Pharm - GYN Potpourri Flashcards
risk factors for vulvovaginal candidiasis
- abx
- hormonal contraceptives
- contraceptive devices
- weakened immune system
- pregnancy
- DM
- sexual activity
mechanism of action of azole antifungals
- inhibit the enzyme lanosterol 14-alpha-demethylase
- This enzyme is necessary for the conversion of lanosterol to ergosterol, a vital component of the cellular membrane of fungi
- reduced fungal membrane ergosterol content and the increased lanosterol-like sterols leads to significant damage to the cell membrane. It becomes increasingly permeable, resulting in cell lysis and death.
Identify the major route of elimination of the imidazoles
hepatic metabolism
list the imidazoles and the triazoles
Imidazoles:
- miconazole
- butoconazole
- terconazole
- tioconazole
- clotrimazole
Triazole:
- fluconazole
half-life of fluconazole
long serum half-life (approximately 24 hours)
the common adverse reactions associated with the imidazoles
o vulvovaginal burning, itching and irritation in 3-7% of women. They are more likely to occur with first application.
abdominal cramps, penile irritation, and allergic reactions can occur but are uncommon
o headache may occur in up to 9% of women.
common GI and hepatotoxicity associated with fluconazole
o GI sx are most frequently reported, including nausea, abdominal pain, vomiting, and diarrhea.
o Hepatotoxicity —
• associated with all azoles primarily oral administration.
• range from mild elevations in transaminases to severe hepatic reactions including hepatitis, cholestasis, and fulminant hepatic failure.
• approximate incidence of mild transient transaminase abnormalities associated with azole drugs is reported to be from 2 to 12 percent.
Given a patient prescribed fluconazole who takes warfarin, state the nature of the interaction and the need to adjust the warfarin dose
o The combined use of fluconazole and warfarin leads to an increase in the prothrombin time due to inhibition of CYP2C9 by the azole.
o A dose reduction of warfarin is necessary when used in combination with azoles, and monitoring of INR around the time of azole initiation is recommended.
criteria for an uncomplicated vaginal yeast infection
o Sporadic, infrequent episodes (≤3 episodes/year)
o Mild to moderate signs/symptoms
o Probable infection with Candida albicans
o Healthy, nonpregnant woman
advantages / disadvantages of fluconazole for tx of uncomplicated yeast infection
- Oral medications are prescription only, therefore, require a medical evaluation with the associated cost.
- One dose
- Oral dosage form
- Convenience
- Maintains therapeutic concentrations in vaginal secretions for 72 hours
- Well-tolerated—GI upset, headache, rash
- Comparable clinical cure rates
- Disadv: take 1 to 2 days longer to relieve symptoms
advantages / disadvantages of topical imidazole products or tx of uncomplicated yeast infection
- Well tolerated, few side effects: local burning or irritation
- Relief in 24 hours or less
- Most topical products are OTC, do not require a medical visit, cost less, and can be self-managed.
- Any woman whose symptoms persist after using an OTC preparation or who has a recurrence of symptoms within 2 months after treatment should be clinically evaluated and tested.
- Creams and suppositories in these regimens are oil-based and may weaken latex condoms and diaphragms. Avoid using these products together.
criteria of a complicated yeast infection
- Severe signs/symptoms
- Candida species other than C. albicans, particularly C. glabrata
- Pregnancy, poorly controlled diabetes, immunosuppression, debilitation
- History of recurrent (≥4/year) culture-verified vulvovaginal candidiasis
Given a woman with a complicated vaginal yeast infection, select the appropriate treatment regimen
- consider fluconazole (150 mg orally) for 2-3 sequential doses 72 hrs apart for tx of complicated infections, depending on the severity
- If the pt prefers topical tx, observational series report that complicated patients require 7 to 14 days of topical azole therapy rather than a one- to three-day course.
initial oral induction and maintenence of recurrent VVC
Use an induction therapy with oral fluconazole 150 mg every 72 hours for three doses followed by oral fluconazole (i.e., 100-mg, 150-mg, or 200-mg dose) weekly for 6 months is the first line maintenance regimen.
appropriate drug regimen for VVC for a woman who is pregnant
- use a topical imidazole (clotrimazole or miconazole) vaginally for seven days
- Fluconazole may increase the risk of miscarriage and high doses may increase the risk of birth defects.
- tx of pregnant women is primarily indicated for relief of symptoms; vaginal candidiasis is not associated with adverse pregnancy outcomes
appropriate drug regimen for VVC for a woman who is breastfeeding
- Fluconazole is excreted in human milk, but the American Academy of Pediatrics (AAP) considers the use of fluconazole compatible with breastfeeding.
- There is no information on the effect of miconazole, butoconazole, clotrimazole, tioconazole, or terconazole on nursing infants, but systemic absorption after maternal vaginal administration is minimal, hence topical use in nursing mothers is reasonable
role of NSAIDS in the treatment of Endometriosis
- NSAIDs may help with pain relief for mild symptoms
- Women who desire pregnancy can use NSAIDs, avoid selective COX-2 inhibitors (Celebrex®, celecoxib) as some studies indicate these drugs can prevent or delay ovulation.
place in therapy for estrogen-progestin contraceptives in the treatment of endometriosis
• Combined estrogen-progestin contraceptives (pills, transdermal patches, vaginal ring) are the first-line treatment for most women with endometriosis-related pain
o can be used long-term,
o are well-tolerated,
o provide contraception
o provide additional benefits including decreased risk of ovarian and endometrial cancers.
o selection is based on patient preference, availability, and cost.
place in therapy for GnRH agonists in the treatment of endometriosis
• Women with severe symptoms (e.g., regularly missing school or work because of pain), symptoms that do not respond to the above therapies, or recurrent symptoms are offered a trial of GnRH agonist with add-back hormonal therapy
mechanism of action of GnRH agonists
o GnRH agonists bind to receptors in the pituitary leading to a down-regulation of the pituitary-ovarian axis and hypoestrogenism results.
adverse effects of GnRH agonists
o The main side effects of GnRH agonists result from the hypoestrogenic state; the majority of women become hypoestrogenic within the first four weeks of therapy; with almost all women are hypoestrogenic by eight weeks.
Explain the use of progestins as add-back therapy to GnRH agonist therapy
- used with GnRH agonist for pelvic pain from endometriosis
i. Combo preserves bone density & reduces vasomotor effects of GnRH agonist
ii. Daily calcium supplements should be should be considered
iii. Improves adherence to GnRH agonist therapy
iv. First line if hormonal add-back is used**
Explain the use of estrogen/progestin combinations as add-back therapy to GnRH agonist therapy
- for those that don’t tolerate high-dose progestin because of mood changes, weight gain, bloating
i. Use not approved by FDA
ii. Combo is effective in treating pelvic pain from endometriosis and reducing GnRH side effects
iii. Bone mineral density loss may occur with very low doses of hormones
Given a woman with mild to moderate symptoms related to endometriosis, select the most appropriate regimen to manage her symptoms
a. Frist line: usually estrogen-progestin contraceptives for endometrial pain→because can be used long-term, are well-tolerated, provide contraception, provide additional benefits including decreased risk of ovarian/endometrial cancers
b. First line if mild-moderate symptoms and no US evidence of endometrioma: NSAIDs + continuous hormonal contraceptives
c. NSAIDs used for pain relief in mild symptoms
d. Selection based on patient preference, availability and cost
Given a woman using GnRH with or without add-back therapy, select the monitoring parameters to assess bone mineral density
a. Without add-back therapy: can cause significant bone loss so check on it, limit treatment to 6 months
i. Accelerated loss in 20s-30s = increased osteoporotic fractures in 60s-70s
b. With add-back therapy: monitor lipids because combination can lead to significant reduction in HDL and increase in LDL and triglycerides. Combination decreases bone loss
State the role of the aromatase inhibitors in the treatment of endometriosis
Should be reserved for women with severe, refractory endometriosis-related pain. Endometriosis is an off-label use of these medications
Identify the effect of aromatase inhibitors effect on bone density
Can cause bone loss with prolonged use
place in therapy for aromatase inhibitors
usually prescribed in combination with GnRH agonist or an oral estrogen-progestin contraceptive to suppress follicular development
place in therapy for danazol
should only be considered after all other therapies have failed→should be limited to 6 months of therapy
adverse effects of danazol
a. Weight gain (5% body weight), muscle cramps, decreased breast size, acne, hirsutism, oily skin, decreased high density lipoprotein levels, irreversible deepening of voice, increased liver enzymes, hot flashes, mood changes, depression
b. Dose-dependent
Given a woman with dysmenorrhea choose the most appropriate NSAID therapy
a. Start with: Phenylpropionic NSAID→ibuprofen (Motrin 400-800mg Q6 hrs)/naproxen (Aleve 220mg Q8-12hrs)→take on schedule bases instead of PRN and continue for 2-3 days based on symptoms
b. If don’t get adequate response to those: Fenamate NSAID→mefenamic acid (Ponstel 500mg loading dose, 250mg Q6hrs x3 days)→unique because inhibits prostaglandin synthetase and blocks action of prostaglandins that are already formed
State the effect of NSAIDs on fertility
a. Prostaglandins play important role in ovulation so→NSAIDS (esp. COX-2 inhibitors) can prevent/delay ovulation
b. If trying to conceive, usually okay to take since agents only used at time menstruation
i. If having trouble conceiving→suggest discontinuing NSAIDs altogether
State the role of estrogen-progestin combinations in the treatment of dysmenorrhea
a. First line for women with dysmenorrhea who also need contraception
b. Contain potent synthetic progestins, which suppress ovulation and cause endometrium to become thin over time→thin endometrium has small amounts of arachidonic acid (substrate of most prostaglandin synthesis→changes in endometrium causes reduction in menstrual flow and uterine contractions at menses→decrease dysmenorrhea
c. Also prevent ovulation→may also decrease dysmenorrhea
