Pharmacology Preg+Lactation Flashcards
1
Q
Polymorphisms of CYP450 Isoenzyme is an altered ________ results in _______
A
CYP2D6, ultra rapid metabolization
2
Q
Codeine is broken down into
A
Greater quantities of morphine than normal
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
4
Q
For the mother, what changes occur to B2 receptor?
A
Changes at B2 adrenergic receptor , alter tocolysis, require less ephedrine
5
Q
Physiological changes during pregnancy including changes in ____, _____, _______ affect AUDME
A
CV, resp, hemodynamics
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
7
Q
What happens to uptake on IA during pregnancy ?
A
Increase MV and Decrease FRC Increase pulmonary uptake
8
Q
An increase in CO during pregnancy leads to
A
Distribution of drug to all tissues.
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 .
10
Q
When there is an increase peripheral perfusion?
A
There in an increase of return of drug during elimination phase.
11
Q
Hydrophyillic drugs such as _______-have a ___vd
A
NMB; small
12
Q
What happens to plasma albumin concentration ?
A
Decreased by 30%
13
Q
As far as protein concentration, it only affect
A
Highly protein bound drugs
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.
15
Q
What happens to TBW with pregnancy? Significance?
A
Increase on average by 8L ; Affect distribution
16
Q
What happens to intravascular plasma?
A
Increase by 40%
17
Q
The ECF gain in pregnancy depends on
A
Weight gain and edema
18
Q
Not clear if this is increased despite increase in CO
A
Hepatic blood flow
19
Q
Recommended Caffeine amount and why?
A
Because of Decrease enzyme activity
20
Q
CYP450 IsoEnzymes activities that are increased are
A
CYP 34A, CYP2D6, CYP2C9
UGT
21
Q
UGT enzymes that are induced are
A
UGT1A4 and UGT2B7
22
Q
The enzyme affecting phenytoin and how?
A
Enzyme CYP2C9 induces phenytoin and increase it metabolism
23
Q
The enzyme affecting midazolam and how?
A
Enzyme CYP3A4 induces midazolam and increase it metabolism
24
Q
The enzyme affecting morphine and how?
A
Enzyme UGT2B7 induces morphine and increase it metabolism
25
CYP450 IsoEnzymes activities that are Decreased are
CYP1A2 and CYP2C19
26
Enzyme responsible for Codeine and Morphine ________ and it it increased or decreased?
CYP2D6; Increased
27
Which enzyme activity reduces caffeine and theophyiline metabolism?
CYP1A2
28
What happens to RBF not when in labor in general?
Increase by 60-80%
29
Increase ________excretion of unchanged drugs
Renal
30
Most commonly administered medication and renal excretion implication?
Cephalosporin (Ancef most common); Because of increased renal excretion , may need more FREQUENT dosing
31
Activity of transport proteins is__________
Increased
32
Transporter proteins is_______and may contribute to what about digoxin?
Renal P-Glycoprotein; increase clearance of digoxin in pregnancy , may have to get level and increase dose
33
What about drugs that are metabolized by the liver?
They may require increase or decrease in dose depending on the METABOLIC PATHWAY
34
If a drugs is excreted unchanged by the kidney it often require what kind of dosage adjustments
Increase dose
35
Placental transfer in mainly via ____and favors movement of ________ drugs
Diffusion; Lipophillic
36
Fetal pH vs Maternal pH meaning?
Fetal pH lower than maternal pH ; weak bases become more ionized in the fetus. Limit transfer back across the placenta.
37
Ion trapping is irrelevant but fetal acidosis can
Significantly increase the fetal concentration of drugs such as local anesthetics. Trapped LA can lead to TOXIC buildup
38
Placenta have that type of enzymes
UGT enzyme that can catalyze phase II conjugation
39
Placenta acts as a mini ________ and you may need to ______dose
liver; increase
40
Why you may need to increase dosing due to placenta "mini" liver work ?
UGT enzymes in placenta doing work
| UGT in liver doing work
41
Fetal circulation makes drug undergo
1st pass hepatic metabolism
42
Elimination of drugs by fetus mainly reliant on
Placental transfer
43
Fetus has minimal renal BF due to _____ until term pass into
Increase renal vascular resistance; Amniotic fluid to be swallowed.
44
Which hormone enhances sedation?
Progesterone
45
Endorphins during pregnancy
Enhanced anti-nociception ; less fentanyl or opioids or anesthetic requirements.
46
Inhalational Anesthesia changes : MAC____due to
MAC reduced by 30% during gestation ; progesterone
47
When does MAC return to normal
12-72 hours after delivery
48
Opioids on MAC
Decreases MAC so endorphins may also factor in.
49
What is MAC really measuring?
movement
50
CO and IV anesthetic dose
| Changes in Pregnancy?
Increase CO = Increase in IV anesthetic dose to produce central effects.
8-18% decrease in dose requirements for IV anestheticvs
51
Local anesthesia changes
Increases spread of Neuraxial block
52
Epidural Blood volume is ________ = ________ capacity of epidrual space and ________volume of lumbar CSF
Increased; decreased; decreased
53
What happens to LA?
Increased Sensitivity to LA probably progesterone.
| Decrease the dose of LA
54
CSF little bit + small volume
Increase effect
55
CSF little bit + Large volume
Decrease effect
56
Changes in anesthesia in threshold can be reproduced using
Exogeneous progesterone and Estrogen
57
Parts of brain appear to be involve are
Spinal cord Kappa and delta opioid receptors
| Descending spinal alpha-2 noradrenergic pathways
58
How long does the analgesia changes last?
24-48 hours after delivery
59
2 alpha -2 agonist involves in pain reduction
Clonidine
| Precedex.
60
Drugs that can cause harm to fetus during pregnancy are called
Teratogen
61
Teratogens are
substances that act to irreversibly alter growth, structure or function of the developing embryo,
62
Major malformations 3 types
1. Incompatible w/ survival such as ancephaly
2. Requires major surgical correction (cleft palage, CHD)
3. Causes mental retardation
63
Minor malformations are the one that
Do not alter quality of life such as ear tags , extra digits
64
When possible , use
non-pharmacological techniques whenever possible
65
What are some exogenous causes of birth defects? (REDIM)
Radiation, infections, maternal metabolic disorders, Drugs, environmental chemicals
66
All or nothing exposure
Exposure in 1st 2 weeks of conception are all of nothing (no effect or spontaneous fetal loss)
67
What is the classic period of susceptibility during period of organogenesis?
2 1/2 to 8 weeks after conception
68
Giving Thalidomine
at _________ leads to _______
at _______leads to ______
35-37 days ; ear malformations
| 41 -44 days: AMELIA or PHOCOMELIA
69
After organogenesis, up to ____weeks, embryonic deveoopment mainly consist of _______
8; increase organ size.
70
What is the best time to do surgery if needed ?
2nd Trimester
71
Doing surgery during 1st trimester may lead to ______While doing in on 3rd trimester may lead to _______.
Spontaneous abortion
| Go into labor
72
CNS development goes up to
16 weeks
73
Heart development goes up to
6 1/2 weeks
74
Upper limb development goes up to
7 weeks
75
When is the classic Teratogenic period
31 days to 71 days
76
After 8 weeks only
GROWTH is affected mainly
77
FDA pregnancy Category A
Controlled studies of pregnant women show no risk in 1st trimester
78
FDA pregnancy Category B
Animal studies show no risk, or animals show risk UNCONFIRMED In humans
79
FDA pregnancy Category C
Animal studies show risk, caution is advised, benefits may outweigh risks
80
FDA pregnancy Category D
Evidence of risk to human fetus, benefits may outweigh risks in serious conditions
81
FDA pregnancy Category X
Risks outweighs benefit
82
Remember all category drugs
in a speficic category do not all have the same risks
83
Aspiring has been associated with
Gastrochisis
84
Use of 1st trimester Aspirin can cause
increased risk of pregnancy loss
85
Use of 2nd trimester Aspirin can cause
Undescended TESTICULAR syndrome
86
AVOIDED In 3rd trimester due to significant fetal risk
NSAIDS
87
NSAIDS in 3rd trimester is avoided and may cause
Renal injury --> Oligohydramnios and
| Intrauterine constrictions of ductus arteriosus = Increased risk with advanved gestational age.
88
Best to use during pregnancy
Tylenol
89
Excessive ANTEPARTUM use of OPIOIDS lead to
Neonatal opioid withdrawal symptoms
90
Maternal opioid treatment 30 days before conception and in ______associated with
and in 1st trimester associated with various cardiac birth defects, Spina Bifida and Gastrochisis
91
Diazepam 1st trimester exposure
Increase risk for
- cleft lip/palate
- Neural defects
- Intestinal atreasia
- Limb defects VACTERL --TEF
92
Perinatal use of diazepam associated with
Hypotonia
Hypothermia
Respiratory depression
93
Avoid this benzo
Diazepam.
94
Benzo should only be used in the
first trimester.
95
Benzodiazepine classified as FDA category X
Temazepam
96
Most common serious neurological problem during pregnancy
Epilepsy
97
Anticonvulsants and placental
All anticonvulsant cross the placenta and each have their own syndrome
98
Most common defect with anticonvulsants are
Cleft lip and palate
| Congenital Heart defects
99
Decrease in ______levels can be induced by anticonvulsants
Folate
100
Fetal ANTICONVULSANT syndrome (think OCD)
Orofacial
CV'
Digital malformations
101
Fetal HYDANTOIN syndrome S-FLEP
```
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
Phenytoin primary defect (HOU)
Heart defect -> Septum defects
Oralfacial clefts
Urogenital defects
103
Action of phenytoin and factors
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
Induce fetal hepatic metabolism of coagulation factors
Phenytoin
105
Mnemonic PHEN
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
Carbamazepine (tegretol ) associated with FIC
Fingernail Hypoplasia
Incidence of developmental delay
Craniofacial deficits
107
Fetal CARBAMAZEPINE Syndrome resemble FHS (S-FLEP)
Fedal Hydantoin syndrome but SPECIFiCALLY associated with Spina Bifida
108
This medication also alter coagulation factors
Phenobarbital
109
Phenobarbital associated with (DOC)
Decreased intellectual and cognitive development in neonates and children
Orofacial clefting
Congenital Heart defects
110
Maternal use of phenobarbital can result in
hemorrhagic disease of newborn and neonatal withdrawal symptoms after delivery.
111
Fetal PHENOBARBITAL syndrome
Minor dysnorphic features similar to those seen in Fetal Hydantoin syndrome
112
Valproic acid leads to (COCAH)
```
Cardiac defects
Orofacial clefting
Craniosynostosis
Atrial septal defect
HYPOSPADIAS
```
113
Fetal VALPROATE Syndrome (ED- FLUM-TTHH)
```
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
rate of overall malformations?
6%
115
Patient is taking Lamotrigine and the risk is same
As general population , counsel little information available
116
TCAs associated with a _____risk for congenital malformations compared with other antidepressants
greater
117
TCAs disadvantages.
Lots of SE, bad reaction with Ephedrine
118
SSRIs
no higher risk for major malformations or developmental , risk vary per agent
119
SSRIs are
Sertraline
Paroxetine
Fluroxetine
Citalopram
120
Antidepressants causing the most defect
TCAs
121
Sertraline associated with
Risk for septal defects
| Omphalocele
122
Citalopram associated with
Septal heart defects
123
Paroxetine associated with
RV outflow obstruction
124
Fluoxetine associated with (PAPPLS)
```
Perinatal complications
Preterm delivery
Admistion to specail care unit
poor neonatal adaptation
low mean BW
Shorter body length
```
125
Late term use of SSRIs associated with
Persistant Pulmoary HTN of Newborn
126
No reports of teratogenecity related use of inotropic agents (DDD)
Dopamine
Dobutamine
Digoxin
127
Maternal administration of propanolol may result in
Modest fetal growth restriction
128
Propranolol administration within 2 hours leads to
neonatal bradycardia
129
Atenolol associated with
birth weight
| Preterm delivery
130
ACE inhibitors no teratogenicity
during 1st trimester
131
Later in pregnancy, ACEI can
Fetal renal failure
| Oligohydramnios which may result in fetal limb contractures, craniofacial and pulmonary hypoplasia
132
This medication structurally similar to thyroxine and is 37% iodine by weight
Amiodarone
133
Amiodarone is associated with (GAH)
Goiters
Abnormal neurodevelopments
Hypothyroidism
134
Inhaled B2 agonists _____and _______ not been associated with congenital malformations.
Cromolyn sodium, corticosteroids.
135
Preferred SABA
Albuterol
136
Preferred LABA
Salmeterol
137
Preferred to inhaled corticosteroids
Budesonide
138
Severe persistent asthma may require______associated with
Systemic oral corticosteroids therapy; Low Bw and increase risk for cleft lip and palate
139
2 methylxanthines drugs _____ and_____ Do they affect pregnancy
Theophylline and aminophylline; NO
140
Theophilline and pregnancy
Protein binding and metabolism are both reduced in pregnancy
141
Fetal WARFARIN Syndrome (NDSNMG)
```
Nasal Hypoplasia
Depressed nasla
Stippled epiphyses
Nail hypoplasia,
Mental retardation
Growth restriction
```
142
For warfarin period of ___and _______ is especially critical
6-9 weeks
143
2nd and 3rd trimester exposure of WARFARIN can cause
| GBDM
microcephaly
blindness
deafness
Grow restriction
144
Anticoagulant , does not cross the placenta
Heparin and LMWH
145
Anticoagulant to avoid during pregnancy
LMWH
146
Ondansetron is _______than promethazine
less sedating
147
Agent use for refractory N/V
Methylprednisolone
148
Use of _______ before ____weeks gestation associated with increase risk of cleft lip /palage
Glucocorticoids, 10 weeks
149
Agent class with protective effect against malformation
Antihistamines
150
Associated with pseudoephedrine and defect attributable to ________
Vascular disruption
Gastrochisis
Small intestinal atresia
Hemifacial and microsomia
151
Leading cause of maternal mortality in GENERAL
Sepsis
152
Should not be administered after 5th week of pregnancy
Tetracyclines, binds to developing enamel and cause discoloration of the teeth during 1st trimester
153
Tetracyclines during 2nd trimester
Deposit in developing osseous sites and inhibit bone growth beginning in the 2nd trimester
154
Should not be used in pregnancy or children are
Quinolones (ciprofloxain and norfloxacin) may cause ARTHRITIS
155
Leading cause of maternal death in labor (outside of anesthesia)
Hemorrhage
156
Leading cause of maternal death with ANESTHESIA
Airway issues
157
Generally appropriate to administer
Vaccine during pregnancy.
158
NO risk with
Inactivated virus or bacterial vaccines or toxoids
159
Contraindicated vaccines are
Varicella, MMR, TB or BCG
160
Influenza vaccine should be
Inactivated virus
161
Caffeine intake
less than 200mg not associated with increase risk of miscarriage
162
No more than ____cup of coffee recommended
1
163
Highly teratogenic drugs are
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
Highly Teratogenic drugs are
Thalidomide
Ribavirin
Isotretinoin ---ACUTANE use for acns
Acitrecin
165
Highly Teratogenic drugs : Use for erythemia nodoum leprosum and multiple myeloma
Thalidomide
166
Highly Teratogenic drugs Used for hepatitis C and viral hemorrhagic fevers
Ribavirin
167
Highly Teratogenic drugs: Used for severe psoriasis
Acitrecin
168
Best advice for drug use is important
prevent unneccessary stopping breastfeeding or discontinuing appropriate drug treatment
169
Strongly contraindicated during breastfeeding
Cytotoxic and immunosuppressive (cyclophosphamide, methotrexate)
170
Mothers with BF infants with this disorder should avoid many drugs
Glucose-6-phosphat4e dehydrogenase *G6PD deficiency
171
Mothers with BF with G6PD should avoid (BNQ)
Sulfanamides (including combination of sulfamethaxazole and trimethopim *bactrim, Nitrofurantoin and primaquine
they are not broken down correctly
172
Drugs that increase secretion of prolactin : increases milk production
DPH MD SRM
```
Dopamine agonists such as
Phenothizines
Haloperidol
Metoclopramide
Domperidone
Sulpride
Risperidone
Methyldopa
```
173
Drugs that decrease secretion of prolactin:
| DED BCLQ
```
Diuretics
Estrogen
Dopamine agonists such as
Bromiciptine
Cabergoline
Lisuride
Quinagolide
```
174
Women who smoke have
Lower milk production
175
As general rule: Dopamine Agonist ______prolactin and dopamine antagonists _____Prolactin
Less
| more
176
Drugs transfer to breast milk is via
passive diffusion
177
Rate of passive transfer into breast milk depends on
lipid solubility
molecular weight
degree of ionization
protein binding
178
What kind of drugs are often not detectable in infants
More than 85% maternal protein binding
179
Readily transferred to breast milk
Ethanol
180
The amount of a drug in breast milk is a variable fraction of
Maternal blood concentration which is proportional to the maternal dose.
181
Lactation is not fully
Established during the first several days
182
During the first several days postpartum
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
During few days postpartum neonatal
metabolism and elimination are poorly developed
184
Several days of maternal opioid analgeasia with drugs such as
Meperidine
| and codine may results in neonatal accumulation and side effects.
185
May give drugs
In PACU in the immediate postpartum
186
AS a general rule if a drug has been acceptable during pregnancy,
it is reasonable to continue it during breastfeeding unless there are drug specific factors to the contrary
187
This drugs may eventually lead to drug accumulation in infants and adverse effects
Lamictal
188
2 things to avoid in general in terms of medications and breast feeding
Medications should be taken after breast feeding
| Long acting preparations should be avoided
189
NSAIDS and breastfeed____ except
no effects EXCEPT for ASPIRIN
190
FDA and Ketorolac
Black box warning contraindicated in nursing mothers because of the potential adverse effects of prostaglandin inhibiting drugs on neonates. MAY REOPEN SHUNT
191
% of ultrametabolizers
1-28%
192
Normal maternal dose of those drugs no obvious adverse effects
Codeine
Tramadol
Morphine
Meperidine (significant neurobehavioral depression by the 3rd day)
193
Infants of BF mothers taking codeine
may have CNS depression because CYP2D6 ultra rapid metabolization to morphine leading to high concentration in breast milk. ONLY with CODEINE
194
Opiod not associated with issue with
oxycodone
195
Sedative used during lactation, should be _____acting (LOMA)
```
Short acting
Lorazepam
oxazepam
midazolam
Alprazolam
```
196
Drugs use during lactation safe anticonvulsants are
Carbamazepine
| Valproic acid
197
Drugs use during lactation CONTRAINDICATED anticonvulsants are
Lamotrigine (Lamicatal)
198
Drugs use during lactation safe antidepressants are
Sertraline
| Paroxetine
199
Drug use during lactation UNsafe antidepressants are
Fluoxetine (long half life)
200
Drugs use during lactation CONTRAINDICATED Cardiovascular meds are
Amiodarone --> unpredictable, iodine release from its metabolism may cause HYPOTHYROIDISM
Long half life
201
Beta blockers ________more likely to accumulate in neonate
Renally excreted
202
Atenolol with breast feeding
Neonatal cyanosis
| Bradycardia
203
Drugs use during lactation SAFE Cardiovascular meds are
ACEI and antihypertensives
204
Statins and lactating mother
Not recommended during BF because may disrupt infant lipid metabolism
205
Although protein binding of digoxin limit infant drug exposure
liver disease can lead to decrease in protein binding leading to infant exposure
206
Safe respiratory drugs
Salbutamol, Terbutaline and Salmeterol inhalers
207
Prednisone and lactation
Even at high dose of 80mg/day less than 10% transfr so its safe
208
Safe anticoagulation during lactation
Warfarin (98% bound) and heparin
209
Antiinfective drugs and lactation
Sulfanamides displace bilirubin from albumin
| best avoided during 1st 5 days of life or in premies with HYPERALBUMINEMIA
210
Breast feeding 2 contraindicated vaccines are
Yellow fever
| Smallpox
211
Tetracyclines and breastfeeding
Avoid due to tooth staining and delayed bone growth
212
Nursing mothers should limit their intake to a moderate level of
2-3 cups a day
213
Breast milk will only contain what percentage of caffeine?
1%
214
Recommended caffeine dose is
200mg
