Special Cases

Question 1

Renal Impairment

Answer 1

short acting agents (e.g. gliclazide as a choice sulphonylurea)

increase the dosage interval; e.g. for Gentamicin

non-renally excreted alternative e.g. biliary route (e.g. gliclazie in diabetes and amlodipine in HTN)

some drugs must be avoided in renal impairment e.g. metformin in mod impairment (use gliclazide or tolbutamide instead)

some drugs require renal excretion to act - may be ineffective in renal impairment e.g. thiazide diuretics

loading dose not normally affected

Question 2

Pregnancy

Answer 2

anti-epileptics: fatal to both parties if untreated, but many drug Rx are highly teratogenic; preferred treatment; given with 5mg folic acid to reduce chances of neural tube defect

anticoagulants: no warfarin, but can use LMWH
- pregnancy produces a thrombophilic state (clots more likely)
- prevents post-partum haemorrhage
- important consideration in mothers with artificial heart valves
- warfarin is teratogenic; avoid in trimester 1 and 3; use LMWHs instead if possible

antibiotics: BNF 5.1 - choosing antibiotics in pregnancy
antihypertensives: lavetalol (beta-blocker), nifedipine (ca-chanel), methyldopa use
antidiabetics: insulin, metformin, and glibenclamide = relatively safe
antidepressants: SSRIs associated with heart defects; TCAs = safer

Question 3

liver impairment

Answer 3

hepatic clearance
protein binding
sodium retention (avoid NSAIDS)
effects on coagulation (INR may be increased)
effects on coagulation (INR may be increased)
gastric effects (absorption and bleeding)
CNS effects
-sedation

Question 4

Renal: aminoglycosides

Answer 4

AMINOGLYCOSIDES:
transported into tubular cells » direct nephrotoxic effect
requires monitoring of blood levels
once daily doses may help reduce nephrotoxicity

GENTAMICIN PRESCRIBING:

• dosing regime:
  
  • once daily 5mg/kg; max 5000mg
  • multiple daily dosing; 3-5mg/kg/day in 3 divided doses
• caution in obese patients; use IBW
• monitoring timing:
  
  • once daily: ‘pre-dose’ level 18-24h after first dose, aim 65, or abnormal renal function = wait for result before next dose
• monitor UO and take U&Es at least 3 times per week; check levels; withhold dose if any renal function concerns
• try to avoid concurrent use of other nephrotoxic drugs e.g. vancomycin
• be alert for patients reporting hearing loss or balance disturbance (toxicity)

Question 5

dialysis

Answer 5

• dialysis process factors can affect clearance:
  - duration of procedure
  - rate of blood flow to dialyser
  - surface area and porosity of dialyser
  - composition and flow rate of dialyser
  - PD: rate of peritoneal exchange and concentration gradient between plasma and dialysate
  - not all drugs can be used while on dialysis

Question 6

drugs causing renal impairment

Answer 6

• ‘CANDA’:
  - contrast media
  - ACE inhibitors
  - NSAIDS
  - diuretics
  - angiotensin receptor blockers (ARBs)