Drugs and the kidney Flashcards
What are most drugs converted to in the kidney in order to be excreted?
An inactive compound
Does the kidney excrete more polar drugs more readily than non-polar drugs?
Yes
Can non-polar drugs be reabsorbed by the kidney?
Non-polar (uncharged drugs) can be reabsorbed by kidney
What drugs can pass through the GF?
What is the clinical importance
Glomerular capillaries allow drugs of MW < 20kDa to be filtered freely, but not when bound on albumin (albumin MW ~ 68kDa
Clinical importance
Anti-coagulant drug warfarin
98% bound to albumin : 2% into filtrate
This results in a long half-life – stays in the body a long time
Issues of toxicity with continued dosing – e.g. excess bleeding
Which part of the kidney does the secretion of drugs occur?
Occurs mainly in proximal tubule
What transports charged drugs?
Give some examples
What does ionisation depend on?
Non-specific cation and anion transporters for charged drugs or metabolites, e.g.
Morphine (weak base) – cation transporter
Penicillin (weak acid) – anion transporter
Most drugs are weak acids or bases – degree of ionization depends on drug pKa and pH of environment
What are diuretics?
What other effects can diuretics cause?
Diuretics cause an increase in urine output (diuresis)
Many diuretics also produce increased
Na (natriuresis) / and K excretion (hypokalaemia)
What are the side effects of diuretics?
Very important drugs – hypertension, acute pulmonary oedema, heart failure
What are the 2 major groups of diuretics and what do they cause?
Mainly affect H2O excretion:
Water
Ethanol (Decreases ADH release)
Osmotic diuretics
Increase in electrolyte excretion: Carbonic anhydrase inhibitors Loop diuretics Thiazides K- sparing diuretics
Describe the mechanism of action of diuretics
Site 1:
Re-absorption of Na with passive movement of organic molecules (glucose, amino acids) and H2O
Site 2:
Re-absorption of Na in exchange for H - Role of carbonic anhydrase
Site 3:
Transport of NaCl by a co- transporter for Na, K, 2Cl
Thick ascending Loop of Henle is NOT permeable to H2O
Interstitial fluid in this region becomes hypertonic
Re-absorption of H2O from the collecting duct (controlled by ADH)
Distal Convoluted Tubule (DCT)
Site 4: Re-absorption of Na/Cl (co-transporter), followed by H2O
Site 5: Na is reabsorbed (through ENaC channels) in exchange for K efflux (through K channels) - stimulated by aldosterone
Site 6: Another Na-H exchanger - also stimulated by aldosterone
Mannitol - an agent that mainly affects water excretion
Is it filtered and reabsorbed?
What does it cause at high concentrations?
Where does it act?
Inert substances, freely filtered but not reabsorbed
High concentrations -> Osmolarity in tubules -> Reabsorption of H2O
Acts at PCT, DCT, and collecting duct
Little effect on electrolyte excretion
What are the uses of agents that mainly affect water excretion (mannitol)?
Uses
Reduce intracranial and intraocular pressure
Mannitol does not enter the CNS -> creates an osmotic gradient
-> H2O leaves the CNS (into plasma)
Prevent acute renal failure
Mannitol can prevent ANURIA
Distal nephron can dry up when filtration is very low
Excretion of some types of poisoning
How do drugs that excrete Na cause water to follow?
Drugs increase urine flow by increasing excretion of Na (natriuresis) – where Na goes -> H2O follows (osmosis)
How can an increase in NaCl excretion decrease oedema?
Inc NaCl excretion ECF vol Blood vol Cardiac output Oedema
How do Carbonic anhydrase inhibitors work?
Mild diuretics
Inhibit the activity of CA - decrease formation of protons in the luminal cells of PCT (Site 2)
Loss of NaHCO3 into lumen - loss of H2O
Also used in non-renal effects - in glaucoma, aqueous humor formation is dependent on CA activity
