Pharmacology of Breast Cancer Medications

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Questions and Answers

What is a common adverse effect associated with the use of drugs to reduce the risk of invasive breast cancer in postmenopausal women?

Weight gain

Nausea

Increased libido

Menopausal symptoms (correct)

Which of the following accurately describes fulvestrant?

A pure estrogen receptor agonist

An intramuscular injection given monthly

A selective estrogen receptor degrader (correct)

A drug that acts only on ovarian estrogen receptors

What is the primary mechanism of action of anastrozole?

Inhibits estrogen receptor activity in all tissues

Blocks estrogen synthesis in the ovary only

Increases ovarian estrogen production

Inhibits estrogen synthesis in the adrenal glands (correct)

Which patient population is anastrozole indicated for?

Postmenopausal women with breast cancer Signup and view all the answers

Which of the following is a derivate of testosterone used as a progestogen?

Norgestrel Signup and view all the answers

What should be considered when using estrogens for primary ovarian failure?

They carry a risk of increased thromboembolism Signup and view all the answers

Which of the following progestogens is inactive orally due to hepatic metabolism?

Progesterone Signup and view all the answers

Which type of drugs can be used to treat estrogen-sensitive breast cancer?

Selective estrogen receptor modulators (SERMs) Signup and view all the answers

What is the primary mechanism of action of Clomiphene?

It inhibits estrogen binding to its receptors in the anterior pituitary. Signup and view all the answers

Which of the following adverse drug reactions (ADRs) is associated with the use of Estrogens?

Increased risk of thromboembolism Signup and view all the answers

Which of the following statements about newer progestogens is true?

Desogestrel and gestodene are options for women experiencing adverse effects. Signup and view all the answers

Which Selective Oestrogen Receptor Modulator (SERM) has an antioestrogenic action specifically on mammary tissue?

Tamoxifen Signup and view all the answers

What potential adverse effects are commonly associated with progestogens?

Acne and fluid retention Signup and view all the answers

Why is estrogen administration contraindicated during pregnancy?

It can cause genital abnormalities in offspring. Signup and view all the answers

What effect does Tamoxifen have on bone metabolism?

It helps maintain balance between osteoblasts and osteoclasts. Signup and view all the answers

How does Mifepristone function in the context of pregnancy termination?

It sensitizes the uterus to the action of prostaglandins. Signup and view all the answers

What is the main clinical use of Ulipristal?

For emergency contraception within 120 hours of unprotected intercourse. Signup and view all the answers

What is a common consequence of long-term estrogen administration in postmenopausal women?

Menstruation-like withdrawal bleeding Signup and view all the answers

Which of the following correctly describes the action of Raloxifene?

It primarily inhibits estrogen action in breast and uterus. Signup and view all the answers

When can oral contraceptives be initiated during the menstrual cycle?

At any point, assuming the woman is not pregnant. Signup and view all the answers

What is the likelihood of multiple births in women treated with Clomiphene?

Approximately 5% to 7% Signup and view all the answers

Which of the following contraceptive methods combines a progestogen with an estrogen?

The combined oral contraceptive pill Signup and view all the answers

What is a recommended practice when starting oral contraceptives after day 5 of the menstrual cycle?

Backup barrier contraception may be recommended. Signup and view all the answers

Which of the following progestogens is known for having weak androgenic actions?

Desogestrel Signup and view all the answers

Which group of women is most suitable for using progestogen-only oral contraceptives?

Women who smoke cigarettes Signup and view all the answers

What effect do enzyme-inducing drugs have on the effectiveness of oral contraceptives?

They increase the clearance of oral contraceptives. Signup and view all the answers

Which emergency contraceptive is effective up to 120 hours after unprotected intercourse?

Ulipristal acetate Signup and view all the answers

Which adverse effect is associated with the administration of oxytocin?

Water retention and hyponatraemia Signup and view all the answers

What is a key characteristic of the action of ergometrine in treating postpartum hemorrhage?

It induces strong uterine contractions. Signup and view all the answers

What is the typical failure rate of Levonorgestrel when administered for emergency contraception?

1.1% to 2.4% Signup and view all the answers

For which condition is Mifepristone primarily used?

Medical abortion Signup and view all the answers

What is a significant concern when using Medroxyprogesterone as an intramuscular contraceptive?

Long-term infertility following administration Signup and view all the answers

Which of the following is NOT a risk associated with combined hormone replacement therapy (HRT)?

Increased risk of heart disease Signup and view all the answers

What is the primary action of testosterone in prepubertal boys?

Premature closure of the epiphyses Signup and view all the answers

Which method of administration provides testosterone that is rapidly metabolized?

Orally Signup and view all the answers

What is the role of cholesterol in hormone production?

It is a precursor for all steroid hormones. Signup and view all the answers

How long is the elimination half-life of free testosterone?

10–20 minutes Signup and view all the answers

Which effect is NOT likely a consequence of testosterone administration in adults?

Increased cognitive abilities Signup and view all the answers

What is the primary concern regarding the long-term use of synthetic androgens?

Infertility Signup and view all the answers

Which route of administration is associated with testosterone's anabolic effects?

Transdermal patches Signup and view all the answers

What mechanism is primarily responsible for inducing vomiting associated with certain adverse drug reactions (ADRs)?

Activation of dopamine D2 receptors in the chemoreceptor trigger zone (CTZ) Signup and view all the answers

Which prostaglandin is NOT typically used in obstetrics for therapeutic abortion?

Aspirin Signup and view all the answers

What is a known adverse effect of Ritodrine when used as a myometrial relaxant?

Toxicity in the neonate Signup and view all the answers

Which drug is commonly used to manage menorrhagia by reducing prostaglandin production?

Mefenamic acid Signup and view all the answers

What is a clear benefit of short-term hormone replacement therapy (HRT)?

Improvement of symptoms like hot flushes Signup and view all the answers

Which of the following conditions does NOT benefit from hormone replacement therapy (HRT)?

Coronary heart disease Signup and view all the answers

How do prostaglandins facilitate uterine contractions?

By inducing coordinated uterine contractions and cervical relaxation Signup and view all the answers

What is the primary role of Atosiban in obstetrics?

Oxytocin antagonist that delays preterm labor Signup and view all the answers

Study Notes

Lesson 34: Gonadal Hormones

Gonadal hormones are primarily produced by the testes and ovaries, but a small amount is also produced by the adrenal glands' zona reticularis (DHEA and androstenedione).
These adrenal hormones can be converted into testosterone or estrogen in peripheral tissues.
Gonadal hormones play significant roles in sexual development, reproduction, and maintaining secondary sexual characteristics.

Types of Gonadal Hormones

Estrogens
Progesterone
Testosterone
Luteinizing Hormone (LH)
Follicle-stimulating Hormone (FSH)

Neurohormonal Control of the Female Reproductive System

Gonadotropin-releasing hormone (GnRH) from the hypothalamus stimulates the anterior pituitary to release FSH and LH.
FSH and LH stimulate follicle development in the ovaries, which leads to estrogen release.
LH also triggers ovulation at mid-cycle and controls progesterone secretion from the corpus luteum.
Estrogen controls the proliferative phase of the endometrium and provides negative feedback on the anterior pituitary.
Progesterone controls the secretory phase and provides negative feedback to both the hypothalamus and anterior pituitary.

Hormonal Changes and Phases of the Menstrual Cycle

The diagram and graphs represent hormonal fluctuations (FSH, LH, estrogen, progesterone) throughout the menstrual cycle.
Different phases are clearly marked (follicular, ovulation, luteal).
Correspondingly, ovarian histology and endometrial histology are illustrated.

Neurohormonal Control of the Male Reproductive System

GnRH controls gonadotropin secretion in both sexes.
FSH is essential for seminiferous tubule integrity and gametogenesis.
Interstitial cell-stimulating hormone (ICSH) stimulates interstitial cells to produce testosterone.
Testosterone induces anabolic effects, such as muscle and bone growth in males.

Drugs Affecting Reproductive Function

Estrogens:
- Synthesized by ovaries and placenta, and in small amounts by the testes and adrenal cortex.
- Key endogenous estrogens: estradiol, estrone, estriol.
- Estradiol is the most potent.
- Numerous exogenous synthetic forms, including ethinylestradiol.
- Effects depend on the stage of sexual maturity.
- In hypogonadism, stimulates secondary sexual characteristics and accelerates growth.
- In amenorrhea, induces an artificial cycle with progestogen.
- In sexually mature women, used for contraception with a progestogen.
- In menopause, prevents symptoms and bone loss.
- Physiological effects: reduces risk of atherosclerosis in premenopausal women, increases blood coagulability, sensitizes myometrium to oxytocin (labor), prevents osteoporosis, and closes epiphyses in both sexes.
- Mechanism of action involves binding to nuclear receptors (ERα and ERβ), leading to genomic effects. Additionally, rapid vascular actions are mediated by nitric oxide (NO).
- Pharmacokinetics: well-absorbed in the gastrointestinal tract but metabolized in the liver.
- Adverse drug reactions (ADRs): breast tenderness, nausea, vomiting, anorexia, edema, thromboembolism risk, gallbladder disease, possible genital abnormalities in offspring, menstruation-like bleeds with intermittent use.
- Contraindicated during pregnancy.
Selective Estrogen Receptor Modulators (SERMs):
- Tamoxifen: antioestrogenic action in mammary tissue, oestrogenic actions on plasma lipids, and endometrium and bone.
- Mechanism of action: partial agonist of estrogen receptors, upregulates TGF-β to retard malignancy, and controls bone balance.
- Use: adjuvant therapy for breast cancer in postmenopausal women.
- Clomiphene: inhibits oestrogen binding, increases GnRH and gonadotrophin secretion, stimulates ovaries, increases estrogen secretion and induces ovulation.
- Use: treatment of infertility caused by anovulation.
- Raloxifene: antioestrogenic effects on breast and uterus, and oestrogenic effects on bone, lipid metabolism and blood coagulation.
- Use: reduce invasive breast cancer risk in postmenopausal women with osteoporosis or high risk of breast cancer.
- Fulvestrant: selective estrogen receptor degrader (SERD) ER antagonist.
- Use: in ER-positive, metastatic breast cancer.
Aromatase Inhibitors:
- Anastrozole: blocks estrogen synthesis in the adrenal glands, but not the ovaries, providing an alternative in postmenopausal women with breast cancer
Clinical Uses (summary):
- Oestrogen: replacement therapy, contraception
- Antioestrogens/SERMs and aromatase inhibitors: treatment of oestrogen-sensitive breast cancer, alternative for breast cancer in postmenopausal women, ovulation induction.

Progestogens

Secreted by the corpus luteum (second part of menstrual cycle) and placenta (pregnancy).
Minor amounts secreted by the adrenal cortex and testes.
Act on nuclear receptors.
Progesterone receptor density is controlled by estrogen.
Multiple progestogen groups exist; some are biologically inactive orally (due to liver metabolism).
Some derivatives have androgenic activity (e.g., norethisterone, norgestrel, ethynodiol).
Newer progestins include desogestrel, gestodene (used in contraception).
Adverse Reactions (ADRs): weak androgenic actions, acne, fluid retention, weight change, depression, libido changes, breast discomfort, premenstrual symptoms, irregular cycles, breakthrough bleeding, thromboembolism.

Antiprogestogens

Mifepristone: partial agonist at progesterone receptors; sensitizes the uterus to prostaglandins; oral administration, 21-hour plasma half-life.
Used in combination with a prostaglandin analogue as a medical abortion alternative.
Ulipristal: selective progesterone receptor modulator, blocks ovulation.
Emergency contraception up to 120 hours after intercourse.
Used to reduce uterine fibroid size preoperatively.

Oral Contraceptives

Combined pill:
- Contains estrogen (e.g., ethinylestradiol) and progestogen (e.g., levonorgestrel).
- Taken 21 days out of 28.
- "Third-generation" pills include norgestrel, desogestrel, gestodene.
- Mechanism of action: suppresses FSH, prevents ovulation, alters endometrium
Progestogen-only pill:
- Levonorgestrel, norethisterone, ethynodiol
- Taken continuously; less reliable and irregular bleeding is common.
- Contraceptive method of choice for some women due to possible contraindications with combined oral contraceptives.
Emergency contraception:
- Levonorgestrel (morning-after pill); single or double-dose regimens within 72 hours of intercourse.
- Ulipristal acetate (morning-after pill); single dose up to 120 hours after intercourse.
- Medroxyprogesterone: intramuscularly as contraception; infertility risk long term.
- Mifepristone (Mifeprine): antagonist to progestagen receptors, promotes abortion within a week after intercourse; used up to week 9; often combined with prostaglandins for abortion.

Drugs Acting on the Uterus

Myometrial Stimulants (Oxytocics):
- Oxytocin: induces or augments labor.
- Ergometrine: treats postpartum hemorrhage; initiates strong uterine contractions
Prostaglandins (PGs):
- PGE 2, PGF, dinoprostone, carboprost, gemeprost, misoprostol (analogues): induce contractions and cervical relaxation to facilitate uterine expulsion or for inducing abortion.
Myometrial Relaxants:
- Ritodrine: beta-2 adrenergic receptor agonist used to delay preterm labor; used in selected patients with otherwise uncomplicated pregnancies (22-33 weeks).
- Atosiban: oxytocin antagonist that delays preterm labor.

Postmenopausal Hormone Replacement Therapy (HRT)

HRT commonly uses estrogen and may include a progestogen.
Short-term benefits: improves symptoms (hot flushes, vaginal dryness), prevents osteoporosis.
Drawbacks: does not reduce the risk of heart disease, age-related cognitive decline (or specific decline), cyclical withdrawal bleeding. Increased risks of endometrial cancer, breast cancer (related to duration of use), venous thromboembolism, especially in women already at higher risk and if combinatio

Androgens

Testosterone: main natural androgen; synthesized in interstitial cells of testes and smaller amounts in ovaries, adrenal cortex; cholesterol is the precursor.
- Actions in general the same as those of testosterone, influenced by age and sex.
Administration: subcutaneous implants or transdermal patches, intramuscular depot injection, orally.
- Prepubertal boys: causes premature closure of long bone epiphyses.
- Pubertal boys: develops secondary sexual characteristics.
- Adults: increased muscle mass, strength, libido; potential for water retention.
Pharmacokinetics: short elimination half-life (10–20 min).
- Synthetic androgens are less rapidly metabolized and may be excreted unchanged in the urine.
Adverse Reactions (ADRs): prolonged use may cause infertility, edema, and hepatic issues (e.g., liver cancer).

Antiandrogens

Cyproterone acetate: progesterone derivative used in prostatic cancer, as an adjunct with GnRH agonists or in precocious puberty, masculinization, and acne in women.
Flutamide: non-steroidal antiandrogen that is used in the treatment of inoperable prostate cancer treatment.
Finasteride: inhibitor of 5alpha-reductase, enzyme that converts testosterone to dihydrotestosterone, used for benign prostatic hyperplasia (BPH).

Anabolic Steroids

Nandrolone: increases protein synthesis and muscle growth.
- Used in treating aplastic anemia to stimulate erythropoiesis
- But clinical use overall has been limited.
Adverse Reactions (ADRs): cholestatic jaundice, liver tumors, and increased risk of coronary heart disease with high doses.

GnRH Analogues

GnRH analogues: given by subcutaneous infusion, stimulate gonadotropin release.
- Continuous administration: inhibits gonadotropin release
Indications: treatment of inoperable prostate cancer and infertility treatment.
- Treatment of inoperable prostate cancer is started after androgen receptor antagonists(e.g., flutamide).
Danazol: synthetic steroid that inhibits gonadotropin secretion used for sex-hormone dependent conditions such as endometriosis, breast dysplasia, and gyneccomastia. Also used to reduce hereditary angioedema swelling attacks.
Adverse Reactions (ADRs): gastrointestinal issues, weight gain, fluid retention, dizziness, menopausal symptoms, muscle cramps.

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This quiz covers key concepts and mechanisms related to the pharmacological agents used in the prevention and treatment of invasive breast cancer, especially in postmenopausal women. Questions focus on drug actions, adverse effects, and the specific patient populations these medications target.