drugs and kidney Flashcards
what happens to most drugs?
most are metabolised by the liver to an inactive compound that can be excreted by kidney
does the kidney excrete non-polar or polar drugs more readily?
polar (charged)
what can happen to non-polar drugs?
non-polar/uncharged drugs) can be reabsorbed by kidney
what protein might drugs bind to?
albumin
sources of excretion in the nephron
glomerular filtration and tubular secretion
what drugs will be filtered freely through the glomerulus?
drugs that are freely soluble in plasma and have a small molecular weight
when will drugs not be freely filtered through the glomerulus?
glomerular capillaries allow drugs of MW < 20kDa to be filtered freely, but not when bound on albumin
give an example of the clinical importance of drugs being bound to albumin?
when the anti-coagulant drug warfarin is in the body, 98% is bound to albumin and 2% goes into the filtrate
this results in a long half-life so the drug stays in the body a long time - this results in issues of toxicity with continued dosing (e.g. excess bleeding)
drugs being bound to albumin causes what?
causes them to have a long half-life
where does tubular secretion of drugs mostly occur?
proximal convoluted tubule
how do charged drugs/metabolites leave the proximal convoluted tubule? give examples
through non-specific cation and anion transporters
Morphine (weak base), cation transporter
Penicillin (weak acid), anion transporter
what is the relevance of the transporters being non-specific? give an example of how this works?
no selective binding sites, meaning competition can occur between drugs at these transporters
e.g. Penicillin (antibiotic) and Probenecid (removes uric acid, treat gout). If Probenecid is administered with Penicillin the half-life of penicillin is increased as they both act at the anion transporter
most drugs are…
weak acids or bases - the degree of ionization depends on drug pKa and pH of environment
effects that diuretics cause:
an increase in urine output (diuresis)
ALSO SOMETIMES CAUSE: increased Na (natriuresis) / and K excretion (hypokalaemia)
what can diuretics be used to treat?
act to lower the overall extracellular volume
hypertension
acute pulmonary oedema
heart failure
what are the 2 major groups diuretics can be split into (function)?
-affect H2O excretion
(Ethanol- ADH release,
Osmotic diuretics)
-increase electrolyte excretion (Carbonic anhydrase inhibitors Loop diuretics Thiazides K- sparing diuretics)
carbonic anhydrase
the enzyme that converts water and carbon dioxide into bicarbonate and hydrogen ions (in the tubular cell)
flow of H ions out of the tubular cell into the lumen via the Na/H antiporter - so Na+ enters the tubular cell
net result = reabsorption of sodium bicarbonate in the PCT (na and hco3 combine in the tubular cell)
name the 6 sites diuretics can act at:
- PCT Re-absorption of Na
with passive movement of
organic molecules - PCT Re-absorption of Na+ in exchange for H+ (carbonic anhydrase)
- LoH Transport of NaCl by a co- transporter for Na, K, 2Cl
- DCT Re-absorption of Na/Cl (co-transporter) followed by H2O
- DCT Na is reabsorbed through ENaC channels in exchange for K efflux (through K channels. stimulated by aldosterone
- DCT Another Na-H exchanger - also stimulated by aldosterone
sites 5 and 6
stimulated by aldosterone which means they can produce:
- K loss in response to Na reabsorption
- alkalosis due to increased proton excretion
osmotic agents
agents that mainly affect H2O excretion
example of an osmotic agent and how it works
mannitol - usually administered via i.v.
- weak diuretic, so at high concentrations it increases the osmolarity of the tubules, decreasing water reabsorption
- acts at the PCT, DCT and the collecting duct
- has little effect on electrolyte excretion
uses of this mannitol (osmotic agent)
Reduce intracranial and intraocular pressure
-mannitol does not enter the CNS, so creates an osmotic gradient for H2O to leave the CNS into plasma
Prevent acute renal failure
-this drug can can prevent ANURIA
Excretion of some types of poisoning
agents that affect electrolyte excretion - general mechanism
these are drugs increase urine flow by increasing Na+ excretion (natriuresis), as where Na goes H2O follows (osmosis)
increasing NaCl excretion will therefore decrease ECF volume and blood volume, leading to a decrease in cardiac output and a decrease in oedema
example of agents that affect electrolyte excretion
- carbonic anhydrase inhibitors
- loop diuretics
- thiazide drugs
- K- sparing diuretics
