Post on 17-Dec-2014
description
transcript
• 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
• Pharmacokinetics is what the body does to a drug,
• pharmacodynamics is what the drug does to the body.
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.
• 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.
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.
• 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.
• 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.
• 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 = 10-20
mg/kg
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
• 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.
• 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).
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.
• 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.
• 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 .
• 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.
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.
Thanks
Pediatrics prescribing
• Legal responsibility lies with the doctor who signs the prescriptions??