Sweaty's Drugs: Neonatal, HRT Flashcards Preview

Reproductive > Sweaty's Drugs: Neonatal, HRT > Flashcards

Flashcards in Sweaty's Drugs: Neonatal, HRT Deck (45)
Loading flashcards...

general signs of drug withdrawal in infant

onset: varies depending on amount of drug accumulated and rate of release from tissue
lasts: weeks to months
signs: autonomic hyperactivity, irritable, excessive crying, poor feeding, abnormal reflexes
Tx: may have to re-expose and taper down


signs of opiate withdrawal in infant

CNS hyperactivity: tremor/ seizure, irritable, increased wakefulness, crying, hyperactive reflexes, frequent yawn/sneeze
autonomic hyperactivity: sweat, nasal stuffiness, mottling, fever
GI tract: diarrhea, poor feeding
CAN mimic other diseases


Determinants for drugs to cross placenta

1. lipid solubility
2. ionization
3. Mol. Wt less than 600
4. duration/timing of drug MOST important
5. maternal plasma protein drug binding
6. placental development and blood flow
7. energy dependent transporters (consider polymorphisms)


effects of placental drug metabolism

can increase/decrease fetal exposure
can also get SOME metabolism in fetal liver (only some blood goes straight to liver and liver is immature)


requirements for teratogen designation

1. characteristic set of malformations
2. exert effects at a particular stage of fetal development
3. show dose dependent incidence


What 2 species are candidate drugs required to be tested in?
Whys 2?

one rodent: usually rats
one non-rodent: usually rabbit
better chance of identifying teratogens: may be oversensitive


Mechanisms that contribute to teratogenity

1. folate antagonism
2. neural crest disruption
3. endocrine disruption
4. oxidative stress
5. vascular disruption
6. specific receptor or enzyme mediated events


SSRI in pregnancy

depression and SSRI can have adverse effects on fetus and pregnancy
SSRI effect in fetus: pulmonary artery HTN, others


Pregnancy Category

risk benefit relationship
A: studies in PREGNANT WOMEN have not demonstrated risk in pregnancy
B: ANIMAL studies have not demonstrated risk; no adequate human reproduction study
C: ANIMAL studies have shown adverse effect on fetus OR no animal/human reproduction studies
D: evidence of fetal risk, but potential benefits may be acceptable despite risk in some circumstances
X: human or animal studies demonstrate fetal abnormalities, risk clearly outweighs benefit


Differences in infant drug metabolism (compared to adult)
1. metabolic capacity
2. body composition: fat, TBW
3. plasma binding capacity
4. renal function
5. GI absorption
6. IM absorption
7. liver and brain/body weight ratio
8. enzymes
9. BBB permeability
10. general trends

1. poor
2. less fat, more total body water
3. lower: increases free drug in highly bound drugs
4. immature: can alter elimination
5. slower
6. faster
7. larger liver and brain to body weight ratio
8. immature
9. BBB more permeable
10. longer T1/2, change in pharmacokinetics as neonate ages (over days rather than weeks or months)


How are drugs adjusted for children?

based on weight although surface area would be more accurate


1. What drugs will concentrate in breast milk?
2. Drugs less likely to be transferred?
3. Drugs/methods preferred when breastfeeding?

1. concentrate: BASIC, LIPID soluble
2. less transferred: high protein bound drugs
3. short T1/2 drugs, dose after feeding, most cautious early-post partum


Groups of drugs that are problematic in breast feeding

1. CNS acting drugs: sedation, infant dependence
2. thyroid suppressors
3. chloramphenical: blood dyscrasia, bone marrow suppression
4. antidepressants: not sure of effect but lots passes to baby


mechanisms of paternal teratogenicity
major drug classes?

1. mutation in DNA or altered gene expression
2. direct contact with fetus
drug classes: antivirals, anticancer, traditional and mAb, retinoids
unexpected: androgen receptor antagonist, DMARD, anti epileptic



website to find drug toxicity in utero and through breast milk



part of TOXNET for breast milk


Which menopausal signs will improve over time without treatment?
Which will not improve without treatment?

vasomotor: improve without Tx (may take years)
vaginal dryness: does not improve without Tx
undetermined: sleep and mood problems


CEE (conjugated equine estrogens) alone for HRT: Risks vs. Benefits

more balanced than CEE plus MPA
decreased risk: breast CA


CEE plus MPA (medroxyprogesterone acetate) for HRT: Risks vs. Benefits

increased risk: CHD, breast CA, stroke, PE, gallbladder disease, dementia, urinary incontinence
decreased risk: hip fracture, DM, vasomotor symptoms


Although most risks of HRT dissipate after Tx is discontinued, what risk remains?

breast CA


When is HRT appropriate?

moderate to severe menopausal symptoms in EARLY menopause (not for chronic disease prevention)


HRT: vaginal estrogen

genitourinary symptoms without vasomotor symptoms


CI for estrogen

1. undiagnosed abnormal genital bleeding
2. breast CA, estrogen dependent CA
3. DVT, PE, stroke, MI
4. liver dysfunction
5. allergic to preparation
6. pregnancy


Caution with estrogen

1. dementia
2. gallbladder disease
3. hypertriglyceridemia
4. prior cholestatic jaundice
5. hypothyroid
6. fluid retention plus cardiac or renal dysfunctionn
7. hypocalcemia
8. prior endometriosis
9. hepatic hemangiomas


Who gets HRT according to 10 yr CHD risk?
1. less than 5 years since LMP
2. 6-10 yrs
3. greater than 10 yrs

1. low risk: oral; mod. risk: transdermal
2. very low: oral; low to mod.: transdermal
also AVOID in anyone that is high risk for developing CHD


non-pharm Tx of vasomotor symptoms in menopause

cognitive behavioral therapy
other with caution: weight loss, stress reduction, soy isoflavones, stellate ganglion block



non-hormonal: antidepressant
Tx: vasomotor Sx (only FDA approved non hormonal)



non-hormonal: antidepressant
Tx: vasomotor Sx (off label)



non-hormonal: antidepressant
Tx: vasomotor Sx (off label)



non-hormonal: antidepressant
Tx: vasomotor Sx (off label)
AE: also anorexia, dry mouth, vomiting