Pharmacology Flashcards

1
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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2
Q

how can pregnancy affect pharmacokinetics of drugs

A

affects any of the four basic kinetic processes:

  • absorption
  • distribution
  • metabolism and elimination
  • excretion
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3
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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4
Q

describe absorption changes during pregnancy

A

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

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5
Q

describe distribution changes during pregnancy

A

increased Vd: increase in plasma volume and fat

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

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6
Q

describe metabolism changes during pregnancy

A

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

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7
Q

describe excretion changes during pregnancy

A

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

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8
Q

how can pregnancy affect pharmacodynamics

A

site of drug action: metabolites at sites of biological action (changes in blood flow)

receptor response to drugs : mechanism of action (changes in receptors)

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9
Q

describe the exchange of materials across the placenta

A
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10
Q

What does placental transfer depend on?

A
  • molecular weight (smaller sizes will cross more easily)
  • polarity (unionised molecules cross more readily)
  • lipid solubility (lipid soluble drugs will cross)
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11
Q

how does foetal distribution differ from adults?

A
  • circulation is 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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12
Q

how does foetal metabolism differ from adults?

A
  • reduced enzyme activity, though increases with gestation

- different p450 isoenzymes to adults

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13
Q

how does foetal excretion differ from adults?

A
  • 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
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14
Q

what are some drug associated problems in pregnancy

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

- fetotoxicity: 2nd & 3rd trimester

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15
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

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16
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
17
Q

describe folate antagonism

A

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

18
Q

describe neural crest cell disruption

A

caused by retinoid drugs

results in:

  • aortic arch anomalies
  • ventricular septal defects
  • craniofacial malformations
  • oesophageal atresia
  • pharyngeal gland abnormalities
19
Q

describe enzyme mediated teratogenesis?

A

drugs which inhibit or stimulate enzymes to produce therapeutic effects may also interact with specific receptors and enzymes damaging foetal development
eg NSAIDs cause oro-facial clefts and cardiac septal defects

20
Q

what is fetotoxicity?

A

toxic effect on the foetus later in the pregnancy

possible issues:

  • growth retardation
  • structural malformations
  • foetal death
  • functional impairment
  • carcinogenesis

eg ACEI or ARBs can cause renal dysfunction and growth retardation

21
Q

how are drugs stages for use in pregnancy?

A
  • 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
22
Q

examples of known teratogens to avoid during pregnancy

A
  • anticonvulsants (valproate, carbamazepine, phenytoin): neural tube defects
  • anticoagulants (warfrin): haemorrhage, multiple malformations in CNS
  • antihypertensives (ACEI): renal damage, restict normal growth patterns
  • NSAIDs: premature closure of ductus arteriosus
  • alcohol: foetal alcohol syndrome
  • retinoids: ear, CNS, cardiovascular, and skeletal disorders
23
Q

what is the issue with drugs and lactation?

A

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

24
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
25
Q

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

A
  • consider possibility of pregnancy (planned or not!)
  • warn 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
26
Q

what are the principles of prescribing pregnancy?

A
  • try non-pharmacological treatment first
  • use 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
27
Q

what are the principles of prescribing in breast feeding?

A
  • avoid unnecessary drug use
  • check on up to date drug 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)