Male / Female Health Flashcards
Osteoporosis:
-Risk Factors
-Complications
-When should osteoporosis be screened?
-Labs/Diagnosis
Risk Factors: females, POST-MENOPAUSAL WOMEN, increasing age, ethnicity (white and Asian women), lifestyle (low Ca/vitamin D, excessive alcohol, smoking, physical inactivity –> bones grow from STRESS), medical conditions (DM, eating disorders, GI disease, hyperparathyroidism, RA, autoimmune diseases)
Complications:
-Vertebral fractures: occur WITHOUT falls, can be initially painless, but may cause gradual loss of height
-Hip fractures: MOST DEVASTATING with higher costs, disability, and higher mortality
-Wrist fractures: can be an EARLY indicator in young people of poor bone health
Screening: BMD in ALL women >/=65 yo and men >/=70 yo
-Earlier if hx of fractures associated with falls or have risk factors
-Fracture Risk Assessment Tool (FRAX): developed by WHO to estimate risk of osteoporotic fracture in the next 10 years for post-menopausal women and men >50 yo
Labs/Diagnosis:
-Bone Mineral Density (BMD): GOLD standard to diagnose using dual-energy X-ray absorptiometry (DEXA) and calculates T-score
-T scores: normal >/=1; osteopenia -1 to -2.4; osteoporosis: -2.5 or less
-Ultrasound: provide bone density screening in only one area of body
What medications can contribute to osteoporosis?
Aromatase inhibitors, GnRH AGONISTS
STEROIDS (>/=5mg/day of prednisone or equivalent) >/=3 months), thyroid hormones (in excess), Depo-medroxyprogesterone
Lithium, ANTICONVULSANTS (carbamazepine, phenytoin, phenobarbital –> INDUCERS of vitamin D and estrogen metabolism), SSRIs
PPIs (increase pH which can decrease Ca carbonate), loop diuretics if taken long-term, TZDs, tenofovir, heparin
**Men who usually have bone loss similar to women are ones on steroids (ex. COPD exacerbations/bronchitits) or GnRH agonists for prostate cancer
Prevention measures for osteoporosis
- Fall preventative measures - reduce or adjust medications that cause sedation or orthostasis (ex. anti-HTN, sedatives, hyponotics, narcotic analgesics, psychotropics)
-Home safety assessment, safe clothing/shoes usage, adequate lighting, safe floors, handrails
-Control of other medical conditions (dementia, PD, prior stroke, urinary/fecal urgency, imapired vision/hearing) - Lifestyle measures - (weight-bearing exercises, muscle-strengthening exercises*, smoking cessation, reduction of alcohol intake
*3. Calcium - DIETARY intake preferred, but often hard to achieve
-Calcium carbonate (Tums, Cis Cal, Caltrate, Oysco): 40% elemental Ca++, but requires acidic environment for absorption (take w/ food that do NOT have Ca in them)
-Calcium citrate (Cal-citrate): 21% elemental Ca++; better absorption (ideal in pts taking PPIs)
-Recommended intake: 1000-1200mg/day (body cannot absorb more than 500-600mg at a time –> divide doses)
- Vitamin D - required for Ca++ absorption
-Deficiency: serum 25-OH-vitamin D <30 ng/mL
-Treat deficiency w/ cholecalciferol (D3) 125-175 mcg (5000-7000 IU) QD or ergocalciferol 1,250mcg (50,000 IU) weekly
-General intake is controversal of 600-2000 IU/day (safe upper limit of 4000 IU/day, but okay to exceed in deficiency)*
Osteoporosis: Prevention/TX (TX criteria)
Prevention meds: bisphosphonates (except IV ibandronate), estrogen-based therapies, raloxifene, Duavee (conjugated estrogens/bazedoxifene)
TX meds: bisphosphonates, denosumab, parathyroid hormone analogs (teriparatide, abaloparatide), clacitonin
TX criteria:
-Osteoporosis: postemenopausal women or men >50 yo w/ T score less than or equal to -2.5 at femoral neck, total hip, or lumbar spine OR PRESCENCE OF FRAGILITY FRACTURE REGARDLESS OF BMD
-High risk Osteopenia: T score between -1 and -2.5 AND FRAX score of major osteoporosis-related fracture>/= 20% or >/=3% for hip fracture (ex. PD would be high risk)
First line: bisphosphonates x3-5 years w/ low fracture risk (limited time due to risks of bone AVEs)
-Alternative: denosumab, raloxifene or Duavee if high risk of vertebral fractures
-HIGH risk (hx of severe vertebral fractures): teriparatide, abaloparatide
Last line or NOT recommended:
-Estrogen w/ or w/o progestin: for prevention ONLY in post-menopausal women w/ vasomotor symptoms (use lowest dose for shortest duration)
-Calcitonin: for treatment ONLY if other options NOT SUITABLE (less effective and has risk of cacner w/ long-term use)
Bisphosphonates:
-Drugs/Brands
-MOA
-TX
-ROA/Dosing frequency for osteoporosis
Drugs: alendronate (Fosamax, Binosto -effervescent tablet), alendronate/cholecalciferol (Fosamax D), risedronate (Actonel, Atelvia), ibandronate (Boniva - D/C), zoledronic acid (Reclast, Zometa - hypercalcemia of malignancy)
MOA: inhibits osteoblast activity and bone resoprtion
-Reduce vertebral and hip fracture risk (EXCEPT: ibandronate only reduces vertebral fractures)
TX: prophylaxis of osteoporosis in post-menopausal women, osteoporosis TX, glucocorticoid-induced osteoporosis
-Osteoporosis TX in men: alendronate, risedronate, zoledronic acid
-Zoledronic acid preferred if esophagitis present due to risk for esophagitis cancer
ROA/Dosing frequency for osteoporosis:
-Alendronate: PO, QD or weekly
-Risedronate: PO QD, weekly, or monthly
-Ibadronate: PO monthly OR IV Q3 months
-Zoledronic acid: IV Qyear
Bisphosphonates: Administration counseling points
-PO: take in morning when after waking up; must stay upright for 30 minutes (60 minutes for ibandronate) and drink 6-oz of water ONLY (no other liquids - drug is “sticky”)
-Avoid other beverages, foods, or drugs within first 30 minutes
-Separate from calcium, antacids, iron, and Mg by at least 2 hours
-Atelvia (DR risedronate): requires acidic gut for absorption (do NOT use w/ PPIs or H2RAs)
-Missed doses: if taken QD, skip missed dose and take next dose at normal schedule; if taken Qweek, take missed dose next morning do NOT take two doses on same day; if taken Qmonth: take dose morning you remember unless less than one week from next dose
-Caution with ASA or NSAIDs (can worsen GI irritation)
-Dental work should be completed prior due to jaw decay/necrosis risk
Bisphosphonates (PO and IV):
-AVEs
-Warnings
-CIs
AVEs: DYSPHAGIA, DYSPEPSIA/HEARTBURN, N/V, HYPOCALCEMIA, hypophosphatemia (mild transient), abdominal pain, musculoskeletal pain
-Risedronate: HA, HTN, skin rash, UTI, infection
-IV: all listed, but dsyphagia and GI problems PLUS acute-phase rxn (flu-like syptoms)
-Zoledronic acid: edema, hypotension, fatigue, dehydration
Warnings:
-ONJ (Osteonecrosis of Jaw): increased risk w/ invasive dental procedures, poor hygiene, cancer diagnosis, or chemotherapy/steroids
-Atypical femur fractures; bone pain/muscle pain
-Esophagitis, esophageal ulcers, erosions, strictures, etc.: follow adminsitration for PO
-Hypocalcemia: must be corrected prior to use
-Renal impairement: do NOT use if CrCl <35 mL/min (aledronate) of <30mL/min (ibandronate, risedronate)
-Zoledronic acid: use caution in ASA-sensitive asthma (risk of bronchoconstriction), avoid in pregnancy (teratogenic)
CIs: HYPOCALCEMIA
-Inability to stand or sit upright for 30 minutes (60 minutes for ibandronate)
-Abnormalities of esophagus for PO agents
-High risk of aspiration (effervescent tablet or oral solution)
-Zoledronic acid: CrCl <35mL/min or evidence of acute renal impairment
Raloxifene:
-Brand
-MOA
-ROA
-TX
-Administration
-AVEs
-CI
-BBW
Brand: Evista
MOA: selective estrogen receptor modulator (SERM) that decreases bone reasorption for prevention of osteoporosis
ROA: PO
TX: osteoporosis prophylaxis in postmenopausal women
Administration:
-Seperate raloxifene and levothyroxine by several hours
-D/C 72 hours prior to and during prolonged immobilization
AVEs: HOT FLASHES, PERIPHERAL EDEMA, ARTHRALGIA, LEG CRAMPS, muscle spasms, flu symptoms, infection
CI: PREGNANCY, hx or current VTE
BBW: risk of VTE (DVT/PE), increased risk of death due to stroke in women w/ CHD or at risk of coronary events
Conjugated estrogens/bazedoxifene:
-Brand
-MOA
-ROA
-TX
-AVEs
-Warnings
-CI
-BBW
Brand: Duavee
MOA: equine estrogen/SERM combination
ROA: PO
TX: prevention of osteoporosis in post-menopausal women WITH INTACT UTERUS
-Estrogen only drug that will continue for the uterus to grow if no opposing progesterone (potentially cancerous)
AVEs: N/D, dyspepsia, abdominal pain, muscle spasms
Warnings:
-*Increased risk of breast cancer and ovarian cancer *
-Increased risk of retinal vascular thrombosis
-Lipid effects (increased HDL, increased TG, decreased LDL)
CI:
-ANY HX OF BREAST CANCER
-PREGNANCY
-UNDIAGNOSED UTERINE BLEEDING
-HX OR ACTIVE VTE, MI, or stroke
-Protein C, S, or antithrombin deficiency
-Hepatic impairment
BBW: endometrial cancer due to unopposed estrogen, increased risk of DVT and stroke, dementia (women >/=65 yo)
Calcitonin:
-Brand
-MOA
-ROA
-Adminstration
-AVEs
-Warnings
Brand: Miaclacin
MOA: inhibits bone resorption by osteoclasts (less effective than other osteoporosis agents so rarely used)
ROA: nasal spray (one spray in one nostril QD alternating nostrils), injection (SQ or IM)
Administration:
-Keep refrigerated
-Nasal spray: store at room temp once warmed (refrigerate unused bottles), discard after 30 doses, prime pump before first use by pressing the two white side arms toward bottle and release at least five sprays
AVEs: back pain, myalgia, nausea, dizziness, injection site rxns/flushing
Warnings:
-HYPOCALCEMIA associated w/ tetany (involuntary contractions) and seizures
-Increased RISK OF MALIGNANCY w/ long-term usage
-HYPERSENSITIVITY rxns to SALMON-derived products
-Antibody formation
-Nasal spay: nasal ulcerations, epistaxis, rhinitis (nasal exams recommended)
Parathyroid hormone 1-34 analogs:
-Drugs/Brands
-MOA
-ROA/Dosing frequency
-Administration
-TX
-AVEs
-Warnings
Drugs: teriparatide (Forteo), abaloparatide (Tymlos)
MOA: analogs of human parathyroid hormone which stimulates osteoblast activity and INCREASES BONE FORMATION
ROA/Dosing Frequency: SQ daily
Administration:
-Keep refrigerated
-Forteo: protect from light
-From osterosarcoma risk, restricted use to 2 years or less
TX: osteporosis TX in both males and females, glucorticoid-induced osteoporosis (Forteo)
AVEs: ARTHRALGIAS, LEG CRAMPS, NAUSEA, ORTHOSTASIS/DIZZINESS
-Tymlos: increased uric acid, antibody development, erythema at injection site (58%)
Warnings:
-OSTEOSARCOMA (BONE CANCER): risk dependent on dose and duration of useage (dO NOT use in bone malignancy or metabolic bone diseases)
-HYPERCALCEMIA
-Orthostatic hypotension,
-Caution w/ urolithiasis (urinary stones)
Denosumab:
-Brand
-MOA
-ROA/Dosing frequency
-AVEs
-Warnings
-CI
-BBW
Brand: Prolia, Xytega
MOA: MAB that binds to RANKL (Nuclear factor kappa-B ligand) which is a receptor on osteoclasts to prevent formation which decreases bone resorption and increases bone mass
ROA/Dosing frequency (osteoporosis): SQ Q6 months
TX: *osteoporosis TX (preferred over bisphosphonates for impaired renal fxn)
-Xytega: hypercalcemia of malignancy, bone cell tumor, and prevention of bone metastasis *
AVEs: HTN, FATIGUE, EDEMA, N/V/D, DECRASED PO4, dyspnea, HA
-If D/C, bone loss can be rapid (consider alternative to maintain BMD)
Warnings:
-ONJ (Osteonecrosis of jaw): increased risk w/ invasive dental procedures, poor dental hygience, cancer, chemotherapy/steroids
-Atypical femur fractures; bone, joint, or muscle pain
-Hypocalcemia
-Infections (skin, urinary tract)
-Skin rxns (dermatitis, eczema, rash)
CI: HYPOCALCEMIA; PREGNANCY
BBW: SEVERE HYPOCALCEMIA in patients with advanced kidney disease (dialysis)
Romosozumab:
-Brand
-MOA
-ROA/dosing frequency
-TX
-AVEs
-CI
-BBW
Brand: Evenity
MOA: allows Wnt/beta-catenin pathway to proceed, promoting osteogenesis and inhibiting bone reabsorption
ROA: SQ two injections a month
-Limited to 12 month duration due to decreased efficacy overtime
-Keep refrigerated and let sit at room temp for 30 minutes priot to injection
TX: osteoporosis
AVEs: arthralgia, HA, injection site rxns
CI: hypocalcemia
BBW: increased risk of MI, stroke, and CV death
Menstrual Cycle:
1. A normal cycle ranges from __-__ days (average of ___ days) and day one of the cycle is ___________.
- What are the different phases of the cycle?
- When an oocyte is released, it lives for ____. An ovulation kit tests for _______ to determine the best time for intercourse for that day and the following ___ days.
- _________ is released when the fertilized egg attaches to the lining of the uterus that can be detected by a pregnancy test. These levels are highest in the urine during the _______(morning/evening).
- 23-35; 28; bleeding occurs (menses)
- -Follicular: follicle stimulating hormone (FSH) spurs follicle development causing estrogen to surge (estrogen peaks at end of phase which will cause LH and FSH to increase)
-Ovulatory: LH surge triggers ovulation 24-36 hours later –> release of egg (ova) from ovary
-Luteal: start of ovulation begins the luteal (last) phase during which the corpus luteum develops in ovaries and lasts for about 14 days (progesterone predominant in this phase)
- 24 hours; luteinizing hormone (LH); 2 days
- Human chorionic gonadotropin (HCG); morning (since urine is most concentrated in morning)
*What are general recommendations for pre-conception health? *
- Folic acid supplementation (vitamin B9) - folate deficiency can cause birth defects of brain and spinal cord (neural tube defects), pregnancy patients need 600mg of dietary folate/day (non-pregnant adults: 400mg/day)
- Smoking cessation, avoidance of alcohol and illict drugs
- Vaccinations - avoidance of illness
- Avoidance of toxic chemicals - ex. NIOSH drugs
- Consult HCP to evaluate teratogenic potential of all current medications
Non-pharmacological and OTC contraceptive methods
- Temperature and cervical mucus methods - tracks basal body temperature (temp in the AM) to predict ovulation (typical temp is 96-98F which increases to 97-99F during ovulation) in conjunction with mucus tracking; FDA approved apps (Natural Cycles) to help aid
2.Diaphragms and caps - should be done with spermicide
- Condoms - female or male
-Help prevent STIs if latex or polyurethane (plastic), NOT “natural” sheepskin
-Use w/ nonoxynol-9 spermicide can cause irritation and increase risk of HIV transmission
-Lubricants can reduce friction and decrease likelihood of condoms breaking, never recommend oil-based lubricant for latex or non-latex synthetic condom (use water or silicone-based lubricant)
- Others - foams, films, creams, suppositories, sponges, jellies
-*Contain spermicide, nonoxynol-9 *–> do NOT use w/ anal sex (irritating and can increase risk of STIs
Rank contraception methods in terms of efficacy
Most Effective: implant > intrauterine device > male sterilization > female sterilization (permanent)
Then: injectable > pill > patch > ring > diaphragram
Then: male condom > female condom > withdrawl > spronge
Least Effective: fertility-awareness based methods > spermicide
**Spermicide should be used with other methods
Hormonal Contraceptives:
1. How do hormonal contraceptives work to prevent pregnancy?
- What does the FDA require about oral contraceptives (OCs)?
- What other indications can hormonal contraception be used for?
- Inhibit production of FSH and LH, preventing ovulation; alter cervical mucus, inhibiting sperm from penetrating egg
- Require a patient package insert (PPI) to be provided
- *Decrease menstrual pain, menstrual irregularities, acne, anemia (by reduced blood loss)/heavy menstrual bleeding
-Combination oral contraceptives (COCs) first line for polycystic ovary snydrome (PCOS), endometriosis *
Hormonal Contraceptives”:
1. Types of birth control (hormone content, dose)
- What differs about progestin-only pills (POPs)?
- -Hormones: progestin only or estrogen/progestin (combined hromonal contraceptive = CHC)
-Monophasic: same dose of estrogen/progestin throughout pack
-Biphasic, triphasic, and quadriphasic: mimic estrogen and progestin levels during menstrual cycle with different changes in dose throughout pack (ex. biphasic = 2 different doses, triphasic = 3 different doses)
2
-MOA: suppress ovulation, thicken cervical mucus to inhibit sperm penetration, and thin the endometrium
-Primarily used in women who are breastfeeding since estrogen decreases milk production, also safe in migraines with aura (since no estrogen)
-Require good adherence: pills taken QD within 3 hours of schedule time
Hormonal Contraceptives: Duration
1. Most combined oral contraceptive (COCs) involve ___ days with ___-___ pills containing active hormone and during _________, bleeding occurs.
- What are extended-cycle COCs and continuous contraceptive?
- ____________ is specifically approved as a continuous contraceptive whereas the others are off-label.
- For how long should patches and vaginal rings be used for and then removed?
- Depo-Provera is injected every ________. What is the ROA?
- 28; 21-24; the last week
- -Extended-cycle COCs: 84 days of active pills folowed by 7 days of inactive or very-low dose estrogen pills (bleeding occurs Q3 months)
-Continuous cycle COCs: pt takes only hormonal pills (no placebo) to suppress menses altogether - Amethyst
- Three weeks using then week 4 off
- Three months; IM or SC
Combination Oral Contraceptives (COCs):
1. What do “Lo”, “Fe”, “24”, “Nor”, and “Pro” indicate?
- List monophasic that contain:
-21 active pills + 7 inactive pills (21/7)
-24 active pills + 4 inactive pills (24/4)
-24 active pills + 2 pills with just EE (same dose) + 2 inactive pills (21/2/2)
- -Lo: indicates less estrogen and less estrogenic AVEs
-Fe: indicates iron supplement included
-24: indicates shorter placebo time –> 24 active + 4 placebo = 28 day cycle
-Nor: contains norethindrone (ex. Nora-BE)
-Pro: indicates a progestin in the product (ex. Depo Provera) - -21/7: Junel Fe 1/20, Microgestin Fe 1/20, Sprintec 28, Loestrin 1/20, Yasmin 28, Apri, Aviane, Cryselle-28, Levora-28, Nortrel 1/35, Ocella, Porvtio-28, Zovia 1/35
-24/4: Yaz, Loestin 24 Fe (D/C), Beyaz, Minastrin 24 Fe, Nikki
-21/2/2: Lo Loestrin Fe
Combination Oral Contraceptives (COCs):
1. List triphasic, and quadriphasic formulations.
- List extended cycle and continuous formulations.
- What formulations contain drospirenone, what is unique about drospirenone? What are some CIs to these formulations?
- -Triphasic: have “tri” in the name –> Tri-Sprintec, Ortho Tri-Cyclen Lo, Notrel 7/7/7, Trivora-28, Vellvet
-Quadriphasic: Natazia
- -Extended cycle: Jolessa (84 days of EE + LNG + 7 days placebo); 84 days of EE/LNG + 7 days of low dose EE: Seasonique, Camrese, Camrese Lo, Amethia
-Continuous: Amethyst (28 days EE + LNG, no placebo)
3.. Yasmin 28, Yaz, Loryna, Ocella, Nextstellis, Nikki, Safyral, Syeda, Beyaz
-Drospirenone: mild-potassium sparing diuretic which can decrease bloating, PMS symptoms, and weight gain; also low androgenic activity (less acne)
-CI: renal or liver disease
Contraceptive Brand Names:
1. Microgestin Fe 1/20
- Sprintec 28
- Errin
- NuvaRing
- Tri-Sprintec
- Yasmin 28
- Norethindrone/EE/Fe
- Norgestimate/EE
- Norethindrone
- Etonogestrel/EE vaginal ring
- Noregestimate/EE
- Drospirenone/EE
Contraceptive Brand Names:
1. Junel 1/20
- Yaz
- Lo Loestin Fe
- Seasonique
- Xulane
- Loestrin 1/20
- Norethindrone/EE/Fe
- Drospirenone/EE
- Norethindrone/EE/Fe
- Levonorgestrel/EE x84 days then EE x7 days
- Norelgestromin/EE patch
- Norethindrone/EE
Contraceptive Brand Names:
1. Amethyst
- Camila
- Nora-BE
- Opill
- Depo-Provera
- Levonorgestrel/EE
- Norethindrone
- Norethindrone
- Norgestrel
- Medroxyprogesterone injection
Estrogen: AVEs
-Nausea, breast tenderness/fullness, bloating, weight gain, increased BP (usually about 5-8mmHg), melasma (dark skin patches often on face)
-Serious AVEs: thrombosis (heart attack, stroke, DVT, PE) –> increased risk w/ age, smoking, HTN, DM, or overweight
-Symptoms to recognize for thrombosis: ACHES
A: Abdominal pain that is severe –> can indicate mesenteric or pelvic vein thrombosis
C: Chest pain - sharp, crushing, or heavy pain, SOB
H: Headaches –> sudden and severe w/ vomiting or weakness/numbness on one side of body
E: Eye problems: blurry vision, flashing lights, or partial/complete vision loss –> blood clot in eye
S: Swelling or sudden leg pain
Progestin: AVEs
-Breast tenderness, HA, fatigue, and depression
-*Drospirenone: slightly higher risk of clotting, incresaed K levels (do NOT take w/ kidney, liver, or adrenal gland disease or those w/ high K baseline)
-Injectable depot medroxyprogesterone acetate: loss in BMD (vitamin D and calcium supplementation recommended)*
Other Hormonal Contraceptive Effects:
1. Most contraceptives have reversible fertility except for ________ which has a delay in return to fertility.
- Breakthrough bleeding (spotting) usually resolves within _____-_____ time frame. This is more common in continous contraception where the spotting may resolve within ____-____ time frame.
- How to adjust for persistent spotting.
- Medroxyprogesterone injection (Depo-Provera)
- 2-3 months; 3-6 months
- -Check adherence
-Wait at least 3 cycles before switching; if early or mid-cycle spotting, estrogen dose may need to be increased; if later in cycle, progestin dose may need to be increased
-Currently taking <30 mcg estrogen QD –> increase estrogen dose
-Currently taking >/=30 mcg estrogen QD –> try different progestin
Other Hormonal Contraceptive Effects:
1. CIs for estrogen-containing contraceptive
- BBWs
CIs:
-Hx of DVT/PE, stroke, CAD, thrombosis of heart valves or acquired hypercoagulation
-Hx of breast, ovarian, liver, or endometrial cancer
-Liver disease; uncontrolled HTN (>160/100mmHg); severe HAs or migraines w/ aura (especially if >35 yo of age); DM w/ vascular disease; unexplained uterine bleeding
- BBWs:*
-ALL CHC products (pills, ring, patch): do NOT use in women >35 yo who smokes due to serious CV events
-Estrogen + progestin transdermal patch: do NOT use in BMI >/=30 kg/m2 –> increased risk of thromboembolism
-Depo-Provera: loss of BMD w/ long-term use
For the following condition/scenario, list what type of contraceptive is preferred:
1. Acne or hirsuitism
- Breastfeeding
- Increased clotting risk
- Migraine
- Use COC w/ lower-androgenic activity (ex. norgestimate - Sprintec 28; desogestrel; dienogest) OR no adrogenic activity (ex. drospirenone - Yaz, Yasmin)
- Progestin-only (POPs) or nonhormonal method
- Progestin-only (POPs) or nonhormonal method
- If with aura, progestin-only or nonhormonal method; if no aura, any method
For the following condition/scenario, list what type of contraceptive is preferred:
1. Mood changes/disorder
- Nausea
- Overweight
- Postpartum
- Monophasic COC - extended or continuous w/ drospirenone preferred
- Take at night with food, consider decreasing estrogen dose or switching to POP, vaginal ring, or nonhormonal method (ideally after 3 month trial)
- Any method - counsel on possibility of reduced effectiveness w/ patch (do NOT use patch in obesity)
-Do NOT use DMPA (depot medroxyprogesterone acetate) if trying to avoid weight gain - Do NOT use CHCS for 3 weeks or 6 weeks if additional VTE risk factors –> can use progestin-only or nonhormonal method during this time
For the following condition/scenario, list what type of contraceptive is preferred:
1. Premenstrual dysphoric disorder
- Wishes to avoid monthly cycle/menses
- Fluid retention/bloating
- Heavy menstrual bleeding (menorrhagia)
- HTN
- Choose product containing drospirenone, SSRI may be needed
- Extended or continuous formulations; alternative: monophasic 28-day formulatio and skip placebo pills
- Choose product containing drospirenone
- Natazia (COC), Mirena (levonorgestrel-releasing IUD) are indicated; COCs w/ only 4 placebo pills, continouous, or extended regimens
- If uncontrolled, progestin-only or nonhormonal method
Hormonal Contraceptive DDIs
Injectables bypass first-pass metabolism, decreasing DDIs
DDIs that decrease hormonal contraceptive efficacy:
1. Some ABXs and antifungals - rifampin (induction can be prolonged and back-up contraception needed for 6 weeks after D/C), rifabutin, rifapentine, and griseofulvin
- Anticonvulsants - carbamazepine, oxcarbazepine, phenytoin, primidone, topiramate, perampenel
- *St. John’s Wort
- Smoking tobacco
- Ritonavir*-boosted PIs, bosentan, mycophenolate
- Colsevelam: separate by at least 4 hours
- Mounjaro (for COCs): use back-up contraception (non-PO or barrier) for 4 weeks after initiation and dose increases
Risks w/ Hepatitic C TX: Mavyret NOT recommended with any formulation containing >20mcg of EE due to risk of liver toxicity
-Check any new hepC drugs
Drospirenone: additive hyperkalemia (ex. aldosterone antagonists, potassium supplements, salt substitutes, ACEis, ARBs, heparin, canagliflozin, calcineurin inhibitors)
Oral Contraceptives: Administration
1. For COCs, , it takes ____ days of active pills to achieve contraceptive efficacy and backup contraception is required during this time frame UNLESS COC is started within ___ days after start of period.
- For COCs, what are the different starting methods: start today, sunday start, and first day start?
- When should POPs be started, and for how long should back-up contraception be used? What is different about POPs versus COCs?
- 7; 5
- -*Start today (“Quick start”): best practice recommendation –> maximizes time protected from unintentional pregnancy
-Sunday start: starts Sunday after onset of menstruation for pts that prefere menstraution occur during the week and is complete before the following weekend —> can lead to missed doses if pt runs out of refills over weekend
-First day start: starts first day of menses –> since started within 5 days after start of period, no back-up method of birth-control needed, protection immediate*
- At any time; use backup for first 48 hours unless started within 5 days of menses; all active pills (NO placebo)
What are general instructions for missed pills (when to use back-up contraception and consider emergency contraceptives)?
Always check package insert - very specific instructions per product
COCs:
-1 late or missed pill (<48 hours since last dose): take ASAP and take next dose as scheduled (even if that is 2 pills/day), NO back-up contraception required, emergency contracption (EC): NOT usually needed (consider if missed doses earlier in same cycle or in week 3 of previous cycle)
-2 missed pills (>/=48 hours since last dose): take most recent pill ASAP (discard other missed pills) and take next dose as scheduled (even if 2 pills/day); if during week 3, omit hormone-free week and start next pack of pills right after finishing current pack; back-up contracption for 7 days; EC: consider if unprotected sex in last 5 days on week 1 or consider during week 2 or 3
POPs (if >3 hours past scheduled dose):
-Take pill ASAP and take next dose on schedule
-Back-up contraception for 48 hours
-EC: consider if unprotected sex in last 5 days
Other forms of birth control:
1. _____ formulation has a higher systemic estrogen exposure with increased risk of thromboembolism. What are some brand names for these formulations?
- Xulane and Zafemy may be less effective in women who weigh > ____ lbs.
- ________ is a reusable vaginal ring that can be washed and stored when removed then reinserted for 1 year.
- ________ is a progestin-only pill approved without a prescription.
- What are formulations of progestin-only pills that contain a fixed dose of norethindrone? What is the one that is drospirenone-only?
- Patches; Brands: Xulane, Zafemy, Twirla
- 198 lbs
- Annovera
- Opill
- -Fixed dose of norethindrone: Errin, Camiliar, Nora-BE
-Drospirenone-only: Slynd
What are some long-acting reversible contraceptives and their considerations?
-
Hormonal interuterine devices containing levonorgestrel: Mirena, Skyla, Kyleena, Liletta
-Cause lighter menstrual bleeding or amenorrhea and minor or no cramping
-Can be left in place from 3-8 years - Copper-T IUD (Paragard)
-Can be used for up to 10 years, but can cause heavier menstrual bleeding and cramping
-Can be used for emergency contraception or regular birth control - Implant (Nexplanon)
-Plastic rod placed subdermally in arm
-Releases etonorgestrel for three years
Emergency Contraception (EC) Options: compare effectiveness, timing, and considerations
-For hormonal methods, MOA and AVEs
Copper IUD (Paragard): most effective, within 5 days
-Considerations: must be placed by HCP and lasts up to 10 years
Ullipristal acetate 30mg (Ella): more effective than levonorgestrel, ASAP within 5 days
-Considerations: Rx required, must be taken after every episode of unprotected sex, less effective if >195 lb or BMI > 30, progestin-containing contraceptive should NOT be used in combo or within 5 days of administratoin (decreased efficacy of ullipristal concern)
-MOA: chemically related to mifepristone, but works differently –> prevents or delays ovulation and may alter endometrium to impair implantation (contraversal for some pts)
-AVEs: HA, nausea, abdominal pain, sometimes changes in menstrual cycle timing
Levonorgestrel 1.5mg tablets (Plan B One-step): least effective from above options, ASAP within 3 days
-Considerations: OTC and can purchase multiple doses, must be taken after every episode of unprotected sex, less effective if >165 lbs or BMI >25
-MOA: preventing or delaying ovulation, thickens cervical mucus
-AVEs: primarily nausea (if easily nauseated, take OTC antiemetic –> if vomits within 2 hours of taking medication, consider repeat dose)
Emergency Contraception (EC): Counseling
- Consider OTC antimetic - if vomit after taking dose, contact HCP or take another dose if OTC
- If you do NOT get your period in three weeks or it is more than a week late, take a pregnancy test
- You may wish to get a package of EC for future use.
- Regular hormone contraceptives should be started on same or following day (except: ulipirstal: start hormonal contraception after 5 days)
- Only use one type of oral EC pill. Do NOT use different types together.
Diaphragm: Counseling for Administration
- Wash hands thoroughly. Place one tablespoon of spermicide in diaphragm and disperse inside and around the rim.
- Pinch ends of cup and insert the pinched end into vagina
- Leave in for 6 hours after intercourse. Should NOT be placed greater than 24 hours.
- Reapply spermicide if intercourse repeated or diaphragm is in place for more than 2 hours before sex by inserting jelly with applicator.
- Wash with mild soap and warm water after removal. Air dry.
- Can be used for 2-5 years depending on material. Check frequently for holes between uses.
Contraceptive counseling on administration for:
-Foams, creams, suppositories, and jellies
-Sponge
-Patches
Foams, creams, suppositories, jellies:
-Place deep into vagina 10-15 minutes before intercourse where they melt (except for foam: bubbles)
-Reinsert if more than 1 hour passes before intercourse
Sponge:
-Wet the sponge and squeeze to activate
-Place deep in the vagina right before intercourse
-Leave in for at least 6 hours after intercourse up to 24 hours. Remove and discard.
Patches:
-Apply to clean, dry skin of buttocks, stomach, upper arm, or upper torso weekly for 21 of 28 days. Do NOT apply to breasts.
-Start on either day 1 (no-back up needed) or Sunday (back up 7 days if not day 1)
-If patch becomes loose or falls off for >24 hours during three weeks of use or if >7 days have passed during fourth week wher no patch required, risk of pregnancy –> use backup contraception for one week starting new patch
NuvaRing:
1. Off-label, NuvaRing can abe kept in place for up to 4 weeks for what purpose? What should be done if the ring is left in over 4 weeks?
- True or False: The exact position of the ring in the vagina does not matter.
- When starting, when should the ring be inserted, and how long should back-up contraception should be used?
- What should be done if the ring is expelled or removed prematurely?
- How shoudl NuvaRing be stored?
- To prevent period; confirm no pregnancy, insert new ring, and use back-up contraception for 7 days
- True
- Insert first day of menstrual bleeding (if inserted on day 2-5 of cycle, use back-up contraception for the first 7 days
- -Week 1 and 2: if ring out >3 hours, rinse with cool/lukewarm water and reinsert and use back-up contraception for 7 days while ring in place. Consider EC if intercourse within last 5 days.
-Week 3: discard and insert new ring and use back-up contraception for 7 days
- Refrigerate prior to dispensing, but store up to four months at room temperature
Infertility:
-Define
-TX options and how they work for females
-What are some of the risks to treatment?
Infertility: unable to get pregnant after one year or longer of unprotected sex
Female TX options:
1.* Clomiphene - selective estrogen receptor modulator (SERM) - agonists and antagonists of estrogen in certain tissues, causes LH and FSH to surge to trigger ovulation
- Letrozole - aromatase inhibitor - estrogen negative feedback (estrogen production suppressed to result in initial FSH surge)
- Gonadotropins - act as LH, FSH or HCG; often used after poor response to clomiphene or letrozole or to spur egg release for procedures (ex. intrauterine insemination, in vitro fertilization)*
-Brand names contain parts of words of reproduce, men(strual), follicle, gonadotropin, pregnancy, and ovary: Menopur, Follistim AQ, Gonal-f, Pregnyl, Novarel, Ovidrel
- Leuprolide (Lupron) - gonadotropin releasing hormone agonist (GnRHA) or exogenous HCG –> more commonly used in breast or prostate cancer
Risks:
Clomiphene: hot flashes from LH surge, clotting risks
-Clomiphene, gonadotropins: can cause multiple eggs to be released (risk of multiple births)
Pregnancy:
1. ________________ is the organization that publishes for safe and effective drug use in pregnancy.
- Which trimester is the most prone to teratogenic effects from drugs?
- What is gravida (G) and para (P) classifications for pregnancy?
- What should always be recommended first to pregnant patients with conditions?
- *American College of Obstetricians and Gynecologists (ACOG)
- First trimester (weeks 0-12): where most organ development occurs*
- -Gravida (G): number of times pt has become pregnant
-Para (P): number of times pt has given birth - Lifestyle modifications including behavioral interventions, smoking cessation, and reduction of alcohol and tobacco use
Pregnancy:
1. What vitamin and minerals are recommended in pregnancy?
- Vaccine recommendations
- Preclampsia - define and recommendations
- -Dietary folate of 600mcg/day or folic acid supplementation
-Calcium: 1000mg/day and Vitamin D 600IU/day –> without proper amounts, mother’s bone health will be sacraficed to provide for baby - Inactivated influenza vaccine any trimester, single dose of Tdap every pregnancy between weeks 27-36, RSV vaccine if weeks 32-36 during September to January
-ALL live vaccines CI
3.
-Preclampsia: elevated BP and evidence of oragn damage that typically occurs after 20 weeks of gestation (only cure is delivery of baby)
-Add low-dose ASA at end of first trimester of pregnancy for at risk pts (ex. DM, renal disease, hx of preclampsia, chronic HTN)
Pregnancy Risk: Old and New Classficiations
Old Classification:
-A: studies in amimals and women had NO risk in first trimester, risk of fetal harm remote
-B: animal studies have NOT demonstrated fetal risk, but NO well-controlled studies in pregnant women
-C: animal studies have shown harm to fetus, but NO well-controlled studies in pregnant women (use only if benefit outweighs risk)
-D: positive evidence to risk of human fetus, but benefits may outweigh risk w/ life-threatening or serious diseases
-X: studies in animals or women should fetal abnormlaities and risk clearly outweighs benefits –> CI in pregnancy
New classifciation: sections updated in package insert
1. Pregnancy section - includes risk of adverse developmental outcomes, drug’s pharmacology (dose adjustments, AVEs, disease risks), pregnancy exposure registry information (encourage women to participate - information collected while pregnant, breastfeeding, newborn baby)
- Lactation section -* includes whether drug/metabolites are present in human milk*, effects on infants, and effects on milk production
- *Females & Males of Reproductive Potential - any effects on infertility and requirements for preganncy testing and contraception *
Common teratogens
Acne: isotretinoin, topical retinoids
ABXs: quinolones, tetracyclines
Dyslipidemia, HF, and HTN: statins, RAAS inhibitors (ACEIs, ARBs, aliskiren, Entresto)
Hormones: most, including estradiol, progesterone (including megestrol), raloxifene, Duavee, testosterone, contraceptives
Migraine: dihydroergotamine, ergotamine
Others: hydroxyurea, lithium, methotrexate, misoprostol, NSAIDs, paroxetine, ribavirin, thalidomide, topiamate, warfarin, weight loss drugs, valproic acid/Divalproex
Pregnancy: for the following condition, state the preferred management and considerations
1. Morning Sickness, N/V
- GERD/Heartburn
Morning Sickness, N/V:
-First line: lifestyle (avoid an empty stomach, eat smaller and more frequent meals, drink plenty of water, avoid spicy or odorous foods, avoid environmental triggers)
-If lifestyle measures fail: pridoxine (vitamin B6) +/- doxylamine (RX: doxylamine/pyridoxine - Bonjesta, Diclegis)
-Ginger listed as “possibly effective” for morning sickness
-Hyperemesis gravidarium: severe N/V causing weight loss, dehydration, and electrolyte imabalances –> seek medical attention
GERD/Heartburn:
-First line: lifestyle (eat smaller and more frequent meals, avoid foods that worsen GERD, if when sleeping: elevate head of bed and NOT eating 3 hours prior to sleep)
-If lifestyle measures fail: antacids (calcium carbonate –> can also help supplement calcium)
-If heartburn NOT relieved by antacids, can consider H2RA or PPI for add-on
Pregnancy: for the following condition, state the preferred management and considerations
1. Flatulence
- Constipation
- Cough, Cold, and Allergies
Flatulence: simethicone (Gas-X, Mylicon)
Constipation:
-First line: lifestyle (fluid intake, fiber intake, and physical activity)
-If lifestyle measures fail: fiber (psyllium, calcium polycarbophils, methylcellulose) w/ fluids preferred, alternative: docusate or PEG
-Many prenatal vitamins contain iron which can worsen constipation
Cough, Cold, and Allergies:
-First line: cromolyn
-Second line: first-generation anthistamines (DOC: chlorpheniramine), second-generation antihistamines now often recommended too, if nasal spray for chronic allergy needed budsonide is DOC
-Avoid: liquid formulations that contain alcohol; dextromethorphan and guaaifenesin have limited safety data; oral decongestants should (ex. pseudophedrine) should be avoided during first trimester
Pregnancy: for the following condition, state the preferred management and considerations
1. Pain
- Asthma
- Iron deficiency anemia
Pain:
-Non-pharm: hot/cold packs, light massage, or physical therapy can limit or avoid use of analgesics
-First line: APAP for mild pain
-Avoid: NSAIDs including ASA (except low-dose for preeclampsia) especially at 20 weeks or later –> premature closure of fetal ductus arteriosus and kidney problems
-Opioids should ONLY be used if there are NO alternatives
Asthma:
-Rescue therapy: ICS-formoterol or albuterol
-Maintenance therapy: budesonide DOC, but all ICS are considered safe (LABAs can be continued w/ ICS if needed)
Iron Deficiency Anemia: supplemental iron, prenatal vitamins with iron
Pregnancy: for the following condition, state the preferred management and considerations
1. HTN
- DM
HTN: labetalol, nifedipine XR, methyldopa
-CI: ACEIs, ARBs, aliskiren, Entresto
-Low dose ASA recommended in chronic HTN pt to prevent preeclampsia
DM: insulin DOC if NOT controlled w/ lifestyle, alternatives: metformin and glyburide
-Low dose ASA recommended in T1DM and T2DM for preeclampsia prevention
Infections in Pregnancy:
1. In general, what ABXs are considered safe?
- Recommendations for vaginal fungal infections
- Recommendations for UTIs
- Recommendations for toxoplasmosis
- PCNs (including amoxicillin and ampicillin), cephalosporins, erythromycin, azithromycin
- Topical antifungals (Creams, suppositories) x 7 days
-Avoid: fluconazole -
Must treat even if asymptomatic (can lead to premature birth and perinatal mortality)
-First line: cephalexin or amoxicillin x 7 days
-Alternatives: nitrofurantoin, Bactrim, fosfomycin
-Nitrofurantoin, Bactrim: consider last line during 1st trimester and should NOT be used in last 2 weeks of pregnancy - Since most asymptomatic, test prior with IgM and IgG test
-Avoid dirty food and water (uncommon in US), *unpasteurized dairy products, and cat feces *
Pregnancy: Management of the following conditions
1. Venous Thromboembolism (VTE): TX and Prophylaxis
- Mechanical Valve
VTE: risk developing increased during first 6 weeks postpartum
-TX: LMWH preferred over UFH (due to ease of administration) –> monitor anti-Xa levels, drawn 4 hours post-dose or aPTT (UFH)
-*Prophylaxis: pneumatic compression devices +/- LMWH > UFH
-Warfarin teratogenic, oral factor Xa inhibitors and direct thrombin inhibitors NOT been adequately studied*
Mechanical valve: if on warfarin, generally converted to LMWH and may be switched back to warfarin after 13th week of pregnancy then back to LMWH close to delivery
Pregnancy management of the following conditions:
1. Hypothyroidism
- Hyperthyroidism
Hypothyroidism: levothyroxine –> will require 30-50% dose increase during pregnancy
-Do NOT leave untreated (complications: miscarriage, preeclampsia, low birth weight, cognitive impairment, growth retardation)
Hyperthyroidism: mild cases will NOT require TX
-First trimester: propylthiouracil (PTU)
-Later trimesters: methimazole
-Both agents have liver damage risk
-Avoid: radioactive ioidine
Breastfeeding (Lactation):
1. Babies receiving breast milk partially or exclusively should receive _________ supplementation daily. ________ supplementatoin may be needed four months after age until infant can obtain from diet. Note the doses of the supplements as well
- ________ or ________ are resources to check for drug safety during breastfeeding. In general, what properties of drugs are more likely to have higher concentrations in breast milk?
- What medications should be avoided during lactation?
- What medical condition should NOT breastfeed during pregnancy?
- Vitamin D (400 IU); Iron (1mg/kg QD)
-
LactMed or Brigg’s Drugs in Pregnancy and Lactation
-Properties: non-ionized, small molecular weight, low volume of distribution, high lipid solubility
-Majority of drugs are safe while breastfeeding - -Codeine and tramadol: risk of excessive sleepiness, breathing difficulty, and/or death (especially in mothers who were CYP2D6 ultra-rapid metabolizers
-Chemotherapy, illict drugs, radioactive compounds
-*Avoid if possible: amphetamines, amiodarone, ergotamines, lithium, metronidazole, phenobarbital, statins - HIV*
Menopause:
-Define menopause and induced menopause
-S/Sx
Menopause: last menstraul period over 12 months ago (typically in ages 40-58 yo: average of 52 yo)
Induced menopause: both ovaries removed, chemotherapy, or radiation can cause menopause prematurely
S/Sx: asymptomatic to severe
-Vasomotor symptoms (from decreased estrogen and progesterone levels): hot flashes (flushing and sensation of heat in upper body and face sometimes followed by chills), night sweats (hot flashes during sleep)
-Genitourinary symptoms (from decline in estrogen in vaginal mucosa): vaginal dyness, burning, dysparerunia (painful intercourse)
Menopause:
-Criteria for hormone therapy
-What hormone therapy to use
Criteria for hormone therapy: healthy, symptomatic women within 10 years of menopause,
-Extending TX beyond age 60 yo may be acceptable (ex. pt w/ osteoporosis) if lowest possible dose used and woman advised of risks
-Consider QOL priorities and personal risk factors (ex. age, time since menopause, risk of blood clots, heart disease, stroke, breast cancer) before risk –> use non-hormonal TX in risk factors (ex. SSRIs, SNRIs, fezolinetant)
Hormone therapy:
-Estrogen: most effective in vasomotor symptoms; if pt has uterus, use combination form of progesterone (unopposed estrogen increases risk of endometrial cancer); local formulations preferred for vaginal symptoms only; transdermal, local (topical), and low-dose PO estrogen have lower clot risks
-Progestin: given as combo w/ estrogen (ex. norethindrone, levonorgestrel, drospirenone) or seperate (most commonly medroxyprogesterone -MPA); micronized progestin (ex. Prometrium) considered safter than synthetic (ex. MPA); can cause mood disturbances and it takien intermittently spotting can occur
Menopause Brands:
1. Estrace
2. Climara
3. Premarin
4. Provera
5. Prometrium
- 17-beta-estradiol, vaginal cream
- Estradiol, transdermal patch
- Conjugated equine estrogens, vaginal cream, oral tablet, injection
- Medroxyprogesterone, oral tablets
- Micronized progesterone, oral tablet
Menopause Brands:
1. Estring
2. Vivelle-Dot
3. Duavee
4. Vagifem
5. Intrarosa
- 17-beta-estradiol, vaginal ring
- estradiol, transdermal patch
- conjugated estrogens/vazedoxifene, oral tablet
- 17-beta-estradiol, vaginal tablet
- Prasterone, vaginal insert - for dyspareunia
Menopause Formulations:
1. _______ and ________ patches are applied twice weekly
- ______ and ______ patches are applied once weekly.
- _________ may have lower risk of breast cancer and CV events.
- Where should the patches, topical gels, and spray be applied?
- Vivelle-Dot; Minivelle
- Climara; Menostar
- Micronized progestin (less risk than synthetic)
4.
-Patch: lower abdomen, below waistband
-Spray (Evamist): inside of forearm (between elbow and wrist)
-Gels: Divigel to upper thigh, Elestrin to upper arm and shoulder, Estrogel to entire arm from wrist to shoulder
Ospemifene:
-Brand
-MOA
-ROA
-TX
-AVEs
-Warnings
-BBW/CIs
Brand: Osphena
MOA: estrogen agonist/antagonist
ROA: PO
TX: dyspareunia, moderate/severe vaginal dryness (NOT for mild, for short-term)
AVEs: hot flashes, vaginal discharge, hyperhidrosis, muscle spasms
Warnings: should NOT be used in severe heaptic impairment
BBW/CI: same as other-estrogen containing products (do NOT use in women >35 yo and smokers, hx of CVD, hx of cancers, migraines w/ aura)
Non-hormonal products for Menopause:
-Natural Products
-Drugs
-Drugs NOT recommended
Natural products: black cohosh, evening primrose oil, red clover, soy, flaxseed, dong quai, St. John’s Wort, chasteberry
Drugs for Vasomotor Symptoms:
-SSRIs and SNRIs: paroxetine (Brisdelle) has lower dose than for depression (CYP2D6 inhibitor: blocks effiacy of tamoxifen), others (NOT FDA-approved): citalopram, escitalopram, venlafaxine, desvenlafaxine
-Fezolinetant (Veozah): neurokinin B antagonist to modulate thermoregulatory center (CI: cirrhosis, severe renal impairment, use with 1A2 inhibitors)
-Gabapentin (NOT FDA approved), oxybutynin (NOT FDA approved)
NOT recommended:
-Fluoxetine, sertraline: lack of evidence
-Pregabalin, clonidine: AVEs outweight benefits
-Bioidentical hormone therapy
Hypogonadism in Males:
-Drugs that lower testosterone
-TX
Drugs that lower testosterone: methadone (especially for opioid dependence), chemotherapy (prostate cancer), cimetidine, spirinolactone
TX: testosterone
-Controversal due to unclear benefits and risks
-Risks: CV (use low testosterone levels), clot risk, increase of Hct (polychythemia), noncancereous prostate growth, abuse potential
-Restricted use in BPH
-Formulations: injections (SC or IM: painful), topical
Testosterone:
-Formulations/Brands
-Administration considerations
Formulations:
-Topical gels/solutions: Androgel, AndroGel Pump, Vogelxo, Testim, Fortesta, Natesta (nasal gel)
-Injections: testosterone cypionate (Depo-Testosterone), testosterone undecanoate (Aveed), testosterone enanthate (Xyosted),
-Implantable pellets (Testopel)
-PO capsules: tesosterone undacanoate (Jatenzao, Kyzatrex, Tlando)
Administration:
-Gels: apply at same time each morning, falmmable until dry
-Xyosted: contains sesame oil
Testosterone:
-AVEs
-Warnings
-CIs
-BBW
-Monitoring
AVEs: increased appetite, acne, edema, hepatotoxicity, reduced sperm count, increased SCr, sensitive nipple, sleep apnea
-Natesto: nasal irritation, prime pump ten times then insert actuator into nostril
-Injections: pain
-Androgel Pump: before first use, prime by pushing down three times
-Apply deodorant prior to apply olutions to underarms
-For maximal absorption, wait 2-6 hours after apply gels/solutions before showering or swimming
Warnings: increased risk of breast cancer, prostate cancer, CV events, VTE, dyslipidemia, gynecomastia, polycythemia, priapism, caution in hepatic impairment, may worsen BPH
CIs: breast cancer, prostate cacner, pregnancy, breastfeeding
-Aveed: allergy to castor oil or benzyl benzoate
-Depo-Testosterone: serious cardiac, hepatic, or renal disease
BBW:
-Topical gel/soluation: secondary exposure to testosterone in children can result in virilization
-PO testosterone undecanoate and SC testosterone ethanate: increase BP and increase risk of CV events
-Aveed: pulmonary oil microembolism rxns (cough, dyspnea, throat tightening, anaphylaxis) –> observe in healthcare setting 30 minutes after each injection, only available through REMS program
Monitoring: testosterone levels, PSA, liver function, cholesterol, Hct (some
Drugs that cause erectile/sexual dysfunction + Medical Conditions
- Alcohol
- Antidepressants: especially SSRIs and SNRIs (including decreased libido)
- Antipsyhcotics: first generation (ex. chlorpromazine), prolactin-raising second generation (ex. risperidone, palperidone)
- BPH medications: finasteride, dutasteride, silodosin (mostly retrograde ejaculation)
- Anti-hypertensive medications: beta-blockers, clonidine, others
Medical conditions: cardiovascular disease (for ED), depression, stress, neurological illnesses (ex. in ED - spinal cord injury, stroke)
Erectile Dysfunction:
-Natural Products
-TX
Natural Products: yohimbe, L-arginine, panax ginseng
-L-arginine: “possibly effective”, can cause similar AVEs to PDE5is (flushing, HA, dizziness)
-Yohimbe: insufficient evidence, causes GI AVEs, anxiety, tachycardia, arrhythmias
-Ginseng: bleeding risk
TX:
-First line: PDE5is –> started low and titrated to effective dose (TX failure can be due to lack of sexual stimulation, timing of dose, and eating a large meal w/ dose)
-Efficacy similar among PDE5is, but can switch to another drug in class
-*Tadalafil: indicated for ED, BPH, and pulmonary HTN
-Sildenafil: indicated for ED and pulmonary HTN
-PDE5is intolerated/CI: alprostadil*
Phosphodiesterase Type 5 Inhibitors (PDE5is):
-Drugs/Brands
-MOA
-ROA
-TX
Drugs: sildenafil (Viagra, Revatio), vardenafil (Levitra, Staxyn), tadalafil (Cialis, Adcirca, Alya), avanafil (Stendra)
MOA: nitric oxide (NO) –> guanylate cyclase –> increased cGMP –> relaxes smooth muscle in arteria –> blood flows into vessicles
-PDE5is prevent PDE from degrading cGMP
ROA: PO
TX: ED, pulmonary HTN (Revatio, Adcirca, Alya, BPH (Cialis)
Phosphodiesterase Type 5 Inhibitors (PDE5is):
-Administration considerations
-*Take w/ or w/o food –> sildenafil and vardenafil have decreased efficacy when taken w/ high-fat or large meal (common cause of TX failure)
-For ED, no more than one dose/day recommended*
-Stendra can be taken closest to sexual activity
-Take about 15 minutes (avanafil), 30 minutes (tadalafil when taken PRN), or 1 hour (sildenafil, vardenafil) before sexual activity
Phosphodiesterase Type 5 Inhibitors (PDE5is):
-AVEs
-Warnings
CIs
AVEs: HA, flushing, dizziness, dyspepsia, blurred vision, difficulty w/ color discrimination, increased sensitivity to light, epistaxis, diarrhea, myalgia, muscle/back pain (mostly w/ tadalafil which can last up to two days)
Warnings:
-Impaired color discrimination (dose-related): pts w/ retinis pigmentoas may have higher risk
-Hearing loss, w/ or w/o tinnitis/dizziness
-Vision loss: rare, but due nonarteritic anterior ischemia optic neuropathy (NAION) - risk factors: low cup-to-disc ratio, CAD and other vascular conditions, age >50 yo, Cuacasian –> avoid with retinal disorders
-Hypotension: due to vasodilation –> higher risk w/ fluid depletion, resting BP <90/50, or autonomic dysfunction
-Priapism: seek emergency medical care if errection lasts >4 hours (blood in penis is NOT getting replaced - risk for necrosis/amputation)
-CVD –> caution w/ low or very higher BP or recent cardiac events –> if chest pain occurs, seek immediate medical help
CIs: use w/ nitrates or riociguat (guanylate cyclase stimulator)
Phosphodiesterase Type 5 Inhibitors (PDE5is): DDIs
-Nitrates (severe hypotension): avoid long-acting nitrates completely; short-acting nitrates shuld not be be used until 12 hours after avanafil, 24 hours for sildenafil or vardenafil, and 48 hours for tadalafil
-Riociguat should NOT be used within 24 hours of sildenafil or within 24 hours before or 48 hours after tadalafil
-Additive hypotension w/ alpha-blockers, antihypertensive drugs, and alcohol –> pt should be stable on alpha-blocker (w/o excessive dizziness/hypotension) before starting PDE5i; if Cialis being used for BPH, do NOT use alpha-blockers concurrently
-*oderate and strong CYP3A4 inhibitors: lower starting dose for PDE5i and/or extended dosing intervals
-Strong CYP3A4 inducers: decrease drug levels –> monitor effecitveness*
Phosphodiesterase Type 5 Inhibitors (PDE5is): Dosing in ED
-Typical starting doses of sildenafil, vardenafil, tadalafil, and avanafil
-When to dose reduce and what is lowered dose
-Tadalafil: daily dosing, on-demand dosing
Starting doses:
-sildenafil (Viagra): 50mg PO –> take 1 hour before sexual activity
-vardenafil: 10mg PO –> take 1 hour before sexual activity
-tadalafil (Cialis): 10mg PO –> take at least 30 minutes before sexual activity
-avanafil: 100mg PO –> take 15-30 minutes before sexual activity
Dose reduction if: 65 yo or older, using an alpha-blocker, using a CYP3A4 inhibitor, or severe renal or liver disease –> dose reduce by 50%
-sildenafil (Viagra): 25mg, vardenafil/tadalafil: 5mg, and avanafil: 50mg
Tadalafil:
-Daily dose: 2.5-5mg PO QD
-On-demand dose: 5-20mg PO PRN
Alprostadil:
-Brand
-MOA
-ROA
-Administration considerations
-TX
-AVEs
-CIs
Brand: Caverject, Caverject Impulse, Edex, Muse
MOA: prostaglandin E1, a vasodilator that allows blood to flow into cavernosal arteries
ROA: injection (Caverject, Caverject Impulse, Edex), *urethral pellets *(Muse)
Administration: refigerate urethral pellets before insertion
TX: ED in men who cannot tolerate or have CI to PDE5is
AVEs: penile pain, pripaism, HA, dizziness
-Intracavernous injection: hematoma, bruising at injection site
-Uretheral pellets: urethral burning or bleeding
CIs:
-Conditions that predispose pt to priapism (ex. sickle cell anemia, multiple myeloma, leukemia)
-Intracavernous injection: anatomical deformation or fibrotic conditions of enis, penile implants
-Urethral pellets: urethral stricture, balanitis, severe hypospadias and curvature, urethritis, venous thrombosis
Flibanserin:
-Brand
-MOA
-ROA
-TX
-AVEs
-Warnings
-BBW
-DDIs
Brand: Addyl
MOA: 5-HTA agonist and 5-HT2A antagonist
ROA: PO
TX: hypoactive sexual desire disorder in pre-menopausal females only
AVEs: dizziness, somnolence, nausea, fatigue, insomnia, dry mouth
Warnings: hypotension, syncope, CNS depression
-Avoid in pregnancy or breastfeeding
BBW:
-*CI with alcohol due to increased risk of severe hypotension and syncope (REMS program required) *
-CI in combo w/ moderate or strong CYP3A4 inhibitors or hepatic impairment
DDIs:
-Use with CNS depressants can increase risk of hypotension and syncope
-Major substrate of CYP3A4 and inhibits P-gp (concurrent moderate/strong CYP3A4 inhibitiors CI)
Bremelanotide:
-Brand
-MOA
-ROA
-TX
-Warnings
-CIs
Brand: Vyleesi
MOA: nonselective melanocortin receptor agonist
ROA: injection (SC)
TX: hypoactive sexual desire disorder in pre-menopausal females only
Warnings: increased BP and decreased HR after each dose, skin hyperpigmentation, nausea, delayed gastric emptying
-Avoid in pregnancy (effective contraception should be used)
CIs: uncontrolled HTN or known vascular disease
Benign Prostatic Hyperplasia (BPH):
-Pathophysiology
-Symtpoms and complications
Pathophysiology:
-Testosterone converted to dihydrotesterone (DHT) via 5-alpha-reductase increasing number of prostate cells
-Explansion causes gland to press/pinch urethra contributing to lower urinary tract symptoms (LUTS) via direct bladder outlet destruction and increased smooth muscle tone and resistance
-Irritation causes bladder wall to contract even when it contains small amount of urine, causing frequent urinartion and bladder weakens and loss ability to empty itself
Symptoms/Complications:
-Hesistency, intermittent urine flow, straining or weak stream of urine
-Urinary urgency and leaking/dribbling
-Urinary frequency, especially nocturia
-Incomplete emptying of lbadder
-Bladder outlet obstruction
-In severe blockage, acute renal failure
Drugs that can worsen BPH
-Centrally-acting anticholinergic (ex. benztropine)
-Drugs w/ anticholinergic effects (antihistamines, decongestants, phenothiazines, TCAs)
-Caffeine
-Diuretics
-SNRIs
-Testosterone products
Benign Prostatic Hyperplasia (BPH):
-Natural Products
-Assessment of symptoms
-TX
Natural products: guidelines do NOT recommend, but various products investigated
-Saw palmetto: unlikely to be effective based on contradictory and incosistent data
-Pygeum, pumpkin seed (beta-sitosterol), rye pollen: shown some improvement in symptoms
-Lycopene: used for prostate cancer prevention, but NO good evidence in BPH
Symptom assessment: questionnaires (ex. American Urological Association Symptom Score = AUASS or International Prostate Symptom Score = I-PSS)
*TX: *
-Mild disease: watchful waiting, annual assessments
-Moderate/severe disease: medications or minimally invasive procedures or surgery (ex. transurethral resection of prostate = TURP)
-Alpha blockers: first line in moderate/severe symptoms, work quickly, do NOT shrink prostate
-5 alpha-reductase inhibitors: delayed onset, shrink prostate size
-PDE5is: tadalafil +/- 5 alpha-reducatase inhibitor
Alpha-1 Inhibitors:
-Drugs/Brands
-MOA
-ROA
-Admnistration considerations/dosing
-TX
Drugs:
-Non-selective alpha-1 inhibitors: doxazosin (Cardura, Cardura XL), terazosin
-Selective alpha-1a inhibitors: tamsulosin (Flomax, w/dutasteride - Jalyn), alfuzosin (Uroxatral), silodosin (Rapaflo)
MOA: inhibit alpha-1 adrenergic receptors, causing relaxation of smooth muscle in prostate and bladder neck, reducing bladder outlet obstruction and improving urinary flow
-Alpha-1A receptors: primarily found in prostate
-Alpha-1B and -1D: dominant in heart and arteries
ROA: PO
Administration:
-Non-selective: given QHS to minimize initial “first-dose” effect of orthostasis/dizzines (caution especially in nocturia), titrate slowly
-Tamsulosin: 0.4mg PO QD
-Work quickly, but 4-6 weeks may be required to assess beneficial effects (do NOT shrink prostate and do NOT change PSA levels)
-Cardura XL: OROS frmulation, can leave ghost tablet
TX: BPH
-Off-label: bladder outlet obstruction in women
Alpha-1 Inhibitors:
-AVEs
-Warnings
-CIs
-Monitoring
-DDIs
AVEs: dizziness, fatigue, HA, abnormal ejaculation (especailly w/ tamsulosin and silodosin; retrograde ejaculation/sexual dysfunction w/ silodosin), fluid retention, rhinitis (tamsulosin)
-Non-selective alpha inhibitors (ex. doxazosin) have more AVEs of orthostasis, dizziness, HA
Warnings:
-Orthostatic hypotension/syncope, typically w/ first dose, if therapy interrupted for several days, dosage increased too rapidly, or antoher anti-HTN or PDE5i is started
-Intraoperative floppy iris syndrome (IFIS) can occur in cataract surgery if currently on previously treated
-Priapism –> seek medical attention if an errection lasts >4 hours
-Angina –> D/C if symptoms begin or worsen
CIs: concurrent use of silodosin or alfuzosin w/ strong CYP3A4 inhibitor; hepatic impairment (Child-Pugh class C for silodosin, B/C for alfuzosin); severe renal impairment (silodosin)
Monitoring: BP, PSA, urinary symptoms
DDIs:
-Caution when co-administered w/ PDE5is (hypotension) –> do NOT use in combo w/ tadalafil for BPH
-Caution w/ other drugs that lower BP
-Tamsulosin, alfuzosin, silodosin: majory CYP3A4 substrates –> do NOT use w/ strong inhibitors
-Silodosin: cannot use w/ strong P-gp inhibitors (ex. cyclosporine)
-Alfuzosin: caution with other QT-prolonging drugs and CVD
5 Alpha-reductase Inhibitors:
-Drugs/Brand
-MOA
-ROA
-Administration considerations
-TX
Drugs: finasteride (Proscar, Propecia, w/ tadalafil - Entadfi), dutasteride (Avodart, w/ tamsulosin - Jalyn)
MOA: inhibits conversion of testosterone to dihydrotestosterone (DHT)
-Finasteride: selective 5 alpha-reductase type II enzyme (more prevalent in prostate)
ROA: PO
Administration:
-Pregnant women should NOT take or handle these medications (API can be absorbed through skin from broken or crushed tablets and can be detrimental to the fetus –> NIOSH)
-Delayed onset –> TX for 6 months may be required for maximal efficacy
-Swallow dutasteride whole (do NOT chew or open contents - oropharyngeal irritation)
TX: BPH w/ enlarged prostate (improves symptoms, decreases risk of urinary retention and need for surgery, decreases size of prostate, decrease PSA levels), alopecia (Propecia)
5 Alpha-reducatase inhibitors:
-AVEs
-Warnings
-CIs
-Monitoring
-DDIs
AVEs: impotence, decreased libido, ejaculation disturbances, breast enlargement and tenderness, rash
-Sexual side effects decrease w/ time and return to baseline at one year of use in some men
Warnings: may increase risk of high-grade prostate cancer
CIs: women of child-bearing potential, pregnancy, children
Monitoring: PSA, urinary symptoms
DDIs:
-Finasteride and dutasteride: minor CYP3A4 substrates
-Do NOT use Proscar if using Propecia for hair loss
Overactive Bladder (OAB):
-Pathophysiology
-S/Sx
-Risk factors
Pathophysiology:
-Detrusor muscle innervated by parasympathetic nervous system (Ach acting on muscarinic receptors) is inappropriately stimulated causing involuntary contractions and feeling of urinary urgency
-M3 receptor is responsible for both emptying contractions and involuntary bladder contractions
S/Sx: urinary urgency w/ or w/o incontinence, urinary frequency, nocturia, urinary incontinence (involuntary leakage of urine)
Risk factors: age >40, obesity, neurologic conditions (ex. PD, stroke, dementia), DM, prior vaginal delivery, restricted mobility, hysterectomy, pelvic injury
Define the types of urinary incontinence (UI): urge, stress, functional, overflow, mixed
Urge: sudden urge to urinate, associated w/ neuropathy and often in those w/ DM, strokes, dementia, PD, or MS
Stress: urine leaks during any form of exertion (ex. exercise, coughing, sneezing, laughin) as a result of pressure on bladder
Functional: no abnormality in bladder, but may be cognitiviely, socially, or physically impaired thus hindering access to toilet
Overflow: leakage that occurs when quantity of urine stored in bladder exceeds capacity often w/o urge to urinarte *(BPH most common cause)
Mixed: combination of urge and stress UI*
Drugs that increase incontinence
alcohol, cholinesterase inhibitors, diuretics, sedatives
Overactive Bladder (OAB):
-Non-pharmacological TX
-TX for urge incontinence/mixed incontinence
-TX for stress incontinence
-TX for nocturia
Non-pharmacological: behavioral therapy considered first-line (ex. bladder training, delayed or scheduled voiding, pelvic floor muscle exercises such as Kegel exercises, urge control techniques, fluid management, avoiding bladder irritants such as caffeine, weight loss)
Urge/Mixed Incontinence:
-First line: behavioral therapy + anticholinergic or beta-3 agonist for 4-8 weeks for adequate trial
-Anticholinergics: long-acting (Ex. oxybutynin ER or transdermal) often used initially (less AVEs), selective anticholinergics (darifenacin, solifenacin) have less cognitive AVEs
-Beta-3 agonists: similar efficacy to anticholinergics, just different AVEs
-OnabotulinumtoxinA (Botox): higher efficacy, but NOT first-line due to cost and injection
-Nerve stimulation or surgical TX
Stress Incontinence: medications use NOT FDA-approved with minial efficacy
-Pseduophedrine, duloxetine
Nocturia: desmopressin (CI: pts w/ increased fluid retention risk, BBW: hyponatremia)
Anticholinergics for Urge/Mixed Urinary Incontinence:
-Drugs/Brands
-MOA
-ROA
-Administration considerations
Drugs: oxbutynin (Ditropan XL, Oxytrol, Oxtrol for Women, Gelnique), tolterodine (Detrol, Detrol LA), trospium, solifenacin (Vesicare), darifenacin, fesoterodine (Toviaz)
MOA: “antimuscarinic” drugs that competitively bind to muscarinic receptors and block ACh, preventing contraction of detrusor muscle
-More selective for M3 receptors: solifenacin, darifenacin
ROA:
-Oxybutynin: IR, ER (Ditropan XL), patch (Rx: Oxytrol, OTC: Oxytrol for Women), gel (Gelnique)
-Rest: PO
Administration:
-Decrease dose in renal impairment (CrCl <30) w/ fesoteridine, solifenacin, tolterodine, and trospium (do NOT use tropsium XR)
-Ditropan XL: OROS formulaion, can leave ghost shell
-Oxytrol patch: place on dry, intact skin on abdomen, hips, or buttock; avoid reapplication to same site within 7 days; available OTC for women >/=18 yo; applied twice weekly
-Package labeling is NOT clear if metals present in Oxytrol (Rx and OTC) –> consider removing before MRI
-Gelnique: apply to dry, intact skin on abdomen, thighs, or upper arms/shoulders; rotate sites
-Trospium XR: take OES
AnticholinergiAnticholinergics for Urge/Mixed Urinary Incontinence:
-AVEs
-Warnings
-CIs
-DDIs
AVEs: dizzinss and drowsiness (greatest w/ oxybutynin), xerostomia (dry mouth), constipation, dry eyes/blurred vision, urinary retention, application site rxns (topical gel/patch)
Warnings:
-Agitation, confusion, drowsiness, dizziness, blurred vision, hallucinations, and/or HA which may impair physical or mental abilities (caution in performing tasks that require mental alertness, on Beers Criteria)
-Angioedema of face, lips, tongue, and/or larynx
CIs:
-Uncontrolled narrow angle glaucoma, urinary retention, gastric retention, decreased gastric motility
-Oxytrol for Women OTC: pain or burning when urinating, blood in urine, unexplained lower back or side pain, cloudy or foul-smelling urine, male sex, age <18 yo, urinary or gastric retention, glaucoma, accidential urine loss only due to coughing, sneezing, or laughing
DDIs:
-Additive effects w/ medications that have anticholinergic side effects
-Lowest dose of tolterodine, solifenacin, darifenacin, and fesosterodine should be used w/ strong CYP3A4 inhibitors
-Acetylcholinesterase inhibitors for dementia increase ACh in CNS –> although OAB drugs primarily stay in periphery, some may experience CNS side effects (may worsen dementia symptoms)
AnticholinergiAnticholinergics for Urge/Mixed Urinary Incontinence:
-Formulations with less AVEs / Management of Dry mouth for Urge/Mixed Urinary Incontinence:
-Oxybutynin patch and gel: less dry mouth and constipation than PO forms
-Long acting formulations have less AVEs (ex. oxbutynin ER)
-Selective anticholinergics (ex. darifenacin, solifenacin): less cognitive AVEs
-Non-pharm: avoid mouthwarshes w/ alcohol, use ice chips, water, sugar-free candy or gum
-Beta-3 agonists have less incidence of dry mouth and anticholinergic AVEs
Beta-3 Agonists:
-Drugs/Brands
-MOA
-ROA
-TX
-AVEs
-Warnings
-DDIs
-Monitoring
Drugs: mirabegron (Mybetriq), vibegron (Gemtesa)
MOA: relax detrusor muscle and increase bladder capacity via beta-3 receptor activation
ROA: PO
TX: in combo or alone for urge/mixed incontinence
AVEs: nasopharyngitis, HA, constipation, diarrhea, dizziness
-Mirabegron: UTI
Warnings: urinary retention in pts w/ BPH and when used w/ anticholingergics
-Mirabegron: increased BP, angioedema of face/lips/tongue/larynx
DDIs (mirabegron): moderate CYP2D6 inhibitor (caution in NTIs that are metabolized by 2D6 and digoxin), levels of metoprolol may be increased, levels of tamixofen decreased
Monitoring: urinary symptoms, BP (mirabegron)
