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Repro > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

What is the biggest risk period for teratogenic drugs? [1]

A

Organogenesis -weeks 3-8

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2
Q

What are the major mechanisms of teratogenesis? [6]

A

Folate Antagonism (prevents DNA/cell formation)
Neural Crest Cell Disruption
Specific receptor or enzyme/mediated teratogenesis
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? [4]

What defects does folate antagonism cause? [3]

A

MTX
Trimethoprim

Anti-convulsants:

  • Phenytoin
  • Carbamazepine
  • Valproate
  • Neural Tube
  • Oro-facial
  • Limb
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4
Q

What drugs can disrupt neural crest cells? [2]

A

Notably Retinoids like isotretinoin

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5
Q

What defects does Neural Crest Cell disruption cause? [5]

A
  • Aortic Arch anomalies
  • Ventricular Septal Defects
  • Craniofacial malformation
  • Oesophageal atresia
  • Pharyngeal Gland Abnormalities
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6
Q

How does specific receptor/enzyme-mediated teratogenesis work? Give one example of a drug and its teratogenic effects

A

Drugs designed to inhibit/stimulate an enzyme or receptor can have negative effects on the developing foetus

E.g. NSAIDS lead to Orofacial clefts and septal defects

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7
Q

Some drugs are dangerous to the foetus in the 2nd/3rd trimester, i,e. fetotoxic instead of teratogenic. What issues can they cause? [5]

A 
Functional impairment
Growth retardation
Structural malformation
Carcinogenesis
Foetal death
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8
Q

Example of a fetotoxic drug [2] and what problems do they cause [2]

A

Any ACEI or ARB is fetotoxic

Causing Renal Dysfunction and growth retardation

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9
Q

How do we categorize 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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10
Q

What does a drug of risk A mean?

A

Human studies show no foetal risk

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11
Q

What does a drug of Risk B mean?

A

Either:

  • Animal studies safe and no human studies
  • Animal studies risky but human studies safe
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12
Q

What does a drug of Risk C mean?

A

Either:

  • No adequate studies
  • Animal studies risky and no human studies
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13
Q

What does a drug of risk D mean?

A

Proven foetal risk in humans but sometimes outweighed by benefit

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14
Q

What does a drug of risk X mean?

A

Proven foetal risk is never outweighed by benefit

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15
Q

Assume all will transfer to some extent but certain drugs are more easily absorbed into the foetal circulation. Name 3 factors

A
  • Smaller molecular weight
  • Non-polar
  • Lipid soluble
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16
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

17
Q

How does pregnancy affect the mothers Absorption of drugs?
2 problems with oral route
1 difference to be considered with intramuscular route
1 difference with inhalation drugs

A

Oral can be difficult with morning sickness

Gastric emptying and increased gut motility can affect absorbed single > regular doses

Intramuscular route: increased blood flow so increased absorption

Inhalation - Increased CO and decreased tidal volume can increase absorption of inhaled drugs

18
Q

How does pregnancy affect a woman’s Distribution of drugs? [2]

A

Increased Plasma and fat –> Increased Volume of Distribution > Requires higher dose)

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

19
Q

How does pregnancy affect a woman’s metabolism of drugs? What 2 groups of drugs can this affect?

A

Oestrogen/progestogens affect P450 enzymes in the liver:

  • Induces enzymes –> drop in phenytoin levels
  • Inhibits others –> Rise in theophylline levels (COPD, asthma)
20
Q

How does pregnancy affect a woman’s Excretion of drugs? [1]

A

GFR increases so renally cleared drugs are excreted faster

21
Q

Name 6 major drug classes that should be avoided in pregnancy? Give one example and its associated teratogenic effect.

A
  • Anticonvulsants (phenytoin, carbamazepine, valproate > NTDs)
  • Anticoagulants eg warfarin - hemorrhage + malformations
  • Antihypertensives -ACEI/ARBs - renal damage, growth restriction
  • NSAIDs - premature closure of ductus arteriosus
  • Alcohol - FAS
  • Retinoids - ear, CNS, CVS and skeletal malformations
22
Q

Whats the major danger of warfarin in pregnancy?

A

Foetal or maternal Haemorrhage

Also teratogenic –> CNS/Skeletal malformations

23
Q

What drugs should be avoided during breastfeeding? [5]

A 
Immunosuppressants
Some Anti-convulsants
Amiodarone
Lithium
Radio-iodine
24
Q

What should you consider when prescribing to a woman of childbearing age? [4]

A
  • Are they pregnant?
  • Warn of risks and advise re-attending should they decide to get pregnant
  • Contraception?
  • Can you treat non-pharmacologically?
25
Q

What else should you think about when prescribing to a breast feeding woman? [2]

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

26
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? [2]
What do you normally give but what are the associated dangers? [2]

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

27
Q

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

A

Ensure shes on at least 1 form of contraception and undergoes monthly pregnancy checks to avoid Neural crest Cell Disruption.

28
Q

What are 4 prescribing practices in pregnant women?

NB Don’t under treat a disease that could damage the foetus

A
  • Use lowest effective dose
  • Use shortest treatment possible
  • If possible avoid 1st 10 wks of pregnancy
  • If possible stop or reduce before delivery

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