18 - D. Changes with renal impairment

D. Changes with renal impairment:

© SPMM Course may be 600ml/min as compared to 1200ml/min in young adults. Creatinine measurements can yield spurious results; hence GFR formulas must be used to correct for age and other variables. Nearly 40% renal function is lost by the age 80. The average decline is around 10mL/min/1.73m2 per decade after age 30. This takes an adult GFR from 130mL/min/1.73m2 to a value of 80mL/min/1.73m2 when the age is 80 (The Baltimore Longitudinal Study). B. Changes in neonates:  Neonates have a higher proportion of total body water and extracellular body water  Neonates have a lower proportion of adipose tissue.  The glomerular filtration rate is lower in those aged less than 3-5 months  Neonates have lower gastric acidity and have an increased gastric emptying time  Neonates have a more permeable blood—brain barrier  The microsomal enzyme activity in the liver is lower in those than 2 months  Neonates have a lower plasma concentration of albumin C. Changes in pregnancy: Pregnancy is associated with several pharmacokinetic changes:  Delayed gastric emptying,  Decreased GIT motility,  Increased volume of distribution (5%),  Decreased drug-binding capacity,  Decreased albumin level  Induced liver metabolic pathway,  Increased GFR & renal clearance. Psychotropic medication usually passes from the maternal blood to the foetus due to lack of strong barrier, but rate and amount of transfer are variable. Higher doses are associated with higher serum level in the infant. D. Changes with renal impairment:  Benzodiazepines should be used with caution  The half-life of diazepam remains unchanged in end-stage renal disease, but its metabolite, desmethyldiazepam, may accumulate, causing excessive sedation.  The half-life of lorazepam is increased from 8–25 hours in healthy adults to 32–72 hours in end-stage renal disease  At a low level of renal function, lorazepam dosage should be reduced by 50% to avoid

© SPMM Course excessive sedation.  Imipramine and amitriptyline can be given at their usual dosage as renal impairment does not increase their half-lives  Half normal dose is used for citalopram in patients with renal impairment or in elderly  The half-life of paroxetine is considerably increased with severe renal impairment, requiring dosage reduction.  The dosage of fluoxetine and fluvoxamine does not have to be reduced in the elderly or patients with renal impairment  Sertraline manufacturers do not recommend its use in renal impairment  Haloperidol does not require a dose reduction in renal impairment unless excessive sedation or hypotension occurs.  Amisulpride is renally excreted almost exclusively. Hence, renal failure will be a relative contraindication to use this drug. Product monograph suggests alternate day dosing or dose reduction if no other alternatives are possible.  Risperidone and its active metabolite 9-hydroxy-risperidone are substantially excreted in the urine so that in renal impairment the elimination half-life is prolonged  Lithium is best avoided or given at low dosages.