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Pharmaco > Class 11- pregnancy > Flashcards

Class 11- pregnancy Flashcards

1
Q

FETAL AGE

A
  • Calculated from the day of fertilization, difficult to determine
  • Used in research
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2
Q

GESTATIONAL AGE

A
  • Date of the first day of the last menstruation period (LMP)
  • Used in clinical practice
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3
Q

Implementation and pre-differentiation

A

(weeks 1-2)
• Fertilization and implantation
• Teratogen drugs do not cause malformations at this stage
• If impact = spontaneous abortion

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4
Q

Embryonic period

A

(weeks 3-9)
• Organogenesis, organ formation at different times
• Maximum sensitivity to teratogenic drugs, critical period for structural abnormalities

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5
Q

Fetal period

A

(weeks 10-40)

• Functional growth and maturation of organs and systems

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6
Q

TERATOGENIC EXPOSURE

A
  • Exposure that has the ability to alter normal embryonic or fetal development
  • Infectious agents, drugs, chemicals, agents found in the environment (e.g. lead), physical agents (e.g. radiation), trauma.
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7
Q

Congenital abnormalities

A

Metabolic, morphological or functional abnormality present at birth that is fatal or causes physical or mental disability

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8
Q

MAJOR ABNORMALITIES

A
  • Seriously interfere with sustainability, quality of life, physical wellbeing or social acceptability
  • 1 to 3% in the general population
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9
Q

MINOR ABNORMALITIES

A
  • No significant medical or cosmetic consequences

* 10-15% of children

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10
Q

ABSORPTION

GASTROINTESTINAL

A

• increase Gastrointestinal motility
•increase gastric pH
• Nausea and vomiting
• Decrease in the absorption of certain drugs
• Dehydration can affect serum levels of certain medications (e.g.
lithium)

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11
Q

ABSORPTION

CUTANEOUS

A
  • increase skin hydration
  • increase perfusion
  • These parameters increase the skin absorption of drugs
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12
Q

DISTRIBUTION VOLUME

A
  • increase total body water
  • increase plasma volume, amniotic fluid, placenta, fetus
  • increase fat mass
  • increase distribution of water-soluble and fat-soluble drugs
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13
Q

DISTRIBUTION PLASMA PROTEIN-BINDING

A
  • decrease plasma proteins (albumin and alpha-glycoprotein)
  • decrease ability of drugs to bind
  • increase free fraction of certain drugs
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14
Q

LIVER METABOLISM

A
  • Changes in the activity of certain liver enzymes

* increase or decreasce serum concentration of drugs

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15
Q

RENAL ELIMINATION

A
  • increase glomerular filtration rate

* increase elimination of certain drugs

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16
Q

Schizophrenia and pregnancy

A
  • 59 % : deterioration of symptoms
  • 29 % : improvement of symptoms
  • Cessation of medication increase the risk of relapse of 65 % in this population
  • Higher risk of post partum psychosis
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17
Q

HALOPERIDOL and pregnancy

A
  • First-intention antipsychotic for acute episodes of agitation or psychosis
  • Less hypotension, sedation and anticholinergic effects than other first-generation antipsychotics
  • Risk of extrapyramidal reactions (increased with long-acting formulations)
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18
Q

Atypical antipsychotics and pregnancy

A

No teratogenic risk demonstrated
OLANZAPINE
• Best-documented molecule
OTHERS
• Quetiapine, risperidone and paliperidone could also be
considered
• Clozapine reserved for refractory conditions
• Little data for aripiprazole and ziprasidone

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19
Q

Antipsychotics – Follow-up

A

MOTHER ASSESSMENT
• Increased risk of gestational diabetes : early detection by orally induced hyperglycemia
NEONATAL ASSESSMENT
• CBC if maternal exposure to clozapine : day 3, week 2, week 4

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20
Q

Depression in pregnancy

RISKS OF NOT TREATING

A

• Mother’s decompensation (risk of impulsivity or judgment disorder)
• Obstruction to prenatal follow-up and infant arrival preparation
• Non-compliance with medical treatments
• Changes in physiological functions (risk of premature labour)
• Breaking the social network
• “Direct” effects on the fetus: switching to transplacental
cortisol levels, risk of suicide and infanticide, risk of exposure to tobacco, alcohol and drugs

21
Q

Treatment of depression in pregnancy

A

PHARMACOLOGICAL TREATMENT
• Recommended if moderate to severe depression or a history of severe or recurrent depression
• Prioritize monotherapy
OTHER TREATMENT OPTIONS
• Psychotherapy if mild to moderate depression
• Electroconvulsive therapy (effective and safe during pregnancy)

22
Q

Antidepressants in pregnancy

A

SSRIs
• Citalopram, fluoxetine and sertraline have been the subject of the largest number of studies : data do not demonstrate a teratogenic risk
• Paroxetine associated with an increased risk of cardiovascular malformation, so it is best to focus on other drugs SNRI
• Reassuring data with venlafaxine (better documented than others)
BUPROPION
• Reassuring data
MIRTAZAPINE
• Insufficient data
TRICYCLIC ANTIDEPRESSANTS
• Data are not in favour of a teratogenic risk
• Caution for drug interactions and possible side effects
MONOAMINE OXIDASE INHIBITORS (MAOI)
• Not recommended
• Lack of information
• Risk of exacerbation of hypertension and hypoperfusion

23
Q

Antidepressants

AT THE END OF THE PREGNANCY

A
  • Symptoms of withdrawal are possible for the baby (agitation, lack of tone), but generally transient and mild
  • Reduce the dose or stop a little before giving birth
24
Q

SSRI AND RISK OF AUTISM

A

• Observed risk increases are often insignificant after adjustment of confounding variables, including maternal condition
Compare the risks and benefits of using an SSRI, but also the major risks of not treating the maternal condition

25
Q

Bipolar disorder and pregnancy

A

• Pregnancy is a risk factor for decompensation
• Risk of relapse 37 % (medication) vs 85 % (medication cessation
• Several pharmacological treatment options are teratogenic… Nearly 70% choose to stop treatment
• Higher risk of postpartum depression and postpartum
psychosis

26
Q

Lithium and pregnancy

A

• Heart defects
• Absolute risk between 0.9 and 6.8%
• Basic risk of 1% in the general population
PERIOD AT RISK
• Embryogenesis
• Between 5 and 10 weeks (LMP)
May be considered for patients whose condition is well
controlled with this medication before pregnancy

27
Q

Lithium – Follow-up

A

MOTHER ASSESSMENT
• Serum concentration of lithium (increased clearance and expansion of plasma volume may decrease serum
concentrations during pregnancy)
• Kidney function, ionogram, serum calcium, TSH (at least every trimester, and every month during first trimester)
FETAL ASSESSMENT
• Ultrasound of cardiac anatomy (16th and 20th week) if
exposure during the 5th and 10th weeks of pregnancy

28
Q

Epival and carbamazepine and pregnancy

A
  • Cardiac malformations, labiopalatines cleft, skeletal malformations, urogenitals, craniofacials and digitals, microcephaly
  • Neural tube defects (valproate and carbamazepine)
  • Abnormalities of neurobehavioural development
  • Absolute risk of 5-10% (10-15% for valproic acid)
  • Dose-response relationship
29
Q

Lamotrigine and pregnancy

A
  • The + studied, lower risk of malformation in the first-generation antiepileptic drugs
  • Controversial relationship with labiopalatine clefts
  • Could be considered during pregnancy
30
Q

Gabapentin and pregabaline and pregnancy

A

• Little data, but does not demonstrate a teratogenic risk

31
Q

Topiramate and pregnancy

A

• Limited data, but demonstrate increased teratogenic risk, especially for labiopalatine clefts

32
Q

Bipolar disorder and pregnancy

CONTINUE OR DISCONTINUE TREATMENT ?

A
  • Frequency and severity of last episodes
  • Known precipitating factors
  • Comorbidities
  • Support network
  • Patient preferences
33
Q

Bipolar disorder and pregnancy

IF TREATMENT IS DISCONTINUED

A
  • Gradually (> 2 weeks)
  • Watch for signs of decompensation
  • In some cases, treatment is resumed after first trimester
34
Q

Anticonvulsants decrease OC levels

A

Carbamazepine, Topiramate (> 200mg/day)

35
Q

Anticonvulsants with no influence on OC levels

A

Gabapentine
Pregabaline
Lamotrigine

36
Q

OC can decrease of 50 % ???? concentrations

A

lamotrigin

37
Q

Contraception

Other solutions

A
  • Use an oral contraceptive with 50 mcg of ethinylestradiol if available on the market, if not at least 35 mcg
  • Reduce the time «off» the OC (3-4 days or take continuous)
  • Intra-uterine device (IUD)
  • Depo-Provera IM q 10 weeks instead of 12 weeks
  • Barrier contraceptive method can be suggested in addition
38
Q

Benzodiazepines and pregnancy

A

• Data do not suggest an association between benzodiazepine exposure and a major risk of abnormality
Possibility of labiopalatin cleft
• Data especially with diazepam, but controversial
• Period at risk: organogenesis phase
• Better to avoid them in the first trimester
• Use small doses
• Stop 1 to 2 weeks before delivery to prevent neonatal toxicity
or withdrawal symptoms

39
Q

Choosing the right benzodiazepine

A

• Short half-life or intermediate, without active metabolite
(lorazepam or oxazepam)
• Clonazepam is an alternative if insufficient effectiveness

40
Q

Transfer of drugs to breast milk

A 
PASSIVE DIFFUSION
• Free molecules, not bounded to plasma proteins, diffuse from mother’s blood to breast milk according to concentration gradient
• Molecular mass must be < 600 daltons
• The majority of drugs
DIRECT INTERCELLULAR DIFFUSION
• Molecules whose molecular mass is < 200 daltons pass directly through intercellular space
ACTIVE TRANSPORT
• Rare (e.g. immunoglobulins)
41
Q

Pharmacokinetics and lactation

A

BIOAVAILABILITY
• Prefer drugs with low bioavailability or poorly absorbed delivery routes
PLASMA PROTEIN BINDING
• Important factor to determine passing of a drug into breast milk
• Free fraction diffuses into breast milk
• The more strongly a drug is bound to plasma proteins, the less likely it is to diffuse into breast milk
ELIMINATION HALF-LIFE
• Long half-life = risk of accumulation in children
MOLECULAR MASS
• Smaller = more diffusion in breast milk
LIPOSOLUBILITY
• Lipophilic molecules spread more easily and faster in breast milk
• For example, antidepressants or benzodiazepines

42
Q

Potential for side effets

Most commonly seen while breastfeeding

A
  • Analgesics or narcotics
  • 11 %, drowsiness
  • Antidepressants, sedatives or antiepileptic drugs
  • 7 %, drowsiness
  • Antihistaminics
  • 9 %, irritability
43
Q

ATYPICAL ANTIPSYCHOTICS and lactation

A
  • Generally considered safe
  • Olanzapine and quetiapine are the best choices
  • Monitor sedation and extrapyramidal reactions
44
Q

CLOZAPINE and lactation

A
  • To avoid
  • Higher concentrations in breast milk
  • Risk of neutropenia
45
Q

Antidepressants and lactation

A
  • Generally safe SSRIs: sertraline and paroxetine at the smallest effective dose
  • TCA (imipramine and nortriptyline) could also be used
46
Q

Lithium and lactation

A

GENERALLY NOT RECOMMENDED
• Moderate concentrations in exposed children
• Can become toxic quickly in the presence of dehydration
IF LITHIUM IS PRESCRIBED
• Very tight follow-up
• Measuring the concentration in the blood of the mother AND the baby

47
Q

Anticonvulsivants and lactation

A

VALPROIC ACID / DIVALPROEX
• Breastfeeding compatible
• Follow-up: sedation, hepatotoxicity, signs of bleeding
CARBAMAZEPINE
• Compatible with breastfeeding, but generally avoided due to the risk of hematological toxicity
• Possible accumulation in children with immature metabolic pathways
• Follow-up: sedation, weight gain, liver function
LAMOTRIGINE
• Generally not recommended
• High to moderate passage in breast milk, but little effect in children (sedation, rash)

48
Q

Benzodiazepines and lactation

A 
PRIORITIZE
• Less lipophilic molecules
• Short or intermediate half-life
• No active metabolite
• Lorazepam or oxazepam are good choices
MONITOR
• Sedation
• Lethargy
• Respiratory difficulties

Pharmaco (11 decks)

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