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 recepotr or enzyme/mediated teratogensis
Sex Hormone disruption
Oxidative Stress
Vascular Disruption

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3
Q

What drugs can disrupt the production of DNA and new cells by antagonizing folate?

A

MTX
Trimethoprim

Anti-convulsants:
- Phenytoin
- Carbamazepine
- Valproate

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4
Q

What defects does folate antagonism cause?

A
  • Neural Tube
  • Oro-facial
  • Limb
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5
Q

What drugs can disrupt neural crest cells?

A

Notably 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 designed to inhibit/stimulate an enzyme or receptor can have -ve effects on the developing foetus

E.g. NSAIDS lead to Orofacial clefts and 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 categorize the danger of a drug to a foetus?

A

A, B. C. D & 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

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12
Q

What does a drug of Risk B mean?

A

Either:
- Animal studies safe & no human studies
- Animal studies risky but human studies safe

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13
Q

What does a drug of Risk C mean?

A

Either:
- No adequate studies
- Animal studies risky & 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 outweighed by benefit

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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 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 & increased tidal volume can increase absorption of inhaled drugs

19
Q

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

A

Increased Plasma & fat –> Increased Volume of Distribution (requires higher dose)

Increased plasma –> Lower proportion of proteins –> More free drug fraction

20
Q

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

A

Oestrogen/progestogens affect P450 enzymes in the liver:
- Induces enzymes –> drop in phenytoin levels
- Inhibits others –> Rise in theophylline levels

21
Q

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

A

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

22
Q

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

A
  • Some anticonvulsants (phenytoin, carbamazepine & valproate)
  • Warfarin
  • 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 or maternal Haemorrhage

Also teratogenic –> CNS/Skeletal malformations

25
Q

What drugs should be avoided during breastfeeding?

A

Immunosuppressants
Some Anti-convulsants
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?
  • 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

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

Pick something that reduces 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