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Systems: Reproduction AB > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

How many pregnant women will uses drugs (medications) during pregnancy?

A

Approximately 50%-90% of pregnant women will take a drug during pregnancy.

  • Prescribed 60%
  • OTC 90%
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2
Q

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

A
  • Hypertension
  • Migraine
  • Asthma
  • Mental health disorders
  • Epilepsy
  • Long term anticoagulant therapy
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3
Q

What are the 4 basic kinetic processes?

A
  • Absorption
  • Distribution
  • Metabolism and elimination
  • Excretion
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4
Q

Why is data very limited for drugs in pregnancy?

A

Very few studies are carried out during pregnancy

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5
Q

What absorption changes occur via the oral route during pregnancy?

A
  • May be more difficult “morning sickness” nausea/vomiting

- Increase in gastric emptying and gut motility

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6
Q

What absorption changes occur via the IM route during pregnancy?

A

Blood flow may be increased, so absorption may also increase using this route

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7
Q

What absorption changes occur via the inhalation route during pregnancy?

A

Increased cardiac output and decreased tidal volume may cause increased absorption of inhaled drugs

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8
Q

What changes occur to distribution during pregnancy?

A
  • Increase Vd: Increase in plasma volume and fat will change distribution of drugs.
  • Increase fraction of free drug: Greater dilution of plasma will decrease relative amount of plasma proteins.
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9
Q

What metabolism changes can occur during pregnancy?

A

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

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10
Q

Give an example of a drug with increases metabolism in pregnancy?

A

Phenytoin

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11
Q

Give an example of a drug with decreased metabolism in pregnancy?

A

Theophylline

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12
Q

What excretion changes occur during pregnancy?

A
  • GFR is increased in pregnancy by 50% leading to increased excretion of many drugs.
  • This can reduce the plasma concentration, and can necessitate an increase in dose of renally cleared drugs.
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13
Q

How can pregnancy affect pharmacodynamics?

A

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
  • Adverse effects may be different
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14
Q

What are the functions of the placenta?

A
  • Attach the foetus to the uterine wall
  • Provide nutrients to the foetus
  • Allow the foetus to transfer waste products to the mother’s blood
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15
Q

What materials cross the placenta from mother to foetus?

A
  • Oxygen
  • Glucose
  • Amino acids
  • Lipids, fatty acids & glycerol
  • Vitamins
  • Ions; Na, Cl, Ca, Fe
  • Alcohol, nicotine + other drugs
  • Viruses
  • Antibodies
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16
Q

What materials cross the placenta from foetus to mother?

A
  • CO2
  • Urea
  • Other waste products
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17
Q

What does placental transfer depend on?

A
  • Molecular weight (smaller sizes will cross more easily)
  • Polarity (non-polar cross more readily)
  • Lipid solubility (lipid soluble drugs will cross)
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18
Q

How does foetal distribution differ from adults?

A
  • Circulation different (e.g. Umbilical vein to liver)
  • Less protein binding than adults therefore more “free” drug available
  • Little fat, so distribution different
  • Relatively more blood flow to brain
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19
Q

How does foetal metabolism differ from adults?

A
  • Less enzyme activity, though increases with gestation

- Different isoenzymes to adults

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20
Q

How does foetal excretion differ from adults?

A
  • NB excretion is into amniotic fluid – this is swallowed and can allow recirculation
  • Drugs and metabolites can accumulate in amniotic fluid
  • Placenta not functioning at delivery so can be issues with excretory function
21
Q

When is teratogenicity an issue?

A

During the 1st trimester

22
Q

When is fetotoxicity an issue?

A

2nd and 3rd trimester

23
Q

What problem is there with people who have chronic conditions?

A

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

24
Q

What percentage of foetal abnormalities are attributable to drugs?

A

2%

25
Q

When is the biggest risk of teratogenicity?

A

3-8 weeks

26
Q

What are the mechanisms of teratogenicity?

A
  • Folate Antagonism
  • Neural Crest Cell Disruption
  • Endocrine Disruption: Sex Hormones
  • Oxidative Stress
  • Vascular Disruption
  • Specific Receptor- or Enzyme-mediated Teratogenesis
27
Q

What is folate action key process in?

A

DNA formation and new cell production

28
Q

What are the mechanisms of folate antagonism?

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)
29
Q

What does folate antagonism tend to result in?

A

Tend to result in neural tube, oro-facial or limb defects

30
Q

What can retinoids cause in pregnancy?

A

Neural crest cell disruption

31
Q

What problems can neural crest cell disruption lead to?

A
  • Aortic arch anomalies
  • Ventricular septal defects
  • Craniofacial malformations
  • Oesophageal atresia
  • Pharyngeal gland abnormalities
32
Q

What can NSAIDs cause in pregnancy?

A

Orofacial clefts and cardiac septal defects

33
Q

What is enzyme mediated teratogenesis?

A

Drugs which inhibitor stimulate enzymes to produce therapeutic effects may also interact with specific receptors and enzymes damaging foetal development.

34
Q

What is fetotoxicity?

A

Toxic effect on the foetus later in the pregnancy

35
Q

What possible fetotoxcity issues can occur?

A
  • Growth retardation
  • Structural malformations
  • Foetal death
  • Functional impairment
  • Carcinogenesis
36
Q

What can ACEI/ARBs cause in pregnancy?

A

Renal dysfunction and growth retardation

37
Q

How are drugs stages for use in pregnancy?

A
  • A: No foetal risk
  • B: Animal studies show no risk but no human studies or animal studies show risk but human do not
  • C: No human data
  • D: Evidence of foetal risk but benefits outweigh them
  • X: Foetal risk outweigh possible benefit
38
Q

Give examples of known teratogens to avoid during pregnancy.

A
  • Anticonvulsants
  • Anticoagulants
  • Antihypertensives
  • NSAIDs
  • Alcohol
  • Retinoids
39
Q

What is the teratogenic effect of anticonvulsants?

A

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

40
Q

What is the teratogenic effect of anticoagulants?

A

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

41
Q

What is the teratogenic effect of antihypertensives ?

A

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

42
Q

What is the teratogenic effect of NSAIDs?

A

Premature closure of the ductus arteriosus.

43
Q

What is the teratogenic effect of alcohol?

A

Foetal alcohol syndrome/effects

44
Q

What is the teratogenic effect of retinoids?

A

Ear, CNS, cardiovascular, and skeletal disorders

45
Q

What are the issues with drugs and lactation?

A
  • Most drugs will be present at lower doses through breast-feeding than in utero
  • Important to know what concentration will be in breast milk
46
Q

What drugs should be avoided when breast feeding?

A
  • Cytotoxics
  • Immunosuppressants
  • Anti-convulsants (not all)
  • Drugs of abuse (especially opiates)
  • Amiodarone
  • Lithium
  • Radio-iodine
47
Q

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

A
  • 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
48
Q

What are the principles of prescribing pregnancy?

A
  • 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 the first 10 weeks of pregnancy if possible
  • Consider stopping or reducing dose before delivery
  • Don’t under treat disease which may be harmful to the fetus
49
Q

What are the principles of prescribing in breast feeding?

A
  • Again avoid unnecessary drug use
  • Check on up to date drug information
  • May be a lack of information
  • If licensed and safe in paediatric use (esp under 2 years), a drug is likely to be safe in breast feeding
  • Choose drugs with pharmacokinetic properties that reduce infant exposure (eg highly protein bound)

Systems: Reproduction AB (35 decks)

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