EXAM 4 COMBINED- KHAN

What are the names of the natural androgens?

• testosterone

• DHT

• DHEA

• Androstenedione

Which anatomical structures are responsible for androgen secretions in MEN?

testis, adrenal cortex

Which anatomical structures are responsible for androgen secretions in WOMEN?

corpus luteum, adrenal cortex

Why is DHT more potent than testosterone?

DHT has a -H group AT POSITION 5

How is testosterone secretion regulated?

LH is the main stimulus for T secretion

What are the androgenic properties of testosterone?

• growth- penis, scrotum, prostate, seminal vesicles, larynx, vocal cord

• increase body hair, sebum secretion

• lean body mass alterations

What are the receptor properties of androgen receptors?

• nuclear receptors

• ligand+ receptor act as transcription factor and modulate gene expression

What are the 2 subtypes of 5-alpha reductase? What tissues are each subtype expressed in?

Type 1- non-genital skin, bone liver

Type 2- urogenital tissues/skin

How is testosterone converted into estradiol?

using aromatase enzyme

What anabolic property in men is mediated partly by estradiol?

skeletal growth

How is testosterone ester produced? What is the site of esterfication?

How it is produced? Esterifying a fatty acid to make it 17b-hydroxyl group of testosterone

SITE OF ESTERFICATION—> POSITION 17

How is testosterone released from its esters?

hydrolysis of the ester in vivo

Why are testosterone esters not used as much as other formulations?

• painful

• variable conc

What is a problem with testosterone patches?

skin reactions

What is the main problem with testosterone gels and topical solutions (1%)?

transfer to children through contact

Where is testosterone gel and topical solution (1%) applied

gel- upper arms, shoulder

topical- armpits

What are two formulations of testosterone made to reduce accidental contact of testosterone to normal individuals?

• nasal gel

• topical gel for front/inner thigh

What is the BBW for testosterone undecanoate?

POME (pulmonary oil microembolism)

What are the ADRs of androgens (testosterone)?

• decreased T and sperm production

  • bc of negative feedback inhibition

• increased appetite

• gynecomastia

• prostate growth, increase PSA

• acne

• edema

• hepatotoxicity

What is BPH?

noncancerous enlargement of the prostate

What is the selectivity of each 5a- reductase inhibitor?

• Finasteride - selective

• Dutasteride- nonselective

Names of 5a-reductase inhibitors:

• Finasteride (Proscar)

• Dutasteride (Avodart)

What is the MOA and the effect on prostate gland of 5a- reductase inhibitors?

MOA: inhibit 5a-reductase (conversion of Testosterone to DHT)

Effect: decrease prostatic volume, increase urine flow

What is an ADR of 5a-reductase inhibitors?

low libido

What are the names (brand/generic) of the selective and non-selective a1-antagonists?

Selective- Tamsulosin (Flomax)

Nonselective- Terazosin (Hytrin), Doxazosin (Cardura)

Which alpha 1 receptor is located in the prostate?

alpha 1a receptor

What are ADRs of non-specific a1-antagonists?

dizzy, hypotension, fatigue

What are the names, MOA, and ADRs of PDE-5 Inhibitors?

Names: Sildenafil(Viagra), Tadalafil(Cialis), Vardenafil(Levitra)

MOA: inhibit PDE-5, increase cGMP, relaxation in penis

ADRs: HA, flushing, blurred vision

Why do PDE-5 Inhibitors interact with nitrates?

PDE-5’s: Inhibit breakdown of cGMP, increase cGMP

Nitrates: Increase GC, which increases conversion to cGMP

Both: increase cGMP= severe vasodilation

What are some major concerns with PDE-5 Inhibitor use?

• vision loss

• hearing loss

• hypotension

• priapism

Which PDE-5 Inhibitor can also be used for BPH?

Tadalafil (Cialis)

What are the effects when GnRH agonists are administered in pulsatile/intermittent fashion?

proper release of gonadotropins (FSH and LH)

What are the names of the GnRH agonists?

• Nafarelin

• Leuprolide

• Goserelin

What is the cellular signaling of GnRH?

• GnRH receptors are GCPRs

• Gq—> PLC—> IP3—> DAG and Ca++

What are the effects when GnRH agonists are administered continuously? What initial effect do you expect in sex hormones levels?

Effect: inhibit the release of gonadotropins (FSH and LH)

Initial effect: increase in sex hormones

Do you see an increase in sex hormone levels with GnRH antagonists?

no! only in GnRH agonists

What are the MOA and effect of GnRH antagonists?

MOA: GnRH receptor antagonists

Effect: inhibit LH surge

What are the names of the GnRH antagonists?

• Cetrorelix

• Ganirelix

• Elagolix

ALL END IN -LIX

What are the composition of gonadotropin preparations? (aka the names of each and whether they have LH, FSH, or both)

1. human menopausal gonadotropin (hMG)- FSH+ LH

2. Urofollitropin (uFSH)- FSH

3. Recombinant follitropin alpha - FSH

4. Human chorionic gonadotropin (hCG)- LH

tip: the ones with “follitropin” only have FSH

What are the LH and FSH functions in male and females?

• Male

  • LH- acts on leydig cells to stimulate testosterone production

  • FSH- stimulate spermatogenesis

• Female

  • LH- follicular growth, induce ovulation, stimulate corpus luteum

  • FSH- follicular development

What are the ADRs of hCG and FSH?

• hCG

  • injection site rxns, HA, depression, edema, gynecomastia

• FSH

  • injection site rxns, multiple births, HA, pain

  • OVARIAN ENLARGEMENT

  • HYPERSTIMULATION syndrome

Why are dopamine agonists used in infertility tx?

basically if you have hyperprolactinemia that can cause infertility, so were treating the underlying condition in this case (high levels of prolactin decreases GnRH pulses, LH, and FSH)

What are the MOA, names, and ADRs comparison of dopamine agonists?

names: bromocriptine, cabergoline

MOA: D2 receptor agonist

ADRs: n/v, HA, postural hypotension

REMEBER CAB> BRO because greater efficacy, less ADRs

Why is metformin used to treat infertility?

• increases insulin sensitivity by increasing AMPK

• in PCOS there is insulin resistance, by treating that, we increase fertility

What is the MOA of danazol?

suppress pituitary-ovarian axis

What is the MOA of tranexamic acid?

inhibits fibrinolysis (binds to plasminogen and plasmin= can’t form fibrin)

What are some other agents used in infertility, menstral-related disorders, and endometriosis?

• clomiphene- estrogen antagonist

• aromatase inhibitors (Anastrozole, Letrozole)- induce ovulation

What are the effects of estrogen in COC?

• LH, FSH suppressed (E+P)

• impair transit or sperm, egg, and fertilized ovum (E+P)

• suppress FSH, decrease follicular development

What are the effects of progesterone in COC?

• LH, FSH suppressed (E+P)

• impair transit or sperm, egg, and fertilized ovum (E+P)

• inhibit LH surge

• decrease frequency of GnRH pulses

What are the effects of progestin in progestin-only contraceptives?

• same effects as in progesterone in COC +

• increase cervical mucus

• endometrial alterations—> impair implantation

What are the advantages of progestin-only contraceptives?

• no clotting risk

• no period/menstruation

• can use when estrogen is CONTRAINDICATED

  • like in migraine with aura, breast feeding, HTN

What are the advantages and disadvantages of COC?

• advantages

  • decrease endometrial and ovarian cancer risk

  • minimal breast cancer risk

• disadvantages

  • DVT (estrogen)

What agents increase the metabolism of OC?

• antiepileptics (seizure medications)

  • carbamazepine, phenobarbital, phenytoin

What is the problem with antibiotics and OC?

antibiotics inhibit enterohepatic recycling of OC’s

What are the 2 classes of progesterone?

1. 17a-hydroxyprogesterone derivatives

2. 19-norandrostane derivatives

What are the androgenic side effects of norethindrone and norgestrel?

• hirsutism

• acne

• oily skin

What are the advantages of using norgestimate?

less androgenic properties

How do you identify whether a compound is a 19-norandrostane derivative?

• will not have -CH3 at position 19

• will have ethynyl group

What are the advantages of drosperinone?

• no androgenic effects

What are the side effects of drospirinone?

• hyperkalemia

• higher risk of blood clot

What is the adverse effect of MPA?

DECREASE BONE DENSITY

How do you identify the functional group and site of esterification in MPA?

• has methyl (CH3) group on POSITION 6

• ESTERFICATION IS AT 17a-hydroxy position

Answer the following about extended cycle formulations:

• how often do you have a period?

• ______ days of E+P, then ____ days of placebo/low EE pills

• Brand name example

• period every 3 months

• 84 days of E+P, then 7 days of placebo/low EE pills

• Brand name: Seasonique

Answer the following about the transdermal patch (Xulane):

• contains what 2 hormones?

• higher what than pills?

• C/I?

• Duration/ how often it is applied?

• contains norlgestromin and EE

• higher AUC than pills

• C/I:

  • women >35 years old who smoke

  • women with a BMI ≥30 kg/m²

• apply once weekly for 3 weeks, 1 week off

Answer the following about long-acting reversible contraceptives:

• Name the 3 long-acting reversible contraceptives (brand/generic)

• Name what type of implant/device it is

• Which is non-hormonal?

• WHAT IS THE DURATION?

• 3 devices- IUD (Mirena), Copper IUD (Paraguard), Subdermal Implant (Nexplanon)

• Copper is NON-HORMONAL

• Duration:

  • IUD- 5 or 8 years

  • Copper- 10

  • Subdermal implant- 3 years

What are the effects of emergency contraceptive Plan B? When does Plan B need to be taken to provide protection from pregnancy?

• Plan B is just levonorgestrel so it…

  • blocks LH surge, prevents ovulation, thickens cervical mucus

• taken within 72 hours (3 days)

What are the effects of emergency contraceptive ELLA? When does ELLA need to be taken to provide protection from pregnancy?

• aka Ulipristal acetate

• effect: selective progesterone receptor modulator (NOT ANTAGONIST)

  • inhibits ovulation

• MUST BE TAKEN WITHIN 5 DAYS (of unprotected sex)

What is Mifepristone’s MOA?

• progesterone receptor antagonist

• induces abortion

What is Misoprostol’s MOA?

• causes uterine contractions/ potent oxytoxic

• “prostaglandin analog”