Male Hormonal Drug Therapy Quiz

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Questions and Answers

Which of the following is NOT a target for drug therapy related to male gonadal hormone function?

GnRH receptor

Acetylcholinesterase (correct)

5α-reductase

Androgen receptor

What is the primary function of 5α-reductase?

Stimulating the production of testosterone

Inhibiting the production of dihydrotestosterone (DHT)

Binding to androgen receptors

Converting testosterone to dihydrotestosterone (DHT) (correct)

Which of the following drugs is an androgen receptor antagonist?

Abiraterone

Finasteride

Flutamide (correct)

Testosterone

Which of the following drugs is an irreversible inhibitor of CYP17,21-lyase?

Abiraterone (A) Signup and view all the answers

What is the main therapeutic goal in treating Benign Prostatic Hypertrophy (BPH)?

Reduce tissue growth in the prostate to restore urinary function (B) Signup and view all the answers

What is the difference between anabolic activity and androgenic activity?

Anabolic activity refers to muscle growth, while androgenic activity refers to male sexual characteristics. (A) Signup and view all the answers

Which of the following drugs is a superagonist of the GnRH receptor?

Leuprolide (B) Signup and view all the answers

What are the primary biological targets for drugs that treat male hormone deficiency?

GnRH receptors and androgen receptors (B) Signup and view all the answers

Which of these is a common reason for using androgen analogs?

To treat male hormone deficiency (C) Signup and view all the answers

Which of the following drugs are used to treat Benign Prostatic Hypertrophy (BPH) by specifically inhibiting DHT synthesis?

Finasteride and Dutasteride (A) Signup and view all the answers

Which of the following statements accurately describes the mechanism of action of tamoxifen and fulvestrant in relation to estrogen receptors?

Tamoxifen acts as an antagonist at ERα receptors in breast tissue, inhibiting breast cancer growth, while acting as an agonist at ERβ receptors in bone, promoting bone density. (B) Signup and view all the answers

Which of the following is NOT a characteristic of clomiphene?

Clomiphene is primarily used for its ability to stimulate ovulation by inhibiting the production of gonadotropins. (D) Signup and view all the answers

Which of the following best describes the differing effects of tamoxifen and fulvestrant on breast cancer growth?

Both tamoxifen and fulvestrant act as antagonists at ERα receptors, effectively inhibiting breast cancer growth, but fulvestrant exhibits a broader range of anti-tumor activity. (B) Signup and view all the answers

The differing effects of tamoxifen and fulvestrant are primarily attributed to:

Their differential binding affinity for co-activators involved in ER-mediated transcription. (B) Signup and view all the answers

Clomiphene's mechanism of action primarily involves:

Blocking estrogen receptors in the pituitary gland, leading to increased gonadotropin secretion. (E) Signup and view all the answers

What is the primary mechanism of action of spironolactone?

Competitive antagonism at androgen and mineralocorticoid receptors (B) Signup and view all the answers

Which of the following is an active metabolite of spironolactone?

Canrenone (C) Signup and view all the answers

Which of these drugs is a 5a-reductase inhibitor that is primarily used for male pattern baldness?

Finasteride (A) Signup and view all the answers

Which of these drugs is a mechanism-based inhibitor of 5a-reductase?

Finasteride (D) Signup and view all the answers

What is the primary clinical use for finasteride (Proscar)?

Treatment of benign prostatic hyperplasia (BPH) (A) Signup and view all the answers

Which of the following is NOT a potential side effect associated with spironolactone?

Hypoglycemia (D) Signup and view all the answers

What is the half-life of spironolactone?

1-3 hours (A) Signup and view all the answers

Which of the following conditions is associated with anti-androgen activity?

All of the above (D) Signup and view all the answers

What is the impact of inhibiting steroid 5a-reductase?

Decreased levels of dihydrotestosterone (DHT) (D) Signup and view all the answers

Which of the following drugs is an inhibitor of steroid synthesis?

Abiraterone (B) Signup and view all the answers

Which of the following is considered a type 2 5a-reductase inhibitor?

Finasteride (A) Signup and view all the answers

What is the chemical reaction that 5a-reductase catalyzes?

Conversion of testosterone to dihydrotestosterone (DHT) (D) Signup and view all the answers

What is the primary effect of spironolactone on potassium levels?

Increases potassium levels (A) Signup and view all the answers

What is the main difference between the clinical uses of finasteride and dutasteride?

Finasteride is primarily for hair loss, while dutasteride is primarily for BPH (D) Signup and view all the answers

Which of the following statements accurately describes the mechanism of action of estrogen/progesterone drugs?

They act as agonists, binding to and activating specific receptors on target cells. (C) Signup and view all the answers

What is the primary function of the hypothalamic-pituitary-gonadal (HPG) axis in females?

To control the menstrual cycle and ovulation. (B) Signup and view all the answers

Which of the following structures is responsible for the synthesis of estrogen in females?

Ovaries (C) Signup and view all the answers

Which of the following is a common indication for the use of anti-estrogen drugs?

Treatment of certain types of breast cancer. (C) Signup and view all the answers

Which of the following is an estrogen antagonist?

tamoxifen (B) Signup and view all the answers

What is the primary function of medications like exemestane, anastrozole, and fuletrozole?

Inhibiting estrogen synthesis (A) Signup and view all the answers

Which of the following hormones is NOT directly produced by the pituitary gland?

Progesterone (D) Signup and view all the answers

What is the role of the hypothalamus in the HPG axis (hypothalamus-pituitary-gonad axis)?

Releasing hormones that regulate pituitary hormone production (C) Signup and view all the answers

Which of the following medications directly inhibits a specific type of steroid hormone synthesis?

Exemestane (C) Signup and view all the answers

What is the primary difference between an estrogen agonist and an estrogen antagonist?

Agonists activate estrogen receptors, whereas antagonists inhibit them. (D) Signup and view all the answers

Which of the following medications is a partial agonist of Progesterone receptors?

Danazol (B) Signup and view all the answers

Which of the following best describes the function of the HPG axis?

Manages the production and release of hormones that regulate reproduction. (A) Signup and view all the answers

Which of the following is a natural estrogen produced in the liver from androstenedione?

Estrone (D) Signup and view all the answers

What type of receptor does tamoxifen bind to?

Estrogen Receptor (A) Signup and view all the answers

Which of the following is a primary mechanism of action for hormonal contraceptives?

Prevention of ovulation (A) Signup and view all the answers

What is the primary effect of ethinyl estradiol on the body?

Stimulation of estrogen receptors (C) Signup and view all the answers

What is the correct relationship between estradiol and its analogs?

Ethinyl estradiol is a more stable form of estradiol, with less risk of breakdown. (B) Signup and view all the answers

What is the primary target for progestins?

Progesterone Receptor (B) Signup and view all the answers

What is the mechanism by which antagonists, like Fulvestrant, block estrogenic activity?

They bind to estrogen receptors and prevent co-activator binding, blocking gene transcription. (C) Signup and view all the answers

What is the main difference between the effects of aromatase inhibitors and selective estrogen receptor modulators (SERMs) like tamoxifen?

Aromatase inhibitors prevent estrogen production, while SERMs block estrogen receptors. (C) Signup and view all the answers

Which of the following compounds is a selective estrogen receptor modulator (SERM) that exhibits both agonist and antagonist activity?

Tamoxifen (B) Signup and view all the answers

What is the primary therapeutic use of clomiphene?

Treatment of infertility (C) Signup and view all the answers

Which of the following conditions is NOT typically treated with an aromatase inhibitor?

Hormonal contraception (A) Signup and view all the answers

Which of the following is a key difference between progesterone receptors and estrogen receptors?

Progesterone receptors require a D4-A ring (3-ketone) for activation, while estrogen receptors do not. (B) Signup and view all the answers

What is the primary mechanism of action of levonorgestrel, a progestin often used in hormonal contraceptives?

It inhibits the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH), preventing ovulation. (B) Signup and view all the answers

Which of the following is a potential adverse effect associated with high doses of estrogen analogs?

Increased risk of endometrial cancer (C) Signup and view all the answers

Which of the following describes the mechanism of action of conjugated estrogens?

They are prodrugs that require hydrolysis of 3-sulfate to release active estrogens. (D) Signup and view all the answers

Study Notes

Endocrine Pharmacology: Gonadal Hormones

Female Gonadal Hormone Analogs, Antagonists & Inhibitors: This section covers medications that target female reproductive hormones.
Estrogen Analogs (ER Agonists): These analogs stimulate estrogen receptors. Specific examples include estradiol, ethinyl estradiol, conjugated estrogens, and esterified estrogens.
Selective ER Agonist/Antagonist: Tamoxifen, toremifene, and bazedoxifene are examples of drugs with dual action, stimulating or blocking estrogen receptors depending on the context.
ER Partial Agonists: Clomiphene is a partial agonist, showing both stimulatory and inhibitory effects.
ER Antagonists: Fulvestrant is an example, blocking estrogen receptors.
Progestin Analogs (PR Agonists): Progesterone, medroxyprogesterone, levonorgestrel, megestrol, norethindrone, and drospirenone are categorized as progestin analogs.
PR Partial Agonists: Danazol is a PR partial agonist.
PR Antagonists: Mifepristone is a PR antagonist.
Estrogen Synthesis Inhibitors (Aromatase Inhibitors): These drugs, like exemestane, anastrozole, and letrozole, prevent the conversion of androgens to estrogens.
Hypothalamus-Pituitary-Gonadal (HPG) Axis: The hypothalamus and pituitary gland release hormones that regulate the production of estrogen and progesterone by the ovaries, crucial for the menstrual cycle.
Hormone Function: The lecture discusses how hypothalamic/pituitary hormones govern female gonadal hormone function, estrogens, and conditions with altered hormone levels.

Lecture Objectives - 1

Female Gonadal Hormone Function: This section explores aspects of the stimulation (hypothalamic, pituitary) and biosynthesis of estrogens, mechanisms behind conditions with altered hormones (e.g., menopause), and biological targets for drug therapy.
Estrogen/Progesterone Drugs: Details the structures and relationship to function, pharmacokinetics (how they move through body), indications, contraindications, and adverse effects of estrogen and progesterone.
Anti-Estrogen/Progesterone Drugs: Focuses on the structures and relationship to function of drugs that block/modulate estrogen and progesterone actions.

Toxicological Agents

Aromatase Inhibitors: Prevent the conversion of androgens to estrogens, useful in hormone-related cancers.
ER Agonists: Enhance or mimic the effects of natural estrogen.
ER Antagonists: Block estrogen receptors, used to treat hormone-dependent cancers.
PR Agonist/Antagonist: These affect progesterone receptor activity and are used in conditions like endometriosis, contraception, and abortion.

Natural Estrogens

Estradiol (E2): Major estrogen produced by the ovaries.
Estrone (E1): Produced in the liver, from estradiol, or androstenedione.
Estriol (E3): Also produced by the liver, from estradiol or androstenedione.

Cellular Response to Estrogen

Genomic Effects: Dominant, involving gene transcription, through interactions of estrogen and their target genes that create cellular function
Non-genomic effects: involve signaling pathways affecting cellular activities that don't involve gene transcription.
Specific Isoforms: The tissue-specific actions of estrogens are due to the presence of ER-α and ER-β receptors, in varying ratios in different parts of the body.
Ligand Binding: The mechanism of action of estrogens involves the binding to its respective receptors (ERα and ERβ), leading to conformational changes, and interactions with coactivators and/or corepressors.
Transcription: Triggers specific gene expression, affecting cellular function

Cellular Response to Progesterone

Progesterone Receptors (PRs): These receptors regulate gene expression in response to progesterone
Cellular events: Similar to estrogen receptors (PRs), progesterone receptors (PRs) induce a chain of events involving gene transcription.
E2/PR Effects: The difference in function between estrogen (E2) and progesterone receptors (PR) often involves activating differing sets of genes.
Isoforms: PR receptors, like ER receptors, come in isoforms that can have different effects within tissues

Conditions Benefitted from Hormone Therapy

Hormone Deficiency/Replacement: For conditions like hypogonadism, hypogonadism, and post-menopause.
Excessive Ovarian Androgen Production: For conditions such as hirsutism and amenorrhea (irregular menstruation).
Cancer Treatment: Antagonists/inhibitors target ER/PR for treating breast cancer, for example.

ER Agonists: MOA & SAR

Mechanism of action: Act on estrogen receptors (ERα and ERβ), in different tissues, by inducing responses relating to gene transcription.

ER Agonist Analogs

17a-alkyl Groups: Improve stability of the drug from oxidation to estrone.
Conjugated Estrogens: Prodrugs that need hydrolysis.

ER Agonists & Side/Adverse Effects

Cancer Risk: Increased risk of estrogen-dependent cancer, particularly in patients with pre-existing risk factors.
Bleeding: Uterine bleeding in postmenopausal women is a common side effect, and risk increases with higher doses.
Other Risks: Risk of gallbladder disease and increased cholesterol.

Progestins & Progesterone Analogs

Mechanism of Action: Progestins activate progesterone receptors, involved in various functions.
SAR (Structure-Activity Relationships): Aspects like 4-ring structures, C3-ketones, and C19-methyl groups are significant for proper function/activity
Side Effects: Increased blood pressure, electrolyte imbalances and hormonal effects.

Selective PR Agonists

Drug Selectivity: Differing affinities for various receptors.

ER Selective/Partial Agonists & Antagonists

Tamoxifen (Nolvadex): Used in breast cancer treatment.
Toremifene (Fareston), Raloxifene (Evista), Bazedoxifene (Duavee): Used in different hormonal health conditions.
Clomiphene: Partial agonist, used to treat infertility.
Fulvestrant (Faslodex): Antagonist, used in breast cancer.

ER antagonists: MOA & SAR

Mechanism: Block normal estrogenic activity.
Structure-activity relationship: structurally very similar to substrates, but without activation effects, unlike agonist type substances.

Partial Agonists/Antagonists at ER Receptor

Clomiphene: Partial agonist, with effects on pituitary gonadotrope ER receptors (stimulating ovulation), involved in infertility treatment, with potential side effects.
Fulvestrant: Antagonist used in treatments of breast cancer.

Agonist/Antagonist at Estrogen Receptors

Tissue Specific: The tissue effects of selective antagonists/agonists differ because of the different isoform distribution and ratios within different tissue sites..

Tamoxifen, Toremifene, Bazedoxifene

Mechanism and Structure: Details for the antagonists relating to their unique structural and functional properties.

Progesterone Receptor Partial Agonist Danazol

Uses: Primarily for endometriosis.
Mechanism: Weak PR agonist / androgen receptor agonist.

RU-486 (Progesterone Receptor Antagonist)

Use: Emergency contraceptive, medical abortion
Mechanism: Antagonist at progesterone receptors, preventing active function of progesterone at target tissues.

Aromatase Inhibitors

Examples: Exemestane, anastrozole, letrozole
Mechanism: Inhibit the production of estrogens from androgens.

Aromatase Inhibitors: Side Effects & DDIs

Effects: Edema, nausea, dizziness, sweating and hot flashes
Other issues: Elevated cholesterol, higher risk of fractures or osteoporosis
Drug Interactions: Potentially interact with other medications.

Male Gonadal Hormone Analogs, Antagonists & Inhibitors

Testosterone Analogs, Agonists:
Androgen Receptor Antagonists:
Androgen Synthesis Inhibitors: