PEDIA PHARMA

• What significant changes occur in the physiologic processes during the first year of life that influence pharmacokinetic variables?

  There are significant changes in the physiologic processes that influence pharmacokinetic variables.
• Why is it important to pay attention to neonates and children in pharmacokinetics?

  Because significant changes in physiologic processes influence pharmacokinetic variables during this age group.
• What are the critical factors affecting placental drug transfer and drug effects on the fetus?

  • Physicochemical properties of the drug
  • Molecular weight
  • Degree of ionization under physiologic conditions
  • Product formulation
  • Disintegration and dissolution of solid dosage forms
  • Drug release characteristics
  • Co-solutes and complex formation
  • Rate of drug crossing the placenta
  • Duration of exposure to the drug
  • Distribution characteristics in fetal tissues
  • Stage of placental and fetal development
  • Effects of drugs used in combination
• What are the unique factors that may affect drug absorption in neonates and children?

  Blood flow at the site of administration and gastrointestinal function.
• How does gastrointestinal function change in neonates and children?

  Gastrointestinal function rapidly changes during the first few days of life.
• What are the factors unique to children that influence drug absorption?

  • Parenteral route: Blood flow
  • Oral route: GI function
  • Stomach
  • Intestine
  • Biliary tract
  • Age
• What is the gastric acid secretion pH range for full-term infants?

  The gastric acid secretion pH range is 6-8.
• When does gastric acid secretion begin in full-term infants?

  Gastric acid secretion begins soon after birth.
• What is the implication of low pH for drug administration in neonates?

  Drugs partially or totally inactivated by low pH should not be given orally.
• How does gastric pH change during development?

  Gastric pH changes significantly, with the highest alkaline values occurring during the neonatal period.
• What are the effects of gastric pH on drug absorption in neonates?

  1. Increased bioavailability of acid-labile drugs like Penicillin or ampicillin.
  2. Decreased absorption of weak organic acids like phenobarbital and phenytoin, necessitating higher doses.
• At what age does gastric acid approach adult values in full-term infants?

  Gastric acid approaches adult values around 3 months in full-term infants.
• What is the gastric emptying time in neonates during the first few days of life?

  The gastric emptying time is prolonged, averaging 6-8 hours.
• How does gastric emptying time affect drug absorption?

  Prolonged gastric emptying time may delay the absorption of drugs that are absorbed in the small intestine.
• What are the effects of gastric motility in neonates?

  • Irregular and slow motility
  • Unpredictable small intestine absorption
  • Slow peristalsis can lead to more drug absorption and potential toxicity
  • Increased peristalsis can decrease contact time and absorption
• How does the biliary function of neonates affect drug absorption?

  Neonates have a reduced bile acid pool and biliary function, decreasing the ability to solubilize and absorb lipophilic drugs.
• What is the impact of skin hydration on transdermal drug absorption in neonates?

  Transdermal drug absorption is increased due to a more hydrated stratum corneum in neonates.
• What factors influence percutaneous absorption in neonates?

  • Directly related to skin hydration
  • Inversely related to the thickness of the stratum corneum
  • Thinnest in premature neonates
  • Greater extent of cutaneous perfusion
• How does blood flow affect drug absorption in neonates?

  Blood flow at the site of administration affects absorption, which can be decreased in conditions like cardiovascular shock.
• What happens to drug absorption when blood perfusion is compromised?

  Drug absorption may be slower than usual when blood perfusion is compromised.
• What are the consequences of reduced plasma protein binding in neonates?

  • Increased presence of free (unbound) drugs
  • Greater drug effects or toxicity even with normal plasma concentration
  • Risk of kernicterus from drugs displacing bilirubin from albumin
• What is the major factor affecting drug metabolism in neonates?

  The major factor affecting drug metabolism in neonates is hepatic enzymes.
• What are the phases of drug metabolism and their characteristics?

  • Phase I: Oxidation, Reduction, Hydrolysis
  • Phase II: Conjugation, Acetylation, Sulfation
  • Phase II enzyme activity is decreased in newborns and increases into childhood.
• How does the metabolic rate of toddlers compare to adults?

  The metabolic rate of toddlers (12-36 months) exceeds that of adults.
• What effect does maternal drug use have on neonatal liver enzyme maturation?

  Maternal drug use can lead to early maturation of liver enzymes, resulting in faster metabolism and lower drug concentration.
• What is the effect of decreased ability to metabolize drugs in neonates?

  It leads to slow clearance rates and prolonged elimination half-lives of many drugs.
• What are the implications of altered drug metabolism in neonates?

  • Slow clearance of drugs
  • Prolonged elimination half-lives
  • Increased risk of adverse effects from drugs metabolized by the liver
• What is metabolism in the context of pharmacology?

  The process by which the body breaks down drugs.
• What is the effect of lower drug concentration with usual neonatal doses?

  It results in less therapeutic effect.
• Why do children between 1 to 3 years require higher drug doses per kg compared to adults?

  They have a metabolic rate that exceeds that of adults.
• What happens when a mother receives drugs that stimulate hepatic enzyme maturation, such as Phenobarbital?

  It results in faster metabolism and less therapeutic effect due to low drug concentration.
• What are the activities involved in Phase 1 of drug metabolism?

  • Oxidation
  • Reduction
  • Hydrolysis
• How does the activity of cytochrome P450 mixed function oxidase in early neonatal life compare to adults?

  It is slower, at 50–70% of adult values.
• What is the consequence of prolonged elimination of drugs that depend on the oxidation pathway in neonates?

  It leads to slow clearance rates and prolonged elimination half-lives.
• Name two drugs that have prolonged elimination in neonates due to decreased metabolism.

  Phenytoin and Diazepam.
• What must be considered when administering drugs to neonates?

  The process of maturation and appropriate dosing adjustments.
• What is Phase 2 of drug metabolism characterized by?


  • Conjugation with glycine, glucuronide, and sulfate
  • Responsible for synthesizing more water-soluble compounds
  • Enhances renal or biliary elimination
• How does oral drug absorption differ in neonates compared to children and adults for specific drugs?

  • Acetaminophen: Decrease
  • Ampicillin: Increase
  • Diazepam: Normal
  • Digoxin: Normal
  • Penicillin G: Increase
  • Phenobarbital: Decrease
  • Phenytoin: Decrease
  • Sulfonamides: Normal
• What factors influence drug distribution in the body?

  • Physicochemical properties of the drug
  • Cardiac output/regional blood flow
  • Blood tissue pH
  • Degree of protein/tissue binding
  • Body composition
• What is the major factor influencing drug distribution in the body?

  Body composition.