Sweaty's Drugs: Neonatal, HRT Flashcards Preview

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Flashcards in Sweaty's Drugs: Neonatal, HRT Deck (45):
1

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

2

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

3

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)

4

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)

5

requirements for teratogen designation

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

6

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

7

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

8

SSRI in pregnancy

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

9

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

10

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)

11

How are drugs adjusted for children?

based on weight although surface area would be more accurate

12

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

13

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

14

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

15

TOXNET

website to find drug toxicity in utero and through breast milk

16

LACTMED

part of TOXNET for breast milk

17

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

18

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

more balanced than CEE plus MPA
decreased risk: breast CA

19

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

20

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

breast CA

21

When is HRT appropriate?

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

22

HRT: vaginal estrogen

genitourinary symptoms without vasomotor symptoms

23

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

24

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

25

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
3. AVOID
also AVOID in anyone that is high risk for developing CHD

26

non-pharm Tx of vasomotor symptoms in menopause

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

27

paroxetine

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

28

fluoxetine

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

29

escitalopram

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

30

venlafaxine

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

31

clonidine

non-hormonal
MOA: lowers peripheral vascular reactivity, raises sweating threshold
Tx: vasomotor Sx (off label)
AE: dry mouth, insomnia, drowsy

32

gabapentin

non-hormonal
MOA for VMS: unclear
Tx: vasomotor Sx (off label)
AE: dizzy, unsteady, drowsy

33

MOA and AE for antidepressants used for vasomotor Sx

MOA for VMS: unknown
AE: nausea, headache, insomnia, sex dysfunction

34

17 B estradiol

oral, transdermal, vaginal estrogen

35

ethinyl estradiol

oral estrogen

36

conjugated estrogen

oral estrogen

37

medroxyprogesterone acetate

oral progestogen

38

norethindrone acetate

oral, transdermal progestogen

39

drospirenone

oral progestogen

40

micronized progesterone

oral progestogen

41

levonorgestril

transdermal progestogen

42

What is the MOST effective therapy for both VMS and Urogenital atrophy in menopause?

estrogen +/- progestogen
AE: breast tenderness, uterine bleeding, N/V, headache, weight change, rash, pruritus, cholecystitis

43

Why is transdermal estrogen preferred?

avoid first pass metabolism that promotes prothrombotic hemostatic changes in factor IX, protein C resistance, tPA activator
less weight gain
oral increases: coagulation effects, CRP, fibrolytic markers, worse effect on triglycerides
both benefit: lipid profile (oral more so)

44

bazedoxifene

estrogen and SERM combo
agonist is some tissues, antagonist in others
use: menopause (reduces endometrial over growth)

45

What happens when HRT is stopped?

bone reposition accelerates, vulvovaginal atrophy recurs
half have VMS return