Sweaty's Drugs: Neonatal, HRT Flashcards
(45 cards)
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
- lipid solubility
- ionization
- Mol. Wt less than 600
- duration/timing of drug MOST important
- maternal plasma protein drug binding
- placental development and blood flow
- 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
- characteristic set of malformations
- exert effects at a particular stage of fetal development
- 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
- folate antagonism
- neural crest disruption
- endocrine disruption
- oxidative stress
- vascular disruption
- 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 A B C D X
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)
- metabolic capacity
- body composition: fat, TBW
- plasma binding capacity
- renal function
- GI absorption
- IM absorption
- liver and brain/body weight ratio
- enzymes
- BBB permeability
- general trends
- poor
- less fat, more total body water
- lower: increases free drug in highly bound drugs
- immature: can alter elimination
- slower
- faster
- larger liver and brain to body weight ratio
- immature
- BBB more permeable
- 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
- What drugs will concentrate in breast milk?
- Drugs less likely to be transferred?
- Drugs/methods preferred when breastfeeding?
- concentrate: BASIC, LIPID soluble
- less transferred: high protein bound drugs
- short T1/2 drugs, dose after feeding, most cautious early-post partum
Groups of drugs that are problematic in breast feeding
- CNS acting drugs: sedation, infant dependence
- thyroid suppressors
- chloramphenical: blood dyscrasia, bone marrow suppression
- antidepressants: not sure of effect but lots passes to baby
mechanisms of paternal teratogenicity
major drug classes?
- mutation in DNA or altered gene expression
- direct contact with fetus
drug classes: antivirals, anticancer, traditional and mAb, retinoids
unexpected: androgen receptor antagonist, DMARD, anti epileptic
TOXNET
website to find drug toxicity in utero and through breast milk
LACTMED
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
- undiagnosed abnormal genital bleeding
- breast CA, estrogen dependent CA
- DVT, PE, stroke, MI
- liver dysfunction
- allergic to preparation
- pregnancy
Caution with estrogen
- dementia
- gallbladder disease
- hypertriglyceridemia
- prior cholestatic jaundice
- hypothyroid
- fluid retention plus cardiac or renal dysfunctionn
- hypocalcemia
- prior endometriosis
- hepatic hemangiomas
