Modul UKAI 2015 Farmakokimia

7/25/2019 Modul UKAI 2015 Farmakokimia

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Matrikulasi UKAI 2015

Farmakokimia- Infeksi, Endokrin & ! "on Infeksi dan

#ernafasan

A$ustina %etiaati, M'%(', A)t

1

u*uan #em+ela*aran

1' Maasisa mam)u memaami as)ek kimia

medisinal obat anti infeksi meli)uti anti+akteri dan

antiirus

2' Maasisa mam)u memaami as)ek kimia

medisinal obat yang bekerja pada sistem endokrin

.' Maasisa mam)u memaami as)ek kimia

medisinal dalam sistem pernafasan

2


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eferensi

#atri(k, '', 2005, An Introduction to Medicinal

Chemistry, .rd edition, 3ford Uniersit4 #ress'

.

#endauluan

#aul Erli(+a)ak kemotera)i men$$unakan sen4aa

kimia untuk men$o+ati infeksi6

Prinsip kemoterapi: chemicals could directly interfere the

microorganism at the concentration tolerated by the host

Konse)7 MAI 9UE

The process: selective toxicitythe chemicals has greater

toxicity to the microorganism than to the host cells

Chemotherapeutic index= minimum effective dose ofdrug/maximum dose can be tolerated by the host

:


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#aul Erli(

;eelo)ed in 1


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Anti+a(teria ar$et

?

Me(anism of anti+a(terial a(tion

1' Ini+ition of (ell meta+olism 7 sulphonamide

2' Ini+ition of +a(terial (ell all s4ntesis7 -lactam

.' Intera(tion of )lasma mem+rane

:' ;isru)tion of )rotein s4ntesis

5' Ini+ition of nu(lei( a(id trans(ri)tion and

re)li(ation

8


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Ini+ition of (ells meta+olism

%UF"AMI;E%

1


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Analo$ue of sul)onamide it redu(ed to3i(it4

%ulfatia=ole an earl4 sulfonamide6 form insolu+le meta+olite

and (an )roe fatal if it (an +lo(k kidne4

inese & @a)anese meta+olite more i$er tan Ameri(an

%trate$47 replacing thiazole group with more electronwithdrawing group

11

More a(tie tan sufadia=ine

Used to )reent to)i(al infe(tion


12


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%o sta+le in te +od4, intake on(e a eek

#eni(illin su)erseded sulfonamide, still use in )resent

medi(ation to treat urinar4 tra(t infe(tion, e4e,

mu(ous & $ut infe(tion


1.

Me(anism of A(tion

;i4dro)teroat s4ntase is im)ortant en=4me to

)rodu(e tetra4drofolate a )er(usore of foli( a(id--ne(essar4 to +a(terial surial6

B4 does sulfonamide s)esifi( to kill +a(teria (ells

itout armful to uman (ellsC

1:


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%ulfonamide a(ts as an ini+itor +4 mimi(kin$ #A9A-normal

su+strate of di4dro)teroat s4ntetase similar stru(ture6

eersi+le-(om)etitie en=4me ini+itorleel of(on(entration is determined te a(tion

esistan(e of sulfa, (aused +4 mutation of tar$et en=4me

%ulfonamide )reent #A9A +indin$ to

di4dro)teroat s4ntase

15

ter antimeta+olite-rimeto)rim

ien in (om+ination it sulfameto3a=ole

CO!"#O$%&O'()

1>


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Ke4 )oint

#rin(i)le of (emotera)47

desi$n of (emi(als it

sele(tie to3i(it4 a$ainst

+a(terial (ells rater tan

mamalia (ells

9a(terial (ells are differ from

mamalian (ells so tat sele(tie

tar$et (an +e addressed to dru$

deelo)ment

1?

I"!I9I E BA %D"!E%I%-#eni(illin

18

9ios4ntesis of )eni(illin )er(usor


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Im)ortant fa(t a+out )eni(illin

9a(teri(idal tan +a(teriostati(

%ensities to +eta-la(tamase

A(tie a$ainst diidin$ +a(teria

Ma4 (auses aller$i( rea(tionras to ana)4la(ti(

rea(tion

Ineffe(tie if $ien orall4a(id de$radation in

stoma(

1


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%tru(ture-a(tiit4 relationsi)

H-la(tam rin$ is im)ortant to tea(tiit4

Free (ar+o34li( a(id is essential+indto ammonium ion of l4sin

9i(4(li( rin$ is im)ortant

A(4lamino is essential ile sulfur isussual +ut not essential

2?

B4 dose )eni(illin easil4 de$raded +4

a(idC

in$ strainfie mem+er rin$ fused to four mem+er

rin$s

28


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!E G- AAM7 E#!A%#I"%

First dis(oered (e)alos)orin isolated from

Acremonium chrysogenum

ess )oten(4 tan )eni(illin +ut it (an em)lo4 +ot

in $ram )ositie or ne$atie +a(teria

2


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Mono+a(tam

.?

ter Ini+itor of ell Ball %4ntesis

.8

ter Ini+itor of ell Ball %4ntesis


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.


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1' Ini+itor of ;"A irus )ol4merase-A(4(loir

:?

A(4(loir

Meta+olite of a(4(loir is

nu(leoside-like stru(tureN

& as similar +ase stru(ture

to deo34$uanosine

"u(leoside tri)os)ate is

)er(usore for ;"A

s4ntesis/re)li(ation

Ini+it ;"A )ol4merase

:8


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A(4(loir

Ini+it ;"A )ol4merase +4 to me(anism7

16 A(4(loir tri)os)ate +ind to ;"A )ol4merase

and ini+it it

26 ;"A )ol4merase atta( a(4(loir tri)os)ate to

$roin$ ;"Aacyclo*ir as chain terminator

Does acyclovir stop proliferation in normaland infected cells?

: )osition

#urine stru(ture is o3idi=ed +4

2anthine o2idase to form a(4(loir

52

A(4(loir analo$ues

an(i(loir, analo$ue of a(4(loir, as

4dro34met4lene $rou)

al$an(i(loir$an(i(loir )rodru$


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#en(i(loir is $an(i(loir analo$ue

Fam(i(loir is )en(i(loir analo$ue,

as 2 al(ool $rou) masked +4 ester

$rou)less )olar+etter a+sor)tion

n(e a+sor+ed, a(et4l $rou) are

4drol4sed +4 esterase & in lier

)urine $rou) o3idi=ed +4 aldehyde

o2idaseform )en(i(loir

5.

A(4(loir analo$ues

Antiiral dru$ a$ainst "A

iruses7 !I

5:


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%tru(ture and life (4(le of !I

55

Ini+itor of iral reerse trans(ri)tase

eerse trans(ri)tase is ;"A )ol4merase

allen$e7 o to make te dru$ sele(tie onl4 to ini+it it in

irus not in ost (ellC

"u(leoside-like stru(ture, need . )os)or4lation to $et

a(tie nu(leotide tri)os)ate

;ifferen(e7 (ellular en=4me are needed to do )os)or4lation

5>

"UE%I;E EE%E A"I#A%E I"!I9I "I6


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Jidoudin

First, a))roed as anti-!I

Analo$ue deo34timidine .O-4dro3il re)la(ed +4 a=ido $rou)

Analo$ue deo34(4tidine

Ini+it (ain $roin$ of ;"A7 (ain terminator

5?

!4dro)o+i( mole(ule tat +ind to allosteri( +indin$ site tat

4dro)o+i( in nature

"on-(om)etitie & reersi+le ini+itor

58

"" "UE%I;E EE%E A"I#A%E I"!I9I ""I6

Ini+itor of iral reerse trans(ri)tase


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a)id emer$en(e (asemutation K10." in +indin$

site

%trate$47 (om+ine "I & ""I

5

Modul UKAI 2015 Farmakokimia

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