Drug therarpy Pregnancy and NEONATES Flashcards
What are the physioloogical changes during pregnancy ?
Every system in the body is affected by pregnancy plasma volume plasma albumin concentration haemoglobin concentration changes in body fat (adipose tissue laid down for lactation)
Uses of drugs in pregnancy
Treatment of problems due to pregnancy
– mineral/vitamin deficiency
– hypertension (pre-eclampsia)
– (morning sickness)
Treatment of problems not due to
pregnancy
– infections
– on-going chronic disease
Pharmacokinetics of drugs during
pregnancy
Absorption –decreased GI motility causes
increased drug absorption.
• Distribution – protein binding is decreased which
causes increased free drug availability.
• Metabolism – increased hepatic metabolism occurs
for some drugs .
• Excretion – in the 3rd trimester, increased renal
blood flow and GFR causes some drugs to clear the
body faster.
Effects on embryo and foetus
Effects on embryo and foetus • The effect drug may vary: • No or little effect • Serious – foetal toxicity; spontaneous abortion • Death of foetus • Foetal malfunction • Foetal malformation
Other indirect risks to the
foetus
• Drugs at delivery - CNS depression • Drugs of addiction • Drugs excreted into the milk – aspirin - Reye’s syndrome – Iodine-containing drugs • Effect on lactation
Treatment of ongoing condition in
mother
– diabetics
– Grave’s disease
• carbimazole crosses placenta
Folic acid- Treatment used in preganancy
– reduces chances of anaemia
– possibly prevents neural tube defects
The challenge of providing effective
medical care for pregnant women
Avoid harm to embryo, foetus, neonate.
• Dilemma of the fact that the risk of most drugs
have not been established.
• Cannot and should not avoid drug therapy of the
mother as the health of the foetus depends on the
health of the mother. E.g. seizures, DM, SLE or
infections all have to be treated
What are teratogens and what does it cause ?
Teratogens are substances or other factors that can cause congenital abnormalities, which are also called birth defects. … Examples of teratogens include certain chemicals, medications, and infections or other diseases in the mother.
What are the factors pharmkonitects affect in children etc?
Factors such as gastric pH and emptying time, intestinal transit time, immaturity of secretion and activity of bile and pancreatic fluid among other factors determine the oral bioavailability of pediatric and adult populations
Drugs inactivated by low pH gastric
contents should not be given orally.
• Peristalsis is irregular and slower.
• Rate of gastric emptying is variable.
Physiologic Impacts on
Pharmacokinetics
The physiologic processes that influence pharmacokinetics in children include: – GI function- – Tissue blood flow – Body fluid levels – Plasma protein concentrations – Liver function – Renal function.
Drug distribution in neonates
he volume of distribution of drugs changes in children with aging. These age-related changes are due to changes in body composition (especially the extracellular and total body water spaces) and plasma protein binding.
Higher doses (per kg of body weight) of water-soluble drugs are required in younger children because a higher percentage of their body weight is water (see Figure: Changes in body composition with growth and aging). Conversely, lower doses are required to avoid toxicity as children grow older because of the decline in water as a percentage of body weight.
Neonates have higher total body water than adults. • Body fat is about 15%. • Protein binding of drugs is lower in neonates.
Absorption in children
Absorption from the GI tract is affected by
Gastric acid secretion Bile salt formation Gastric emptying time Intestinal motility Bowel length and effective absorptive surface Microbial flora
What is the absorption affected by in children ?
Absorption from the GI tract is affected by
Gastric acid secretion Bile salt formation Gastric emptying time Intestinal motility Bowel length and effective absorptive surface Microbial flora
Neonates Metabolism
Neonates exhibit substantially lower drugmetabolizing activities of oxidases and
conjugating enzymes
• Dose-response relationships of some drugs
may change markedly during first few
weeks after birth
Drug Elimination
Glomerular filtration rate is lower in neonates. • Drugs that require renal function for elimination are removed from the body very slowly during first trimester.
Metabolism in children /neonates
drug metabolism and elimination vary with age and depend on the substrate or drug, but most drugs, and most notably phenytoin, barbiturates, analgesics, and cardiac glycosides, have plasma half-lives 2 to 3 times longer in neonates than in adults.
The cytochrome P-450 (CYP450) enzyme system in the small bowel and liver is the most important known system for drug metabolism. CYP450 enzymes inactivate drugs via
Oxidation, reduction, and hydrolysis (phase I metabolism)
Hydroxylation and conjugation (phase II metabolism)
Metabolism 2
Phase I metabolism activity is reduced in neonates, increases progressively during the first 6 mo of life, exceeds adult rates by the first few years for some drugs, slows during adolescence, and usually attains adult rates by late puberty. However, adult rates of metabolism may be achieved for some drugs (eg, barbiturates, phenytoin) 2 to 4 wk postnatally. C
cYP450 activity is inhibited or an inadequate drug level when CYP450 activity is induced. Kidneys, lungs, and skin also play a role in the metabolism of some drugs, as do intestinal drug-metabolizing enzymes in neonates.
Phase 2
Phase II metabolism varies considerably by substrate. Maturation of enzymes responsible for bilirubin and acetaminophen conjugation is delayed; enzymes responsible for morphine conjugation are fully mature even in preterm infants.
What do drug metabolites depend on ?
Drug metabolites are eliminated primarily through bile or the kidneys. Renal elimination depends on
Plasma protein binding
Renal blood flow
GFR
Tubular secretion
Pharmacodynamics in children
Beginning with growth to biochemical maturation and eventually to structural maturation, at which point the organ can respond fully to the events initiated by a drug.
Inadequate response to an effective concentration of drug may result from presence or absence of receptors to postreceptor signal • Some drugs may act by affecting the enzyme functions.
