RATIONAL DRUG THERAPY

1
RATIONAL DRUG THERAPY

• DR.SELVAN

2
INTRODUCTION

• Choosing a safe and effective treatment regimen
  for pediatric patients can be challenging.
  Multiple patient variables such as developmental
  physiology, past medical history, pharmacokinetic
  and pharmacodynamic properties, desired
  therapeutic outcomes and psychosocial issues need
  to be considered when designing appropriate drug
  therapy regimen for children.

3
Developing a pediatric drug regimen

• Pharmacokinetic consideration
• a) Absorption
• Oral drug absorption
  in children can be unpredictable owing to
  variation in gastric pH , emptying time and
  intestinal transit time. At birth gastric pH is
  neutral and it reaches adult values by 3 months
  of age
• b) Distribution
• Drugs administered
  parenterally have erratic and unpredictable
  distribution in neonates due to poor perfusion,
  decreased muscle mass, and difference in
  percentage of TBW

4

• Plasma protein concentration which is
  lower in neonates can affect the plasma levels of
  highly protein bound drugs like phenytoin. They
  approach adult levels by 10 to 12 months of age.
• C) Metabolism
• Hepatic enzymatic
  activity is reduced in neonates but as the infant
  grows its ability to metabolise medication
  increases.
• D) Elimination
• At birth GFR is lt 50
  of adult value. Hence elimination is prolonged
  and dosing intervals for renally eliminated drugs
  like gentamicin needsto be adjusted accordingly.
  By 6 months of age the GFR increases to 90 of
  adult value.

5
2) Pharmacodynamic consideration

• The aim of this consideration is
  to maximize drug effect and minimize drug
  toxicity.
• The drug effect may be either
• a) concentration dependent
  e.g.. Amino glycosides.
• b) Time dependent
• e.g.. Penicillin.

6
Drug selection

• 1) Patient specific factors
• a) physiologic
• 1.Hyperbilirubinemia Ceftriaxone can
  displace bilirubin and induce kernicterus in
  newborn.
• 2. Newborn immaturity
• G.I. malabsorption oral drugs are
  unreliably absorbed during
  the first month.
• Renal insufficiency penicillin and
  amino glycosides need extended dosing interval.
• Hepatic insufficiency Phenobarbital,
  morphine and diazepam in newborns need low doses
  and extended intervals.

7

• 3.Malnutrition Drugs like phenytoin, warfarin
  have increased action due to decreased protein
  binding.
• 4.Short bowel syndrome Oral drugs have erratic
  absorption.
• 5.Coordination of swallow Oral drugs can be
  swallowed by kids gt3 years old.
• B) PSYCHOLOGICAL
• Cognitive ability Decreased understanding
  of directions can lead to non compliance or
  delayed recognition of side effects.

8

• C) PSYCHOSOCIAL Low socio economic status,
  illiteracy, broken homes have problems with
  purchasing and compliance of drugs.
• D) COMPLIANCE It depends on
• palatability
• schedule
• volume
• side effects

9

• Drug specific factors
• A drug with
  wide therapeutic index has a wide margin of
  safety than one with narrow therapeutic index.
  Hence they are selected for initial treatment if
  possible.
• e.g. wide paracetamol, BZDs, cephalosporins,
  penicillins, ranitidine.
• narrow aminoglycosides,
  anticonvulsants, digoxin, heparin,
  opiates,theophylline, chemotherapy agents.

10
3) Routes of administration

• 1) Oral route
  
  Easiest, least expensive and most convenient. Its
  not appropriate in very young infants and in
  short bowel syndrome.
• 2) Rectal route
• Its reserved for those
  who cannot take oral medications. However drug
  distribution with it is not uniform.
• 3) Parenteral route
• Its the most
  reliable method of administration and preferred
  in severely ill patients.

11
4) Drug dosing

• Methods based on weight
• simple, convenient, and widely accepted.
• Drugs with wide therapeutic index can be rounded
  off to a standard dose whereas those with narrow
  index have to be correlated with plasma drug
  levels
• Methods based on BSA
• More accurate.
• Used for chemotherapeutic agents,and
  antiretroviral agents.

12

• Methods based on age
• Least accurate.
• Appropriate only for children with avg. ht. and
  wt
• DRUG INTERACTIONS
• Can occur between several drugs or between drugs
  and food
• Usually due to overlapping of metabolism of two
  drugs.
• Inducers CBZ, phenobarbitol, phenytoin,
  rifampicin.
• Inhibitors cisapride, erythromycin, valproate,
  fluconazole.

13

• PREVENTING MEDICTION ERRORS
• - Decimal point placement for doses less than
  one put a leading zero in front of the decimal
  point.
• Abbreviation should be avoided
• Legibility
• Maximum dosing for children gt 40 kg adult dose
  should be used.

14
GUIDELINES FOR RATIONAL PRESCRIPTION

• Make a specific diagnosis
• Consider the pathophysiology of diagnosis
  selected If the disorder is well understood the
  prescriber is in a better position to select
  effective therapy.
• Select a specific therapeutic objective or goal
  and medications should be selected based on it.
• Select a drug of choice

15

1. Determine the appropriate dosing regimen to
   obtain desired therapeutic levels and the drug
   must be inexpensive, easily available and should
   be prescribed in generic name.
2. Drug interaction and adverse effects must be
   taken into account before initiating combination
   of drugs.
3. Device a plan for monitoring the drugs action and
   determine an end point for the therapy.
4. Plan a programme for patient education.