Pharm Block Ii Gonadotropins & Androgens

Front 1

function of GnRH

Back 1

stimulated release of FSH and LH from the pituitary to regulate androgens, estrogens, and progestins

Front 2

GnRH replacements

Back 2

GnRH itself, leuprolide, nafarelin, buserelin, desorelin, histrelin, goserelin

Front 3

GnRG as a diagnostic tool

Back 3

-distinguish between constitutionally delayed puberty (low LH) and hypogonadotropic hypogonadism

Front 4

GnRH as a drug

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stimulation of gonadal function in hypogonadotropic hypogonadism, delayed puberty or cryptorchidism
-must be given in pulses by an IV pump
-not used due to cost and inconvenience of pump

Front 5

GnRH analogues used for:

Back 5

-suppression of gonadal function--"chemical castration"
-continuous administration block gonadotropin release by downregulating GnRH receptors
-also in precocious puberty and prostate/breast cancer

Front 6

problems associated with using GnRH analogues

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-initial increase in gonadotropins
-hot flashes in men and women
-headache and abdominal discomfort
-vaginal dryness and atrophy
-osteoporosis in women

Front 7

GnRH receptor antagonists

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-now imporved so they don't release histamine
-able to avoid initial gonadotropin release
-EX: ganirelix for androgen replacement therapy

Front 8

Natural Gonadotropins

Back 8

-follicle-stimulatin hormone
-leutinizing hormone
-human chorionic gonadotropin

Front 9

Urofollitropin (Fertinex)

Back 9

FSH, no LH

Front 10

menotropin OR human menopausal gonadotropins

Back 10

purified FSH and LH

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Human Chorionic Gonadotropin

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LH like activity

Front 12

follitropin alpha and beta

Back 12

recombinant FSH

Front 13

uses of urofollitropin or menotropins

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-stimulation of follicular growth for ovulation
-urofollitropin used only after clomiphene
-used daily then use hCG to induce ovulation
-urofollitropin used in polycystic ovary syndrome
-both also used to stimulate spermatogenesis

Front 14

uses of hCG

Back 14

-induce ovulation
-induce masculinization in men
-with menotropins to induce spermatogenesis
-treat cryptochidism
-test Leydig cell function for testosterone production

Front 15

adverse effects of gonadotropins

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-ovarian enlargement or hyperstimulation
-ectopic pregnancy
-pulmonary and vascular complications

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contraidications of gonadotropin use

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-primary ovarian failure
-ovarian cysts
-dysfunctional abnormal bleeding

Front 17

adverse effects of hCG

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-angioedema
-gynecomastia
-ovarian enlargement
-ovarian hyperstimulation syndrome
-pelvic pain

Front 18

contraindications for hCG

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-dysfunctional abnormal bleeding
-ovarian failure
-prostate carcinoma

Front 19

major androgens

Back 19

testosterone and dihydrotestosterone

Front 20

testosterone production

Back 20

-from androsenedione
-by 17 beta hydroxysteroid dehydrogenase
-controled by LH

Front 21

5 alpha reductase

Back 21

-produces dihydrotestosterone from testosterone
-two forms: 5 alpha R1 (liver, non-genital skin, and brain), 5 alpha R2 (liver and urogenital tract)

Front 22

site of testosterone production

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-testes in male
-adrenal gland in females and children

Front 23

testosterone feedback

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-must be converted to estridiol by aromatase
-estradiol blocks GnRh
-inhibin block FSH

Front 24

androgen administration

Back 24

-transdermal patch: Testoderm and Androgel
-esters at C17: prepionate, cypionate, enanthate groups
-17 alpha aklyl derivatves: Danazol, Fluoxymesterone, Stanozolol, Methyltestosterone

Front 25

androgen pharmacokinetics

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-11 min half life
-98% bound to albumin or sex hormone binding globulin
-conjugated in liver for urine escretion
-most in urine from adrenal production

Front 26

testosterone esters pharmacokinetics

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-parentteral admin. slows absorption and lengthens duration
-proprionate: 2-3 days
-cypionate and enanthate: 1-2 weeks
-esterases remove esters and metabolized like testosterone

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17 alpha alkyl derivatives pharmacokinetics

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-derivatives-specific metabolism
-modifications alter absorption and excretion
-some excreted unmetabolized

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actions of androgens

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-depends on age and gender
-males: secondary sex characteristics, anabolic growth, epiphyseal closure (by 17 beta estradiol), thinkening of skin, sebum production
-female: virilization

Front 29

androgen therapeutic for hypogonadism

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-male hypogonadism to allow noraml development
--prepubertal: vigorous and prolonged treatment with long acting testosterone ester
--adult: less intense regimen

Front 30

androgen therapeutic for hypopituiarism

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-for boys only
-thyroid and cortisol therapy must be started first
-GH should be started first in dwarfism
-use gradual increase for max anabolic effect

Front 31

androgen therapeutic for refractory anemias

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-oxymetholone derivative has high anabolic activity
-stimulates erythropoietin
-not used so much becasue of erythropoietin use

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androgen therapeutic for wasting states

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-use testosterone esters, oxymetholone, oxandrolone
-for reversal of protein loss
-does well in AIDS-related wasting

Front 33

minor therapeutic uses of androgens

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-gynecological disorders
--synthetic androgens with estrogen reduce breast engorgement
-prevent postmenopausal endometrial bleeding due to use of estrogen alone
-anti-estrogen action of high doses can treat breast cancer

Front 34

uses of 17 alpha alkyl derivatives

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treatment of hereditary angioneurotic edema
-danazol is most effective
-stanozolol is used prophylactically
-promotes production of C1 esterase inhibitor--a non-androgen activity

Front 35

effects of anabolic androgen abuse

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-usually use veterinary or designer drugs
-reduction of testosterone and gonadotropins
-leades to low sperm count, testicular atrophy, gynecomastia, liver damage/tumor, increased LDL, decreased HDL

Front 36

adverse effects of androgens

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-usually due to pharmacodynamics
-most noticeable in women and children
-premature epiphyseal closure
-hirsutism, deep voice, baldness, clitoral hypertorphy in women
-edema from Na and water retention

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adveres effects of 17 alpha alkyl derivative

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-amenorrhea
-endometrial bleeding
-jaundice, hepatic tumors, frank liver damage

Front 38

contraindications of androgen use

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-prostatic cancer
-heart failure
-liver cirrhosis
-renal disease
-hypoproteinemia

Front 39

GnRH and analogues as anti-androgens

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-block androgen syntesis
-gonadorelin, leuprolide, naferelin block LH by continuous administration
--receptor down regulation
-lowers testosterone production to castration levels

Front 40

finesteride

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-5 alpha reductase inhibitor
-blocks testosterone to DHT
-reduces prostate volume and prevents hair loss
-careful because lowers PSA, indicator of BPH

Front 41

androgen receptor antagonists

Back 41

-flutamide: treat prostate cancer with GnRH blockade
-bicalutamide: less hepatotoxic than flutamide
-cyproterone acetate: orphan drug for severe hirsutism
-spironolactone: weak antagonist, hirsutism