Pharmacology in pregnancy and breast feeding

Question 1

in terms of the pregnnant mother: ABSORPTION changes in pregnancy -

Answer 1

Oral route: May be more difficult if there is nausea/vomiting, Increase in gastric emptying and gut motility, Can increase time to peak absorption but reduce overall concentration, This is unlikely to be a problem with regular dosing, but may affect single doses. Intramuscular route: Blood flow may be increased, so absorption may also increase using this route. Inhalation: Increased cardiac output and decreased tidal volume may cause increased absorption of inhaled drugs

Question 2

DISTRIBUTION CHANGES - in the woman

Answer 2

Changes in total body water and fat will change distribution of drugs, Greater dilution of plasma will decrease relative amount of plasma proteins, These two effects cancel each other out so effectively there is no change seen in the distribution.

Question 3

METABOLISM CHANGES + - in the woman

Answer 3

Oestrogen and progestogens can induce or inhibit P450 enzymes in the liver – increasing of reducing metabolism, Examples: Phenytoin levels reduced due to induction of metabolism, Theophylline levels increased due to inhibition of metabolism.

Question 4

EXCRETION CHANGES + - in the woman

Answer 4

GFR is increased during pregnancy by 50%, This leads to increased excretion of many drugs, This can reduce the plasma concentration and may necessitate dose increase

Question 5

Pharmacodynamic changes - in the woman

Answer 5

Pregnancy may affect site of action & receptor response to drugs, Concentration of drug, metabolites at sites of biological action (changes in blood flow), Mechanism of action (changes in receptors), Efficacy may be different

Question 6

what does placental transfer depend on inn terms of Fetal Pharmacokinetics and Placental Absorption

Answer 6

Molecular weight (smaller sizes will cross more easily), Polarity (non-polar cross more readily, Lipid solubility (lipid soluble drugs will cross), Placenta may also metabolise some drugs, Safest to assume all drugs will cross placenta.
Cross placenta if: small, non-ionized, High lipophilicity

Question 7

describe fetal pharmacokinetics in terms of its - Distribution

Answer 7

Circulation different, Less protein binding than adults = more ‘free’ drug, Little fat makes distribution different, Relatively more blood flow to the brain

Question 8

describe fetal pharmacokinetics in terms of its - Metabolism

Answer 8

Less enzyme activity, though increases with gestation, Different isoenzymes to adults

Question 9

describe fetal pharmacokinetics in terms of its - Excretion

Answer 9

Excretion is into amniotic fluid – this is swallowed and can allow recirculation, Concentration and metabolites can accumulate in amniotic fluid, Placenta not functioning at delivery so can be issues with excretory function.

Question 10

safety of drugs in pregnancy, when does teratongenicity effect and when does fetotoxicity effect?

Answer 10

terato - 1st tirmester, feto - 2nd and 3rd trimesters

Question 11

what are the different mechanisms of teratogenicity?

Answer 11

Folate Antagonism, Neural Crest Cell Disruption, Endocrine Disruption: Sex Hormones, Oxidative Stress, Vascular Disruption, Specific Receptor- or Enzyme-mediated Teratogenesis

Question 12

describe the process of folate antagonism

Answer 12

Key process in DNA formation and new cell production, Two groups of drugs: one blocks the conversion of folate to THF, the other blocks other enzymes in the pathway, Results in neural tube, oro-facial or limb defects

Question 13

outline the process of neural crest cell disruption

Answer 13

Retinoid drugs – individuals on retinoid are usually given contraception as well, Aortic arch anomalies, Ventricular septal defects, Craniofacial malformations, Oesophageal atresia, Pharyngeal gland abnormalities

Question 14

outline the process of enzyme-mediated teratogenesis

Answer 14

Drugs which inhibit or stimulate enzymes to produce therapeutic effects may also interact with specific receptors and enzymes damaging fetal development.
E.g. NSAID’s - orofacial clefts anf cardiac septal defects.

Question 15

what is fetotoxicity?

Answer 15

Toxic effects on the fetus later in pregnancy. Possible issues: Growth retardation, Structural malformations, Fetal death, Functional impairment, Carcinogenesis.
Example = ACEIs/ARBs – renal dysfunction and growth retardation.

Question 16

outline the FDA’s categorisation of risks

Answer 16

• A = risk not shown in human studies
• B = risk not confirmed in human studies but seen in animal studies
• C = risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
• D = risk shown in humans, only use if benefit outweighs risk
• X = benefit does not outweigh risk = contraindicated

Question 17

examples of knnown teratogens, other than those below

Answer 17

alcohol, androgens, benzos, carbemazepine, lithium, phenytoin, retinoids, tetracycline, warfarin.

Question 18

Teratogen

Answer 18

Effect

Question 19

Anticonvulsants - Sodium Valproate/ Carbamazepine/ Phenytoin

Answer 19

Valproate is associated with neural tube defects, as is carbamazepine and phenytoin

Question 20

Anticoagulants - Warfarin

Answer 20

Warfarin is associated with haemorrhage in the fetus, as well as multiple malformations in the central nervous system and skeletal system.

Question 21

Antihypertensive agents - ACEi’s

Answer 21

ACE inhibitors cause renal damage and may restrict normal growth patterns in the unborn child.

Question 22

NSAID’s

Answer 22

Premature closure of the ductus arteriosus.

Question 23

Alcohol

Answer 23

Fetal alcohol syndrome/effects

a small head.
a smooth ridge between the upper lip and nose, small and wide-set eyes, a very thin upper lip, or other abnormal facial features.
below average height and weight.
hyperactivity.
lack of focus.
poor coordination.

Question 24

Retinoids

Answer 24

Ear, CNS, cardiovascular, and skeletal disorders

Question 25

issues with using drugs during lactation…

Answer 25

Most drugs given to lactating women are detectable in breast milk, Concentrations are usually low – preventing infants receiving therapeutic amounts, Some drugs do carry serious toxicity and are to be avoided, Recommendations for feeding mothers:
Safe drug = take 30-60 mins after nursing and 3-4 hours before the next feeding.

Question 26

examples of drugs to avoid when breastfeeding other than those below

Answer 26

Cytotoxics, Immunosuppressants, Anti-convulsants (not all), Drugs of abuse, Amiodarone, Lithium, Radio-iodine

Question 27

Drug

Answer 27

Comments

Question 28

Tetracycline

Answer 28

Risk of permanent tooth staining in infant

Question 29

Isoniazid

Answer 29

Risk of pyridoxine deficiency in the infant

Question 30

Barbiturates

Answer 30

Lethargy, sedation and poor suck reflexes

Question 31

Chloral hydrate

Answer 31

Drowsiness if infant fed at peak

Question 32

Diazepam

Answer 32

Drug accumulation and sedation

Question 33

Methadone

Answer 33

Risk of withdrawal if breast feeding stops

Question 34

Iodine

Answer 34

Thyroid suppression and risk of cancer

Question 35

Propylthiouracil

Answer 35

Can suppress thyroid function in infant

Question 36

what herbal remedies pose threat to infants?

Answer 36

fenugreek, comfrey

Question 37

what are the principles of prescribing for women of chiuld-bearinng age?

Answer 37

Always consider possibility of pregnancy (planned or not!)
Warn women of possible risks
When treating medical conditions, advise women to attend before getting pregnant if planning to (optimise treatment)
Discuss contraception
If necessary, do not prescribe without contraception

Question 38

Principles of prescribing in pregnancy

Answer 38

• If you can, try non-pharmacological treatment first
• Use the drug with the best safety record
• Check the SPC for the most up to date information
• Use the lowest effective dose
• Use the drug for the shortest possible time, intermittently if possible
• Avoid use during the first 10 weeks of pregnancy
• Don’t under treat disease which may be harmful to the fetus

Question 39

Principles of prescribing in breast feeding

Answer 39

• Avoid unnecessary drug use
• If licensed and safe in paediatric use (< 2 years), a drug is likely to be safe in breast feeding
• Choose drugs with pharmacokinetic properties that reduce infant exposure

GOOD DISTRIBUTION, METABOLISM AND EXCRETION