Description is given abot All factors that affect paediatric, pharmacokinetic factors, dose monitoring

1. PAEDIATRICS
VRUSHALI NEVE
ASST. PROFESSOR
PHARMACOLOGY DEPT.

2. Introduction
 Paediatrics is branch of medicine dealing with development,
disease and disorder of children
 Infancy and childhood is rapid growth and development.
 Various organs, body system and enzymes that handle drug
develop at different rates hence drug dosage, formulation,
responses to drugs ,ADR, vary throughout childhood
 Childhood subdivided into following period:
1.Neonate: first 30 days of life
2.Infant : from 1month to 1year
3.Child: from 1year to 12 years

3. International committee of harmonization(2000) has
suggested that childhood be divided into following age
range for purpose of clinical trial and licensing of
medicines:
 Preterm newborn infant(less than 36 week)
 Term newborn infants(0-27days)
 Infants and toddlers(28days-23months)
 Children(2-11years)
 Adolescents (12to 16-18 years)

4. DEMOGRAPHY
 In 1992 there were 11.8 million children aged less than 16 years
in UK
 In 1901 ,149 per 100 babies died before their first birthday
 By 1902 this had fallen to seven
 Mortality is higher among babies with low birth weight
 To prevent sudden infant death syndrome include placing the
baby to sleep on its back, keeping room temperature
between16- 20C and over wrapping babies with cloths and
avoid exposure to cigarette smoke

5. THENORMALCHILD
• Growth and development are important indicators of a child’s
general well-being and pediatric practitioners should be aware
of the normal development milestones in childhood.
• The World Health Organization (WHO) has published the
widely used growth charts.
• Three important tools in developmental assessment.
– Height
– Weight
– Head circumference

6. In addition to the above, assessments of hearing, vision, motor
development and speech are undertaken at the child health clinics.

7. Drug deposition
Pharmacokinetic factors:
Factors that affect drug deposition are as follows:
A. Absorption:
1.Oral absorption: oral absorption may be influenced by gastric and
intestinal transit time , gastric and intestinal ph and gi content.
Posture ,disease state, therapeutic intervention as nasogastric
aspiration can affect absorption process
Rate of absorption is much slower in neonates than in older infant
and children

8.  Gastric Emptying Infants/Neonate:- Prolonged gastric
emptying time. But lower peristaltic movement than older child
and adults.
 Gastrointestinal enzyme activities:-
– It is lower in the newborn than in the adult. Activities of
amylase and lipase, beta- glucuronidase, and glutathione
peroxidase enzymes are low in infants up to 4 months of age.

9. 2.Intramascular absorption: Absorption in infants and children after
i.m. injection is faster than in neonatal period .
Examples : Diazepam-Rapid Absorption ,
Phenobarbital- Poor absorption
3.Topical absorption: recent advances in transdermal drug delivery
system have led to increased use of this rout of administration.
4.Buccal absorption: this rout is used when patient is unable to tolerate
medication via oral route. highly lipophilic drugs can rapidly cross
buccal mucosa.
Ex. Fentanyl is available in USA as lolipop formulation which is used
to relax children before painful procedure.

10. B. Distribution: Number of factors that determine drug distribution
in body are subject to change with age:
- Total Body Water
– Plasma Protein binding of drug
– Volume of Distribution
1.Protein binding : Despite normal blood ph, free fatty acid, bilirubin
level in infants, binding to plasma proteins reduced as a result of low
concentration of globulin and albumin
2 Total Body Water : 94% in the fetus, 85% in premature infants,
78% in full-term infants, and 60% in adults.
3.VD :The decrease in plasma protein binding of drugs can increase
their apparent volumes of distribution

11. C. Drug metabolism: At birth majority of enzyme systems
responsible for drug metabolism are absent or present in reduced
amount compared with adult value. Reduced capacity of metabolic
degradation at birth is followed by dramatic increase in metabolic
rate in older infant and young child
D. Elimination : The processes of glomerular filtration, tubular
secretion,and tubular reabsorption determine the efficiency of renal
excretion. These processes may take several weeks to 1 year after
birth to develop fully.
• Glomerular filtration rate is about 2–4 mL/min in term infants
• In infants, if possible then avoid Chloramphenicol and Amino
glycoside, because their metabolites are accumulated due to
Immature function of kidney.

12. Drug therapyinpediatrics
1. Dose calculation
2. Choice of dosage form
3. Disease Condition
4. Adverse reaction
5. Counseling

13. 1.Dose calculation:-
• Height and Weight growth are rapidly changing
factors in childhood, which also influence
significantly some pharmacokinetic parameters.
So, this
• Doses should be obtained from pediatric book
for children.. For example, In India IAP-Drug
formulary is reliable source for pediatric
practice and their important drugs.

14. Paediatric dosage calculations used pediatric formulas such as
Fried’s rule, Young’s rule, and Clark’s rule

15. 2.Choice of preparation
1. Buccal rout: drug may be absorbed rapidly from this
rout or swallowed and absorbed from stomach
2. Oral Route:
 Tabletsare lessconvenient
 Liquid preparation are easyto administer in accurate dose
and to form in desirable dose by dilution
3. Parenteral Route:-
• Site ofAccess
• Safety from fluidoverload
• Aware about Excipients

16. • Dose regimin selection :-
Factors to be considered when selecting a drug regimen or
rout of administration for a
pediatric patient are…
– Age/Weight/Surface area
– Assess the appropriate dose
– Assess the most appropriate interval
– Assess the route of administration
– Consider the expected response and
monitoring parameters
– Interactions
– Legal consideration

17. 3.Diseases condition:
A. Liverdisease:-
• Drugs with a high hepatic extraction ratio (>0.7)such drugs
include morphine, meperidine,lidocaine, and propranolol).
• Clearance of these drugs is affected by hepatic blood flow. A
decreased hepatic blood flow in the presence of such disease
states as cirrhosis and congestive heart failure is expected to
decrease the clearance of drugs with high extraction ratios.
• Theophylline clearance may decrease by 45% in a child with
acute viral hepatitis.

18. • B.Renal disease :-Renal failure decreases the dosage requirement
of drugs eliminated by the kidney. Once again, because of
limited studies, dosage adjustments in pediatric patients are
based largely on data obtained in adults.
• Serum drug concentrations should be monitored for drugs with
narrow therapeutic index and eliminated largely by the kidney
(e.g., aminoglycosides and vancomycin) to optimize therapy in
pediatric patients with renal dysfunction.
• For drugs with wide therapeutic ranges (e.g., penicillins and
cephalosporins), dosage adjustment may be necessary only in
moderate to severe renal failure.

19. • C.CysticFibrosis:-
• Drug therapy in pediatric patients with cystic fibrosis has been
reviewed. For unknown reasons, these patients require increased
doses of certain drugs.
• Studies have reported a higher clearance of such drugs as
gentamicin, tobramycin, netilmicin, amikacin, dicloxacillin,
cloxacillin, azlocillin, piperacillin, and theophylline.

20. 4.Adverse reaction in therapy:-
• Mechanism is not cleared in adverse effect of many drugs in
child. But it may be due to immature p’kinetic parameters and
some medication errors.
• Some well known adverse effect
• Tetracycline Teeth brown coloration
• Corticosteroids- Growth suppression in Prepubertal child.
• Paradoxical hyperactivity in child after phenobarbital
treatment
• Aspirin treatment - Reye’s syndrom

21. 5.Counseling adherence andconcordance
• Parents are often responsible for the administration of medicines
to their children and therefore the concordance and adherence of
both parties must be considered.
• Non-adherence may be caused by several factors such as patient
resistance to taking the medicine, complicated dosage regimens,
misunderstanding of instructions and apparent ineffectiveness or
side effects of treatment.
• Several general principles should be considered in an attempt to
improve adherence.

22. Monitoringparameters
1.Vital sign
Parameters Age (2-5 years) Age (5-12) years
Heart rates
(beats/ min)
100-120 80-100
Systolic Blood
pressure (mmHg
80-90 90-110
Respiratory rates
(beats/ min)
25-30 16-25

23. 2.BIOCHEMICAL PARAMETERS
Parameters Age (2-12years) Age (>18) years
Albumin (g/L) 30-50 35-55
Bilirubin
(microM/L)
<15 <17
Creatinine(micro
M/L)
30-80 50-120
Hemoglobin(g/dL) 11-14 13.5-18(male)
12-16(female
WBC (*109/L) 5-14 3.5-11

24. THANK YOU