Chapter 20: Women's health Flashcards
drug metabolism in women
women have more CYP450, 3A4 substrates
better able to metabolize drugs affected by the P450 system
drug absorptionin women
longer gastric emptying times which affect bioavailability and absorption
affeted by estrogen levels
less alcohole dehydrogenase than men
lipophilic drugs are more readily distributed in women
drug distribution in women
women tend to have lower body weights and BMI but a higher proportion of body fat
drug excretion in women
differs due to weight differences
drug pharmacodynamics in women
differences with cardiovascular drugs and opiate analgesics
longer QT interval makes more susceptible to arrhythmias
greater analgesic effect in women, also more likely to cause n/v
what is important to rule out first when consiering a diagnosis of PMS or PMDD
anemia
thyroid disorder
depression or other mood disorders
therapeutic issues in womens health
menopause
hormone replacement therapy
osteoporosis
oral contraceptives
menstruation disorders
endometriosis
treatment options for PMS and PMDD
medication
exercise
dietary changes
supplements
counseling and mind-body approaches
medications that can be used in the treatment of PMS and PMDD
alprazolam (anxiety)
danazol (moderate endometriosis)
ibuprofen
SSRIs (very effective for behavioral & physical symptoms)
herbals that can be used in treatment of PMS or PMDD
evening primrose
chaste tree berry
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supplements used in treatment of PMS and PMDD
calcium, magnesium, B6
medical management of dysfunctional uterine bleeding
first correct volume status, then stabilize bleeding
goal is to prevent endometrial hyperplasia and cancer
menorrhagia
prolonged or excessive bleeding that occurs at regular intervals
metrorrhagia
bleeding at irregular intervals between periods
menometrorrhagia
bleeding at irregular intervals with heavy or prolonged flow
polymenorrhea
bleeding occuring at regular intervals of less than 21 days
oligomenorrhea
infrequent, scanty bleeding occuring at intervals of greater than 35 days
amenorrhea
Primary - no menarch by age 16
secondary - absence of bleeding for more than 6 months in nonmenopausal women
DUB treatment varies depending on
severity and type of bleeding
fertility status
contraception needs
patient preference
side effects
pharmaceutical management of severe uterine bleeding
IV conjugate equine estrogen therapy
combination oral contraceptives
oral progestins
combination oral contraception therapy dosage
35mcg ethinyl estradiol/1mg norethindrone TID x 7 days
then once daily x 3 weeks
average time to stop bleeding with combination oral contraceptive therapy
3 days
progestins used for abnormal uterine bleeding in women who are contraindicated to estrogen therapy
norethindrone 5-15mg daily
medroxyprogesterone acetate up to 80mg daily
side effects of high estrogen doses
nausea
caution with hx of liver disease, over 35, or smoke
common side effects of progestins
headaches and breast tenderness
drugs that CAUSE abnormal uterine bleeding
anticoagulants
antidepressants (usually tricyclics)
antipsychotics
oral contraceptives
oral corticosteroids
phenytoin
tamoxifen
tranquilizers
herbals that can CAUSR abnormal uterine bleeding
garlic, ginko biloba, ginseng, soy, st. john’s wort, arnica
aspen, bladderwrach, capsicum, dong quai, omega-3 fatty acids, parsley
what are the most common causes of iron defiency anemia in the developed world
menstrual blood loss
increased iron requirements in pregnancy
treatment option for menorrhagia (heavy bleeding)
Mirena IUD
estrogen-containing contraceptives (pill, patch, ring)
progestins
NSAIDs
treatment of anovulatory bleeding in women younger than 35
combination oral contraceptive therapy
cyclic progestin therapy
when should polycystic ovary disease be suspected
when there at least 2 of the 3:
oligomenorrhea and/or anovulation
clinical and/or biochemical signs of hyperandrogenism
evidence of polycystic ovaries
anovulatory bleeding in women OLDER than 35
assessment of endometrium because of cancer risk
treatment with COC, IUD, or cyclic progestins
peripheral smear in iron deficiency anemia will show
hypochromic, microcytic red blood cells
lab results with iron deficiency anemia
low serum ferritin and iron
increased total iron binding capacity
treatment of iron deficiency anemia
first increase intake in diet
second oral supplementation (325mg TID)
considerations with iron supplementation
take between meals to enhance absorption
antacids can impair absorption
side effects include constipation, nausea
dosage of oral contraceptive agent should be individualized how
lowest estrogen dose tolerable by patient
tailoring oral contraceptive progesterone
older ones (norethindrone and levonorgestrel) are cheaper but more androgenic so they worsen acne and lipid profiles
less androgenic ones are norgestimate and desogestrel
monophasic oral contaceptives
allow for continous dosing for 3 months
periods only 4x per year
multiphasic oral contraceptives
monthly cycles
combined oral contraceptives
have estrogen and progesterone agents
pros and cons of progesterone only therapy
continuous use with no withdrawal periods
strict schedue adherance needed (at 24 hour intervals)
allow breast feeding without inhibiting milk production
reduced risk of ovarian cancer
who should NOT be prescribed oral contraceptives
hx of CVA, complicated migranes, heart/liver disease, clotting disorders, estrogen-sensitive cancers, undiagnosed vaginal bleeding, possible pregnancy
combination oral contraceptives mechanism of action
inhibits ovulation by suppressing mid-cycle surge of FSH and LH
estrogen inhibits FSH release
progesterone inhibits LH and withdrawl bleeding
cervical mucosa is changes making it inhospitable to sperm
what are the only 2 estrogen ingredients approved for use in the US
ethinyl estradiol
mestranol
most potent progestins approved for use in the US
levo-norgesterol
norethindrone
what is in “the pill”
different amounts of synthetic estrogen and progestins, chemical analogues of the natural hormones estradiol and progesterone
other conditions treated by hormones
polycystic ovary syndrome, endometriosis, anemia r/t menstruation, painful menstruation, mild-mod acne, dysfunctional uterine bleeding
pharmacokinetics of combination oral contraceptives
- rapidly absorbed in intestine
- readily diffuses across lipid bilayers and blood-brain barrier
- metabolized extensively by first pass metabolism (then in liver via CYP450
- excreted enterically
- half-life: 12-30 hours
adverse drug reactions of COCs
- CV: hypercoagulability, DVT, PE, CVA risk
- GI: liver abnormalities, cholelithiasis
- OTHER: may stimulate estrogen sensitive cancer cells
which medications decrease the efficacy of oral contraceptives
ABTs, mineral oil, chloramphenicol, barbituates, chronic alcohol abuse, steroids, primidone, phenytoin, caffeine, theophylline, carbamazepine, bromocriptine, st. john’s wort
which drug increases OCP hormone levels
protease inhibitors
what medications are increased BY oral contraceptives
benzodiazepines
corticosteroids
alternate forms of birth control
OrthoEvra: patch on for 3 weeks, off for a week
NuvaRing: monthly self-inserted vaginal ring
mirena: IUD good for 5 years
seasonale: extended cycle so only 4 periods a year
contraindications for oral contraceptives
HTN, smoker over 35, liver disease, heart disease, thromboembolic disease, breast cancer, undiagnosed vaginal bleeding, pregnancy, major surgery with prolonged immobilization, complicated migraine, diabetic neuropathy, breastfeeding
contraceptive patches should not be worn where?
over breast or broken skin
mechanism of action for injectable contraception
IM formula provides protection for 3 months by thickening cervical mucosa
disadvantages of “the shot”
pain at injection site, weight gain, irregular menses
pharmacokinetics of depo shot
- slow absorption over 12-14 weeks
- widely distributed, ipophilic, crosses blood-brain barrier
- hepatic metabolism via CYP450 system
- half-life: 50 days
adverse reactions of depo shot
- CV: little to no risk with progestin-only injectables
- DERM: acne
- GI: liver toxicity and abnormal liver profile
- META: decreased libido, osteoporosis, glucocorticoid activity
containdications for the depo shot
not for IV use
pregnancy
any vaginal or urinary issue
subdermal implants for contraception
progesterone implant under the skin that is a reliable alternative for women who cannot take estrogen
lasts up to 3 years
side effects of subdermal implants
irregular bleeding, weight gain, acne
intravaginal rings
combined hormone therapy with low systemic dose so there are few side effects and interactions
lasts up to 35 days
compliance rate is high if left in place
diaphragms and cervical caps
uses latex as internal barrier to sperm passage
failure rate approx 11%
spermicides
gels, foams, creams, and coatings on condoms using nonoxynyl-9 as active ingredient which can irritate and may increase HIV transmission
condoms
failure rate approx 10-20%
sponge
must remain in place for 6hrs after intercourse or failure rate is 9-16%
emergency contraception
high dose estrogen to halt mobility in fallopian tube and thicken cervical mucosa
in two divided dosesgiven 12 hours apart (each 100mcg)
first dose within 72 hours of intercourse
“plan B” emergency contraceptive
high progesterone administration of 1.5 mg levonorgestrel in a single dose within 72 hours of intercourse (1
can take as one or divided dose)
OTC
emergency contraception if a woman is already pregnant
will not cause an abortion
drugs used to treat osteoporosis and osteopenia
cacium
vitamin D
biphosphonates
zoledronic acid
selective estrogen modulators (SERMs)
calcitonin
recombinant parathyroid hormone
follow-up for treatment of osteoporosis or osteopenia
no clearly defined protocol
evaulate therapy based on absence of fractures or increased bone density scores
medication goals for treatment of osteoporosis or osteopenia
achieve optimal peak bone mass
minimize further bone loss
decrease falls and fractures
non-pharmacologic treatment for osteoporosis
diet with adequate calcium and vitamin D, exercise, smoking cessation
medical conditions associated with higher risk of osteoporosis
alcoholism, chronic renal disease, cushing’s syndrome, cyctic fibrosis, glucocorticoids, DM, eating disorders, GI disorders, hematological disorders, hyperthyroidism, hyperparathyroidism, hypergonadism, hyperprolactinism, drug induced, neuropathies
what is calcium required for
vascular contraction and dilation, nerve transmission, intracellular signaling, hormonal secretion
what is vitamin D needed for
required for uptake of calcium and phosphorus for gut and absorption into bone
ergocalciferol and cholecalciferol
ergocalciferol is vitamin D2 from plants
cholecalciferol is vitamin D3 from sunlight
FDA recommended daily calcium need
1000mg/day for males 51-70
1200mg/day for females 51-70
females under 70 have an upper limit of 2500
IOM recommended daily vitamin D need
600IU/day for females
800IU/day for males
which medications should be given either several hours befor or after calcium due to its binding potential
levothyroxine, fluoroquinolones, tetracyclines, phenytoin, ACE inhibitors, iron, biphosphonates
which three drugs induce symptoms of acute hypercalcemia when given with vitamin D
calcitrol (Rocaltrol)
paricaltrol (Zemplar)
doxercalciferol (Hectoral)
symptoms of acute hypercalcemia
headache, nausea, dizziness, vomiting, and anorexia
coadministration of vitamin D, calcium, and HCTZ
renal secretion of calciumis inhibited leading to hypercalcemia
vitamin D interferes with the absorption of which other 3 medications
steroids, dilantin, and phenobarbital
contraindications for calcium and vitamin D
vitamin D: parathyroidism
calcium: hx of V. fib, hypercalciuria, hyperphosphatemia, and renal stones
use caution in paitent taking digoxin
first line treatment for post-menopausal women with osteoporosis
bisphosphonates
reduces fractures by 40-70%
examples of bisphosphonates
alendronate (Fosamax)
ibandronate (Boniva)
risedronate (Actonel)
raloxifene (Evista)
etidronate (Aredia
zoledronic acid (Zometa)
challenges with bisphosphonates
correct adminstration
avoiding serious GI upset
poor bioavailability
bisphosphonate mechanism of action
inhibits both normal and abnormal bone reabsorption and slows down bone remodeling in postmenopausal women
bisphosphonate pharmacokinetics
oral forms are poorly absorbed
adhere transiently to bone
no metabolism
excreted in urine
half life about 10 years
clinical uses of bisphosphonates
treatment/prevention of osteoporosis is post menopausal women
treatment of osteoporosis in men
symptomatic Paget’s disease
glucocorticoid-induced osteoporosis in men and women
adverse reactions of bisphosphonates
- CV: A-fib
- DERM: erythema, photosensitivity, rash
- GI: abdominal distention, cramps, pain, constipation, reflux, dyspepsia, gas, ulcer, change in taste
- MS: osteonecrosis of the jaw
- NEURO: headache
contraindications for bisphosphonates
decreased creatinine clearance
hypocalcemia or any history of GI disease and patients with invasive dental work (risk of osteonecrosis)
bisphosphonate patient education
warn patient of joint, muscle, bone jaw pain
advise to take with full glass of water
food to minimize GI upset
there are IV forms for 3 months or yearly administration
conscientious considerations for bisphosphonates
caution in patients with renal impairment
watch for jaw bone necrosis
watch for abnormal diagnostic imaging
monitor serum calcium and phosphorus
bisphosphonate interactions
antacids effect absorption
NSAIDs increases GI side effects
caffeine, mineral water, and orange juice decrease absorption
SERM activity
mimics estrogen antagonists and provide astrogen resorption effects without need for estrogen
SERM pharmacokinetics
60% absorbed fro GI, 95% bound to plasma protein, hepatically metabolized, excreted in feces, half-life 27-32 hours
examples of SERMs
tamoxifen (Nolvadex) - treats breast cancer
toremifene (Fareston) - treats breast cancer and osteoporosis
raloxifene (Evista) - treats osteoporosis
adverse reactions of SERMs
- CV: increased vasomotor symptoms, thromboembolism
- MS: leg cramps
- MISC: hot flashes
- NEURO: dizziness
SERM interaction
warfarin and other highly protein bound drugs
contraindications for SERMs
history of thromboembolic events
women who are pregnant, breast feeding, or may become pregnant
SERM patient education
take full course of therapy
do not double dose if one is missed
drug will not reduce incidence of hot flashes
weight-bearing exercise is helpful
advise on adequate calcium/vitD intake
avoid prolonged sitting as leg cramps could be risk for clot
calcitonin-salmon
synthetic form of calcitonin found in salmon
promotes new bone formation by unknown method
not considered first line therapy
administered as nasal spray
parathyroid hormone therapy
(Teriparatide) Forteo
stimulates new growth of bone in postmenopausal women at high risk for fracture
manufactured by recombinant DNA using e.coli
adverse reactions of forteo
orthostatic hypotension, nausea, leg cramps, increase in serum calcium
contraindications for forteo
risk of osteosarcoma (Paget’s disease, previous skeletal radiation, unexplained elevation of alkaline phosphatase level)
conscientious considerations for hormone replacement therapy
lowest effective dose to control symptoms for the shortest amount of time
consider use of natural products (Cohash) and non-pharmacologic therapy (exercise)
frequent follow-ups
use strogen only if they have NO uterus, otherwise estrogen-progestin
dont use if preventing CVD, osteoporosis, and demetia
conjugated estrogen (Premarin)
mechanism of action
helps modulate pituitary secretion of FSH, LH, and gonadotropins to reduce elevated levels in post-menopausal women,
thus maintaining female reproductive system and secondary sexual characteristics
Premarin pharmacokinetics
well absobed orally, circulates bound to protein, liver CYP450 converts to metabolite, excreted in urine, half-life 1-2 hours
estrogen adverse reactions
- CV: thromboembolism, MI, retinal thrombosis, stroke, HTN
- DERM: acne, oily skin, urticaria, increased pigment
- ENDO: hyperglycemia
- GI: nausea, weight gain, jaundice, vomiting
- META: water retention, hypercalcemia
- MS: leg cramps
- NEURO: lethargy, depression, headache, dizziness
- OB: ovarian, breast, cervical cancer; endometriosis, fibroids, amenorrhea, breast tenderness
premarin interactions
grapefruit juice will increase estrogen levels
will alter requirements for warfarin, oral hypoglycemics, and insulin
smoking will increase risk of cardiovascular events
conscientious considerations for estrogen replacement therapy (Premarin)
caution in smokers with high triglycerides
evaluate any unusual bleeding
lowest dose for shortest period of time
patient education for estrogen replacement therapy
do not double dose
withdrawal bleeding will occur with missed week
may take with food for GI upset
instruct on water retention, pregnancy, sunscreens, PAP screen, and routine wellness checks
clinical use of progestins
decrease endometrial hyperplasia
treatment of secondary amenorrhea and abnormal bleeding caused by homronal imbalance
emergency contraceptive
adverse reactions of progestins
- CV: fluid retention, PULMONARY EMBOLISM
- DERM: alopecia, acne, melasma, chloasma, rashes
- EENT: retinal thrombosis
- ENDO: amenorrhea, brekthrough bleeding, breast tenderness, changes in mestrual flow, spotting, hyperglycemia
- GI: weight gain, nausea, GI-induced hepatitis, gingival bleeding
- NEURO: depression
