pharmacology

Question 1

why might a woman be on medication during pregnancy, childbirth and lactation?

Answer 1

• hypertension
• migraine
• asthma
• mental health disorders
• epilepsy
• long term anticoagulant therapy

Question 2

how can pregnancy affect pharmacokinetics of drugs

Answer 2

affects any of the four basic kinetic processes:

• absorption
• distribution
• metabolism and elimination
• excretion

Question 3

describe absorption changes during pregnancy

Answer 3

oral route: decrease in gastric emptying and gut motility

intramuscular route: blood flow increased = absorption increased

inhalation: increased cardiac output, decreased tidal volume = absorption increased

Question 4

describe distribution changes during pregnancy

Answer 4

increased Vd: increase in plasma volume and fat

increased fraction of free drug: greater dilution of plasma will decrease relative amount of plasma proteins.

Question 5

describe metabolism changes during pregnancy

Answer 5

oestrogen and progestogens can induce or inhibit liver P450 enzymes, increasing or reducing metabolism

eg phenytoin levels reduced due to induction of metabolism or theophylline levels increased due to inhibition of metabolism

Question 6

describe excretion changes during pregnancy

Answer 6

GFR increased = increased excretion of many drugs

this can reduce the plasma concentration, and can necessitate an increase in dose of medicines cleared by the kidney

Question 7

how can pregnancy affect pharmacodynamics

Answer 7

pregnancy may affect:
site of drug action
- metabolites at sites of biological action (changes in blood flow)

receptor response to drug
- mechanism of action (changes in receptors)

Question 8

What does placental transfer depend on?

Answer 8

• molecular weight (smaller sizes will cross more easily)
• polarity (unionised molecules cross more readily)
• lipid solubility (lipid soluble drugs will cross)

Question 9

how does foetal distribution differ from adults?

Answer 9

difference in:

• circulation (umbilical vein to liver, relatively more blood flow to brain)
• “free” drug available (less protein binding)
• fat (less)

Question 10

how does foetal metabolism differ from adults?

Answer 10

• reduced enzyme activity

- different p450 isoenzymes

Question 11

how does foetal excretion differ from adults?

Answer 11

excretion is into amniotic fluid, this is swallowed and can allow recirculation

Question 12

what are the mechanisms of teratogenicity?

Answer 12

• folate antagonism
• neural crest cell disruption
• enzyme-mediated teratogenesis
• endocrine disruption: sex hormones
• oxidative stress
• vascular disruption

Question 13

what are some drug associated problems in pregnancy

Answer 13

• teratogenicity: 1st trimester (3-8 weeks organogenesis)

- fetotoxicity: 2nd & 3rd trimester

Question 14

what problem is there with people who have chronic conditions?

Answer 14

often undertreated due to fear that the drugs will affect the pregnancy

Question 15

describe folate antagonism

Answer 15

key process in DNA formation and new cell production

drugs that affect folate metabolism:

• block conversion of folate to THF by binding irreversibly to enzyme
• block other enzymes in folate pathway

result: neural tube, oro-facial or limb defect

Question 16

describe neural crest cell disruption

Answer 16

caused by retinoid drugs

results in:

• aortic arch anomalies
• ventricular septal defects
• craniofacial malformations
• oesophageal atresia
• pharyngeal gland abnormalities

Question 17

describe enzyme mediated teratogenesis?

Answer 17

drugs may interact with specific receptors and enzymes damaging foetal development

eg NSAIDs cause oro-facial clefts and cardiac septal defects

Question 18

what is fetotoxicity?

Answer 18

toxic effect on the foetus later in the pregnancy

Question 19

how are drugs stages for use in pregnancy?

Answer 19

• A: No foetal risk
• B: Animal studies show no risk but no human studies conducted
• C: No human data
• D: Evidence of foetal risk but benefits outweigh them
• X: Foetal risk outweigh possible benefit

Question 20

examples of known teratogens to avoid during pregnancy

Answer 20

anticonvulsants -> neural tube defects
(valproate, carbamazepine, phenytoin)

anticoagulants -> haemorrhage, multiple malformations in CNS (warfarin)

antihypertensives -> renal damage, restrict normal growth patterns (ACEI)

NSAIDs -> premature closure of ductus arteriosus

alcohol -> foetal alcohol syndrome

retinoids -> ear, CNS, cardiovascular, and skeletal disorders

Question 21

what is the issue with drugs and lactation?

Answer 21

almost all drugs will be present in breast milk (important to know concentration)

Question 22

what drugs should be avoided when breast feeding?

Answer 22

anti-convulsants (not all)

immunosuppressants

cytotoxics

drugs of abuse (especially opiates)

amiodarone, lithium, radio-iodine

Question 23

what are the principles of prescribing for women of child-bearing age?

Answer 23

consider possibility of pregnancy and warn of possible risks

Question 24

what are the principles of prescribing pregnancy?

Answer 24

choose non-pharmacological treatments

pharmacological treatment: lowest dose, shortest duration, avoid first 10 weeks

check the SPC for the most up to date information

Question 25

what are the principles of prescribing in breast feeding?

Answer 25

avoid drugs

drugs: choose pharmacokinetic properties that reduce infant exposure (eg highly protein bound)

check on up to date drug information

Question 26

describe the exchange of materials across the placenta

Answer 26