Androgen Pharm Flashcards
What cells produce Testosterone in men and women?
Leydig Cells
How often is GnRH secreted?
every 30-120 minutes
Where does negative feedback for Testosterone take place?
Anterior Pituitary and Hypothalamus
What is the enzyme int the Leydig cells that converts androstendione testosterone?
17B hydroxysteroid dehydrogenase (17B-HSD)
What proteins is Test. normally bound to?
Albumin (bioavailable)
SHBG sex hormone binding globulin (unavailable)
What are the 2 functions of Testosterone?
Anabolic Androgenic (sexual repro and 2ndry male sex char.)
What are the anabolic Effects of Androgens?
Inc. RMR Lower Blood Glucose Inh. Lipid acc. in adipocytes Skel- Enhances bone formation closure of epi Gr Plate RBCs- Inc production of EPO Muscle- Inc. Protein synth and Inh. Protein Breakdown
What are the Theraputic uses of androgens?
Endometriosis Delayed puberty Hypogonadism Aging Anabolic Effects
What is Hypogonadism?
Androgen deficiency
What is Primary Androgen Def?
Testicular dysfunction. Dec. T
Loss of Neg. FB
What is Secondary Androgen Def?
Hypothalamus
Morbid obesity
Dec in circulating gonadotropins
Low T with low LH andFSH
What are the theraputic androgen preparations?
Methyltestosterone (Oral or SL)
Test. Enanthate (IM)
Testosterone (TD or topical)
What are the adverse effects of Androgen therapy?
Premature epiphyseal closure Inc Musc/tend injuries Hepatic Dysfunction Lipid metabolism Edema, Fluid retention Polycythemia Mental Disturbances
Waht are the theraputic uses of Antiangrogens?
F- Hirsuitism M-Precocious Puberty -BPH -Prostate Cancer -Alopecia
What are the different types of anti-androgens?
Androgen Receptor inhibitors
GnRH Agonists
GnRH Antagonists
Steroid Synthesis Inhibitors
Waht are the drugs included in the And. Rec. Antagonists?
Flutamide
Bicalutamide
What is the Use of And. Rec. Antagonists?
Tx for Prostate cancer
What is are the SA of And. Rec. Antagonists?
Gynecomastia
Rev. Liver Tox
Limited effects when used alone
Admin prior to GnRH analog Tx
What is the purpose of GnRH Receptor agonists?
Prostate Cancer Tx
What drugs are GnRH Receptor agonists?
Leuprolide
Goserelin
What are the SAs of GnRH agonists?
Sexual Dys Bone mineral density loss Anemia Fatigue Initial Surge in T levels that can cause growth of Pros. Cancer
What are the defferences between Degarelix and other GnRH receptor agonists?
Faster
No LH (test) surge
Red LH/FSH prod
Dec Test Production. More effective T supression
What is the drug in the Androgen Biosynth Inhibitors?
Abiraterone
What is the use of Abiraterone?
Mets prostate cancer
Used with prednisone
SA ofAbiraterone
Hepatic Tox
HTN, Hyper K and fluid retention
What are the 5a reductase inhibitors?
Finasteride and dutasteride
What is the use of 5a-reductase inhibitors?
BPH
Male pattern baldness
What is the Mechanism of Tx of Androgenic Alopecia?
Balding people have increased androgen receptor and 5a-reductase (DHT)levels
DHT cause baldness by inducing apoptosis in dermal papilla
What are the SA of 5a reductase inhibitors.
Impotence and Gynecomastia
Lower PSA levels
-False neg in PC screening
-PSA values should be doubled for comparison.
What is the Mechanism of Penile Erection?
Nitric Oxide Act. Guanylyl cyclase cGMP Relaxation ofSM of corpus cavernosum Inc. BF erection
Waht is the MOA of ED Tx Drugs?
Increase in cGMP
What are the PDE5 inhibitor drugs?
Sildenafil
Vardenafil
Tadalafil
Which Pts respond the least well to PDE5 inhibitors?
Cavernous nerve dysfunction
Diabetics and Prostatectomies
What are the SA of PDE5 inhibitors?
Serious crdiac events
Dangerous combo with nitrates/nitrites. Dangerously Low BP
Priapism
Sudden vision loss
How are Testosterone esters made and used?
FA conjugated to Test. (C17 w/ ester bond) Increases lipophilicity Dissolved in oil, given IM Slow Release Ester hydrolysed in vivo Slower metabilism(liver) Longer duration
What are the properties and risks of 17 alkylated derivatives of Test?
Slower Liver Cat.
Oral
Liver and Hepatic Tox can occur (higher risk than with unmod T or Test Esters)
What is the MOA of the Androgen receptor Antagonists?
Inhibits nuclear translocation of AR
Blocks DNA binding
Blocks coactivator recruitment
What is the MOA of the GnRH receptor agonists?
Increased receptor affinity and decreased proteolysis compared to GnRH
Increases LH and test. production
Desensitization and Dn Reg of GnRH receptors on pituitary gonadotropes
What must be added to the GnRH agonists in Tx of prostate cancer?
AR Receptor antagonist
prevents initial Test. Surge that can inc. cancer growth
