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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$47 replacing thiazole group with more electronwithdrawing group
11
More a(tie tan sufadia=ine
Used to )reent to)i(al infe(tion
Analo$ue of sul)onamide it redu(ed to3i(it4
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 & $ut infe(tion
Analo$ue of sul)onamide it redu(ed to3i(it4
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