(quizlet) Pharm E2 - Ortho/Rheum/OBGYN/BH

FDA pregnancy drug categories

A - fail to demonstrate risk

B - animal studies do not indicate risk & no studies in humans, or animal studies show risk but humans fail to show risk

C - animal studies indicate risk & no human studies (most meds)

D - positive evidence of fetal risk, but certain situations where benefits outweigh risk

X - definite fetal risk, & risks outweigh ant benefits

how can nausea & vomiting be treated in pregnancy?

-pyridoxine (vit B6)

-doxylamine

-metoclopramide/promethazine

-HT3 antagonists (ondansetron)

how can heartburn be treated in pregnancy?

-eating smaller more frequent meals

-antacids (w/low sodium)

-sucralfate

-H2RAs

-PPIs

which antiacids should be avoided in pregnancy?

sodium bicarb, magnesium trisilicate

how can constipation be treated in pregnancy?

-inc. fiber & water, moderate exercise

-drug of choice = bulk forming laxatives (methylcellulose, psyllium husk - not absorbed)

-surfactants - docusate

-stimulants occasionally (senna, bisocodyl)

-osmotic laxatives (miralax, lactulose, sorbitol, mag. salts)

what should be avoided when treating constipation in pregnancy?

prolonged/repeated use of mineral oil - dec. fat soluble vitamins absorption

how can hemorrhoids be treated in pregnancy?

-avoid constipation

-external products preferred - preparation H (hydrocortisone, phenylephrine) & Tucks - constrict blood vessels

-Sitz baths

what is the drug of choice for treating diarrhea in pregnancy?

stool bulking agents

-may also use loperamide

what decreases the relative risk of HTN & preeclampsia in pregnancy?

calcium 1-2 g daily

-watch for constipation

what can be used to treat eclamptic seizures?

magnesium sulfate 4-6 g IV

-avoid benzos, phenytoin

what can be used for chronic management of HTN in pregnancy?

(BP >150-160/100-110)

labetalol, methyldopa, DHP CCBs, nitroprusside or nitroglycerin for rapid tx

how is gestational diabetes treated?

-insulin is drug of choice, dietary modification

-glyburide minimally crosses placenta, metformin

how is acute thromboembolism treated in pregnancy?

low molecular weight heparin (enoxaparin)

-tx throughout pregnancy & 6 weeks after delivery

how are UTIs treated in pregnancy?

ALWAYS, even if asymptomatic

-nitrofurantoin, amoxicillin, cephalosporins

what is the drug of choice for pain in pregnancy?

acetaminophen

NSAID use in each trimester

1st & 2nd = cat B

3rd = D (premature closure of ductus arteriosus)

how is postpartum depression treated?

SSRIs, 2nd line = TCAs

-but avoid paroxetine d/t cardiac malformations

what should be supplemented to avoid neural tube defects?

folic acid

tocolytic therapy

drugs used to delay labor/delivery & relax the uterus

-beta agonists (terbutaline), magnesium, CCB, NSAIDs

what is given to high risk women with a history of preterm birth?

17-a-hydroxyprogesterone IM weekly at weeks 16-36

which agents induce labor by facilitating cervical ripening?

prostaglandin analogs (dinoprostone), misoprostol, oxytocin (most common)

potential adverse drug reaction w/oxytocin use

bleeding due to afibrinogenemia

what is most commonly used in epidural infusions?

fentanyl/bupivacaine

epidural side effects

-prolongation of 1st & 2nd stages of labor

-hypotension, pruritus, inability to void

-spinal headaches

synthetic estrogens include

-ethinyl estradiol

-micronized estradiol

-estradiol cypionate

-estradiol valerate

-estropipate

-conjugated estrogens

estrogens: pharmacokinetics

-highly protein bound

-conjugated metabolites excreted in bile

-enterohepatic recycling

-high 1st pass metabolism in liver

which type of patients can receive estrogens alone? **

patients without a uterus (hysterectomy)

-progestins not required to reduce endometrial hyperplasia

adverse effects of estrogens

-uterine bleeding

-endometrial hyperplasia / carcinoma

-inc. breast cancer w/prolonged use

-breast tenderness

-hyperpigmentation

-migraines / HTN

-cholestasis

contraindications to estrogen use

-estrogen-dependent neoplasms

-undiagnosed genital bleeding

-liver disease / thromboembolic disorders

-heavy smokers

which progesterone has anti-mineralocorticoid & anti-androgen effects?

drospirenone

which has higher variability in physiologic effects between agents: estrogens or progestins?

progestins

progestins: physiologic effects

-inc. basal insulin & insulin response to glucose

-competes w/aldosterone in kidney = inc. aldosterone release

-maturation & secretion in endometrium

-may inc. BP & lower HDL

what can be used for long term ovarian suppression if the patient is a poor estrogen candidate?

progestins

-may cause prolonged anovulation & amenorrhea

which HRT therapy should be used in patients who have not had a hysterectomy?

estrogen-progestin therapy

which has a higher dose of estrogen: HRT or low dose oral contraceptives?

low dose oral contraceptives (4-6x)

which dosage form is preferred in women with history of HTN, inc. TG, risk for VTE, and cholelithiasis?

transdermal - avoid 1st pass metabolism in liver

what other agents can be used for vasomotor symptoms of menopause?

-SSRIs, venlafaxine, desvenlafaxine

-gabapentin

-clonidine

how does hormonal contraception work?

selective inhibition of pituitary function resulting in inhibition of ovulation (progestins alone don't always inhibit ovulation)

-negative feedback to GnRH, FSH, LH

-changes in cervical mucus, uterine endometrium, motility & secretion in uterine tubes, dec. likelihood of conception & implantation

what can increase the risk of conception when using contraception?

drugs that increase metabolism of the drug (phenytoin, CYP inducers), antibiotics that inhibit enterohepatic recycling

hormonal contraception: adverse effects

-breakthrough bleeding/failure of withdrawal bleeding

-weight gain, acne, inc. pigmentation, hirsutism

-ureteral dilation (bacteriuria)

-vaginal infections more common & harder to tx

-amenorrhea

-venous thromboembolism, MI, stroke

-cholestatic jaundice

-depression

hormonal contraception: contraindications

-thrombophlebitis, cardiovascular, cerebrovascular issues

-unknown cause of vaginal bleed

-estrogen dependent tumors

-heart failure

-adolescents who haven't undergone epiphyseal closure

-hepatic enzyme inducers

-antibacterials

-pregnancy

what should be administered with postcoital contraceptives?

antiemetics - high incidence of N/V

hormonal contraceptives reduces risk of....

-ovarian cysts

-ovarian/endometrial cancer

-ectopic pregnancy

-iron deficiency

-endometriosis

-acne/hirsutism

when are oral contraceptives normally started?

-1st sunday after onset of menses - avoids withdrawal bleeding on weekends

-pregnancy = 3-4 weeks post delivery

-post abortion = 1st sunday after

how should missed pills be dosed?

single missed pill = take as soon as remembered

two pills = take two a day for two days

three or more = d/c for rest of pills & restart on sunday

what does bleeding on days 1-14 represent on oral contraception? days 15-21?

1-14 = estrogen deficiency

15-21 = progestin deficiency

medroxyprogesterone acetate (depo-provera)

injected every 3 months, but may cause very irregular menstrual bleeding patterns

tamoxifen: mechanism of action

selective estrogen receptor modulator - competitive, partial agonist, inhibitor of estradiol

-agonist in bone & endometrium, antagonist in breast tissue

what is tamoxifen used for?

-palliative care of breast cancer

-breast cancer prevention in high risk

-prevention of loss of lumbar spine bone density

tamoxifen: side effects

-inc. endometrial cancer risk, vaginal bleeding

-thromboembolism

-hot flashes & vomiting

-do not use w/intact uterus

raloxifene: mechanism of action

partial estrogen agonist-antagonist

-estrogenic effects on lipids & bone

-doesn't stimulate endometrium or breast

what is raloxifene used for?

-prevention of postmenopausal osteoporosis

-prevention of breast cancer in high risk women

-safe to use in pts w/uterus

how does clomiphene work?

partial estrogen agonist - binds up hypothalamic estrogen receptors to inhibit feedback loop

-also ovulation induction agent

danazol: how does it work & what is it used for?

-weak progestational, androgenic & glucocorticoid effects

-suppresses ovarian function

-treats endometriosis

-can also be used in hematologic/allergic disorders

danazol: side effects

-weight gain/edema

-dec. breast size

-acne/oily skin

-hair growth

-deepening of voice

aromatase inhibitors include

-anastrozole

-letrozole

-exemestane (irreversible)

aromatase inhibitors: side effects

more intolerable than SERMs d/t dec. estrogen = inc. fractures & menopausal like symptoms

rheumatoid arthritis therapy

chronic = NSAIDs, low dose steroids

acute = high dose steroids

-also DMARDs, knee effusions, steroid injections

osteoarthritis therapies

chronic = acetaminophen, NSAIDs, topical analgesics

-also aspirations, steroid injections

traditional DMARDs include

-methotrexate

-hydroxychloroquine

-sulfasalazine

-leflunomide

-generally have a slow onset of action, need to cover w/NSAIDs & steroids

anti-TNFs (biologics) include

-infliximab (remicade)

-certolizumab (cimzia)

-etanercept (enbrel)

-adalimumab (humira)

-golimumab (simponi)

IL-6 receptor antagonist

tocilizumab (actemra)

CD20 inhibitor

rituximab (rituxan)

JAK inhibitor

Tofacitinib (Xeljanz)

other immunosuppressives that can be used in RA include

-azathioprine

-d-penicillamine

-gold

-anakinra (IL-1 antagonist)

-cyclosporine

-cyclophosphamide

these have fallen out of favor due to unfavorable side effects

which DMARDs have the best efficacy-toxicity ratios?

methotrexate, hydroxychloroquine

which DMARD is usually started first in RA patients?

methotrexate

what should be done before initiation of a DMARD?

-TB testing

-vaccinations up to date

which vaccines can be given to patients actively on RA therapy?

killed & recombinant vaccines ONLY (pneumococcal, IM flu, hep B)

-do not give live vaccines when pt is on a biologic -> can cause an actual infection

when is it recommended that patients get their herpes zoster vaccine if on immunosuppressive therapy?

age 50 instead of normally age 60

methotrexate: mechanism of action

Analog of folic acid with high affinity for dihydrofolate reductase (inhibits folic acid in rapidly growing cells)

-cannot make new nucleotides = no new cells

methotrexate: toxicities

-bone marrow suppression

-stomatitis (ulcers)

-diarrhea, hepatotoxicity

-alopecia, N/V

-pulm fibrosis & pneumonitis

methotrexate: contraindications

-pregnancy (abortive)

-renal insufficiency (CrCl <40)

-chronic liver disease

-blood dyscrasias

methotrexate: monitoring includes

-CBC, LFTs, SCr at baseline, monthly x6 mos then every 1-2 mos

-pregnancy status

what must be given with methotrexate?

folic acid 1 mg

leflunomide: mechanism of action

inhibits pyrimidine synthesis = decreased lymphocyte proliferation

which two DMARDs cannot be used together due to significant risk of hepatotoxicity? ***

leflunomide & methotrexate

leflunomide: side effects

-m/c = diarrhea

-hepatotoxicity, immunosuppression, hematologic toxicity

-teratogenic -> needs cholestyramine washout

hydroxychloroquine: mechanism of action

inhibits neutrophil locomotion, chemotaxis eosinophils, impairs complement-dependent antigen-antibody reactions

-least toxic, least potent DMARD (but safest)

what is the benefit to using hydroxychloroquine?

not associated with myelosuppression, hepatotoxicity, or renal insufficiency = less monitoring

hydroxychloroquine: side effects

-GI (N/V/D)

-retinopathy

-inc. skin pigmentation

-rash, alopecia

sulfasalazine: mechanism of action

prodrug cleaved by colonic bacteria into sulfa pyridine & 5-aminosalicylic acid = modulates inflammatory mediators, TNF inhibitor, free radical scavenger

sulfasalazine: side effects

-GI!! N/V/D, high LFTs

-rash, alopecia

-turns urine/stool yellow/orange

sulfasalazine: interactions

-antibiotics

-iron supplements

-warfarin

tofacitinib (xeljanz): mechanism of action

JAK (janus kinase) inhibitor for moderate to severe RA in patients who fail methotrexate therapy

-JAK facilitates phosphorylation & activation of STAT proteins, which regulate inflammatory gene transcription

which two drug classes for RA cannot be used together due to the risk of too much immunosuppression (& infection)? ***

biologics & JAK inhibitors

JAK inhibitors: black box warning

serious infections, lymphomas, other malignancies

when should the dose of JAK inhibitors be reduced?

in patients with significant renal/hepatic dysfunction, or if used with CYP3A4 inhibitors

what should be tested for before starting a JAK inhibitor?

latent TB

biologics: risks

-inc. risk infection

-inc. risk TB (test prior to therapy initiation)

-d/c while pt is sick

-don't give live vaccines

-very little monitoring

what is the black box warning for TNF-alpha inhibitors?

lymphoproliferative cancer

what is a relative contraindication for TNF-alpha inhibitors? **

CHF --> inc. CV death, exacerbations

-AVOID in EF <50%, NYHA class III

what should be given if a patient experiences anaphylaxis to a biologic agent?

epi, benadryl, steroids

how does abatacept (orencia) work?

binds to CD80/CD6 receptors, preventing interactions between antigen-presenting cells & T-cells = preventing T-cell activation

when is abatacept (orencia) used?

not 1st line - used if patients fail TNF-a inhibitors or have a contraindication to them

rituximab: mechanism of action

monoclonal antibody against CD20 protein on B lymphocytes, causing near complete B cell depletion & decreases antigen presentation to T cells

when is rituximab used?

if a patient has failed methotrexate and/or TNF-alpha inhibitors

how must rituximab be given?

as two infusions two weeks apart with pre-treatment

-can be given w/MTX

tocilizumab (actemra): side effects

-hyperlipidemia

-elevated transaminases

-GI perforation

-induces CYP3A4

what is the max amount of intra-articular steroid injections that should be given per year? what can happen if more are done?

-2/3 per year

-inc. joint destruction, tendon atrophy