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SNRAObPedGer > Pharmacology Preg+Lactation > Flashcards

Pharmacology Preg+Lactation Flashcards

1
Q

Polymorphisms of CYP450 Isoenzyme is an altered ________ results in _______

A

CYP2D6, ultra rapid metabolization

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2
Q

Codeine is broken down into

A

Greater quantities of morphine than normal

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3
Q

Genetic variability that affects morphine is

A

Genetic variability in UGT2B7 may increase formation of morphine-6-glucuronide–> Resp. depression mom and baby

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4
Q

For the mother, what changes occur to B2 receptor?

A

Changes at B2 adrenergic receptor , alter tocolysis, require less ephedrine

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5
Q

Physiological changes during pregnancy including changes in ____, _____, _______ affect AUDME

A

CV, resp, hemodynamics

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6
Q

CO and Absorption: what changes occur?

Give an example

A

Increase in CO to skin and mucous membranes enhances absorption. Example is that if you give a fentanyl patch, increase absorption, may lead to more absorption

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7
Q

What happens to uptake on IA during pregnancy ?

A

Increase MV and Decrease FRC Increase pulmonary uptake

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8
Q

An increase in CO during pregnancy leads to

A

Distribution of drug to all tissues.

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9
Q

What happens when there is a delay in increase in arterial and brain ?

A

A delay in increase arterial and brain anesthetic concentration will result in increased in peripheral perfusion .

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10
Q

When there is an increase peripheral perfusion?

A

There in an increase of return of drug during elimination phase.

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11
Q

Hydrophyillic drugs such as _______-have a ___vd

A

NMB; small

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12
Q

What happens to plasma albumin concentration ?

A

Decreased by 30%

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13
Q

As far as protein concentration, it only affect

A

Highly protein bound drugs

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14
Q

Explain CO and partial pressure and how one affect the other

A

IF you don’t have the partial concentration in the CNS , it doesn’t matter how high your CO is, you can’t go to sleep.

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15
Q

What happens to TBW with pregnancy? Significance?

A

Increase on average by 8L ; Affect distribution

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16
Q

What happens to intravascular plasma?

A

Increase by 40%

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17
Q

The ECF gain in pregnancy depends on

A

Weight gain and edema

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18
Q

Not clear if this is increased despite increase in CO

A

Hepatic blood flow

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19
Q

Recommended Caffeine amount and why?

A

Because of Decrease enzyme activity

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20
Q

CYP450 IsoEnzymes activities that are increased are

A

CYP 34A, CYP2D6, CYP2C9

UGT

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21
Q

UGT enzymes that are induced are

A

UGT1A4 and UGT2B7

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22
Q

The enzyme affecting phenytoin and how?

A

Enzyme CYP2C9 induces phenytoin and increase it metabolism

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23
Q

The enzyme affecting midazolam and how?

A

Enzyme CYP3A4 induces midazolam and increase it metabolism

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24
Q

The enzyme affecting morphine and how?

A

Enzyme UGT2B7 induces morphine and increase it metabolism

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25
Q

CYP450 IsoEnzymes activities that are Decreased are

A

CYP1A2 and CYP2C19

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26
Q

Enzyme responsible for Codeine and Morphine ________ and it it increased or decreased?

A

CYP2D6; Increased

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27
Q

Which enzyme activity reduces caffeine and theophyiline metabolism?

A

CYP1A2

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28
Q

What happens to RBF not when in labor in general?

A

Increase by 60-80%

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29
Q

Increase ________excretion of unchanged drugs

A

Renal

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30
Q

Most commonly administered medication and renal excretion implication?

A

Cephalosporin (Ancef most common); Because of increased renal excretion , may need more FREQUENT dosing

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31
Q

Activity of transport proteins is__________

A

Increased

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32
Q

Transporter proteins is_______and may contribute to what about digoxin?

A

Renal P-Glycoprotein; increase clearance of digoxin in pregnancy , may have to get level and increase dose

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33
Q

What about drugs that are metabolized by the liver?

A

They may require increase or decrease in dose depending on the METABOLIC PATHWAY

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34
Q

If a drugs is excreted unchanged by the kidney it often require what kind of dosage adjustments

A

Increase dose

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35
Q

Placental transfer in mainly via ____and favors movement of ________ drugs

A

Diffusion; Lipophillic

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36
Q

Fetal pH vs Maternal pH meaning?

A

Fetal pH lower than maternal pH ; weak bases become more ionized in the fetus. Limit transfer back across the placenta.

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37
Q

Ion trapping is irrelevant but fetal acidosis can

A

Significantly increase the fetal concentration of drugs such as local anesthetics. Trapped LA can lead to TOXIC buildup

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38
Q

Placenta have that type of enzymes

A

UGT enzyme that can catalyze phase II conjugation

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39
Q

Placenta acts as a mini ________ and you may need to ______dose

A

liver; increase

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40
Q

Why you may need to increase dosing due to placenta “mini” liver work ?

A

UGT enzymes in placenta doing work

UGT in liver doing work

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41
Q

Fetal circulation makes drug undergo

A

1st pass hepatic metabolism

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42
Q

Elimination of drugs by fetus mainly reliant on

A

Placental transfer

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43
Q

Fetus has minimal renal BF due to _____ until term pass into

A

Increase renal vascular resistance; Amniotic fluid to be swallowed.

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44
Q

Which hormone enhances sedation?

A

Progesterone

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45
Q

Endorphins during pregnancy

A

Enhanced anti-nociception ; less fentanyl or opioids or anesthetic requirements.

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46
Q

Inhalational Anesthesia changes : MAC____due to

A

MAC reduced by 30% during gestation ; progesterone

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47
Q

When does MAC return to normal

A

12-72 hours after delivery

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48
Q

Opioids on MAC

A

Decreases MAC so endorphins may also factor in.

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49
Q

What is MAC really measuring?

A

movement

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50
Q

CO and IV anesthetic dose

Changes in Pregnancy?

A

Increase CO = Increase in IV anesthetic dose to produce central effects.
8-18% decrease in dose requirements for IV anestheticvs

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51
Q

Local anesthesia changes

A

Increases spread of Neuraxial block

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52
Q

Epidural Blood volume is ________ = ________ capacity of epidrual space and ________volume of lumbar CSF

A

Increased; decreased; decreased

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53
Q

What happens to LA?

A

Increased Sensitivity to LA probably progesterone.

Decrease the dose of LA

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54
Q

CSF little bit + small volume

A

Increase effect

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55
Q

CSF little bit + Large volume

A

Decrease effect

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56
Q

Changes in anesthesia in threshold can be reproduced using

A

Exogeneous progesterone and Estrogen

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57
Q

Parts of brain appear to be involve are

A

Spinal cord Kappa and delta opioid receptors

Descending spinal alpha-2 noradrenergic pathways

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58
Q

How long does the analgesia changes last?

A

24-48 hours after delivery

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59
Q

2 alpha -2 agonist involves in pain reduction

A

Clonidine

Precedex.

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60
Q

Drugs that can cause harm to fetus during pregnancy are called

A

Teratogen

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61
Q

Teratogens are

A

substances that act to irreversibly alter growth, structure or function of the developing embryo,

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62
Q

Major malformations 3 types

A
  1. Incompatible w/ survival such as ancephaly
  2. Requires major surgical correction (cleft palage, CHD)
  3. Causes mental retardation
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63
Q

Minor malformations are the one that

A

Do not alter quality of life such as ear tags , extra digits

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64
Q

When possible , use

A

non-pharmacological techniques whenever possible

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65
Q

What are some exogenous causes of birth defects? (REDIM)

A

Radiation, infections, maternal metabolic disorders, Drugs, environmental chemicals

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66
Q

All or nothing exposure

A

Exposure in 1st 2 weeks of conception are all of nothing (no effect or spontaneous fetal loss)

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67
Q

What is the classic period of susceptibility during period of organogenesis?

A

2 1/2 to 8 weeks after conception

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68
Q

Giving Thalidomine
at _________ leads to _______
at _______leads to ______

A

35-37 days ; ear malformations

41 -44 days: AMELIA or PHOCOMELIA

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69
Q

After organogenesis, up to ____weeks, embryonic deveoopment mainly consist of _______

A

8; increase organ size.

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70
Q

What is the best time to do surgery if needed ?

A

2nd Trimester

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71
Q

Doing surgery during 1st trimester may lead to ______While doing in on 3rd trimester may lead to _______.

A

Spontaneous abortion

Go into labor

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72
Q

CNS development goes up to

A

16 weeks

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73
Q

Heart development goes up to

A

6 1/2 weeks

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74
Q

Upper limb development goes up to

A

7 weeks

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75
Q

When is the classic Teratogenic period

A

31 days to 71 days

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76
Q

After 8 weeks only

A

GROWTH is affected mainly

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77
Q

FDA pregnancy Category A

A

Controlled studies of pregnant women show no risk in 1st trimester

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78
Q

FDA pregnancy Category B

A

Animal studies show no risk, or animals show risk UNCONFIRMED In humans

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79
Q

FDA pregnancy Category C

A

Animal studies show risk, caution is advised, benefits may outweigh risks

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80
Q

FDA pregnancy Category D

A

Evidence of risk to human fetus, benefits may outweigh risks in serious conditions

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81
Q

FDA pregnancy Category X

A

Risks outweighs benefit

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82
Q

Remember all category drugs

A

in a speficic category do not all have the same risks

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83
Q

Aspiring has been associated with

A

Gastrochisis

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84
Q

Use of 1st trimester Aspirin can cause

A

increased risk of pregnancy loss

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85
Q

Use of 2nd trimester Aspirin can cause

A

Undescended TESTICULAR syndrome

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86
Q

AVOIDED In 3rd trimester due to significant fetal risk

A

NSAIDS

87
Q

NSAIDS in 3rd trimester is avoided and may cause

A

Renal injury –> Oligohydramnios and

Intrauterine constrictions of ductus arteriosus = Increased risk with advanved gestational age.

88
Q

Best to use during pregnancy

A

Tylenol

89
Q

Excessive ANTEPARTUM use of OPIOIDS lead to

A

Neonatal opioid withdrawal symptoms

90
Q

Maternal opioid treatment 30 days before conception and in ______associated with

A

and in 1st trimester associated with various cardiac birth defects, Spina Bifida and Gastrochisis

91
Q

Diazepam 1st trimester exposure

A

Increase risk for

  • cleft lip/palate
  • Neural defects
  • Intestinal atreasia
  • Limb defects VACTERL –TEF
92
Q

Perinatal use of diazepam associated with

A

Hypotonia
Hypothermia
Respiratory depression

93
Q

Avoid this benzo

A

Diazepam.

94
Q

Benzo should only be used in the

A

first trimester.

95
Q

Benzodiazepine classified as FDA category X

A

Temazepam

96
Q

Most common serious neurological problem during pregnancy

A

Epilepsy

97
Q

Anticonvulsants and placental

A

All anticonvulsant cross the placenta and each have their own syndrome

98
Q

Most common defect with anticonvulsants are

A

Cleft lip and palate

Congenital Heart defects

99
Q

Decrease in ______levels can be induced by anticonvulsants

A

Folate

100
Q

Fetal ANTICONVULSANT syndrome (think OCD)

A

Orofacial
CV’
Digital malformations

101
Q

Fetal HYDANTOIN syndrome S-FLEP

A 
Constellations of minor anomalies such as craniofacial anormalies and limb anormalies
Short noses
Flat nasal bridge 
Low seat ears
Eyes spread far apart 
Ptosis
102
Q

Phenytoin primary defect (HOU)

A

Heart defect -> Septum defects
Oralfacial clefts
Urogenital defects

103
Q

Action of phenytoin and factors

A

Competitive inhibitor of the placental transport of vitamin K; baby need more vitamin K,
Decrease fetal coagulation factors 2,7,9,10. AT RISK FOR BLEEDING

104
Q

Induce fetal hepatic metabolism of coagulation factors

A

Phenytoin

105
Q

Mnemonic PHEN

A

P: cleft PALATE and lip
H: small HEAD, HYPOPLASTIC face, Hirsutism, H. defefcts
E: Embryopathy, antiepileptics use
N: hypoplastic NAILS, digit and neuro deficits.

106
Q

Carbamazepine (tegretol ) associated with FIC

A

Fingernail Hypoplasia
Incidence of developmental delay
Craniofacial deficits

107
Q

Fetal CARBAMAZEPINE Syndrome resemble FHS (S-FLEP)

A

Fedal Hydantoin syndrome but SPECIFiCALLY associated with Spina Bifida

108
Q

This medication also alter coagulation factors

A

Phenobarbital

109
Q

Phenobarbital associated with (DOC)

A

Decreased intellectual and cognitive development in neonates and children
Orofacial clefting
Congenital Heart defects

110
Q

Maternal use of phenobarbital can result in

A

hemorrhagic disease of newborn and neonatal withdrawal symptoms after delivery.

111
Q

Fetal PHENOBARBITAL syndrome

A

Minor dysnorphic features similar to those seen in Fetal Hydantoin syndrome

112
Q

Valproic acid leads to (COCAH)

A 
Cardiac defects
Orofacial clefting
Craniosynostosis
Atrial septal defect
HYPOSPADIAS
113
Q

Fetal VALPROATE Syndrome (ED- FLUM-TTHH)

A 
Epicanthal folds
Downturn mouth
Flat nasal bridge
Low set ear
Upturned nasal tip
Microcephaly
Thin vermillion borders
Thin overlapping fingers and toes
Hyperconvex fingernails 
Hypertelorism
114
Q

rate of overall malformations?

A

6%

115
Q

Patient is taking Lamotrigine and the risk is same

A

As general population , counsel little information available

116
Q

TCAs associated with a _____risk for congenital malformations compared with other antidepressants

A

greater

117
Q

TCAs disadvantages.

A

Lots of SE, bad reaction with Ephedrine

118
Q

SSRIs

A

no higher risk for major malformations or developmental , risk vary per agent

119
Q

SSRIs are

A

Sertraline
Paroxetine
Fluroxetine
Citalopram

120
Q

Antidepressants causing the most defect

A

TCAs

121
Q

Sertraline associated with

A

Risk for septal defects

Omphalocele

122
Q

Citalopram associated with

A

Septal heart defects

123
Q

Paroxetine associated with

A

RV outflow obstruction

124
Q

Fluoxetine associated with (PAPPLS)

A 
Perinatal complications
Preterm delivery
Admistion to specail care unit 
poor neonatal adaptation
low mean BW
Shorter body length
125
Q

Late term use of SSRIs associated with

A

Persistant Pulmoary HTN of Newborn

126
Q

No reports of teratogenecity related use of inotropic agents (DDD)

A

Dopamine
Dobutamine
Digoxin

127
Q

Maternal administration of propanolol may result in

A

Modest fetal growth restriction

128
Q

Propranolol administration within 2 hours leads to

A

neonatal bradycardia

129
Q

Atenolol associated with

A

birth weight

Preterm delivery

130
Q

ACE inhibitors no teratogenicity

A

during 1st trimester

131
Q

Later in pregnancy, ACEI can

A

Fetal renal failure

Oligohydramnios which may result in fetal limb contractures, craniofacial and pulmonary hypoplasia

132
Q

This medication structurally similar to thyroxine and is 37% iodine by weight

A

Amiodarone

133
Q

Amiodarone is associated with (GAH)

A

Goiters
Abnormal neurodevelopments
Hypothyroidism

134
Q

Inhaled B2 agonists _____and _______ not been associated with congenital malformations.

A

Cromolyn sodium, corticosteroids.

135
Q

Preferred SABA

A

Albuterol

136
Q

Preferred LABA

A

Salmeterol

137
Q

Preferred to inhaled corticosteroids

A

Budesonide

138
Q

Severe persistent asthma may require______associated with

A

Systemic oral corticosteroids therapy; Low Bw and increase risk for cleft lip and palate

139
Q

2 methylxanthines drugs _____ and_____ Do they affect pregnancy

A

Theophylline and aminophylline; NO

140
Q

Theophilline and pregnancy

A

Protein binding and metabolism are both reduced in pregnancy

141
Q

Fetal WARFARIN Syndrome (NDSNMG)

A 
Nasal Hypoplasia
Depressed nasla
Stippled epiphyses
Nail hypoplasia, 
Mental retardation
Growth restriction
142
Q

For warfarin period of ___and _______ is especially critical

A

6-9 weeks

143
Q

2nd and 3rd trimester exposure of WARFARIN can cause

GBDM

A

microcephaly
blindness
deafness
Grow restriction

144
Q

Anticoagulant , does not cross the placenta

A

Heparin and LMWH

145
Q

Anticoagulant to avoid during pregnancy

A

LMWH

146
Q

Ondansetron is _______than promethazine

A

less sedating

147
Q

Agent use for refractory N/V

A

Methylprednisolone

148
Q

Use of _______ before ____weeks gestation associated with increase risk of cleft lip /palage

A

Glucocorticoids, 10 weeks

149
Q

Agent class with protective effect against malformation

A

Antihistamines

150
Q

Associated with pseudoephedrine and defect attributable to ________

A

Vascular disruption
Gastrochisis
Small intestinal atresia
Hemifacial and microsomia

151
Q

Leading cause of maternal mortality in GENERAL

A

Sepsis

152
Q

Should not be administered after 5th week of pregnancy

A

Tetracyclines, binds to developing enamel and cause discoloration of the teeth during 1st trimester

153
Q

Tetracyclines during 2nd trimester

A

Deposit in developing osseous sites and inhibit bone growth beginning in the 2nd trimester

154
Q

Should not be used in pregnancy or children are

A

Quinolones (ciprofloxain and norfloxacin) may cause ARTHRITIS

155
Q

Leading cause of maternal death in labor (outside of anesthesia)

A

Hemorrhage

156
Q

Leading cause of maternal death with ANESTHESIA

A

Airway issues

157
Q

Generally appropriate to administer

A

Vaccine during pregnancy.

158
Q

NO risk with

A

Inactivated virus or bacterial vaccines or toxoids

159
Q

Contraindicated vaccines are

A

Varicella, MMR, TB or BCG

160
Q

Influenza vaccine should be

A

Inactivated virus

161
Q

Caffeine intake

A

less than 200mg not associated with increase risk of miscarriage

162
Q

No more than ____cup of coffee recommended

A

1

163
Q

Highly teratogenic drugs are

A

2 simultaneously forms of reliable contraception are recommended or required during treatment of either partners sometimes to be continued for months or years after stopping the drug.

164
Q

Highly Teratogenic drugs are

A

Thalidomide
Ribavirin
Isotretinoin —ACUTANE use for acns
Acitrecin

165
Q

Highly Teratogenic drugs : Use for erythemia nodoum leprosum and multiple myeloma

A

Thalidomide

166
Q

Highly Teratogenic drugs Used for hepatitis C and viral hemorrhagic fevers

A

Ribavirin

167
Q

Highly Teratogenic drugs: Used for severe psoriasis

A

Acitrecin

168
Q

Best advice for drug use is important

A

prevent unneccessary stopping breastfeeding or discontinuing appropriate drug treatment

169
Q

Strongly contraindicated during breastfeeding

A

Cytotoxic and immunosuppressive (cyclophosphamide, methotrexate)

170
Q

Mothers with BF infants with this disorder should avoid many drugs

A

Glucose-6-phosphat4e dehydrogenase *G6PD deficiency

171
Q

Mothers with BF with G6PD should avoid (BNQ)

A

Sulfanamides (including combination of sulfamethaxazole and trimethopim *bactrim, Nitrofurantoin and primaquine
they are not broken down correctly

172
Q

Drugs that increase secretion of prolactin : increases milk production
DPH MD SRM

A 
Dopamine agonists such as
Phenothizines
Haloperidol
Metoclopramide
Domperidone
Sulpride
Risperidone
Methyldopa
173
Q

Drugs that decrease secretion of prolactin:

DED BCLQ

A 
Diuretics
Estrogen
Dopamine agonists such as
Bromiciptine
Cabergoline
Lisuride
Quinagolide
174
Q

Women who smoke have

A

Lower milk production

175
Q

As general rule: Dopamine Agonist ______prolactin and dopamine antagonists _____Prolactin

A

Less

more

176
Q

Drugs transfer to breast milk is via

A

passive diffusion

177
Q

Rate of passive transfer into breast milk depends on

A

lipid solubility
molecular weight
degree of ionization
protein binding

178
Q

What kind of drugs are often not detectable in infants

A

More than 85% maternal protein binding

179
Q

Readily transferred to breast milk

A

Ethanol

180
Q

The amount of a drug in breast milk is a variable fraction of

A

Maternal blood concentration which is proportional to the maternal dose.

181
Q

Lactation is not fully

A

Established during the first several days

182
Q

During the first several days postpartum

A

Neonates receives a small volume of colostrum and little drug is excreted through milk at this time. Only a small amount of drugs administered after delivery would reach the neonate.

183
Q

During few days postpartum neonatal

A

metabolism and elimination are poorly developed

184
Q

Several days of maternal opioid analgeasia with drugs such as

A

Meperidine

and codine may results in neonatal accumulation and side effects.

185
Q

May give drugs

A

In PACU in the immediate postpartum

186
Q

AS a general rule if a drug has been acceptable during pregnancy,

A

it is reasonable to continue it during breastfeeding unless there are drug specific factors to the contrary

187
Q

This drugs may eventually lead to drug accumulation in infants and adverse effects

A

Lamictal

188
Q

2 things to avoid in general in terms of medications and breast feeding

A

Medications should be taken after breast feeding

Long acting preparations should be avoided

189
Q

NSAIDS and breastfeed____ except

A

no effects EXCEPT for ASPIRIN

190
Q

FDA and Ketorolac

A

Black box warning contraindicated in nursing mothers because of the potential adverse effects of prostaglandin inhibiting drugs on neonates. MAY REOPEN SHUNT

191
Q

% of ultrametabolizers

A

1-28%

192
Q

Normal maternal dose of those drugs no obvious adverse effects

A

Codeine
Tramadol
Morphine
Meperidine (significant neurobehavioral depression by the 3rd day)

193
Q

Infants of BF mothers taking codeine

A

may have CNS depression because CYP2D6 ultra rapid metabolization to morphine leading to high concentration in breast milk. ONLY with CODEINE

194
Q

Opiod not associated with issue with

A

oxycodone

195
Q

Sedative used during lactation, should be _____acting (LOMA)

A 
Short acting 
Lorazepam
oxazepam
midazolam
Alprazolam
196
Q

Drugs use during lactation safe anticonvulsants are

A

Carbamazepine

Valproic acid

197
Q

Drugs use during lactation CONTRAINDICATED anticonvulsants are

A

Lamotrigine (Lamicatal)

198
Q

Drugs use during lactation safe antidepressants are

A

Sertraline

Paroxetine

199
Q

Drug use during lactation UNsafe antidepressants are

A

Fluoxetine (long half life)

200
Q

Drugs use during lactation CONTRAINDICATED Cardiovascular meds are

A

Amiodarone –> unpredictable, iodine release from its metabolism may cause HYPOTHYROIDISM
Long half life

201
Q

Beta blockers ________more likely to accumulate in neonate

A

Renally excreted

202
Q

Atenolol with breast feeding

A

Neonatal cyanosis

Bradycardia

203
Q

Drugs use during lactation SAFE Cardiovascular meds are

A

ACEI and antihypertensives

204
Q

Statins and lactating mother

A

Not recommended during BF because may disrupt infant lipid metabolism

205
Q

Although protein binding of digoxin limit infant drug exposure

A

liver disease can lead to decrease in protein binding leading to infant exposure

206
Q

Safe respiratory drugs

A

Salbutamol, Terbutaline and Salmeterol inhalers

207
Q

Prednisone and lactation

A

Even at high dose of 80mg/day less than 10% transfr so its safe

208
Q

Safe anticoagulation during lactation

A

Warfarin (98% bound) and heparin

209
Q

Antiinfective drugs and lactation

A

Sulfanamides displace bilirubin from albumin

best avoided during 1st 5 days of life or in premies with HYPERALBUMINEMIA

210
Q

Breast feeding 2 contraindicated vaccines are

A

Yellow fever

Smallpox

211
Q

Tetracyclines and breastfeeding

A

Avoid due to tooth staining and delayed bone growth

212
Q

Nursing mothers should limit their intake to a moderate level of

A

2-3 cups a day

213
Q

Breast milk will only contain what percentage of caffeine?

A

1%

214
Q

Recommended caffeine dose is

A

200mg

SNRAObPedGer (25 decks)

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