Drug therarpy Pregnancy and NEONATES

Question 1

What are the physioloogical changes during pregnancy ?

Answer 1

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)

Question 2

Uses of drugs in pregnancy

Answer 2

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

Question 3

Pharmacokinetics of drugs during

pregnancy

Answer 3

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.

Question 4

Effects on embryo and foetus

Answer 4

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

Question 5

Other indirect risks to the

foetus

Answer 5

• Drugs at delivery - CNS depression
• Drugs of addiction
• Drugs excreted into the milk
– aspirin - Reye’s syndrome
– Iodine-containing drugs
• Effect on lactation

Question 6

Treatment of ongoing condition in

mother

Answer 6

– diabetics
– Grave’s disease
• carbimazole crosses placenta

Question 7

Folic acid- Treatment used in preganancy

Answer 7

– reduces chances of anaemia

– possibly prevents neural tube defects

Question 8

The challenge of providing effective

medical care for pregnant women

Answer 8

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

Question 9

What are teratogens and what does it cause ?

Answer 9

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.

Question 10

What are the factors pharmkonitects affect in children etc?

Answer 10

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.

Question 11

Physiologic Impacts on

Pharmacokinetics

Answer 11

The physiologic processes that
influence pharmacokinetics in children
include:
– GI function- 
– Tissue blood flow
– Body fluid levels
– Plasma protein concentrations
– Liver function
– Renal function.

Question 12

Drug distribution in neonates

Answer 12

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.

Question 13

Absorption in children

Answer 13

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

Question 14

What is the absorption affected by in children ?

Answer 14

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

Question 15

Neonates Metabolism

Answer 15

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

Question 16

Drug Elimination

Answer 16

Glomerular filtration rate is lower in
neonates.
• Drugs that require renal function for
elimination are removed from the body
very slowly during first trimester.

Question 17

Metabolism in children /neonates

Answer 17

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)

Question 18

Metabolism 2

Answer 18

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.

Question 19

Phase 2

Answer 19

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.

Question 20

What do drug metabolites depend on ?

Answer 20

Drug metabolites are eliminated primarily through bile or the kidneys. Renal elimination depends on

Plasma protein binding
Renal blood flow
GFR
Tubular secretion

Question 21

Pharmacodynamics in children

Answer 21

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.