4 Endocrine Androgens Pharm

Front 1

indications for androgen replacement

Back 1

• Hypogonadism

• Cryptorchidism

• Delayed puberty

• Impotence

• Klinefelter’s Syndrome
 Reduced levels of androgens

Front 2

causes of hypogonadism

Back 2

deficient steroidogenesis
target organ insensitivity
5alpha-reductase deficiency
LH-deficiency
GnRH-deficiency
chromosomal abnormality
others
testicular trauma
-irradiation
-mumps orchitis
-hyperprolactinemia
-panhypopituitarism
-orchiectomy
-alcoholism
-aging

Front 3

testosterones
ORAL
IM

Back 3

Testosterone (CLASS III controlled sustance)
natural with bigtime first pass go synthetic
ORAL
fluoxymesterone
Methyltestosterone
IM
Testosterone cypionate
Testosterone enanthate
• IM (slowly absorbed form injection site)(DEPO)

• 2-4 week duration
 Substantial peaks and troughs

Front 4

testosterones
formulations

Back 4

ORAL, IM,
sc pellets (3 months)
transdermal patch (1day)
topical gel (1/day)
buccal tablet (2/day)

Front 5

testosterones
actions

Back 5

int/ext genitals in fetus
puberty induction (increase slowly-they will close epiphysial plate)
secondary sex characteristics
increase N retention and increase RBC mass (^hct)
in females can increase vigor,well being, libido

Front 6

testosterones
adverse Rxs
female

Back 6

Female
Virilization
Uterine atrop
Hirsutism
Clitomegaly
d. breast
voice

Front 7

testosterones
adverse Rxs
males

Back 7

Male-
gynecomastia
priapism
oligosperm (-LH,FSH)
unmask prost CA********

Front 8

testosterones
adverse Rxs
all patients

Back 8

• Increased water retention (attn chf,crf,hepatic)
 Edema, weight gain
• Alopecia
• Acne
• Polycythemia
• Hepatotoxicity (oral preps even hep tumors)
• Lipid problems

Front 9

testosterones
CIs

Back 9

 BPH/Prostate CA
 Hepatic, renal, cardiac disease
 Pregnancy / breastfeeding

Front 10

testosterone
DRUG interactions******

Back 10

 Warfarin (increases effects)
 Epoetin alfa (erythropoietin)(↑ effects)
 Cyclosporine (↑ effects)
 Hypoglycemics & insulin (androgens decrease blood glucose so don't need as much INS)

Front 11

HYPERPROLACTINEMIA
Tx

Back 11

Bromocriptine
Cabergoline

Front 12

Bromocriptine
Cabergoline
MOA

Back 12

(bromo)Dopamine agonist (D1 and D2 Receptors)

• Paradoxical effect:
 Stimulates GH secretion from normal pituitary
• Inhibits GH secretion from tumor

(CABER)DA agonist –D2 receptors
• Inhibits prolactin synthesis & secretion

Front 13

Bromocriptine
Cabergoline
indications

Back 13

• GH excess
 Shrink GH-secreting tumor before surgery
 Acromegaly and giantism

• Treatment for prolactin-secreting tumor
 Affects prolactin secretion (dopamine (-)prolactin (-)lh/fsh (+)T/E)
increases fertility

Front 14

androgen abuse
results

Back 14

oligosperm,testicular atrophy ((-) of lh fsh)

Front 15

DANAZOL
moa

Back 15

C1 Esterase inhibitor=
weak androgen and antiestrogen

Front 16

DANAZOL
indications
SEs

Back 16

• Angioedema (♂ and ♀)
• Fibrocystic breast disease
• Mastalgia (breast pain)
• PMS
SEs
• Similar to oral androgens (but very weak)

Front 17

indications for antiandrogens

Back 17

precocious puberty
CAH,
ANDROGEN secr. & DEPENDANT tumors
(old school used to treat say prostate cancers with E to inhibit the HP axis) now more targeted

Front 18

GNRH superagonists in male scene

Back 18

Leuprolide only mentioned here


and (Goserelin Nafarelin)

Front 19

Leuprolide
MoA
indications
SE

Back 19

GnRH Superagonist (depot admin)
 Turns off LH & FSH secretion by down regulation
(agonist givin continuously not pulsitile)
• ANTI-ANDROGEN
 Precocious puberty
 Congenital adrenal hyperplasia
 Androgen-secreting tumor
****androgen sensitive prostate CA (CHEMICAL CASTRATION)
BPH
(watch the FLAIR when first administered (like DPNMB)

Front 20

Abrelix
MOA
INDICATIONS

Back 20

(the true RELIX magazine is a GoNRh)
GNrH antagonist..depo 1/month
• Advanced Prostate Cancer
 In pituitary, immediate receptor antagonism

Front 21

GNrH antagonist

Back 21

Abrelix

Front 22

Abrelix
SEs

Back 22

GNrH antagonist

• Immediate allergic reaction ******(all other off market for this)can occur even after several doses
reversible chemical castration (though this is the basic use)

Front 23

Androgen Receptor antagonists

Back 23

Flutamide
Bicalutamide
Spironolactone (Weak)

Front 24

bicalutamide
MOA

Back 24

ORAL NONSTEROIDAL Androgen Receptor antagonists (also Flutamide (very potent)
• More potent than spironolactone
 Also more toxic
 Should be used for life threatening situations

Front 25

Flutamide
SEs

Back 25

ORAL NONSTEROIDAL Androgen Receptor antagonists
SE-
• Like menopause
 Decreased Libido, impotence, hot flashes, gynecomastia, mastalgia, anemia, edema

• Hepatotoxicity (more than bicalutamide)can be FATAL---necrosis,failure

• Contraindications
 Hepatic disease
 Pregnancy

Front 26

bicalutamide
indications

Back 26

ORAL NONSTEROIDAL Androgen Receptor antagonists (also Flutamide
the LUTAMIDES stop LUTINIIZING)
for androgen sensitive prostate cancer

Front 27

5-a-reductase inhibitors
named

Back 27

Finasteride
Dutasteride

Front 28

Finasteride
MOa
indications

Back 28

5α-reductase inhibitor (Type II isoform)(dutaSTERIDE I & II)

• Competitive inhibitor
• Blocks T → DHT

• Benign Prostatic Hypertrophy (BPH)

• Alopecia (Propecia)(finestiride only?)
 1/5 the dosage of BPH

Front 29

5-a-reductase inhibitors
side effects

Back 29

Finasteride
Dutasteride
SEs
• Decreased libido, impotence, decreased ejection volume, gynecomastia
• Teratogenic
 T → DHT necessary for normal development of male reproductive tract (disrupt normal development)
• Contraindications
 Children (males DHT important in puberty), females, pregnancy

Front 30

Antiandrogen drug classes

Back 30

GNRH superagonist and antagonists
Androgen R blockers
5 a reductase inhibitors

Front 31

Drugs to TREAT
BPH

Back 31

alpha-1 adrenergic blockers
5 alpha reductase inhibitors

Front 32

Doxazosin
Terazosin
male usages

Back 32

BPH-• Relaxation of smooth muscle tone and relieve the symptoms of urinary obstruction
HTN

Front 33

PHOSPHODIESTERASE 5 INHIBITORS
named
dOA

Back 33

Sildenafil
(Viagra)
Vardenafil these guys PDE 6 also = eye scenes onset 27 minutes------4 Hrs
(Levitra)
Tadalafil PDE II also (?)
(Cialis) 45mn---36hrs

Front 34

Vardenafil
MOA

Back 34

• Selective inhibitors of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5)
 Intracellular signaling pathway
 NO is a vasodilator, it causes vascular relaxation by activating guanylate cyclase
 Guanylate cyclase converst GTP to cGMP
 If ½ life is prolonged, the vasodialtory effect of NO will be extended
 PDE5 inhibitor inhibits the specific cGMP phosphodiesterase that is active in blood vessels of the penis

Front 35

PHOSPHODIESTERASE 5 INHIBITORS
SEs

Back 35

Sildenafil
(Viagra)
Vardenafil
Visual effects
 Due to inhibition of PDE6 in retina
all
• Headache
• Flushing
• Dyspepsia
• Blue-green color vision
• Life threatening hypotension with nitrates

Front 36

PHOSPHODIESTERASE 5 INHIBITORS
CIs

Back 36

 Nitroglycerin (nitrates) – potentiates the effects of nitrates
 CV disease
 Hepatic disease
 Penile structural abnormality
 Priapism
 Pregnancy / breastfeeding
theoretically---retinitis pigmentosum

Front 37

Sildenafil
(Viagra)
Vardenafil
(Levitra)
Tadalafil
(Cialis)
INDICATIONS

Back 37

• Erectile dysfunction

• Assist in sexual arousal in women

• In vitro fertilization
 Increase blood flow to uterus before embryo transfer

• Clinical Trials
 Sildenafil for pulmonary hyptertension

Front 38

anti androgen effects in females
indications

Back 38

hirsutism,PMS, severe cystic disease (SARA really the only good one for females