k7 ft (kelas a2) pharmacology of bph

8/16/2019 K7 FT (KELAS A2) Pharmacology of BPH

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Dr Zulkarnain Rangkuti, MSi

Bagian Farmakologi danTerapeutik,

Fakultas Kedokteran

Universitas Sumatera Utara

DRUGS THERAPY IN BPH


2/21

Classes of medicines:

1.Antiandrogens – 5 α-reductaseinhibitors

2. Long-acting selective α1-blockers

3. Muscarinic receptor antagonists

. Alternative !herap" # $h"toche%icals


3/21

Anti Androgen Therapy

Mechanism of action:

In the prostate and male hair follicles, dihydrotestosterone

(DHT) is the essential androgen.

testosterone

Dihydro-

testosterone

5-alpha

Reductase

Finas

terid

-

testosterone

testosterone

Dihydro-

testosterone

Finas-

teride

+

• Slows the rate of prostate enlargement y reg!lating the

amo!nt of a"ailale androgen (prostatic differentiationand growth depend on dihydrotestosteron)


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Regulation of cell growth in theprostate in BPH

DHT-androgen

receptor comple#

Growth

factors

Unbalanced

DHT

T

$%& (' and )$%& (' and )

Ser!m testosterone (T)

rostate

cell

Increased

*ell growth

*ell death

Ser!m DDihhydrottestosterone(DHT)


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Finasteride (5- alpha ReductaseInhibitor

2 t"pe & 5-alpha 'eductase ( and (( )5-A'(*

+ 5-alpha 'eductase (&

- predo%inant in sebaceous glands in skin, scalp

and liver

- responsible in about 1#3 o circulating /!+ 5-alpha 'eductase ((

-pri%aril" ound in prostate, se%inal vesicles,

epidid"%ides, hair ollicles and liver.

-responsible or about 2#3 o circulating /!

Finasteride ⇒ preferential inhibition of tpe !! iso"me

about #$$ % tpe !


6/21

Finasteride (5- alpha ReductaseInhibitor

$har%acokinetic &

Absorption&

+ orall" active

+ produces a reduction in /! levels 0ithin

hours ater ad%inistration + the eect lasts or about 2 hours

Metabolis%&

+ nasteride 0ill be reduced dih"dronasteride&

- !"pe ( co%ple4 t + 1 da"s

- !"pe (( co%ple4 t + 36 da"s


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!ide e"ects#

$ erectile dysfunction

$ abnor%al e&aculation

$ decrease of libido

$ decreased of se%en released during

se'$ rarely breast swelling

Dr!g Interaction

%lmost none

Dosage - Finasteride talet $mg, once daily - roscar - D!tasteride, inhiitor of type I and II,

,$ mg,D - D!prost

- %"odart


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-Adrenergic Bloc)ers# Rationale

• $rostate s%ooth %uscle tone is %ediated viaα1-adrenergic receptor

• 7lockage o the receptor leads to i%prove%ento 8o0 rate and L9!:1

• Central α-receptors and the eect o agents onthese receptors likel" pla" an additional role

• ensit" o adrenergic receptors changes 0ithprostate si;e and age

• !hree α1-adrenergic receptor subt"peshave been identied )A, 7, *

Sch&inn D'( BJU Int. )$$$*+suppl ).:##-))(

%lpha adrenergic receptors /

- fo!nd at ladder nec0 and prostate


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-Adrenergic Bloc)ers

• Nonselective / Phenox!en"amine

• Sho#t$actin% selective &$!loc'e#

/ P#a"osin( Alf)"osin

• *on%$actin% selective &$!loc'e#s / Te#a"osin

/ Doxa"osin +,a#d)#a-.

/ Alf)"osin$SR

- %lpha loc0ers rela# smooth m!scle in prostate and

ladder nec0 witho!t affecting ladder contractility wee0 onset of action

123 response rate

443 mean impro"ement in !rinary flow

Tolerance to therapy de"elops


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*-Adrenergic Bloc)ers# !u%%ary

• All currently a+ailable *-bloc)ers induce

fast i%pro+e%ent in ,T! and .ow ratepara%eters with si%ilar e/cacy

• They are all well tolerated howe+er0 thead+erse e+ent spectru% di"ers between the

agents / Tera1osin and do'a1osin induce %ore

di11iness0 fatigue0 and asthenia / Ta%sulosin ( Flo%a'2 induces %ore

e&aculatory disturbances

• 3one of the *-bloc)ers alter urodyna%icpara%eters0 prostate +olu%e or seru% P!A

• 3one ha+e been shown to alter the natural

history of the disease or pre+ent AR 4!urgery


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< =ective alone or in co%bination 0ith alpha blockers

< :"%pto%atic relie o re>uenc", urgenc"

or urge incontinence in patients 0ith nor%alrenal unction

< Careul 0ith &

+narro0 angle glauco%a,

+ i%paired liver unction or

+ in the presence o anti-ungals or %acrolides

=4.

- !olterodine

- !rospiu%

.

Muscarinic Receptor 'ntagonists


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Rationale for o%binationTherapy

• Alpha blockers rela4 the s%ooth %uscle o bladder

neck and prostatic capsule#adeno%a, thereb"i%proving s"%pto%s and 8o0 rates, relievingobstruction

• 5 A'(s reduce the action o androgens in theprostate, inducing apoptosis, atroph", and, b"shrinking the prostate i%prove s"%pto%s, relieveobstruction and prevent A9' ? prostate surger"

$%&Is

%rrest disease progression

α'-adrenergicloc0ers

&apidly relie"e symptoms

5


13/21

6edical Therapy of Prostatic !y%pto%s(6T7P!

'esults&

1. Co%bination o @ and ⇒ dela"ed the clinicalprogression o s"%pto%atic 7$/, co%pared to&

- single drug - placebo

2. Co%bination therap" reduced signicantl" therisk

o invasive b" B

+ @ onl" b"

+ onl" b" 3

F Finasterid

DDo#a6osin


14/21

M!D$: :u%%ar"M!D$: :u%%ar"

• Co%bination therap" 0ith do4a;osin andnasteride 0as sae and reduced the risko overall clinical progression %ore than

each drug alone.• @inasteride containing regi%ens reduced

the long-ter% risk o A9' )Acute 9rinar"

retention* and need or invasive therap".

McConnell et al, E =ngl F Med 2663.


15/21

%lternati"e Therapies

Saw Palmetto / Reduces 50 reductase acti1it

/ #$ mg po bid decreases lo&er urinar

tract smptoms in double blind studies

Pygeum africanum tree bark

/ 2ontains 3 anti-inflammator sterols

Pumpkin seed


16/21

:a0 $al%etto7otan"

• :ource -- Serenoa repens 7artra%. --Eative to the :outhern Atlantic coast through the Gul coastro% :outh Carolina through !e4as. !he $al% achieves aheight o -16 eet. @ruit are irregularl" spherical to oblong,

ranging in length ro% 1#2 to 1 inches and 1#2 inchdia%etre, are deep red-bro0n and 0rinkled.

• Active $art

/ 7err"


17/21

:a0 $al%etto$roposed 9ses

• :a0 $al%etto is clai%ed to beeective in the treat%ent ogenitourinar" proble%s, including

benign prostatic h"pertroph" )7$/*

• Dther purported uses

/ to increase sper% production

/ to increase breast si;e in 0o%en / to increase libido

/ %ild diuresis


18/21

:a0 $al%etto$har%acolog"

• Inhibition of 5-alpha reductase +invit#o.

• Antagonis% of 8HT at androgen

receptors

• !o%e e+idence e'ists for

/ Anti-in.a%%atory actions (67A

un)nown / Inhibition of prolactin (67A un)nown

/ Inhibition of prostatic cell proliferation


19/21

$u%pkin )labu :ia%*7otan"

• :ource -- Cucurbitaceæ a%il",Cucurbita pepo L., C. moschata., 0idel"cultivated in Eorth A%erica and

Australia.• Active $arts -- :eeds


20/21

$u%pkin$roposed 9ses

• !he current la" reco%%endations orthe use o pu%pkin is in thetreat%ent o benign prostatic

h"pertroph".

• /istoricall", pu%pkin has been usedto treat tape and other intestinal

parasitic hel%inthic inections.


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k7 ft (kelas a2) pharmacology of bph

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