The kidney and drugs

Question 1

Definition of renal clearance

Answer 1

The volume of plasma from which a substance is completely removed by the kidney in a given amount of time - ml/min

Question 2

Effect of urine pH on drug clearance

Answer 2

• Ionised drugs stay in the tubule
• pH urine 4.8-7.5
• Lipid soluble drugs are almost completely reabsorbed
• For an acidic drug, clearance rate is a lot lower with acidic urine than with alkaline urine
• For an alkaline drug, clearance rate is higher with acidic urine than with alkaline urine

Question 3

Half life of a drug and what is it dependent on

Answer 3

• It is the time necessary to halve the plasma concentration
• Dependent on:
  1. Clearance: rate of drug elimination divided by plasma concentration

2. Volume of distribution: fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma

Question 4

Drugs and adverse renal effects (incl. examples):

1. Antibiotics
2. Chemotherapy
3. NSAIDs
4. ACE inhibitors

Answer 4

1. Antibiotics cause tubular toxicity
   - Aminoglycosides
   - Tetracyclines
2. Chemotherapy causes intensive hydration and crytsalluria
   - Cisplatin
   - Methotrexate
3. NSAIDs cause glomerulopathy
   - Due to salt retention, diuretic potency, papillary necrosis, renal vasoconstriction
4. Ace inhibitors cause pre-renal problems
   - Due to glomerular vasodilation and filtration pressure

Question 5

Why do we not give aminoglycosides to patients with renal failure?

Answer 5

Aminoglycosides are bactericidal antibiotics which act by inhibiting bacterial protein synthesis

• Can’t give it to a patient with renal failure because of DECREASED CLEARANCE, this can lead to excess levels of drug building up and causing ototoxicity
• Ototoxicity is damage to the inner ear, resulting in damage to the organs responsible for hearing and balance. This can also be caused by loop diuretics

Question 6

Targets of diuretic drugs and mechanism of action

Answer 6

1. Proximal tubule
   - Carbonic anhydrase inhibitors e.g ACETAZOLAMIDE
   - No Na+/H+ exchange
   - Na+ stays in duct, higher solute concentration so water moves across
2. Ascending loop of Henle
   - Loop diuretics e.g FUROSEMIDE, BUMETANIDE
   - Inhibit Na/K/2Cl co-transporter
   - Stop NaCl transport out of the tubule into the tissue
   - Causing a decrease in Na and Cl reabsorption
   - Increase in urine production

• Used in: pulmonary oedema due to left ventricular failure and also in chronic heart failure to reduce strain on heart by decreasing blood volume
• Do not use in severe hypokalaemia, hyponatraemia, anuria, renal failure and comatose states associated with liver cirrhosis

3. Distal convoluted tubule
   - Thiazides e.g bendroflumethiazide
   - Target Na/Cl (K+) co-transporter
   - Inhibit Na+ reabsorption at beginning of DCT and delivers more Na+ to the collecting duct, so retain more water
   - Increases K+ loss massively, so given with K+ supplements
   - Less potent than loop diuretics
4. Collecting tubule and duct
   - ADH acts here, making aquaporins (H2O channels)

• Aldosterone agonists such as SPIRONOLACTONE
• K+ sparing diuretics
• Inhibit Na+ reabsorption through Na+ channels
• No Na/K exchange

5. Glomerulus - osmotic diuresis
   - Target the semipermeable membrane
   - E.g MANNITOL
   - Cause movement of fluid from hypo-osmotic to hyper-osmotic in glomerulus i.e from blood to urine