PH2113 Kidneys

What is a diuretic?

Increases urine volume

What is a natriuretic?

Promotes renal sodium excretion

What is an aquaretic?

Increases excretion of solute-free water

What is the MoA of Carbonic Anhydrase Inhibitors (CAIs)?

Inhibits carbonic anhydrase at the PCT

Reducing H+/Na+ exchange (where H+ is actively secreted into tubule in exchange for Na+ entering cell)

Diuresis occurs (as reduced Na+ and therefore water reabsorption)

What conditions are CAIs used for?

Rarely used as diuretic now

Glaucoma

Urinary alkalinisation

Acute mountain sickness

Metabolic alkalosis, adjuvant in epilepsy, CSF leakage

What diuretic is used for acute mountain sickness and why?

CAIs as they decrease CSF formation and decrease pH of CSF

What diuretic is used for urinary alkalinisation, how and why?

CAIs:

form NaHCO3 (alkaline) in kidney lumen

increase urine pH

to increase solubility of uric acid and cystine in urine (for kidney stone prevention)

Treatment given alongside oral bicarbonate as otherwise only works for 3 days before all bicarbonate is excreted

What diuretic is used in glaucoma and why?

topical CAIs such as dorzolamide and brinzolamide

decreases aqueous humour (by decreasing bicarbonate and therefore water) to decrease IOP

What is an example of a CAI? Give its pharmacokinetics

Acetazolamide

PK: well absorbed after oral administration, diuresis within 30mins, max effect at 2 hours, persists for 12hrs

What type of diuretic is Acetazolamide? Explain why it is a weak diuretic

CAI

PD: causes most (85%) of bicarbonate ions to not be reabsorbed at PCT

Efficacy decreases over several days as will increase NaCl reabsorption in the rest of nephron

What are the side effects of CAIs?

Hyperchloremic metabolic acidosis

Renal stone formation

Renal potassium wasting

What diuretic causes hyperchloremic metabolic acidosis?

CAIs as they decrease plasma bicarb conc

so body increases plasma Cl- conc to compensate

causing acidosis

what diuretic causes renal stone formation?

CAIs

cause alkalinisation of urine

phosphate and calcium build up in alkaline urine as relatively insoluble

causing stone formation

What ions or diuretic should be given alongside CAIs?

Oral bicarbonate as CAIs increase bicarbonate excretion

Potassium chloride or potassium sparing diuretic as CAIs increase reabsorption of Na+ in CD so more K+ excreted

What is the MoA of loop diuretics?

Selectively inhibit NaCl reabsorption in thick ascending limb

by inhibiting Na+/K+/2Cl- cotransporter

What is a prototype/example of loop diuretics? Give its pharmacokinetics

Furosemide

rapid absorption in 2-3 hours

duration of action 2-3 hours

eliminated by kidney: glomerular filtration and tubular secretion

What diuretic type is Furosemide and what are the pharmacodynamics?

Loop diuretic - most efficacious diuretics

Inhibit Na+/K+/2Cl- cotransporter