Pharmacology of Diuretics Flashcards
(28 cards)
What are diuretics?
Drugs which increase the excretion of salts and water by the kidneys
How much of the sodium and water filtered by the kidneys is normally reabsorbed?
99%
What are the main clinical uses of diuretics?
Oedematous conditions (increase net filtration):
- Heart failure
- Renal disease
- Hepatic disease
Hypertension
What diuretics are usually used to treat oedematous conditions?
Loop diuretics
K+-sparing diuretics
What diuretics are usually used to treat hypertension?
Thiazide-type diuretics
What is the equation linking BP, TPR and CO?
BP = TPR x CO
How do diuretics help treat oedematous conditions?
Decreased plasma volume increases the protein concentration in capillaries
More water drawn in from tissues to maintain osmolarity
How do diuretics enter the nephron?
Filtered
Secreted at PCT
Give an example of a loop diuretic.
Furosemide
Torasemide
Which type of diuretic is most powerful and why?
Loop diuretics
Loss of counter-current multiplier and a lot of sodium is reabsorbed at the loop (25%)
How do loop diuretics work?
Block NKCC2 in thick ascending limb
Loss of capacity to create hypertonic medullary interstitium required for ADH-induced water reabsorption
What is the main clinical use of loop diuretics?
Oedematous conditions
Explain the potential adverse effects of loop diuretics (5)
Hypokalaemia due to increased Na/K-exchange in CT
Metabolic alkalosis due to reduced plasma volume (contraction alkalosis)
Depletion of plasma Ca and Mg due to decreased potential gradient across thick ascending limb
Ototoxicity - off-target effect on Cl channel of inner ear
Hypovolemia - too much diuresis
Why are loop diuretics also used to treat hypercalcaemia?
Decreases potential gradient across thick ascending limb so positive ions (including Ca) are not reabsorbed
Give an example of a thiazide-type diuretic.
Indapamide
Bendroflumethiazide, metolazone
What do thiazide-type diuretics do?
Block NCCT in DCT
Also reduce TPR by vasodilatation
What are thiazide-type diuretics commonly used to treat?
Hypertension
What are the possible adverse effects of thiazide-type diuretics?
Hypokalaemia
Hyperglycaemia
Hyperuricaemia (competes with uric acid to be secreted)
What may decrease the effectiveness of thiazide-type diuretics?
NSAID use for more than 5 days
How do diuretics potentially cause hypokalaemia?
Increased delivery of Na to collecting tubule
Increased Na reabsorption causes cell depolarisation forcing more K out
Greater volume of urine passing causes K to be washed away maintaining gradient
What can hypokalaemia lead to?
Cardiac arrhythmias
Muscle weakness
How can hypokalaemia be prevented when using loop or thiazide-type diuretics?
K+-sparing diuretics
K supplements
Give two examples of K+-sparing diuretics.
Amiloride
(Triamterene)
Spironolactone
Why do K+-sparing diuretics have low efficacy?
Acts in late distal tubule and collecting duct where not much Na is reabsorbed
