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Reproductive System > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

What is the biggest risk period for teratogenic drugs?

A

Organogenesis or weeks 3-8

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2
Q

What are the major mechanisms of teratogenesis?

A
  • Folate Antagonism (prevents DNA/cell formation)
  • Neural Crest Cell Disruption
  • Specific receptor or enzyme/mediated teratogensis
  • Sex Hormone disruption
  • Oxidative Stress
  • Vascular Disruption
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3
Q

In what two groups of drugs can disrupt the production of DNA and new cells by ANTAGONISING folate?

A
  • Block the conversion of folate to THF by binding irreversibly to the enzyme (eg methotrexate, trimethoprim)
  • Block other enzymes in the pathway (eg phenytoin, carbamazepine, valproate)
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4
Q

What defects does folate antagonism cause?

A

Defects in:

  • Neural Tube
  • Oro-facial
  • Limb
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5
Q

What drugs can disrupt neural crest cells?

A

Retinoids like isotretinoin

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6
Q

What defects does Neural Crest Cell disruption cause?

A
  • Aortic arch anomalies
  • Ventricular septal defects
  • Craniofacial malformation
  • Oesophageal atresia
  • Pharyngeal gland abnormalities
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7
Q

How does specific receptor/enzyme-mediated teratogenesis work?

A

Drugs which inhibit or stimulate enzymes to produce therapeutic effects may also interact with specific receptors and enzymes damaging fetal development.

I.e. NSAIDs causing orofacial clefts and cardiac septal defects

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8
Q

Some drugs are dangerous to the foetus in the 2nd/3rd trimester, i.e. fetotoxic instead of teratogenic. What issues can they cause?

A
  • Growth retardation
  • Structural malformation
  • Foetal death
  • Functional impairment
  • Carcinogenesis
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9
Q

Example of a fetotoxic drug?

A

Any ACEi or ARB is fetotoxic causing renal dysfunction and growth retardation

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10
Q
  • How do we categorise the danger of a drug to a foetus?
A

A, B. C. D and X - with A being good and X being bad

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11
Q

What does a drug of risk A mean?

A

Human studies show no foetal risk (these are safest drugs)

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12
Q

What does a drug of Risk B mean?

A

Animal studies safe and no human studies - animal studies show risk to foetus but human studies safe

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13
Q

What does a drug of Risk C mean?

A

No adequate studies or animal studies she risk and no human studies

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14
Q

What does a drug of risk D mean?

A

Proven foetal risk in humans but sometimes the benefit outweighs risk

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15
Q

What does a drug of risk X mean?

A

Proven foetal risk is never outweighed by benefit

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16
Q

What about a drug promotes placental transfer?

A

Assume all will transfer to some extent but certain drugs are more easily absorbed into the foetal circulation:

  • Smaller molecular weight
  • Non-polar
  • Lipid soluble
17
Q

In what way are foetal Pharmacokinetics different to adults?

A

Distribution:

  • Less protein –> more free drug
  • Less fat –> more free drug
  • More blood flow to brain

Metabolism:

  • Less enzyme activity and different isoenzymes

Excretion:

  • Excreted into amniotic fluid –> Swallowed –> Can be re-circulated
18
Q

How does pregnancy affect the mothers Absorption of drugs?

A
  • Oral can be difficult with morning sickness
  • Gastric emptying and decreased gut motility can affect absorbed dose
  • Increased CO and increased tidal volume can increase absorption of inhaled drugs
  • Blood flow increased, so absorption may also increase (intramuscular route)
19
Q

How does pregnancy affect a woman’s distribution of drugs?

A

Increased plasma and fat –> increased Volume of Distribution (requires higher dose)

Increased plasma –> lower proportion of proteins due to dilutions –> increase fraction of free drug

20
Q

How does pregnancy affect a woman’s metabolism of drugs?

A

Oestrogen and progestogens can induceor inhibit liver P450 enzymes, increasingor reducing metabolism.

  • Phenytoin levels reduced (due to induction of metabolism)
  • Theophylline levels increased (due to inhibition of metabolism)
21
Q

How does pregnancy affect a woman’s Excretion of drugs?

A

GFR increases by 50% so renally cleared drugs are excreted faster

This can reduce the plasma concentration, and can necessitate an increase in dose of renally cleared drugs.

22
Q

Name some major drug classes that should be avoided in pregnancy?

A
  • Anticonvulsants (phenytoin, carbamazepine and valproate)
  • Anticoagulants (warfarin)
  • Antihypertensives (ACEI/ARBs)
  • NSAIDs
  • Alcohol
  • Retinoids
23
Q

Whats the major danger of NSAIDs in pregnancy?

A

Premature closure of the Ductus Arteriosus

24
Q

Whats the major danger of warfarin in pregnancy?

A

Foetal haemorrhage and multiple malformations in the CNS and skeletal system

25
Q

What drugs should be avoided during breastfeeding?

A
  • Cytotoxics
  • Immunosuppressants
  • Anti-convulsants (not all)
  • Drugs of abuse
  • Amiodarone
  • Lithium
  • Radio-iodine
26
Q

What should you consider when prescribing to a woman of childbearing age?

A
  • Are they pregnant?
  • Warn of risks and advise re-attending should they decide to get pregnant
  • Contraception?
27
Q

What else should you think about when prescribing to a breast feeding woman?

A
  • If its licensed and safe for paeds (particularly <2yrs) its probably fine for breastfeeding
  • Choose drugs which reduce infant exposure e.g. a highly protein-bound drug
28
Q

Case - 35yr old overweight woman presents with new diagnosis of hypertension but wants to get pregnant in the next year, what do you do?

A

Normally you’d give an ACEI but they can cause renal dysfunction and growth retardation. Start with non-pharmacological treatments such as weight loss

Then discuss an alternative anti-hypertensive

29
Q

Case - 17yr old girl with severe acne is offered Isotretinoin, what else should you think about?

A

Ensure shes on atleast 1 form of contraception and undergoes monthly pregnancy checks to avoid Neural crest Cell Disruption. Actually demanded in the BNF

30
Q

What should you be thinking about when prescribing in Pregnancy?

A
  • Can you treat non-pharmacologically?
  • Use lowest effective dose
  • Use shortest treatment possible
  • If possible avoid 1st 10 wks of pregnancy
  • If possible stop or reduce before delivery
  • Don’t under treat a disease that could damage the foetus

Reproductive System (26 decks)

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