Drugs in Pregnancy Flashcards
What are the different effects of pregnancy to intake of ftug?
- DEC in intestinal motility -> enlarging uterues & hormones
- INC gastric pH -> weak acids more ionized
- Nausea & vomiting
- INC in maternal blood flow to the skin
- Hyperventilation
- INC body water -> plasma volume expands to 1.5L
- DEC plasma albumin conc
- Progressive INC in renal blood flow
- Altered oral BA & hepa elimination
What are the drugs that are largely bound to albumin circulation therefore inc their conc during pregnancy?
Diazepam
Phenytoin
Valproate
Warfarin
What drugs are given to relax uterine contractions in premature labor?
Terbutaline & Isoxsuprine
What are 2 drugs that can cause serious harm if taken by preggos? Why?
Diethylstilbestrol (Desplex)
-> used to prevent abortion, miscarriage, & premature labor
-> given at <18 wks AOG –> adenocarcinoma of cervix, vagina
Thalidomide
-> was given to prevent nausea & vomiting
-> babies were born w/ flipper-like extremities (Phocomelia)
What is the study of birth defects & their etiology?
Teratology
What are the 4 diff teratogens?
Recreational teratogens
Maternal diseases and infections
Environmental teratogens
Pharmaceutical teratogens
What is the primary effect of teratogens to fetus?
Growth restriction in utero –> SGA
What are diff recreational teratogens?
Tobacco/Cigarettes
Illegal drugs
alcohol
What are the facial features to confirm fetal alcohol syndrome? How many of these should be seen to confirm this condition?
> or equal to 2 required
Short palpebral fissures
Indistinct philtrum
Thin upper lip
What maternal diseases and infections are teratogens?
DM type 1, 2, GDM
TORCH = Topxoplasma, Others (HIV, Varicella, syphilis), Rubella, CMV, HSV
Zika virus
What are the diff envrionmntal teratogen?
Chemicals: Hg, Arsenic, lead
Ionizing radiation
Non-ionizing radioation: ultrasound, MRI, microwave, radiofrequency
What is CDC’s recom exposure to radiation for preggos?
not > 0.1Gy
Whata re the different phatmaceutical teratogens?
Thalidomide
Diethylstilbestrol
ACEis, ARBs, RAAS inhibis
Antiepileptic: Valproic acid, Phenytoin, Carbamazepine
Warfarin
Retinoids
What are the 3 factors that affect drug passage to fetus?
- Disruption of folic acid absorption/metab
- Altered fetal genetic composition
- altered processes of cell diff
What are the diff things that can disrupt folic acid absorption in preggos?
Carbamazepine
Iamotrigine
Phenobarbital
Valproic acid
Phenytoin
Neural tube defects –> Meningomyelocele
Cardiac defects
Oral clefts
When should folic acid be taken?
1st trim of pregnancy and women planning to get pregnant
What are examples of altered fetal genetic composition?
- Gene mutation resulting in low levels of Epoxide hydrolase + Exposure to drugs: Phenytoin/Carbamazepine/Phenobarbital
- Mutation + Folic acid def —> neural tube defects
What drugs can alter process of cell differentiation? How?
Retinoids (Isotretinoin), Valproic acid
Causes homebox genes to malfunction —> Disorganized or chaotic gene expression —> Cardiac, brain, cranium abnormalities
What are homeobox genes?
Nuclear proteins/transcription factors that control expression of other developmentally important genes
What are physiochemical properties of drugs that affect preggos?
Lipid solubility
Degree of ionization
Molecular size
Degree of protein binding
Basic drugs
What is an IV anesthetic that is given right before an Episiotomy or perineal cut before delivery and can easily reach the bby causing sedation & apnea?
Thopental
How does the degree of ionization affect pregnant women?
Higher the degree of ionization = less likely to cross the placenta
What drug can depolarize neuromucular blocker/muscle relaxant used prior to intubuation or cesarean secretion?
Succinylcholine
What is the rel of a drug’s molecular size to preggos? What drugs should we be aware of giving?
Small molecular size = can easily cross the placenta
Morphine
Alcohol
Warfarin
What is the anticoagulant of choice in preggos?
Heparin —> LMW
What is the rel of degree of protein binding to preggos? What are examples of these?
Drugs that bind to maternal proteins will cross less
Igs = large so they can cross
Propylthiouracil = more bound to maternal proteins = crosses less
Betamethasone = minimally-bound to maternal proteins -> preterm labor -> stimulates fetal surfactant production
How are basic drugs able to cross the placenta?
More ionized in the fetal comprtament —> ion trapping & higher fetal levels
What form of glucocorticoid is used in preggos? Why?
Prednisolone
Bcos this is inactivated by the placenta therefore, it won’t cross the placenta & affect the bby
Bcos of the presence of efflux pumps in the placenta, drugs can be ejected & cannot cross the placenta. What are these proteins?
P-glycoprotein
Breast cancer resistance protein
When does fertilization take place? How do you compute for AOG?
2 weeks after last menstrual period
AOG: count from LMP
How can teratogens affect the getus during pre-impalantion (1-2wks after fertilization)?
“All or nonw” = either lethal/no effect
How can teratogens affect the fetus during embryonic period (>2-8 wks after fertilzation)?
Anatomic abnormalities
(Bcos this is the time of organogenesis)
How can teratogens affect the fetus during fetal period (>8-38wks until birth)?
Growth & Devt -> Size & Physiologic/functional abnormalities
What can happen if Warfarin is administered during the embryonic or fetal period?
Embryonic: Bone abnormalities
Fetal: bleeding tendencies
At what age of fetal devt are the CNS, heart, and external genitalia developing?
CNS: 6th wk to 38th wk
Heart: 6th-8th wk
External genitalia: 9th-38th wk
What is the effect of Diabetes to babies?
Large gestational age (LGA)/Big babies
What are the US-FDA drug categories for prengnat women?
Categ A: Controlled studies shows nO RISK
Categ B: NO EVIDENCE OF RISK in humans
Categ C: Risk CANNOT BE RULED OUT
Categ D: (+) EVIDENCE of risk
Categ X: C/I in pregnancy
What US-FDA drug category do Levothyrozine, K supplements, prenatal vitamins fall under?
Category A: controlled studies shows no risk
What US-FDA drug category do Ampicillin, Paracetamol fall under?
Category B: NO EVIDENCE of risk in humans
What US-FDA drug category do Amlodipine, Tramadol, & Gapanentin fall under?
Categ C: risk CANNOT BE RULED OUT
What US-FDA drug category do Diazepam & other Benzodiazepines fall under?
Categ D: POSITIVE EVIDENCE of risk
What US-FDA drug category do THalidomide, HMGCoA reductase inhibtors, fall under?
Categ X: C/I in pregnancy
What is the pregnancy & lactation labeling rule?
Provides accessible & understandible information to pregnant & lactating mothers of the risks a drug may have upon intake
Give all 9 drugs under Category X
- Thalidomide
- Potential teratogens: anticancer drugs, Mycophenolate mofetil, ANtithyroid drugs
- Retinoids
- HMGCoA reductase inhib (Statins)
- Misoprostol
- Bendzodiazepines
- Warfarin
- Androgens
- Ergots
What are the common conditions encountered during pregnancy?
Pain & fever
Infections
Allergies
Colds
HTN
Asthma
Epilepsy
DM
What is the safest drug for pain & or fever in preggos?
Paracetamol
When can we prescribe NSAIDs for pregnant women?
1st trim = safe to use Ibuprofen & Aspirins
3rd trimester = if it exceeds 72h —> pulmonary HTN, oligohydramnios, intraventricula rhemorrhage
When should preggos avoid NSAIDs?
20wks or more
What are the categories of NSAIDs?
1st-2nd trim: Categ C
3rd trim: Categ D
What are safe drugs for infections?
B lactams: Penicillin, ampicillin, amox, cephalosporins
Metronidazole
Macrolides: Erythromycin, Clarithromycin
Anti-TB drugs
What drugs are used for allergies in pregnant women?
H1 blockers: Diphenhydramine, Dimenhydrinate, Doxylamine, Meclizine
What drug for allergy should be avoided in preggos?
Bromfirenamine
What drugs are safe to prescribe for cold of preggos?
Topical decongestants: Oxymetazoline
What is the DOC for chronic HTN in preggos?
Methyldopa
What drug is used for preeclampsia?
Hydralazine
What HTN can bse used in preterm labor for preggos?
Nifedipine
What are the preferred glucocorticoids for asthma of preggos? What are other safe drugs for asthma?
Prednisone & Prednisolone
Other drugs:
Salbutamol, Formoterol
INhaled corticosteroids -> give small dose; easily absorbed
What corticosteroid cannot be prescribed to preggos to tx asthma? Why?
Methylprednisolone = risk of CLEFT LIP/PALATE if given <10wks AOG
What drug for epilepsy has the greatest risk of AEs in pregnant women? What are these conditions that can develop?
Valproic acid
Risks:
Neural tube defects
Significantly lower IQ scores
What are the hormones INC during pregnancy?
Human placental lactogen
Prolactin
Cortisol
Progesterone
What is the DOC for diabetes in pregnancy?
Insulin -> cannot cross placenta
What are the diff drugs that can be admin to preggos for DM? What is their FDA categ?
Categ B:
Aspart
Lispro
NPH
Detemir
Regular insulin
What are anti-DM drugs not recommended in preggos?
Metformin, Dapagliflozin, Liraglutide
What is the use of THalidomide & its C/I to preggos?
Indication: Leprosy
C/I: Phocomelia
What is the use of HMGCoA inhibitors (Statins) & its C/I to preggos?
Indication: Dyslipidemia
C/I: Spontaneou abortion, fetal death, congenital anomalies
What statins are preferred if need more hydrophilic statins?
Rosuvastatin or Pravastatin (Lipophobic)
What is the use of Misoprostol & its C/I to preggos?
Indication: Anti-ulcer drug
C/I: ABortifacient (causes abortion)
If taken @ 1st trim = Moebius syndrome (form of facial paralysis)
What is the use of Benzodiazepines & its C/I to preggos?
I: Sedative, hypnotic
C/I: Facial clefting if taken @ 1st trim
What is the use of Warfarin & its C/I to preggos?
I: AC
C/I: Embryopathy & Fetopathy
-> @1st trim = abn fetal long bones
-> @fetal period = hemorrhage
What is the use of Androgens & its C/I to preggos?
I: Replacement therapy of HYpogonadism
C/I: Masculinizing effects
What is the use of Ergots (Ergotamine & Ergonovine) & its C/I to preggos?
Ergotamine
I: Migraine
C/I: Low birth wt & preterm birth
Ergonovine
I: Powerful uterine stimulant
C/I: avoided in preg
What is the use of Retinoid & its C/I to preggos?
I: Anti-acne & Anti-psoriasis
C/I: Embryopathy (CNS, <3, Thymus, facial defects) —> Microtia, High forehead, Hypoplastic nasal bridge
What anti-thyroid drug is avoided in 1st trimester bcos it can cause Aplasia cutis? When can it be used during preg?
Methimazole
@13 wks of gest
What are recom non-drug tx for fever, pain, & diabetes & HTN in preggos?
Fever: hydration & sponge bath
Pain: warm compress
DM & HTN: dietary adjustments
