ADT

Question 1

action of LHRH agonists

Answer 1

initial surge in LH and testosterone levels in response to LHRH agonists, loss of phasic pituitary stimulation results in plummetting LH levels which causes Leydig cell production of T to drop to castration levels

Question 2

castration level of T

Answer 2

<50 ng/dl

Question 3

action of T and DHT on AR

Answer 3

bind to AR in cytoplasm, this complex then translocates to nucleus and binds to androgen response elements in the promotor regions of target genes

Question 4

T to DHT

Answer 4

passive diffusion through cell membrane to cytoplasms, T conversion to DHT through 5AR, 13 fold more T required if DHT blocked by finasteride for same effect

Question 5

T free and bound

Answer 5

over half bound to SHBG, 40% bound albumin, 3% remains unbound and is functionally active form

Question 6

steroid anti androgen

Answer 6

cyproterone acetate
derivative of 17 OH progresterone
suppresses LH release and T production htrough central progesterional inhibtory effects
reduce circulating T elvels, hypogonadal state, loss of libido and ED
severe CVS complication
gynaecomastia in less than 20% of men

Question 7

non steroidal anti androgen

Answer 7

no anti gonadotropic effects
simply block AR
block normal inhibiting feedback of T, NSAA produce a paradoxic incraease in LH and T
can preserve potentcy
but peripheral conversion of T to oestogren can lead to painful gynaecomastia

Question 8

bicalutamide

Answer 8

most potent and well tolerated NSAA

long serum half life 6 days

Question 9

enzalutamide action

Answer 9

AT antagonist

unlike bicalutamide, inhibits AR function by blocking nuclear translocation and DNA binding

Question 10

Enzalutamide side effects

Answer 10

Diarrhoea
Fatigue
Hot flushes
Seizures <1%

Question 11

Abiraterone

Answer 11

Inhibitor of 17 alpha hydroxylase
Block conversion of pregnenolone to 17 hydroxypregnenolone

Resulting in excess aldosterone and precursors
Causing a suppression of cortisol with rise in ACTH
Untreated rise in mineralocorticoids leads to hypokalaemia, hypertension and fluid overalls
Co administration of prednisolone suppressed increases in ACTH

Question 12

Breast symptoms on ADT

Answer 12

75-80% develop gynaecomastia when taking non steroidal anti androgen
Vs 20% on steroidal anti androgen
50% develop pain
Prevention with radiotherapy 8-10Gy to each breast but does lot prevent pain or tenderness
Tamoxifen 20mg od

Question 13

Hot flushes treatment

Answer 13

Medroxyprogesterone 20mg od ten weeks

Cyproterone acetate 50mg bd for 4 weeks for hot flushes

Question 14

Cautions enzalutamide

Answer 14

Cautions

History or risk of QT-interval prolongation; history or risk of seizure; recent cardiovascular disease