08-Drugs for female reproductive system Flashcards
What occurs with the binding of water soluble hormones bind to the outside surface of the cell?
Leads to manufacture of second messengers (cAMP or IP3) which alter cell function
What occurs when oxytocin binds to receptors outside of the myometrium?
Releases second messengers, increases calcium levels and stimulates uterine contraction
What is an example of a membrane spanning enzyme?
Insulin, binds to receptors which bind to an enzyme and affect activity then causing intracellular effects
What are lipid soluble endocrine hormones?
- Have capacity to bind to receptors inside and outside of the cell
- Ex. estrogen, testosterone, progesterone, thyroid hormone, cortisol, aldosterone
What occurs when the fat soluble endocrine hormones are released by endocrine glands?
Enter systemic circulation, pass biological membranes of the target cell, binds to intracellular receptor, drug-receptor complex is formed aand then can act on the DNA directly inside of the cell
What is an example of a fat soluble endocrine hormone working directly inside of a cell?
Testosterone binds inside muscle tissue (receptor), activates at the level of DNA for muscle to grow bigger
What 2 hormones are produced by the anterior pituitary?
LH and FSH
What are the roles of LH and FSH?
- Acts on sex organs to make sex steroids, important for growth and development
- Sex steroids (testosterone) is important for libido
- Maturation of follicles
The female body is pro-….?
Pro-pregnancy! Female gonads work to facilitate pregnancy
High estrogen levels cause what?
Surge in LH and FSH, which facilitates ovulation
Increased progestin does what?
Creates home for a fertilized egg to land, induces proliferation of the endometrium
What happens if there is no egg fertilized?
No implantation, GnRH, LH and FSH falls, estrogen and progesterone levels fall, signals beginning of the menstrual cycle
What are the three estrogens?
- Estradiol
- Estrone
- Estriol
Estradiol:
- Made by the ovary, conversion of testoserone to estrogen
- Drives changes associated with puberty
- Most potent of the 3 estrogens
Estrone:
- Less potent
- Primary form of circulating estrogen in women with menopasue
- As women age we see an increase in fat deposition (estrogen = fat soluble and stores well in fatty tissue, ovaries fail, estrone from the fat stores is released, circulating levels decline over time, this way there is no major shift
Estriol:
- Primary circulating form of estrogen during pregnancy
- Formed in the placenta
- When you are pregnant you will have the highest amount of estrogen you will ever have
What are the biological effects of estrogens?
- Growth and maturation of female reproductive organs
- Endometrium proliferation and thickening of vaginal mucosa
- Female fat pattern distribution (breast, buttocks and thighs)
- Increased bone deposition
- increased vascularity of the skin
- Decreased LDL formation and increased HDL cholesterol
- Increased coagulation
- Increased production of clotting factors (increases activity of clotting factors, more likely to get clots, if there is a history of increased coagulation or smoking can cause blood clots)
- Production of thin, clear, watery and elastic cervical mucus (allows for passage of sperm during ovulation)
What are the biological effects of progestins?
- Progesterone = most active endogenous progestin
- Increases mucus thickness and prevents sperm entry
- Limits and stabilizes endometrial growth
- Inhibits myometrial contractions (quiets the uterus to protect viability of the embyro)
- Increases body temperature
- Released during pregnancy because the body does not want to become pregnant again once it’s already pregnant
What are combination oral contraceptives?
- Have both an estrogen and a progestin
- Increased half life, orally viable
- Take hormones for 21 days, followed by 7 days of placebo to allow for menstruation to occur
What is important to ensure effectiveness?
Adherence, patient must take the pill every single day, and if they forget one day they can double up the next day and use another form of protection to prevent pregnancy
How do combination contraceptives inhibit ovulation?
- Low dose synthetic estrogens suppress FSH levels
- Low dose synthetic progestins suppress LH surge
- In the absence of LH and FSH, ovarian follicle does not mature and ovulation is inhibited
- Synthetic hormones exploit negative feedback loop preventing follicle maturation and ovulation; much like hormones produced by the placenta to halt the ovarian cycle
- Exploits negative feedback loop already in place
Synthetic progestins produce what?
- Thin and inactive endometrium
- Thick cervical mucus to inhibit sperm migration
What are extended formulations?
84 days of hormones and then 7 days of placebo, will still get normal menstrual cycle, blood does not accumulate, simply for convenience
What is the transdermal patch?
Changed every 7 days for three weeks, week 4 patch three to allow menstruation to occur
What is the vaginal route?
- Nuva ring
- Inserted for three weeks of hormone therapy, removed on week 4 to allow for menstruation to occur
What are some of the benefits of oral contraceptives?- Reduced PS symptoms
- Reduced PS symptoms
- Reduction in risk of certain cancers (colorectal, ovarian and endometrial)
Decreased risk of ovarian cysts and endometriosis - Improvements in mineral bone density and acne
- No effect on fertility
How does combination contraceptive therapy prevent ovarian cancer?
When an ovum is released, damage occurs, repair mechanisms can cause issues, predisposed women may take this to reduce the number of times they will ovulate, and reduce their risk of developing ovarian cancer
What are some of the adverse effect of combination contraceptive therapy?
- Breast milk reduction
- Increased blood glucose
- Hypertension
- Increased appetite, weight gain, fatigue, depression, acne, hirutism (associated with increased levels of progestin)
- Menstrual irregularities (associated with low levels of progestin)
- Nausea, edema, breast tenderness (associated with high levels of estrogen)
- Thromboembolitic disorders (increased especially in women over the age of 35, history of stroke, MI, DVT and pulmonary embolism)
What are the contraindications for combination contraceptive therapy?
- Breast cancers and other estrogen dependent tumors
- Severe hepatic cirrhosis
- Major surgery with prolonged immobilization (increased risk for clots)
- Migraines
- Impaired cardiac function
- Smoking (over age of 35 and 20+ cigarettes a day)
- History of stroke, MI, CAD, SLE and thromboembolic disorders
Caution should be taken when administering combination contraceptives to people with which disorders/conditions?
People with: - Depression - Hypertension - Migraines (without aura) - Diabetes - Epilepsy - Renal/liver dysfunction Look for worsening of symptoms and discuss the options that they may have
What are progestin only contraceptives also known as?
Mini-pills
What are mini-pills?
- Continuous administration, no break
- Low dose formulation may not reliably inhibit ovulation
- Need to be taken every day within the same three hour window or there is risk for spontaneous ovulation
What should a patient do if they want to have sex and they’ve taken their pill outside of the 3 hour window?
Use a barrier method of contraception for 48 hours after missing the pill
What action should a patient take if they’ve had unprotected sex and they took the pill outside of the three hour window?
Emergency contraception is recommended
What effects does the mini-pill have on the female reproductive system?
- Creates a thick and viscous cervical mucous, prevents the movement of sperm across the cervix
- Endometrium is kept in an atrophic state which inhibits zygote implantation
Which patients should use mini-pills?
- Patients who have an intolerance to estrogen
- Patients who will reliably take the pill within the three hour window
What is the oral formulation of progestin only contraceptives called?
Mini-pills:
- Higher rate of failure than combination oral contraceptives
- 3 failures per 100 women per year
What is the subdermal (progestin only) implant called?
How long does it last?
What is its effectiveness?
Nexplanon:
- Offers 3 years of protection
- Very effective
- Not available in Canada, only is Asia and Europe
What is the IM (progestin only) injection called?
Depo-Provera:
- Provides protection for 3 months, protection achieved within 24 hours
- Will prolong or delay time to pregnancy, can take up to 10 months after stopping injections to get pregnant
What is the IUD (progestin) called?
Mirena:
- Secretes progestins and provides coverage for 5 years, good choice for someone who forgets to take their pills
What are some of the adverse effects associated with progestin only contraceptives?
- Greater risk of menstrual irregularities compared to combination OC’s, amenorrhea, prolonged menstrual bleeding, breakthrough spotting
- Increased risk of ovarian cysts and breast cancer
- Increased appetite, weight gain, fatigue, depression, acne, hirutism, headache
What are some of the benefits of progestin only contraceptives?
Well suited for women with:
- Certain types of migraine headaches
- Smokers (>35 years of age)
- Hypertension
- Breastfeeding women
- Nausea with combination oral contraceptives
What are emergency contraceptives?
- Used to prevent unplanned pregnancy related to unprotected sexual intercourse or contraceptive failure
- Used to prevent ovulation
What pills are taken for emergency contraception?
- Two doses of levonorgestrel within 72 hours of intercourse
- First dose taken as soon as possible and 2nd dose taken 12 hours after the first
- Most effective if taken within 24 hours, success rate decreases with each 12 hour delay
What are some of the side effects of emergency contraception?
- Nausea
- Vomiting
- Dizziness
- Headache
- Breast tenderness
- Fatigue
- Diarrhea
Why should an anti-emetic be taken with emergency contraception?
Often causes nausea and vomiting which reduces the efficacy of the drug
What is a factor that decreases the success of emergency contraceptives?
Weight, if a woman is between 75-80 kg it will be less effective, and it will not be effective at all in patients over 80 kg
What are some examples of abortifacents?
- Mifegymiso (RU486)
- Mifepristone
- Misoprostol
What is mifegymiso?
- Used to terminate an unwanted pregnancy with a gestational age of 49 days (measured by LMP)
- No long term effects, normal pregnancy can occur in the future
What is mifepristone?
- Progesterone receptor modulator, single dose, 200 mg PO
- Blocks the effects of progesterone on the endometrium and myometrium
- Progestin antagonist, uterus will contract
What is misoprostol?
- Prostaglandin
- 4 tablets (200 mcg each) taken 24-48 hours post-mifepristone
- Buccal administration
- Induces contraction of the myometrium and cervical dilation
- Encourage them to take an anti-emetic to prevent vomiting which reduces efficacy
What is hormone replacement therapy and what does it treat?
Combination estrogen and progesterone used to treat primary ovarian failure and symptoms of menopause
What are some of the symptoms of menopause?
- Insomnia
- Hot flashes
- Vaginal atrophy
- Mood disturbances
- Irritability
- Osteoporosis
With women with an intact uterus, what does the use of just estrogen increase the risk of?
Uterine cancer, patients who have had a hysterectomy this is not an issue
According to WHI and HERS hormone replacement therapy is associated with an increased risk of what in women aged 60 and older?
- MI
- Stroke
- Breast cancer
- Dementia
- DVT
Level of risk depends on the individual - health history, age, number of years since the start of menopause
Some women with what condition benefit from HRT?
Colon cancer
What are the symptoms/conditions associated with early menopause?
- Mood disturbances, depression, irritability
- Insomnia
- Hot flashes
- Irregular menstrual cycles
- Headaches
What are the symptoms/conditions associated with mid-menopause?
- Vaginal atrophy, increased infections, painful intercourse
- Skin atrophy
- Stress urinary incontinence
- Sexual disinterest
What are the symptoms/conditions associated with post-menopause?
- Cardiovascular disease
- Osteoporosis
- Alzheimer’s-like dementia
- Colon cancer
What is Duavive?
- Estrogen and bazedoxifene, a selective estrogen receptor modulator
- Bazedoxifene antagonizes the effects of estrogen on the uterus, reducing risks of uterine cancer, but demonstrates antagonist activity on bone
- Used for management of symptoms associated with menopause (mainly hot flashes) and reduces the risk of menopause-induced osteoporosis
- Patients get the benefits of estrogen without the risk of uterine cancer
- Generally well tolerated
- There will always be risk for clotting conditions
What are some of the adverse effects of duavive?
- Muscle spasms
- Nausea
- Diarrhea
- Upset stomach
- Abdominal pain
- Throat pain
- Dizziness
- Neck pain
