Pharm - GYN Potpourri

Question 1

risk factors for vulvovaginal candidiasis

Answer 1

• abx
• hormonal contraceptives
• contraceptive devices
• weakened immune system
• pregnancy
• DM
• sexual activity

Question 2

mechanism of action of azole antifungals

Answer 2

• 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.

Question 3

Identify the major route of elimination of the imidazoles

Answer 3

hepatic metabolism

Question 4

list the imidazoles and the triazoles

Answer 4

Imidazoles:

• miconazole
• butoconazole
• terconazole
• tioconazole
• clotrimazole

Triazole:
- fluconazole

Question 5

half-life of fluconazole

Answer 5

long serum half-life (approximately 24 hours)

Question 6

the common adverse reactions associated with the imidazoles

Answer 6

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.

Question 7

common GI and hepatotoxicity associated with fluconazole

Answer 7

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.

Question 8

Given a patient prescribed fluconazole who takes warfarin, state the nature of the interaction and the need to adjust the warfarin dose

Answer 8

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.

Question 9

criteria for an uncomplicated vaginal yeast infection

Answer 9

o Sporadic, infrequent episodes (≤3 episodes/year)
o Mild to moderate signs/symptoms
o Probable infection with Candida albicans
o Healthy, nonpregnant woman

Question 10

advantages / disadvantages of fluconazole for tx of uncomplicated yeast infection

Answer 10

• 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

Question 11

advantages / disadvantages of topical imidazole products or tx of uncomplicated yeast infection

Answer 11

• 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.

Question 12

criteria of a complicated yeast infection

Answer 12

• 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

Question 13

Given a woman with a complicated vaginal yeast infection, select the appropriate treatment regimen

Answer 13

• 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.

Question 14

initial oral induction and maintenence of recurrent VVC

Answer 14

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.

Question 15

appropriate drug regimen for VVC for a woman who is pregnant

Answer 15

• 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

Question 16

appropriate drug regimen for VVC for a woman who is breastfeeding

Answer 16

• 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

Question 17

role of NSAIDS in the treatment of Endometriosis

Answer 17

• 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.

Question 18

place in therapy for estrogen-progestin contraceptives in the treatment of endometriosis

Answer 18

• 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.

Question 19

place in therapy for GnRH agonists in the treatment of endometriosis

Answer 19

• 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

Question 20

mechanism of action of GnRH agonists

Answer 20

o GnRH agonists bind to receptors in the pituitary leading to a down-regulation of the pituitary-ovarian axis and hypoestrogenism results.

Question 21

adverse effects of GnRH agonists

Answer 21

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.

Question 22

Explain the use of progestins as add-back therapy to GnRH agonist therapy

Answer 22

• 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**

Question 23

Explain the use of estrogen/progestin combinations as add-back therapy to GnRH agonist therapy

Answer 23

• 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

Question 24

Given a woman with mild to moderate symptoms related to endometriosis, select the most appropriate regimen to manage her symptoms

Answer 24

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

Question 25

Given a woman using GnRH with or without add-back therapy, select the monitoring parameters to assess bone mineral density

Answer 25

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

Question 26

State the role of the aromatase inhibitors in the treatment of endometriosis

Answer 26

Should be reserved for women with severe, refractory endometriosis-related pain. Endometriosis is an off-label use of these medications

Question 27

Identify the effect of aromatase inhibitors effect on bone density

Answer 27

Can cause bone loss with prolonged use

Question 28

place in therapy for aromatase inhibitors

Answer 28

usually prescribed in combination with GnRH agonist or an oral estrogen-progestin contraceptive to suppress follicular development

Question 29

place in therapy for danazol

Answer 29

should only be considered after all other therapies have failed→should be limited to 6 months of therapy

Question 30

adverse effects of danazol

Answer 30

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

Question 31

Given a woman with dysmenorrhea choose the most appropriate NSAID therapy

Answer 31

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

Question 32

State the effect of NSAIDs on fertility

Answer 32

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

Question 33

State the role of estrogen-progestin combinations in the treatment of dysmenorrhea

Answer 33

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