Women’s, Men’s Health & Antineoplastic Pharmacology – Comprehensive Exam Notes for exam 5

Female Reproductive Physiology & Key Hormones

• Major endogenous estrogens
  • Estradiol → principal, most active
  • Estrone
  • Estriol
  • Synthesized from cholesterol in ovarian follicles; share basic steroid structure
• Pituitary gonadotropins
  • Follicle-stimulating hormone (FSH)
  • Luteinizing hormone (LH)
• Physiologic actions promoted by estrogens, progesterone, FSH & LH
  • Development of primary/secondary sex characteristics
  • Initiation & regulation of menstrual cycle
  • Shaping of body contours, skeletal maturation

Estrogenic Drugs

• Classes
  • Steroidal: conjugated estrogens, estradiol transdermal, estropipate …
  • Non-steroidal: diethylstilbestrol (withdrawn in U.S.)
• Representative preparations
  • Conjugated (Premarin), Esterified (Estratab), Estradiol oral/parenteral (Depo-Estradiol, Delestrogen), transdermal patches (Estraderm, Climara, Vivelle), vaginal forms (Vagifem, Estrace cream), Ethinyl estradiol, Estrone (Aqueous), Estropipate (Ogen)
• Indications
  • Estrogen deficiency disorders: atrophic vaginitis, hypogonadism, ovarian failure/castration, surgical oophorectomy
  • Contraception (combined with progestin)
  • Dysfunctional uterine bleeding
  • Vasomotor menopausal symptoms ("hot flashes")
  • Osteoporosis prophylaxis/therapy
  • Palliative therapy: breast or prostate cancer
• Contraindications
  • Known allergy, estrogen-dependent tumors, undiagnosed vaginal bleeding, pregnancy, active or prior thromboembolic disorders
• Adverse effects
  • Thromboembolic events (most serious); hypertension, thrombophlebitis, edema
  • Nausea (most common); GI upset; photosensitivity, chloasma
  • Amenorrhea, breakthrough bleeding; breast tenderness, headache, fluid retention
• Interactions
  • ↓ Oral anticoagulant activity
  • ↓ Rifampin effect; St. John’s wort induces metabolism
  • Additive toxicity with tricyclic antidepressants; smoking ↑ thrombosis risk
• HRT Update
  • Initiate around menopause for symptom control—not primary prevention of osteoporosis/fracture
  • Avoid in women with past endometrial or breast cancer

Progestins

• Common agents: hydroxyprogesterone, levonorgestrel (Plan B), medroxyprogesterone (Provera, Depo-Provera), megestrol (Megace), norethindrone, norgestrel, progesterone (Prometrium), etonogestrel implant (Implanon)
• Mechanisms
  • Induce secretory endometrial changes; thicken cervical mucus; relax uterine smooth muscle; raise basal body T°; growth of mammary alveolar tissue; negative feedback on FSH/LH
• Indications
  • Functional uterine bleeding (hormonal imbalance, fibroids, cancer); primary/secondary amenorrhea
  • Endometriosis & some cancers (adjunct/palliative)
  • Prevention of conception (alone or with estrogen); emergency contraception; prevention of threatened miscarriage; PMS symptom relief
• Contraindications: mirror those of estrogens
• Adverse effects
  • Liver dysfunction (cholestatic jaundice); thromboembolism (e.g., PE); nausea, vomiting
  • Amenorrhea, spotting; edema, weight change, others
• Special agents
  • Medroxyprogesterone: inhibits gonadotropins → contraception, uterine bleeding, amenorrhea, endometrial & renal cancer
  • Megestrol: palliative for breast cancer; stimulates appetite/weight gain in AIDS & cancer cachexia; ↑ clot risk

Contraceptive Drugs

• Formulations
  • Oral: monophasic, biphasic, triphasic (closest physiologic); extended-cycle; mostly estrogen–progestin combos
  • Non-oral: long-acting Depo-Provera IM; transdermal patch; intravaginal ring; implantable rods
• Mechanism of action
  • Inhibit FSH/LH release → suppress ovulation
  • ↑ Cervical mucus viscosity → ↓ sperm motility
  • Alter endometrium to inhibit implantation
• Additional benefits: cycle regularity, ↓ menstrual blood loss, ↓ ovarian cysts & ectopic pregnancy rates
• Indications: birth control; endometriosis, hypermenorrhea; cyclic withdrawal bleeding; post-coital (emergency) use
• Contraindications: pregnancy, allergy, high-risk/history of thromboembolism, MI, stroke
• Adverse effects
  • Estrogen-mediated: hypertension, thromboembolism (PE, MI, stroke), lipid & carb metabolism changes, ↑ hormone levels
  • Others: edema, dizziness, mood change, GI upset, weight gain, breast changes…
• Interactions
  • ↓ Efficacy with: antibiotics (penicillins, cephalosporins), barbiturates, isoniazid, rifampin
  • OC ↓ efficacy of: β-blockers, warfarin, TCAs, vitamins, hypnotics, anticonvulsants, theophylline, antidiabetics

Osteoporosis

• Definition: low bone mass + fracture risk, affects 25\% of women & 5\% of men > 65 yrs
• Risk factors: Caucasian/Asian, slender build, early estrogen deficiency, smoking, EtOH, low-Ca diet, sedentary, family hx
• Prevention: calcium + vitamin D (especially women > 60 yrs)
• Drug classes
  • Bisphosphonates: alendronate, ibandronate, risedronate, zoledronic acid
  • Selective Estrogen Receptor Modulators (SERMs): raloxifene, tamoxifen
  • Calcitonin
  • Teriparatide (PTH analogue) – stimulates bone formation
  • Denosumab – monoclonal antibody blocking osteoclast activation
  • Romoszumab – sclerostin inhibitor (new)
• Mechanisms
  • Bisphosphonates: inhibit osteoclast-mediated resorption → ↑ BMD; proven fracture risk ↓
  • SERMs: estrogen agonist on bone → ↑ density
  • Calcitonin: directly inhibits osteoclasts
  • Teriparatide: only agent ↑ new bone formation
  • Denosumab: prevents osteoclast activation (SC q6 months + daily Ca/VitD)
• Indications
  • Raloxifene: postmenopausal osteoporosis prevention
  • Bisphosphonates: prevention & tx
  • Teriparatide: very high-risk or prior fracture
  • Calcitonin/Denosumab: treatment
• Contraindications
  • Bisphosphonates: allergy, hypocalcemia, esophageal dysfunction, inability to sit/stand \ge 30 min
  • SERMs: pregnancy, active/past VTE (DVT, PE, retinal), allergy
  • Calcitonin: salmon allergy; Denosumab: hypocalcemia, renal impairment/infection
• Adverse effects
  • SERMs: hot flashes, leg cramps, VTE risk, teratogenic, leukopenia
  • Bisphosphonates: GI upset, esophagitis/burns, osteonecrosis jaw, severe bone/muscle pain
  • Calcitonin: facial flushing, GI upset, ↓ appetite
  • Teriparatide: chest pain, dizziness, hypercalcemia, arthralgia
  • Denosumab: infections
• Key administration pearls
  • Bisphosphonates: take on awakening with 6–8 oz water, \ge 30 min before food/drink/other meds; remain upright \ge 30 min
  • SERMs: discontinue 72 h prior to prolonged immobility (surgery, long trip)

Fertility Drugs

• Ovulation stimulants
  • Clomiphene: SERM, blocks estrogen receptors → ↑ GnRH, FSH, LH → follicle maturation & ovulation
  • Menotropins: mixture FSH+LH → follicle development (also in males for spermatogenesis)
  • Chorionic gonadotropin alfa: recombinant hCG → ovulation & corpus luteum maintenance
• Indications: induce ovulation in anovulatory women; promote spermatogenesis in men
• Adverse effects
  • CV: tachycardia, hypovolemia, DVT
  • CNS: dizziness, headache, anxiety
  • GI: nausea, bloating, constipation, anorexia
  • Others: ovarian hyperstimulation, multiple gestation, visual disturbances, breast pain

Uterine Stimulants & Relaxants

• Oxytocics (uterine stimulants)
  • Oxytocin (Pitocin): induce/augment labor, control postpartum bleeding, incomplete abortion, milk ejection
  • Prostaglandins: dinoprostone, misoprostol → cervical ripening + labor induction
  • Ergot alkaloids: methylergonovine → prevent postpartum uterine atony/hemorrhage
  • Progesterone antagonist: mifepristone + prostaglandin for elective abortion
• Adverse effects: hypo/hypertension, chest pain, GI distress, vaginal pain, leg cramps, fever, blurred vision
• Uterine relaxants (tocolytics) – delay preterm labor (20–37 wks)
  • Indomethacin (NSAID) – ↓ prostaglandins
  • Nifedipine (CCB) – ↓ Ca²⁺ influx in myometrium
  • When ineffective & delivery likely: give maternal corticosteroids (betamethasone, dexamethasone) to mature fetal lungs (24–34 wks)

Herbal Product: Soy (Estrasorb)

• Topical lotion for menopausal symptoms & bone health
• Adverse: nausea, diarrhea, abdominal pain; remains on skin ≈ 8 h

Key Nursing Implications – Women’s Health

• Baseline: VS, weight, glucose, renal/liver function, smoking status, pregnancy status, med Hx
• Estrogens/Progestins
  • Smallest effective dose; IM deep & rotate; oral with food; sun protection; report weight gain; annual Pap & breast exam
• Bisphosphonates: upright 30 min, full water glass, early morning
• SERMs: hold 72 h pre-immobility
• Fertility drugs: strict adherence, keep journal
• Uterine agents: monitor maternal VS, fetal HR; follow protocols during labor or tocolysis
• Monitor for therapeutic & adverse responses throughout

Male Reproductive Physiology & Androgens

• Testosterone: primary androgen; maintains primary/secondary male characteristics, muscle/bone growth, protein anabolism, RBC production, electrolyte retention
• Synthetic testosterone forms: methyltestosterone, fluoxymesterone; transdermal patches (Testoderm – scrotal; Androderm – body), gels (AndroGel)
• Anabolic steroids (Schedule III): oxymetholone, oxandrolone; indicated for weight gain after trauma, anemia, hereditary angioedema, some breast cancers; misuse → sterility, CV disease, liver cancer, dependence
• Danazol: synthetic androgen for hereditary angioedema, female endometriosis, fibrocystic breast disease

Androgen Inhibitors & BPH Therapy

• 5-α-Reductase inhibitors: finasteride, dutasteride
  • ↓ DHT → prostate shrinkage; teratogenic—women must avoid handling crushed tablets; Propecia brand for male baldness
• α₁-Adrenergic blockers: doxazosin, tamsulosin, terazosin, alfuzosin, silodosin → immediate symptom relief by relaxing prostatic & bladder neck smooth muscle; shrinkage from 5-ARI may take \le 6 mo
• Androgen receptor blockers: flutamide, nilutamide, bicalutamide → prostate cancer
• GnRH analogues: goserelin, leuprolide, triptorelin → ↓ pituitary LH/FSH → ↓ testosterone (prostate CA)

Erectile Dysfunction Drugs

• PDE-5 inhibitors: sildenafil, vardenafil, tadalafil, avanafil
  • ↑ NO-cGMP pathway → smooth muscle relaxation → ↑ penile blood flow
  • Contraindicated with nitrates (nitroglycerin, isosorbide) → severe hypotension
• Alprostadil (Caverject) – PGE₁ intracavernosal or urethral

Men’s Health – Key Adverse Effects

• Androgens: fluid retention; liver issues (peliosis, tumors), jaundice; thromboembolism, MI, stroke
• Priapism (ED & androgen drugs) – medical emergency
• PDE-5: unexplained vision loss, hypotension with nitrates
• Finasteride: ↓ libido/erection, gynecomastia, ↓ PSA by ≈50\%

Interactions

• Androgens ± oral anticoagulants → unpredictable INR changes
• Androgens + cyclosporine → ↑ nephrotoxicity risk
• α-blockers + hypotensives → additive ↓ BP; tamsulosin ↑ levels with azoles, macrolides, propranolol, protease inhibitors

Saw Palmetto (Herbal)

• Used for BPH & androgenic alopecia
• Adverse: GI upset, headache, back pain, dysuria
• Caution w/ NSAIDs (e.g., ibuprofen) – interaction risk

Nursing Implications – Men’s Health

• Baseline: VS, weight, electrolytes, renal & liver function, PSA, digital rectal exam, med Hx
• Patches: Testoderm → scrotal skin; Androderm → body skin only
• Pregnant women must avoid crushed/broken hormone tablets
• Monitor for fluid retention, thrombosis, liver enzymes, therapeutic goals

Cancer Overview & Cell-Growth Cycle

• Characteristics: uncontrolled growth, invasion, metastasis; lack growth control & physiologic function
• Terminology
  • Primary vs. secondary lesion; benign vs. malignant
  • Tissue origins: carcinomas, sarcomas, lymphomas/leukemias
  • Paraneoplastic syndromes (e.g., cachexia)
• Etiologic factors: age/sex, genetics, ethnicity, oncogenic viruses, occupational exposures, radiation, immunity
• Cell cycle phases: G0 (rest), G1, S (DNA), G_2, M (mitosis)

Chemotherapy Principles

• Drug groups
  • Cell-cycle specific (CCS): antimetabolites, mitotic inhibitors, topo inhibitors, enzymes
  • Cell-cycle nonspecific (CCNS): alkylators, cytotoxic antibiotics, some misc agents
• Traits: narrow therapeutic index; combination therapy ↑ efficacy; resistance common; nearly all cause adverse effects—dose-limiting toxicity (GI, marrow)
• Terms: emetic potential, myelosuppression/BMS, nadir, extravasation, targeted therapy

Antimetabolites (CCS – S phase)

• Folate antagonists: methotrexate (MTX), pemetrexed, pralatrexate
• Purine antagonists: fludarabine, 6-mercaptopurine, 6-thioguanine, cladribine, pentostatin
• Pyrimidine antagonists: 5-fluorouracil, cytarabine, capecitabine, gemcitabine
• MOA: faulty folate/purine/pyrimidine → halt DNA/RNA; tumor lysis syndrome possible
• Indications: leukemias, GI cancers, breast, lung, pancreas; low-dose oral/topical for psoriasis & RA (MTX)
• Adverse: hair loss, N/V, BMS, multi-organ toxicities, hand-foot syndrome, SJS/TEN
• Leucovorin rescue: supplies reduced folate to normal cells after high-dose MTX → limits BMS

Mitotic Inhibitors (Vinca Alkaloids & Taxanes)

• Vinca: vinblastine, vincristine (fatal if intrathecal), vinorelbine
• Taxanes: paclitaxel, docetaxel, cabazitaxel, eribulin
• MOA: inhibit microtubules → arrest mitosis (late S, G₂, M)
• Indications: testicular, lung, breast, ovarian, Kaposi’s, acute leukemia
• Adverse: alopecia, N/V, BMS, neurotoxicity (vincristine notable), extravasation antidotes available

Topoisomerase Inhibitors

• Alkaloid topo II: etoposide – testicular & small-cell lung (less used due toxicity)
• Camptothecins (topo I): topotecan, irinotecan
  • MOA: inhibit DNA relegation during S → strand breaks
  • Irinotecan notable for severe diarrhea, hematologic toxicity

Antineoplastic Enzymes

• Asparaginase, pegaspargase, Erwinia asparaginase → deplete asparagine → ALL treatment; can impair pancreas → hyperglycemia, pancreatitis

Alkylating Agents (CCNS)

• Nitrogen mustards, nitrosoureas, others: cyclophosphamide, cisplatin, mechlorethamine…
• MOA: cross-link DNA → no replication
• Indications: ovarian, brain, lymphomas, leukemias, breast, bladder
• Adverse: N/V, BMS, alopecia, nephrotoxicity (hydrate), neuropathy, ototoxicity, extravasation injury

Cytotoxic Antibiotics (CCNS)

• Anthracyclines: daunorubicin (HF), doxorubicin (LV failure, cardiomyopathy—dexrazoxane protects)
• Bleomycin (pulmonary fibrosis), mitoxantrone, others
• MOA: intercalate DNA → inhibit synthesis
• Adverse: BMS (except bleomycin), N/V, alopecia, organ toxicities; daunorubicin red urine

Miscellaneous Antineoplastics

• Bevacizumab: angiogenesis inhibitor—blocks tumor blood supply; uses: metastatic colon/rectal, NSCLC, glioblastoma; adverse incl. nephrotoxicity
• Sunitinib: GI stromal, pancreatic NET, renal cell carcinoma
• Hydroxyurea: similar to antimetabolite; SCC & leukemias
• Imatinib: tyrosine kinase inhibitor for CML; many interactions
• Mitotane: adrenal cytotoxic for adrenal carcinoma; ↓ warfarin & phenytoin
• Octreotide: manages carcinoid crisis & VIPoma diarrhea

Hormonal Antineoplastics

• Female-specific
  • Aromatase inhibitors: anastrozole, aminoglutethimide
  • SERMs: tamoxifen, toremifene
  • Progestins: megestrol, medroxyprogesterone
  • Androgens: fluoxymesterone, testolactone
  • Estrogen receptor antagonist: fulvestrant
• Male-specific
  • Antiandrogens: bicalutamide, flutamide, nilutamide
  • Estramustine (antineoplastic estrogen-mustard)

Extravasation Management

• Stop infusion immediately; leave IV cannula; aspirate residual drug
• Consult guidelines: apply antidote, hot/cold packs, elevate, document
• Prevention: meticulous IV site monitoring; vesicant handling—double-flush body fluids, chemo spill kits, PPE

Oncologic Emergencies & Nursing Care

• Emergencies: infections (neutropenia), allergic reactions, pulmonary toxicity, stomatitis ulcerations, bleeding, metabolic aberrations (tumor lysis), severe diarrhea, organ toxicities
• Baseline/ongoing labs: CBC, renal/liver, ejection fraction (doxorubicin), LDH, CPK, bilirubin
• Infection prevention: hand hygiene (most effective), neutropenic precautions
• Supportive: antiemetics 30–60 min pre-chemo, mouth care, manage alopecia & fatigue, contraception counseling, emotional support
• Cytoprotectants: amifostine (cisplatin renal), allopurinol (hyperuricemia)

Audience Response System (Selected Q&A Highlights)

• Smoking with estrogen therapy ↑ thrombosis risk (avoid)
• Bisphosphonate GI pain: stop drug, evaluate; must remain upright \ge 30 min / full water / empty stomach
• Oxytocin hyperstimulation signs → stop infusion, oxygen, left lateral, notify provider
• Missed OC pills (> 48 h): resume & use backup contraception
• Sildenafil + nitrates → dangerous hypotension (contraindicated)
• LDH critical to monitor with testosterone (peliosis, liver)
• Fever post-chemo with WBC <4500 → report immediately (infection)
• Hand hygiene is primary infection-prevention for neutropenic patients
• Vincristine = most significant neurotoxin among cytotoxics; fatal if given intrathecally
• Bleomycin most associated with pulmonary fibrosis; bevacizumab inhibits tumor angiogenesis