Pages Below:
| |
Drugs in Renal Disease
Renal disease can affect drug therapy due to
- Change in the pharmacokinetics of the drug
- Change in the effect of the drug
- Increasing the adverse effects of the drug
Change In Pharmacokinetics
3 reasons for this
- Decreased elimination of the drug
- Need to modify the dose
- Either smaller doses or longer dosage interval or both
- Aim is to maintain therapeutic concentrations
- To know how much to alter the dose by, must determine renal function
- Monitor drug concentrations after alterations have been made
- Decreased protein binding
- because
- hypoalbuminaemia
- change in the structure of albumin
- retention of unknown products which compete for binding sites on
the protein
- Acidic drugs are most affected – they are highly bound to protein,
e.g. phenytoin.
- Situation relieved by renal transplant, but not by dialysis
- Hepatic metabolism
- Hepatic metabolism of some drugs decreases in renal failure –
mechanism unclear. May be due to a metabolic
inhibitor in uraemic plasma
- Drugs affected include propranolol and nicardipine
- situation is relieved by haemodialysis
Change In The Effect Of the Drug
- Reasons for this are not clear, but important examples include
- Opiates, barbiturates and
benzodiazepines all having greater effect on CNS
- Various antihypertensives having
greater postural effects
Increasing The Adverse Effects Of The Drug
- e.g. due to changes in electrolyte balance
- Renal failure can cause hypercalcaemia and/or hypokalaemia.
These both make digoxin more likely to have adverse effects
- Potassium sparing diuretics (e.g. spironolactone) are more likely to
cause hyperkalaemia if renal failure has already impaired potassium
elimination
Examples of drugs to be used with care or avoided in
renal disease
- Aminoglycosides
- Digoxin
- Lithium
- Amphotericin B
- Metformin
- Ethambutol
- Azathioprine
- Captopril
- Enalapril
- Allopurinol
- Atenolol
- Ciprofloxacin
- Trimethoprim
- Methotrexate
|