Drugs and the kidney Flashcards
What makes the kidneys susceptible to drug/ chemical induced damage?
Highly vascular
Large surface area for binding and transport
Reabsorption of water concentrates some drugs in nephron
Excretion route for most drugs
What needs to be considered when prescribing for a patient with impaired renal function?
- Ability to excrete drug (impaired ability can lead to build up to toxic levels)
- Toxicity of drug (nephrotoxic drugs should be avoided if possible as may worsen impairment)
What is a diuretic?
Substance that promotes the formation (and excretion) of urine, usually by promoting renal excretion of sodium (natriuresis)
Commonly used for conditions associated with oedema and hypertension
What are the classes of diuretics?
Loop diuretics Thiazide diuretics Potassium sparing diuretics Carbonic Anhydrase inhibitors Osmotic diuretics
Where is water reabsorbed throughout the nephron?
65% proximal convoluted tubule
20% thin descending limb
Where is sodium reabsorbed throughout the uriniferous tubule?
65% proximal convoluted tubule
25% thick ascending limb
8% distal convoluted tubule/ collecting duct
What is the MoA of carbonic anhydrase inhibitors?
Inhibits Carbonic Anhydrase in tubular cells of PCT preventing reabsorption of HCO3- (as HCO3- cannot be transported across luminal membrane)
Weak diuretic effect as means only a small amount of sodium can be reabsorbed
What are the potential side effects of Carbonic Anhydrase inhibitors?
Metabolic acidosis as it prevents secretion of H+
When are Carbonic Anhydrase inhibitors typically used?
Reduction of intraocular pressure (e.g. in glaucoma)
Mountain sickness prophylaxis
Name a Carbonic Anhydrase inhibitor
Acetalozamide
What is the MoA of osmotic diuretics?
Increase filtrate osmolarity preventing water reabsorption
[work best in PCT and descending limb]
Name an Osmotic Diuretic
Mannitol
What are osmotic diuretics typically used to treat?
Raised intracranial pressure and raised intraocular pressure
How is glucose used as an osmotic diuretic?
In disease states (e.g. uncontrolled DM), glucose reaches a transport maximum (where no more glucose can be reabsorbed) leading to excretion of glucose (and water) in the urine
What is the MoA of loop diuretics?
Inhibit the Na+K+2Cl co-transporter (in the thick ascending limb) by competitively inhibiting Cl- binding
Name a loop diuretic
Furosemide
What are loop diuretics typically used to treat?
Peripheral oedema (e.g. heart failure)
Acute pulmonary oedema
Resistant hypertension
What are the potential side effects of loop diuretics?
Hypovolaemia/ hypotension
Hyponatraemia/ hypokalaemia
Ototoxicity
Name the Thiazide diuretics
Bendroflumethiazide
Hypochlorothiazide
Indapamide
Chlortalidone
What is the MoA of thiazide diuretics?
Inhibit Na+Cl- Co-transporters in the early distal tubule by competitively inhibiting Cl- binding
What are thiazide diuretics typically used for?
Peripheral oedema (e.g. heart failure) Hypertension
What are the potential side effects of thiazide diuretics?
Hyponatraemia/ hypokalaemia
Gout (due to increased uric acid in plasma)
Erectile dysfunction
Hyperglycaemia
[Not ideal in renal impairment as they have to be filtered and secreted]
How can loop and thiazide diuretics cause hypokalaemia?
Increase delivery of NaCl to distal nephron and decrease blood volume which increases potassium secretion by increasing tubular flow rate and activity of Na+/K+ ATPase and activating RAAS (increasing aldosterone)
What potassium sparing diuretics are aldosterone antagonists?
Spironolactone
Elperenone
