CFB NHACHI

DRUG USE IN PREGNANCY AND

BREAST FEEDING
Pregnancy Influenced Issues

 GIT……..constipation 25 to 50, 40 to 80%,

Haemorrhoids, nausea and vomiting 90%.
 Gestational diabetes , 1 to 14%
 PIH about 10%
 Thyroid Abnormalities
 Thromboembolism
PREGNANCY PHYSIOLOGY CHANGES AND PK

 Cardiovascular changes
-- plasma volume expansion
-- increase in cardiac output
-- regional blood flow changes
 Respiratory changes
 Decreased albumin concentration
 Enzyme activity changes
 Increase in GFR
 GIT changes
PK in Pregnancy

Drug Absorption….
• High circulating levels of progesterone slow
GIT emptying and GIT motility. Therefore
there is slow drug absorption.
I.V. administration ….
• Prefered so as to obtain quick response.
Drug Compliance…..
• May be poor due to nausea and vomiting
PK in Pregnancy

Drug Metabolism…
• Hepatic DME are induced during pregnancy . This
can lead to rapid metabolic breakdown of highly
lipid soluble drugs.
Drug Excretion…
• Renal plasma flow is increased by 100% and GFR
by 70%. Therefore drugs which are mainly
excreted by kidney are eliminated more rapidly
than in non pregnant, e.g. ampicillin. Gentamicin
and cephalosporins.
PK in Pregnancy

Blood Flow….
• Increased total blood flow due to increased
fluid rentetion. Therefore this leads to change
in cardiac output, blood pressure and
filtration rate which leads to change in
volume of distribution.
TERATOGENS

 Stage of fertilisation and implantation

 Stage of organogenesis
 Stage of growth and development
TERATOGENS

 At implantation 1 to 2 weeks, teratogens elicits

an all or non effect. (Either death of the embryo
or completely normal development of foetus.
 Embryonic stage (3 to 8 weeks)
 Critical stage of organogenesis is first 8 weeks
of pregnancy.
 After 8 weeks teratogens elicit growth
restriction or functional defects e.g. mental
retardation.
Pregnancy and Drug Use

 TERATOGENS (Principles of Teratology)

- specific
- dose response relationship
- effects depend on
developmental stages
- genotype of mother and
foetus – susceptibility.
- teratogens must reach concepts
Teratogens

 Specificity e.g. thalidomide

 Dose – response relationship
 Effects depend on developmental stages
-- zygote/implantation (1 to 2 weeks, usually not
susceptible to teratogens)
-- embryonic period (1 to 8 weeks, mostly
morphological abnormalities)
-- foetal period (8 to 36 weeks, mostly
physiological abnormalities)
Teratogens

 Genotype of mother and foetus –

susceptibility.
-- increased risk of clefting in foetus carrying
atypical allele for transferring growth factor,
whose mother smokes.
-- reduced risk for foetal alcohol syndrome in
African American women carrying alcohol
dehydrogenase isoform 2
TERATOGENS
DRUG ABNORMALITIES
Thalidomide Phocomelia
Anticancer drug Multiple defects, foetal death
Tetracycline Discoloured and deformed teeth.
Retard bone growth
Phenytoin Craniofacial and limb defect, celft lip.,
cleft palate.
Phenobarbitone Various mulformations
Carbamazepine Cns defects
Retinoids Various abnormalities
Alcohol Foetal alcohol embryopathy
FDA DRUG CATEGORY OF USE IN
PREGNANCY
Category A…
Adequate studies in human demonstrate no
risk.
Category B…
- animal studies indicate no risk but there are no
adequate human studies.
- Animal studies show adverse effects but
adequate studies in humans show no risk.
Continued …

Category B….
Potential risk when
Animal studies indicate adverse effects
There are no human data
THESE DRUGS MAY BE USED WHEN
POTENTIAL BENEFITS OUTWEIGH THE
POTENTIAL RISKS
Continued…..

Category C….

Evidence of human foetal risk but potential

benefit to mother may be acceptable.
Category D…
Studies in animal and humans show adverse
effects and both demonstrate foetal
abnormalities. Risk of use in pregnant women
clearly outweighs any possible benefit.
General Principles

 Medicines should be prescribed during

pregnancy and breastfeeding ONLY if the
accepted benefit to the mother outweighs the
risk to the foetus or neonate.
 All medicines should be avoided if possible
during the first trimester.
 Well known medicines, which have been
extensively used during pregnancy or lactation
should be used in preferance to new medicines.
DRUGS AND BEASTFEEDING

ELIMINATION OF DRUGS IN BREAST MILK IS

USUALLY INSIGNIFICANT DUE TO THE
SMALL AMOUNTS WHICH APPEAR IN
BREAST MILK
Drugs and Breastfeeding

 Risk
--- drugs that are poorly cleared in infant
--- drugs with narrow therapeutic index.
 Factors effecting the milk/plasma concentration
ratio.
-- maternal protein binding
-- protein binding in milk
-- lipid solubility of drug
Drugs and Breastfeeding
Concentration of drugs in milk is determined by,
 Lipophilicity -- ease of passage across
membrane.
-- partitioning into milk fat.
 degree of ionisation
-- pH of milk (7.2) lower than
that of plasma (7.4)
 Plasma protein binding
Important Specific Drug Examples

 Aspirin –Reye’s syndrome (associated with

administration of aspirin to children with or
after a viral infection, symptoms are
-- encephalopathy
-- CNS disturbances
-- chemical liver injury symptoms
 Estrogens, progestegens, estrogens
Specific Examples

-- appear in high concentrations in

milk,
-- may cause hypoglycaemia in
infants/neonates
 B – Blockers ( e.g. atenolol, satolol)
Specific Examples

Anticonvulsants e.g –
phenobabitone
chlodiazepoxide
 primidone
ethosuximide
They appear in high concentration in milk.
Watch breastfeeding infant of epileptic mother
for signs of sedation and incompetent suckling
abilities.
Specific Examples

 Antimicrobials,
-- sulphonamides
-- clindamycin
-- dapsone
-- lincomycin
-- chloramphenicol
Specific Examples

-- lithium
-- benzodiazepines
-- radiopharmaceuticals
-- phenothiazines
-- butyrophenones
--immunosuppressants
-- iodine
-- gold
-- social drugs/drugs of abuse
General precautions

 Drugs safe for pregnancy usually safe during

lactation
 Decrease dose to infant by feeding just prior
administration of next dose
 Infant levels monitored should be less than
therapeutic
alcohol Small quantities probably not harmfull
aspirin Avoid…risk of Reye’s syndrome
atropine Avoid
Drugs not to Use/Used with
bromocriptine Avoid

caution in Breastfeeding.
carbimazole
chloramphinicol
May cause hypothyroidism
May cause bone marrow toxicity in
infant
doxycycline Caution, although probably minimal
levels in milk
phenobarbitone Inhibits infant suckling reflex
thiazides Caution , doses usually small (25 –
50mg) to be harmfull. Large doses may
suppress lactation.
Drugs not to use/use with
caution in pregnancy
DRUG TRIM NOTE Rationalalle
advice
alcohol All avoid Small quantities probably
not harmfull
antiemetics All caution Use promethazine or
chlorpheniramine ONLY
if vomiting is severe
quinine All caution High doses teratogenic.
Benefit outweigh risk
NSAIDs All avoid Paracetamol preferred
Phenobarbitone 1&3 caution Congenital
phenytoin malformations,
prophylactic use of vitK
and folate
recommended.
Vaccines - live All avoid
END