some points on pediatrics pharmacology

1. Pediatrics pharmacology
Dr.Azad Abduljabar Haleem
azad82d@gmail.com

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Childhood: 0 – 18 years
Neonate: 28 days
Infant: 1st year
Toddlers: 2-3 years
Preschoool:3-5 years
School: 5-18 years
Early adolescent:10-14 years
Late adolescent: 14-18 years

3. • Pharmacokinetics is what the body does to a
drug,
• pharmacodynamics is what the drug does to
the body.

4. Absorption
• Neonates; have -reduced gastric acid secretion,
therefore the extent of drug absorption is altered
and less predictable.
• At birth, drugs with an acidic pH will have
decreased absorption.
• Twenty-four hours after birth, acid is released
into the stomach therefore increasing the
absorption of acidic drugs.
• Normal adult gastric acid secretions are achieved
by about 3 years of age.

5. • Gastric motility is decreased during infancy,
thus increasing the absorption of drugs that
are absorbed in the stomach.
• However, drugs absorbed from the intestine
will have a decreased or possibly delayed
absorption.

6. Distribution
• The concentration of a drug at various sites of
action depends on the drug's characteristics
and those of the tissue.
• Most drugs are water-soluble and will
naturally go to organs such as the kidneys,
liver, heart and gastrointestinal tract.

7. • At birth, the total body water and extracellular
fluid volume are much increased, and thus
larger doses of water-soluble drugs are
required on a mg/kg basis to achieve
equivalent concentrations to those seen in
older children and adults.
• This has to be balanced against the diminished
hepatic and renal function when considering
dosing.

8. • Distribution is also affected by a decreased
protein-binding capacity in newborns, and
particularly in pre-term newborns,
• therefore leading to increased levels of the
active free drug for highly protein-bound
drugs.

9. • For example, phenytoin is highly protein-bound
but because there is less protein binding in
neonates (lower plasma protein levels and lower
binding capacity) there is more free phenytoin
than in older children and adults.
• Thus the therapeutic range for phenytoin in
neonates is lower than in the rest of the general
population as it is the free phenytoin that has the
therapeutic action and can cause toxicity.
• • Therapeutic range for neonates = 6-15 mg/kg
• • Therapeutic range for children and adults = 1020 mg/kg

10. Blood-brain barrier:
• The blood-brain barrier in the newborn is
functionally incomplete and hence there is an
increased penetration of some drugs into the
brain.
• Transfer across the barrier is determined by:
• • Lipid solubility
• • Degree of ionization

11. • Drugs that are predominantly un-ionized are
more lipid-soluble and achieve higher
concentrations in the cerebrospinal fluid.
• It is as a result of this increased uptake that
neonates are generally more sensitive to the
respiratory depressant effects of opiates than
infants and older children.

12. • Some drugs will displace bilirubin from
albumin (for example: sulphonamides),
• so increasing the risk of kernicterus
(encephalopathy due to increased bilirubin in
the central nervous system - in at-risk
neonates).

13. Hepatic metabolism
• Hepatic metabolism is generally slower at birth
compared with adults.
• However, it increases rapidly during the first few
weeks of life, so that in late infancy hepatic
metabolism may be more effective than in adults.
• The age at which the enzyme processes approach
adult values varies with drug and the metabolic
pathway.
• For drugs such as diazepam, which are
extensively metabolized by the liver, the decrease
in half-life with age demonstrates this process.

14. • The hepatic metabolism process occurs either
by sulphation, methylation, oxidation,
hydroxylation or glucuronidation.
• Most hepatically metabolized drugs will
undergo one or two of these processes.
• Processes involving sulphation and
methylation are not greatly impaired at birth,
• whereas those involving oxidation and
glucuronidation are.

15. • It might be assumed that neonates would be
at an increased risk of paracetamol toxicity;
however, neonates use the sulphation
pathway instead of glucuronidation and are
able to deal with paracetamol .
• Hydroxylation of drugs is deficient in
newborns, particularly in pre-term babies, and
this is the process that accounts for the huge
variation in diazepam .

16. • Grey-baby syndrome is a rare, but potentially
fatal, toxic effect of chloramphenicol in
neonates.
• It is the result of the inability of the liver to
glucuronidate the drug effectively in the first
couple of weeks of life if correct doses are not
given.

17. Renal excretion
• Drug excretion by the kidneys is mainly
dependent on glomerular filtration and active
renal tubule secretion.
• Pre-term infants have approximately 15% (or less)
of the renal capacity of an adult,
• term babies have about 30% at birth,
• but this matures rapidly to about 50% of the
adult capacity by the time they are 4-5 weeks old.
• At 9-12 months of age, the infant's renal capacity
is equal to that of an adult.

18. Thanks

19. Pediatrics prescribing
• Legal responsibility lies with the doctor who
signs the prescriptions??