BDS 1st year theory class

1. Drugs in Special Conditions
Dr. Pravin Prasad
MBBS, MD Clinical Pharmacology
Assistant Professor, Department of Clinical Pharamcology
Maharajgunj Medical Campus
11 March 2020 (28 Falgun 2076), Wednesday

2. By the end of this discussion, BDS 1st year
students will be able to:
• Understand the special considerations for drug use in
children
• Know the pertinent features to be considered for drug use in
elderly
• Know and apply the precautions needed for drug use in
hepatic and renal diseases

3. Brainstorming….
• Pharmacokinetics?
• What body does to the drug
• Processes involved in pharmacokinetics?
• Absorption, Distribution, Metabolism and Elimination
• Ion trapping?
• Capture of ions in one of the compartments separated by semi-permeable
lipid membrane due to difference in pH of two compartments
• Which process(es) do you think will be affected in special population
groups?

4. Drug use in Children: Special Considertaions
• Absorption:
• lower gastric acidity ad slow intestinal transit- altered absorption of drugs
• Faster transdermal absorption and faster rectal absorption – Diazepam
• Distribution:
• Blood brain barrier (BBB) is more permeable – Kernicterus
• Metabolism:
• Low hepatic drug metabolizing systems in newborns – gray baby syndrome
• After one year age, faster metabolism than adults – phenytoin, carbamazepine
• Elimination
• Low g.f.r and tubular transport – Gentamicin and Penicillin

5. Drug use in Children: Special Considertaions
• Calculation of child dose
• Young’s formula
• Child dose = {Age/(Age+12)} x adult dose
• Dilling’s formula
• Child dose = (Age/20) x adult dose
• Clark’s formula
• Child dose = (Weight (kg) / 70) x adult dose

6. Drug use in Elderly: Special Consideration
• Absorption:
• Decreased gut motility and blood flow to intestines  slower absorption
• Distribution:
• Lower plasma protein  lesser plasma protein binding
• Altered volume of distribution
• Metabolism:
• Decreased hepatic microsomal enzyme activity
• Decreased first pass metabolism
• Overall effect on drug metabolism: not uniform
• Elimination:
• Decreased renal function
• 50 years  75%, 75 years  50%

7. Drug use in Elderly: Special Consideration
• Both pharmacokinetic and pharmacodynamic:
• Likely to be on multiple drugs  Drug interaction
• Exaggerated effects (pharmacodynamic):
• Prone to develop cumulative toxicity on prolonged medication
• Enlarged prostate
• Intolerant to digitalis
• Decreased responsiveness to β adrenergic drugs
• More Likely to develop adverse drug reactions
• Postural hypotension, giddiness, mental confusion

8. Drug use in Hepatic Disease: Special
Consideration
• Liver disease:
• Altered metabolism:
• Prodrugs- less effective
• Increased bioavailability of drugs
with high first pass metabolism
• Decreased metabolism and
elimination of drugs primarily
excreted by hepatic route

9. Drug use in Hepatic Disease: Special
Consideration
• Liver disease:
• Decreased protein synthesis:
• Altered serum albumin:
• Increased unbound fraction of acidic drugs
• Decreased clotting factors:
• Increased activity of anti-coagulants

10. Drug use in Hepatic Disease: Special
Consideration
• Liver disease:
• Pharmacodynamic alterations:
• Sensitivity of brain to depressant action of
morphine and barbiturates in cirrhotics
• Brisk diuresis by diuretics:
• Mental changes in patients with
impending hepatic encephalopathy

11. Drug use in Renal Disease: Special
Consideration
• Kidney disease:
• Nephrotoxic drugs
• Clearance of drug decreases parallel to
creatinine clearance
• Maintenance dose needs to be modified
• Decreased/low plasma proteins

12. Drug use in Renal Disease: Special
Consideration
• Kidney disease:
• Increased permeability of blood-brain
barrier
• Increased activity of opioids,
barbiturates, benzodiazepines
• Accumulation of drugs/metabolite:
• Pethidine  nor-pethidine  seizure

13. Conclusion
• All pharmacokinetic parameters are altered in children and needs
consideration during prescribing
• Special formulas have been devised for calculation of paediatric doses
• Pharmacokinetic as well as pharmacodynamic parameters are altered
in elderly
• Special considerations with regard to drug interaction and adverse
drug reaction needs to be addressed
• Impaired hepatic functions can have profound effects on drug doses
• Drug doses can be modified using creatinine clearance in renal failure
patients

14. Questions??
• Thank you!