RATIONAL DRUG THERAPY
DR.SELVAN
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.
Developing a pediatric drug regimen
1)
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
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 < 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.
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.
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.
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 >3 years old.
B) PSYCHOLOGICAL:
Cognitive ability: Decreased understanding of
directions can lead to non compliance or delayed
recognition of side effects.
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
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.
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 :
It’s the most reliable method of
administration and preferred in severely ill patients.
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.
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.
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 > 40 kg adult dose
should be used.
GUIDELINES FOR RATIONAL
PRESCRIPTION
I.
II.
III.
IV.
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
V.
VI.
VII.
VIII.
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.
Drug interaction and adverse effects must be taken
into account before initiating combination of
drugs.
Device a plan for monitoring the drugs action and
determine an end point for the therapy.
Plan a programme for patient education.