2. Learning objectives
• Classify pediatric patients of various age
groups
• Compare and contrast the absorption,
distribution, metabolism and elimination of
drugs in infants and adults
• List drugs of safety concern in pediatrics
including their mechanism of toxicity.
• Explain the challenges in pediatric
pharmacotherapy
3. Introduction
• Pediatrics is concerned with the health of
infants, children, and adolescents; their
growth and development.
• Pediatric patients are population younger than
18 years
5. Introduction…
• The global under-five mortality rate has
declined by more than half, dropping from 90
to 43 deaths per 1,000 live births between
1990 and 2015.
• This success has resulted largely from
improvements in identification, prevention,
and treatment of diseases of the child.
6. Introduction…
• Although a number of drugs are used in
pediatric patients, only ¼ of the FDA approved
drugs have indications specific for use in the
pediatric population.
• Data on the pharmacokinetics,
pharmacodynamics, efficacy, and safety of
drugs in infants and children are scarce
7. Introduction…
• Lack of drug safety and efficacy information in
the pediatrics has led to disasters such as
– Gray baby syndrome from chloramphenicol
– Phocomelia from thalidomide
– Kernicterus from sulfonamides
8. Introduction…
• Another area of challenge in pediatrics is -
– Identifying an optimal dosage
– Unavailability of pediatrics suitable dosage forms
– Adherence to pharmacotherapy
9. • Children are not just “little adults,” pediatric
patients differ from adults in many cases.
– Body proportions and composition
– Relative size and function of the liver and kidneys
– Drug pharmacokinetics
– Pharmacodynamics and drug safety
Introduction…
11. Pharmacokinetic changes in premature & Neonate
Pharmacokinetic parameter Outcome with Examples
Absorption
GI
higher gastric pH Higher serum concentrations of acid-labile
drugs, such as penicillin, ampicillin,and nafcillin
lower serum concentrations of a weak acid
such as phenobarbital
GI Slow gastric emptying Increased absorbition because of prolonged
contact time with gastrointestinal mucosa
intramusc
ular
Little muscle mass, poor
perfusion to various
muscles, peripheral
vasomotor instability,
and insufficient
muscular contractions
Unpredictable intramuscular absorption. Eg.
phenobarbital has been reported to be
absorbed rapidly, whereas diazepam
absorption may be delayed.
intramuscular dosing is used rarely in neonates
except in emergencies or IV site is inaccessible
Skin underdeveloped
epidermal barrier and
high skin hydration
Increased percutaneous absorption of
corticosteroids, hexachlorophene soaps and
powders, salicylic acid ointment, and rubbing
alcohol.
Therapeutic serum concentration
of theophylline can be achieved for Rx apnea
12. Pharmacokinetic changes in premature & Neonate….
Pharmacokinetic parameter Outcome with Examples
Distribu
tion
High total body
water (85% to 78%
of total body weight)
Increased volume of distribution of tobramycin, and
gentamicin (0.48 L/kg Vs 0.20 L/kg in adults )
Low plasma protein
concentration ,
binding capacity ,and
affinity
Lower PPB of phenobarbital, salicylates, and phenytoin
increased apparent volumes of distribution and require
a larger loading dose
Lower body fat Lower Vd of diazepam (1.4 to 1.8 L/kg in neonates and
2.2 to 2.6 L/kg in adults)
drugs distributed in
breast milk may pose
problems for the
infants
•Drugs not to be used during breastfeeding:
bromocriptine, cyclophosphamide, cyclosporine, doxoru
bicin, ergotamine, lithium,methotrexate,
phenindione, codeine and drugs of abuse (e.g.,
amphetamine, cocaine, heroin, marijuana, and
phencyclidine
•Drugs to be used when benefit outweighs risk
acebutolol, aspirin, atenolol,clemastine, phenobarbital,
primidone, sulfasalazine, and 5-aminosalicylic acid have
been associated with adverse effects
13. Pharmacokinetic changes in premature & Neonate….
Pharmacokinetic parameter Outcome with Examples
Metab
olism
Drug metabolism
is substantially
slower
Acetaminophen metabolism by glucuronidation
is impaired but it is partly compensated by the
sulfation pathway
Glucuronyltransferases of Chloramphenicol take
several months to 1 year to develop fully
Higher serum concentrations of morphine are
required to achieve efficacy b/se morphine is
adequately metabolized to its 6-glucuronide
metabolite (20 times more active than morphine)
Oxidation metabolism of drugs
like phenobarbital, and phenytoin, diazepam is
slower particularly for theophylline, and dose of
these drugs should be decreased
14. Pharmacokinetic changes in premature & Neonate….
Pharmacokinetic
parameter
Outcome with Examples
Eliminati
on
Glomerular
filtration,
tubular
secretion, and
tubular
reabsorption
are normally
low
Clearance of tobramycin and other
aminoglycosides during the first weeks
may be lower and increase with an
increase in age
15. Pharmacodynamic changes in
pediatrics
Pharmacodynamic changes Implication
lower binding affinity of
receptors in the myocardium
of digoxin and increased
digoxin-binding sites on
neonatal erythrocytes
compared to adults
Maintenance dose of digoxin is
substantially higher in infants
than in adults
Adolescence rapid growth Higher Insulin requirements
16. Pharmacodynamic changes…
• Drugs that are considered toxic to pediatrics
– Promethazine, Chloramphenicol, Tetracyclines
– Drugs containing the following additives: Ethanol,
Benzyl alcohol and propylene glycol
• Some drugs may be less toxic in pediatric
patients than in adults (Aminoglycosides)
– Less inherent tissue sensitivity for toxicity
17. Pharmacodynamic changes…
• The safety and efficacy of OTC medication for
cough and cold products (nasal
decongestants, antihistamines, expectorants,
antitussives)in young children has not been
documented
18. Pharmacodynamic changes…
• Fluoroquinolone (e.g., ciprofloxacin) damage the
cartilage and not recommended during pregnancy
and pediatrics but there are exceptions
• Anthrax (postexposure)
• Rx of complicated urinary tract infections and
pyelonephritis caused by susceptible Escherichia coli.
• Endocarditis and multidrug-resistant gram-negative
infections
• Cystic fibrosis
19. Factors to be considered when prescribing a
drug for a pediatric patient
• Risk-benefit of the drug
– Long-term effects on growth, fertility
• Liver and/or kidney function status
• Available dosage form, Route and frequency
of administration
• Drug interaction
• Medication adherence
20. Date: ____________
MRN: ___________
Name __________LG___Age _1yr__ sex ___m___ Weight ___10kg___
Region ____________ Town ___________Woreda ________________
Kebele _____________
Outpatient √ Inpatient
Diagnosis/ICD: _prophylaxis__
Rx
INH 300 mg ½ tab daily for 1 months
Prescribed by: ________________ Dispensed by:
Qualification: ________________ Signature: ________
21. Date: ____________
MRN: ___________
Name ___TK___Age ___6______ sex __f__ Weight
_____________
Region ____________ Town ___________Woreda
________________ Kebele _____________
Outpatient √ Inpatient
Diagnosis/ICD: ____01/08/003/01235_______
Rx
ABC 300mg 0.5 tab po BID
3TC 150mg 0.5 tab po BID
NVP 200mg po 0.5 tab
For 2 months
