20120508-kbk-pemicu 4 blok metabolisme

7/25/2019 20120508-Kbk-Pemicu 4 Blok Metabolisme

http://slidepdf.com/reader/full/20120508-kbk-pemicu-4-blok-metabolisme 1/33

Pemicu 4 BlokMetabolisme

Dept. Pharmacology & Therapeutic



Anamnesis

Laki-laki, 48 tahun, BB >>, lemah, sejak

!ulan yang lalu. "a men#erita sakit

persen#ian $%' #an mengkonsumsi !er!agai

o!at penghilang rasa sakit yang #i!elinya

sen#iri.

"a #iperkirakan mengkonsumsi kortikosteroi#.



Pertanyaan

(. Bagaimana mekanisme kerjakortikosteroi# #alam menghilangkan nyerisen#i)

*. Bagaimana hu!ungan pemakaian o!atterse!ut #engan terja#inya kelainan

+ungsi hormon supraa#renal)

. Bagaimana tatalaksana aalsupraa#renal +ailure)



Adrenocorticosteroids



Control of Aldosterone Secretion



Circadian Rhythm of Cortisol Secretion



GLUCOCORTICOID(CORTISOL : HYDROCORTISONE)

MECHANISM OF ACTION

Steroid

Steroid +receptor

complex

recep

tor

Steroid +receptor

complex

Cellmembra

ne

Nuclearmembr

ane

accceptor

chromatin

*.



Physiological Actions of Glucocorticoids

• Metabolic

• Anti-inflammatory

• Immunosuppression



GLUCOCORTICOID(CORTISOL : HYDROCORTISONE)

IMMUNOSUPPRESSIVE AND ANTI-INFLAMMATION EFFECT

ANTI!N"ANTIB#$%C#MP&!'P(#SP

#&IPI$

A)AC(I$#NIC ACI$

P(#SP#&IPAS! A*

IN(IBIT!$B%

&C#C#)TIC#I$

C%C&##'%!NAS!

&IP#'%!

NAS!

&!,#T)I!N!

P)#STA&AN$INS

P)#STAC %C&IN

T()#MB#'AN!S

(.



Hypothalamic-

Pituitary-Adrenal

(HPA)

Axis



Side Effects of Glucocorticoid Therapy



Anta-onists o.Adrenocortical A-ents

. ynthetic inhi!itors an# glucocorticoi#antagonists

/0 Metyrapone 1 inhi!its ((-hy#ro/ylation,

inter+ering ith cortisol an# corticosteronesynthesis $0.*1g B"D to (g 2"D'

- use# in tests o+ a#renal +unction $00-100mg 3 4hrs. #oses, 5e# !y urine

collection

- treat hypercorticotism6 4 g7#ay



*. Amino-lutethimide 1 !locks theconersion o+ cholesterol topregnanelolone an# causes are#uction in the synthesis o+ allhormonally actie steroi#s9 !reast :a

an# :ushing;s syn#rome #ue toa#renocortical :a6 *10 mg eery hrs.

- enhances meta!olism o+#e/amethasone



20 ,etocona3ole 1 an anti+ungal

imi#a<ole #eriatie9 potent, non-selectie inhi!itor o+ a#renal an#gona#al steroi# synthesis9 t/ o+:ushing;s syn#rome $*00-(*00mg7#'

4. Mi.epristone ) 4567 1

((=-aminophenyl-su!stitute# (-norsteroi#9

has strong anti-progestin actiity9!locks

glucocorticoi# receptor



1. Mitotane 1 a#renal :a9 (*

g7#aily results in re#uction in tumormass9 caution6 a#erse e5ects$80?'

60 Trilostane " =-(@hy#ro/ysteroi# #ehy#rogenaseinhi!itor that inter+eres

ith the synthesis o+ a#renal an#gona#al hormones

- compara!le to aminogluthemi#e



B0 Mineralocorticoid Anta-onists

pirinolactone A #iagnosis o+al#osteronism $400-100mg7#ay +ro 4-8#ays'9 preparing +or surgery $00-40mg7#ay / * ks to re#uce the

inci#ence o+ arrhythmias'9 hirsutism inomen $an#rogen antagonist 10-*00mg7# / *- mos'9 #iuretic

plerenone A in clinical trials

Drospirenone A progestin in a ne oralcontraceptie, antagoni<es the e5ect o+al#osterone



:lassiCcation o+#renocorticosteroi#s

". hort to me#ium-actingglucocorticoi#s6

a. y#rocortisone $cortisol'

!. :ortisone

c. Pre#nisone

#. Pre#nisolone e. Eethylpre#nisolone

+. Eepre#nisone



"". "nterme#iate-acting glucocorticoi#s

a. Triamcinolone !. Paramethasone

c. Flupre#nisolone

""". Long-acting glucocorticoi#s a. Betamethasone

!. De/amathasone

"G. Eineralocorticoi#s a. Flu#rocortisone

!. #eso/ycorticosterone acetate



Therapeutic ses8

. )eplacement Therapy (. #renal "nsuHciency a0 Acute adrenal insu9ciency ss/6 I"T symptoms, #hn, hypoJa, hyperK, eakness,

lethargy,

hypotension cause6 #isor#er o+ the a#renal a!rupt ith#raal o+ glucocorticoi#s at high #oses

orprolonge# use

mgt6 "G 6 D1 0.?Ja:l solution Eonitor +or ui# oerloa# y#rocortisone $cortisol' (00mg !olus, 5e# !y

(00mg eery 8 hrs. 9 once sta!le, may gie *1mg "Ehy#rocortisone eery -8hrs.9 therea+ter, same mgt ith

chronic a#renal insuHciency



/0 Adrenal Insu9ciency cont07 !. :hronic #renal "nsuHciency $##ison;s #isease'

ss/6hyperpigmentation, t. loss, ina!ility to maintain +asting !loo# sugar, eakness,

+atigue,hypotension

cause6 primary a#renal insuHciency, tu!erculosis

mgt6 y#rocortisone *0-0mg7#ay B"D Flu#rocortisone acetate 0.01 A 0.*mg7#ay $alua!le in#icator o+ a#e3uate replacement6 #isappearance o+ hyperpigmentation an#

resolution o+ electrolyte a!normalities' -monitor plasma :T leels or measure urinary +ree cortisol9 #osage a#justments +or stress



Therapeutic ses cont07*. #renocortical hypo- an#

hyper+unctioninga. :ongenital #renal yperplasiass/6 a+ter pu!erty ith in+ertility, hirsutism, amenorrhea an#

acne9 +emale pseu#ohermaphro#itism9 accelerate# linear groth !ut height at maturity is re#uce#9 salt asters A :G collapse $olume #epletion'

cause6 Ienetic #isor#er9 actiity o+ en<ymes re3uire# +or the !iosynthesis o+ corticosteroi# is #eCcient $*( β

hydroxylase)

mgt6 (st seen as acute a#renal crisis oral hy#rocortisone 0.mg7kg7#ay B"D or T"D u#rocortisone acetate 0.01-0.*mg7#ay treatment in-utero6 mothers at risk A glucocorticoi# therapy is initiate# !e+ore (0 eeks gestation 5e# !y genotyping an# se/ #etermination



!. :ushing;s syn#rome

cause6 pituitary a#enoma, tumors o+ the

a#renalglan# ss/6 roun#, phletoric +ace, truncal o!esity,

muscle asting, thinning, purple striae an#easy

!ruising o+ the skin, poor oun#healing,osteoporosis

mgt6 surgery

hy#rocortisone 00 mg "G on the #ay o+ the

surgery, then maintenance oral #ose



B. timulation o+ +etal lung maturation A

!etamethasone (*mg 5e# !y (*mg

(8-*4 hrs. later :.Jonen#ocrine Diseases (0 )heumatic disorders A suppress the

#isease an# minimi<e

resultant tissue #amagemgt6 pre#nisone (0 mg7kg7#ay $taper

therea+ter !y #ecreasing (mg7kg7#ay eery *- ks'

intraarticular in:ection8 triamcinoloneacetonide

osteoarthritis 6 intraarticular injections ithinteral o+ *-

mos. to minimi<e complications



:. Jon-n#ocrine Diseases $cont.'

*. Menal Disor#ers A nephrotic syn#rome mgt6 pre#nisone6 (-* mg7kg / ks, 5e#.

!y gra#ual tapering oer -8 ks oralternate-#ay therapy $#iminishe#

proteinuria in 81? pts in *- ks an# 1?pts ill hae remission in mos.

- mem!ranous glomerulonephritis

mgt6 alternate-#ay pre#nisone 8-(0 ks5e#

!y (-* month perio# o+ tapering




. llergic Disease A epinephrine 0.1mlo+ a (6(000 solution "E or 2,repeate# eery (1 mins up to

#oses is nee#e# $anaphyla/is'

- onset o+ action o+ glucocorticoi# is#elaye#




4. Bronchial sthma A role o+ inammation inthe immunopathogenesis

- onset o+ action is #elaye# +or A (* hrs.

mgt6 "G methylpre#nisolone 0-(*0mginitially 5e#. !y oral pre#nisone 40-0mg#aily as the attack resoles

inhale# steroi#s A re#uces !ronchial

hyperreactiity ith les suppression o+a#renal +unction $#ysphonia ororopharyngeal can#i#iasis'




1. "n+ectious Disease A P. carinii pneumonia Aincreases o/ygenation an# #ecreases theinci#ence o+ respiratory +ailure an#

mortality . inuen<ae type ! meningitis A #ecrease

the long-term neurological impairment

. %cular #isease A 0.(? #e/amethasone

- :7"6 herpes simple/ keratitis $clou#ing o+the cornea' , glaucoma




@. kin #iseases A inammatory #ermatoses

8. I"T #iseases A inammatory !oel #isease

. epatic #iseases A pre#nisolone A 80?

histologic remission in pts. ith chronic, actie

hepatitis

(0. Ealignancies A LL, lymphomas

((. :ere!ral e#ema

(*. Eiscellaneous #is A arcoi#osis $in#uce

remission', throm!ocytopenia $#ecrease !lee#ing

ten#ency', organ transplantation, spinal co# injury



D. $ia-nostic Application

• De/amethasone suppression test A#i5erentiates :ushing;s syn#rome s.stress an# i+ :ushing;s syn#rome,

hether it;s an a#renal or a pituitarytumor

• Baseline cortisol leels are #etermine#

• De/amethasone 0.1mg eery hrs / 48

hrs.• De/amethasone * mg eery hrs. / 48

hrs.



To/icity6• Nith#raal o+ therapy6

ss/6 +eer, myalgias, arthralgias, malaise,pseu#omotor cere!ri $ ↑ICP, papille#ema'

• :ontinue# use at supraphysiologic #oses

ss/6 ui# an# electrolyte a!normalities,

hypertension, hyperglycemia, increase#suscepti!ility to in+ection, myopathy, !ehaioral#istur!ances, cataracts, groth arrest an# +atre#istri!ution, acne, hirsutism, striae, ecchymoses,osteonecrosis, peptic ulcer

• #renal suppression - >* ks. :ontrain#ications6 peptic ulcer, heart #isease or

pn ith :F, in+ections, psychoses, #ia!etes,osteoporosis, glaucoma or herpes simple/

in+ection



Supplemental measures8

• Diet rich in potassium an# lo inso#ium

• :aloric mgt to preent o!esity

• igh protein intake

• ppropriate antaci# therapy

• :alcium an# it D, physical therapy• len#ronate !iphosphonate

20120508-kbk-pemicu 4 blok metabolisme

Documents