cardiac arrhythmias
48
What progressive ECG changes are seen in hyperkalaemia?
Initial
- tall T waves
Progressive
- small or absent P waves
- increased P-R interval
- wide QRS complex
Severe
- sine waves
- asystole
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