Drug Categories, Placental Transfer Flashcards
(107 cards)
1
Q
Category A
A
No risk and find no evidence of harm
2
Q
Category B
A
Animal studies show no risks but there are no controlled studies on pregnant women
3
Q
Category C
A
Animal studies have shown risk but no human studies
4
Q
Category D
A
Positive evidence of potential for fetal risk
-in life threatening situation might use
5
Q
Category X
A
Contraindicated in pregnancy
6
Q
How many commonly used drugs are known as teratogens?
A
20-30
7
Q
What percentage of medications in the physician desk reference are category X?
A
7%
8
Q
When a new medication becomes available, what category is it automatically placed in (even w/o any studies)?
A
Category C
9
Q
Common anesthetic drug categories: Propofol Versed Lidocaine Fentanyl Morphine Succinylcholine
A
Propofol : B Versed: D Lidocaine : B Fentanyl : C Morphine : C Succinylcholine: C
10
Q
Only doses of Succinylcholine above what causes problems?
A
300mg
11
Q
Induction agent drug categories: Etomidate Ketamine Methohexital Propofol Thiopental
A
Etomidate: C Ketamine: B Methohexital: B Propofol: B Thiopental: C
12
Q
Inhaled anesthetic agent drug categories: Desflurane Halothane Isoflurane Sevoflurane
A
Desflurane : B
Halothane : C
Isoflurane : C
Sevoflurane : B
13
Q
Local anesthetic drug categories: 2-Chloroprocaine Bupivacaine Lidocaine Ropivacaine Tetracaine
A
2-Chloroprocaine: C Bupivacaine: C Lidocaine: B Ropivacaine: B Tetracaine: B
14
Q
Opioid drug categories: Alfentanil Fentanyl Sufentanil Meperidine Morphine
A
Alfentanil: C Fentanyl: C Sufentanil: C Meperidine: C Morphine: C
15
Q
Which opioid is the best choice in pregnancy? Why?
A
Sufentanil
- highly lipid soluble
- more rapid uptake by CNS, so less absorption in maternal and umbilical veins
16
Q
Doses of fentanyl below what are usually not an issue?
A
< 1mcg/kg
17
Q
What trimester is fentanyl usually avoided?
A
First
18
Q
Which opioids cross the placenta?
A
All of them
19
Q
Which opioids cross the placental barrier very easily?
A
Meperidine and Morphine
20
Q
Which LA is metabolized so quickly in fetal blood that even with acidosis there is no substantial exposure or ion trapping?
A
2-Chloroprocaine
21
Q
What is the downside to using 2-Chloroprocaine?
A
Doesn’t last long
22
Q
What purpose does the placenta serve?
A
Brings maternal and fetal circulations into close apposition, without substantial interchange of maternal and fetal blood
-for transfer of gases, nutrients, and wastes
23
Q
Uterine arteries divide into?
A
Spiral arteries
24
Q
What spurts blood into the intervillous space?
A
Spiral arteries
25
What are the microscopic tissue layers that separate the fetal and maternal blood?
Fetal Trophoblast
Fetal Connective Tissue
Endothelium of fetal capillaries
26
Why are the tissues that separate the fetal and maternal blood so thin?
To allow easy transfer
27
What is the intervillous space?
Essentially a huge blood sinus
28
What are the 2 sides of the intervillous space, and which side is which?
Chorionic plate: fetal side
| Basal plate: maternal side
29
The intervillous space is divided into what?
Compartments called lobules
30
How much maternal blood can the intervillous space accommodate?
~350mL
31
How does maternal blood enter and drain from the intervillous space?
Enters via spiral arteries
| Drains via decidual veins
32
The umbilical cord contains how many arteries and how many veins?
2 umbilical arteries and 1 umbilical vein
33
Umbilical arteries flow in what direction
Umbilical arteries carry deoxygenated nutrient-depleted blood from the fetus to the placenta
34
What is carried and in what direction in the umbilical vein?
Carries nutrient-rich and waste-poor blood to the fetus
35
What hormones/substances does the placenta produce?
```
Estrogen
Progesterone
Proteins
Enzymes
Polypeptide hormones
```
36
List the transport mechanisms that transport substances across the placenta:
```
Passive transport
Facilitated transport
Active transport
Pinocytosis
Bulk flow
Breaks
```
37
What is passive transport?
Diffusion
- no energy required
- depends on concentration gradients
- O2, CO2, Fatty acids, smaller ions (Na and Cl)
- molecular weights less than 600 Da
38
What is facilitated transport?
Facilitated diffusion
- carrier mediated transport
- relatively lipid-insoluble molecules
- still travel down concentration gradients
- Glu, other carbs
39
What is active transport?
Requires cellular energy
Involves carrier molecules
Substances can move against concentration gradients
Amino acids, water-soluble vitamins, larger ions (Ca, Fe)
40
What are the 2 types of active transport?
Primary and Secondary
41
What is primary active transport?
Movement occurs against concentration gradient
Uses special protein carrier
Uses energy derived from ATP
42
What is secondary active transport?
One substance moving down its concentration gradient acts as a carrier for a substance moving against its concentration gradient
- sodium is usually the carrier
- amino acids usually the molecule being carried
43
What is pinocytosis?
Involves molecules being enclosed in small vesicles that travel through the cell membrane
Requires energy
Ex: immunoglobulins
44
What is bulk flow?
Passage of substances resulting from a hydrostatic or osmotic gradient
Ex: water movement between mother and fetus
45
What is breaks?
Breaks in the villi can allow fetal tissue to enter the intervillous space and transfuse into the mother’s circulation
-erythroblastosis fetalis
46
What is erythroblastosis fetalis?
When the fetal Rh+ red cells enter the vascular system of the Rh- mother
47
What medication prevents erythroblastosis fetalis reaction?
Rhogan
48
Factors that affect rate of diffusion across the placenta
Concentration gradient
Area of the placenta
Permeability of placental membrane
49
Factors that affect the concentration gradient
Concentration in maternal arterial blood
Concentration in fetal arterial blood
Maternal intervillous blood flow
Fetal-placental blood flow
Diffusing capacity of placenta
Ratio of maternal to fetal blood flow in exchanging areas
Binding of substances to molecules and dissociation rates
50
Most of our anesthetic drugs are passed how?
Passive Diffusion
51
What are the determinants of permeability?
```
Molecular size
Lipid solubility
Electrical charge
-charged molecules do not cross easily
-Succs is charged
```
52
Which side typically has more protein (for protein binding drugs)?
Maternal side
53
What is the dividing line between substances that cross easily and substances that don’t?
1000 daltons
| Ex: heparin is >6000 so it will not cross; Coumadin is 330 daltons
54
What crosses the placenta more easily lipid soluble or lipid insoluble substances?
Lipid soluble cross more rapidly
55
What is the Bohr effect?
Describes hemoglobins oxygen binding affinity is inversely related to both acidity and the concentration of CO2
56
How is oxygen transport affected by the Bohr effect in pregnancy?
HGB dissociation curve shifts to the right with rise in H+
- fetal to maternal transfer of CO2 makes mom more acidotic and fetus more alkalotic
- this acidotic shift in mom liberates more O2 from mom
57
What is the oxyhemoglobin dissociation curve shift in mother and fetus?
Mom: right shift
Fetus: left shift
58
Factors that affect drug transfer across the placenta
```
Lipid solubility
Protein binding
pKa/pH
Blood flow
Molecular weight
Ionization
```
59
If fetus becomes acidotic, what happens with drug transfer?
Drug transfer enhances and ion trapping can occur
60
Most of the time, drugs pKa that are closer to physiologic pH have what affect on ionization and onset?
They will be less ionized and have a faster onset
61
pKa of LA:
Procaine
2-Chloroprocaine
Tetracaine
Procaine: 8.9
2-Chloroprocaine: 8.7
Tetracaine: 8.5
62
```
pKa of LA:
Lidocaine
Bupivacaine
Ropivacaine
Mepivacaine
```
Lidocaine: 7.8
Bupivacaine: 8.1
Ropivacaine: 8.1
Mepivacaine: 7.6
63
2-Chloropraine has a pKa of what? But why is it unique?
8.7
| It’s onset is rapid due to the high dosage requirement
64
What anticholinergics cross?
Atropine
| Scopolamine
65
What antihypertensives cross?
Beta blockers
Nitroprusside
NTG
66
What benzodiazepines cross?
Diazepam
| Midazolam
67
What inducation agents cross?
Propofol
Thiopental
Ketamine
68
What inhalation agents cross?
All
69
What LAs cross?
All but 2-chloroprocaine
70
What opioids cross?
All
71
What anticoagulants cross?
Warfarin
72
What vassopressors cross?
Ephedrine
73
What anticholinergics do not cross?
Glycopyrrolate
74
What anticoagulants don’t cross?
Heparin
75
What NMB don’t cross?
All of them
76
What anticholinesterase agents cross?
Neostigmine
Pyridostigmine
Edrophonium
77
Which vassopressor causes a greater placental arterial pressure?
Ephedrine
78
Due to the beta adrenergic effects of ephedrine (at higher doses) on the fetus what is seen in umbilical cord blood?
```
Lower fetal pH
Lower base excess
High PCO2
Glucose
Lactate
Epinephrine
Norepinephrine
```
79
Ephedrine in less than how many mg, is considered ok?
< 30mg
80
Beta blockers are associated with?
```
2x fetal growth restriction
Perinatal mortality
Neonatal bradycardia
Hypoglycemia
Respiratory depression
```
81
What about using esmolol to blunt SNS with laryngoscopy?
It may cause significant and prolonged bradycardia leading to emergent c-section, this is not done!
82
What 2 medications together produce the most depressant effects on mother and fetus?
Morphine and a benzo
83
What doses of fentanyl appear safe for the term fetus?
Fentanyl <1 mcg/kg
84
What affect does epidural opioids have on the mother and fetus?
Minimal effects on fetus
| Rostral spread in mom causes drowsiness
85
What is liposomal encapsulation and how does it affect placental transfer?
An anionic and neutral liposomes increase placental transfer
Cationic liposomes decrease placental transfer and placental tissue uptake
EX: liposomal encapsulation of valproic acid significantly decreases drug transfer and uptake (its a teratogen)
86
How many drugs are known teratogenic drugs in animals, but only how many in people?
Animals: 1200
People: only 30
87
List of teratogenic drugs
```
Alcohol
Ace inhibitors (lisinopril, captopril, ramipril)
Cocaine
DES
Coumadin
Dilantin
Valproic acid
Retin A
Lithium
Thalidomide
Diazepam
```
88
What about use of N2O during pregnancy?
N2O causes a 3x increase in fetal resorption
It rapidly inactivated methionine synthesis and leads to neurological and hematological symptoms from diminished DNA synthesis
Skeletal muscle defects
Situs inversus (reversal of organs)
Neuronal apoptosis in animals
89
What has been found to occur with anesthetic gases and the fetus through pediatric brain growth?
Cause apoptotic neurodegeneration in the developing brain from the 4th month of gestation through pediatric brain growth and myelination of the neural sheath that peaks at age 12
90
What factors worsen the neurodegeneration affects of anthesetic gases?
Longer the gas exposure
| Multiple exposures
91
What affects do kids suffer from this neurodegeneration?
Decreased IQ
Lack of impulse control
Less physical coordination
Prolonged behavioral deficits
92
What anticholinergic should be used with neostigmine? Why?
Atropine
| Neostigmine does cross the placenta and will cause fetal bradycardia, glyco will not cross but atropine will
93
What can occur with large doses of atropine?
It can cause some fetal tachycardia and loss of variability, but does not harm the fetus
94
What analgesic suppresses uterine contractions?
Ketorolac
95
If an OB patient is having a section and is extremely anxious, what can be given?
Small dose fentanyl should not affect fetus
96
What should be used in (obese) patients if partial epidural or inadequate spinal?
Ketamine 10mg IV every 5 minutes
| -not associated with fetal depression or maternal depressed respirations at normal doses
97
Other health care factors that are known teratogenic
```
Radiation
Anesthesia
Some drugs
Hypoxia
Hypo/hyperglycemia
Poor nutrition
```
98
Manifestations of tetragenicity:
Death
Structural abnormalities
Growth restriction
Functional deficiency
99
What should be the focus of an anesthetic for a parturient?
```
Avoid:
Hypoxemia
Hypotension
Acidosis
Hyperventilation
```
100
At what MAC of ISO is uterine perfusion maintained?
1 - 1.5 MAC
101
What results from higher concentrations of anesthetic gas?
Reduced uteroplacental blood flow
Fetal hypoxia
Decreased cardiac output
Fetal acidosis
102
When do we start monitoring the fetus during surgery?
24 weeks (point of viability)
103
What risk does the use of general anesthetic in the 1st and 2nd trimester carry?
Miscarriage
104
What techniques should always be used for anesthesia during pregnancy?
Prophylaxis for aspiration
Left uterine displacement from 20 weeks on
Preoxygenation
RSI - do not ventilate
105
What drug combinations are considered usually safe
```
Propofol
Fentanyl
ISO (forane)
Succs
Rocuronium
Reversal (Neostigmine and Atropine)
```
106
What about PaCO2 do you want to avoid?
Low PaCO2
107
What about hypotension?
Treat aggressively
