pharm

1. Paediatric Pharmacology
Part-2
By,
Nidheesh Kumar. P(520020109565)

2. Yeah, we are still talking about this guy….

3. Contents
• Pharmacokinetics-Excretion
• Pharmacodynamics
• Drug administration
• Dosage forms
• Adherence
• Dosage
• Summary

4. Pharmacokinetics-Excretion
Renal elimination
of drugs
GFR
Tubular function
Renal blood
flow
Affect t1/2
of the drug
Affect the extent
of systematic
action of drug

5. Pharmacokinetics-Excretion
(in comparison to adults)
Premature
Neonate
Neonate Infant Child Adolescent
Renal blood
flow
Decreased Decreased Decreased Equal Equal
Glomerular
filtration
Decreased Decreased Decreased Equal Equal
Tubular
Function
Decreased Decreased Decreased Equal Equal

6. • GFR is much lower in neonates than in older infants, children or adults
• This limitation persists during the first days of life and improves thereafter
• Neonatal GFR based on body surface area
• Birth-: Only 30-40% of the adult value
• 3 weeks: 50-60% of the adult value
• 6-12 months : Reaches Adult value
• A decreased rate of renal elimination in the neonate has also been observed with
aminoglycoside antibiotics (kanamycin, gentamicin, neomycin, and streptomycin).
• Total body clearance of digoxin is directly dependent upon adequate renal function, and
accumulation of digoxin can occur when glomerular filtration is decreased.
• Toddlers have shorter t1/2 than older children and adults probably due to increased renal
elimination and metabolism.
• For example, the dose per kilogram of digoxin is much higher in toddlers than in adults.
The mechanisms for these developmental changes are still poorly understood.

7. Penicillin, for example, are cleared by preterm infants at 17%
of the adult rate based on comparable surface area and 34% of
the adult rate when adjusted for body weight

9. Pharmacodynamics
• There is not much of variation in the
response to drugs in neonates compared
to adults.
• Few exceptions are:
• Drugs that inhibit PG synthesis
(indomethacin) can promote rapid closure of
ductus arteriosus
• Infusion of prostaglandin E1, on the other
hand, causes the ductus to remain open,
which can be lifesaving in an infant with
transposition of the great vessels or tetralogy
of Fallot

10. Pharmacodynamics
• Use of aspirin in children with influenza or chickenpox may increase the risk of
Reye’s syndrome in them.
• Neonates are also more sensitive to the central depressant effects of opioids than
are older children and adults, necessitating extra caution when they are exposed to
some narcotics (e.g., codeine) through breast milk.
• At birth, the function of drug transporters may be very low; for example, P-
glycoprotein, which pumps morphine from the blood-brain barrier back to the
systemic circulation. Low-level function of P-glycoprotein at birth can explain why
neonates are substantially more sensitive than older children to the central nervous
system depressant effects of morphine.

11. Pharmacodynamics
• The administration routes for midazolam, a BZD in children is safe and effective for most
cases, but sometimes unexpected reactions occur. These may include hallucination,
disorientation, uncontrollable crying or verbalization, agitation, restlessness, involuntary
movement, self-injury, and aggressive or violent behaviour, which sometimes requires
restraints. The generic term for such reactions is a paradoxical reaction
• Oral domperidone is associated with QTc prolongation except in infants with a gestational
age less than 32 weeks of amenorrhea (P < .005). Mean QTc prolongation was 14 msec. On
univariate analysis, oral domperidone-induced QTc prolongation was correlated with
gestational age, birth weight, and elevated serum potassium. On multivariate analysis, after
adjustment for gestational age, serum potassium was the only factor independently associated
with interval QT prolongation during treatment.

12. Drug administration(dosage forms)
• Elixir
• Alcoholic solutions in which the drug molecules are dissolved and evenly distributed.
• No shaking is required
• Generally, all doses contain equal amounts
• Suspension
• Contains undissolved drug particles that must be distributed throughout the vehicle by shaking
• Failure in shaking may result in underdosage leading to lack of efficiency of drug initially and
overdosage leading to toxicity of the drug later.
• This uneven distribution is a potential cause of inefficacy or toxicity in children taking phenytoin
suspensions

13. Adherence
• Adherence (formerly called compliance) may be more difficult to achieve in
paediatric practice than otherwise, since it involves not only the parent’s
conscientious effort to follow directions but also such practical matters as
measuring errors, spilling, and spitting out.
• When evaluating adherence, it is often helpful to ask if an attempt has been made to
give a further dose after the child has spilled half of what was offered
• Nonadherence frequently occurs when antibiotics are prescribed to treat otitis
media or urinary tract infections and the child feels well after 4 or 5 days of therapy

14. Adherence
• Because many paediatric doses are calculated—e.g., using bodyweight—
rather than simply read from a list, major dosing errors may result from
incorrect calculations.
• . In the case of digoxin, for example, an intended dose of 0.1 mL containing
5 mcg of drug, when replaced by 1.0 mL— which is still a small volume—
can result in a fatal overdose.

15. Adherence
• Recommendations to improve
adherence:
• Pill boxes
• Calibrated medicine spoon

16. Drug administration(Dosage)
• Most drugs approved for paediatric usage have paediatric doses in mg/kg
• If recommendations not available, then approximations can be done using Age,
Weight and surface area
• Age: Young’s Rule
• Weight: Clark’s Rule
• Doses based on age or weight are more conservative
• Doses based on surface area are more adequate
• Note : Calculated paediatric dose should not exceed adult dose.

17. Clark’s Rule = Weight of the child(in pounds)* Adult dose
150
Young’s Rule = Age *Adult dose
(Age+12)

18. Summary
• Pharmacokinetics
• Absorption
• Low gastric acidity(for 2-3 days in neonate) favours acid labile drugs
• Slow gastric emptying and intestinal motility(also being unpredictable)
• Absorption from skin faster
• Lipase and bile acids low in children causing decrease in absorption of lipid soluble drugs

19. • Distribution: ECF larger than adults with fat content being lower indicating lower
dosages of water soluble with low protein binding capacity and dosage to be based
on surface area of the child.
• Metabolism: Slower metabolism due to
• Lack of metabolizing enzymes like hydroxylases, esterases and conjugases being
poorly developed
• Excretion: Slower excretion in infants because of Decreased Renal blood flow,
Glomerular filtration and Tubular function as compared to adults.
• However, toddlers show increased renal excretion than in adults.
• Dosage forms: Elixir and Suspensions
• Dosages are calculated through Clark’s and Young’s formula

20. Reference: