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Modul UKAI 2015 Farmakokimia
Modul UKAI 2015 Farmakokimia
Tujuan Pembelajaran
1. Mahasiswa mampu memahami aspek kimia
medisinal obat anti infeksi meliputi antibakteri dan
antivirus
2. Mahasiswa mampu memahami aspek kimia
medisinal obat yang bekerja pada sistem endokrin
3. Mahasiswa mampu memahami aspek kimia
medisinal dalam sistem pernafasan
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Referensi
Patrick, G.L., 2005, An Introduction to Medicinal
Chemistry, 3rd edition, Oxford University Press.
Pendahuluan
Paul Ehrlich bapak kemoterapi (menggunakan senyawa
kimia untuk mengobati infeksi)
Prinsip kemoterapi: chemicals could directly interfere the
microorganism at the concentration tolerated by the host
Konsep: MAGIC BULLET
The process: selective toxicity the chemicals has greater
toxicity to the microorganism than to the host cells
Chemotherapeutic index= minimum effective dose of
drug/maximum dose can be tolerated by the host
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Paul Ehrlich
Developed in 1910
Effective to kill protozoal disease
of sleeping sickness
(trypanosomiasis)
It was not wide used to treat wide
range of bacterial infection
Replaced by penicillin
ANTIBACTERIA
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Antibacteria Target
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Structure-Activity Relationship
p-amino is essential for
activity
Aromatic ring & sulfonamide
functional group is
important
Aromatic ring must be para
subtitude
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Mechanism of Action
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Other antimetabolite-Trimethoprim
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Key point
Principle of chemotherapy:
design of chemicals with
selective toxicity against
bacterial cells rather than
mamalia cells
Bacterial cells are differ from
mamalian cells so that selective
target can be addressed to drug
development
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Mechanism of Action
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Inhibition of transpeptidase
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Resistance to penicillins
Is happened in gram
negative or positive?
Porin transport penicillins
pass through cell
membrane
In gram negative bacteria,
there are -lactamase in
membran layer
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Penicillin degradation
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Penicillin resistance
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Structure-activity relationship
-lactam ring is important to the
activity
Free carboxylic acid is essential bind
to ammonium ion of lysin
Bicyclic ring is important
Acylamino is essential while sulfur is
ussual but not essential
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Mechanism of Action
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Fifth generation
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Aminoglycoside: streptomycin
Tetracycline
Chloramphenicol
Macrolide (eq: erythromycin)
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ANTIVIRUS
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Virus Structure
Capsid (core protein), consist of
subunit called protomer.
Protomer form capsid by self
assembly
Nucleic acid is protected by
capsid form structure:
nucleocapsid
Nucleocapsid may contain enzyme
to replicate in host cell (RNAdependent RNA polymerase)
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Acyclovir
Metabolite of acyclovir is
nucleoside-like structure
& has similar base structure
to deoxyguanosine
Nucleoside triphosphate is
percusore for DNA
synthesis/replication
Inhibit DNA polymerase
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Acyclovir
Inhibit DNA polymerase by two mechanism:
1) Acyclovir triphosphate bind to DNA polymerase
and inhibit it
2) DNA polymerase attach acyclovir triphosphate to
growing DNA acyclovir as chain terminator
Does acyclovir stop proliferation in normal
and infected cells?
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Acyclovir analogues
Bioavailabililty of acyclovir is
low has to be developed!
Valaciclovir (prodrug) has L-valyl
ester group Absorbed effective in
gut wall than acyclovir
Polarity and ionization of valaciclovir
is similar to acyclovir no more able
to cross the gut wall by passive
transport
How to solve this?
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Acyclovir analogues
Add D-valine group instead of L-valine to valaciclovir
These peptide drive prodrug is transported to the cells by
active transport
Protein transport: human intestinal proton-dependent
oligopeptide transporter-1 (hPET-1) & human intestinal
di/tri-peptide transporter (HPT-1)
Once valaciclovir is absorbed, it is hydrolized to acyclovir in
liver & gut wall
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Acyclovir analogues
Desciclovir, prodrug of acyclovir
which has no carbonyl in C6 position
Purine structure is oxidized by
xanthine oxidase to form acyclovir
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Acyclovir analogues
Penciclovir is ganciclovir analogue
Famciclovir is penciclovir analogue,
has 2 alcohol group masked by ester
group less polar better absorption
Once absorbed, acetyl group are
hydrolysed by esterase & in liver
purine group oxidized by aldehyde
oxidase form penciclovir
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Zidovudin
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Introduction
The important player in adrenergic nervous is
adrenaline and noradrenaline
Noradrenaline = norephinephrine
neurotransmitter released by symphatetic nervous
which feed smooth muscles and cardiac muscles
Adrenaline = ephinephrine hormone released
along with noradrenaline from adrenal medula
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EVALUASI MAHASISWA
Latihan soal format UKAI sesuai dengan materi
yang diajarkan
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Latihan 1
Seorang pasien perempuan, berusia 32 tahun, didiagnosis
kanker payudara stadium III. Setelah biopsi ringan
didapatkan informasi histologi sel kanker payudara pasien
mempunyai ER yang berlebihan. Kemoterapi yang tepat
diresepkan untuk pasien tersebut adalah .....
a. Doxorubicin
b. 5-Flurourasil
c. Tamoxifen
d. Bevacizumab
e. Paclitaxel
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Latihan 2
Sebuah industri farmasi mengembangkan sediaan sirup obat
antibiotik baru untuk kasus infeksi penyebab diare pada suatu
daerah. Bagian riset dan pengembangan obat industri tersebut
melakukan uji kultur pada bakteri penyebab infeksi dan
disimpulkan bakteri tersebut resisten terhadap golongan laktam. Obat apakah yang diformulasikan industri farmasi
tersebut?
A. Sefiksim
B. Sefriakson
C. Amoksisilin
D. Eritromisin
E. Aztreonam
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Latihan 3
Seorang pria, 27 tahun, mengalami demam tinggi dan lesi
urtikaria pada kulitnya. Pemeriksaan klinis sampel darah pasien
disimpulkan bahwa wanita tersebut terinfeksi adenovirus. Dokter
meresepkan tablet gangsiklovir yang mempunyai target aksi
nukleotida virus tersebut. Apakah proses pada sel yang
dipengaruhi oleh obat tersebut?
A. Transkripsi DNA
B. Translasi
C. Replikasi DNA
D. Modifikasi protein
E. Pematangan mRNA
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Latihan 4
Sebuah industri farmasi mengembangkan formulasi sediaan obat
oral berupa analog hormone estrogen untuk indikasi kanker
payudara. Manakah pernyataan berikut ini yang sesuai untuk
obat tersebut?
A. Meningkatkan konsentrasi protein kinase A di sitoplasma
B. Obat terikat pada reseptor di sitoplasma
C. Obat meningkatkan fosforilasi tirosin pada reseptor
D. Obat mengaktifkan enzim adenilat siklase
E. Obat mengaktifkan diasil gliserol
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Latihan 5
Seorang wanita berumur 25 tahun datang ke rumah sakit dengan
keluhan jerawat bernanah. Dokter meresepkan sirup doksisiklin
pada pasien tersebut. Apakah target aksi antibiotik tersebut?
A. Menghambat replikasi DNA
B. Menghambat sintesis Mrna
C. Menghambat sintesis protein
D. Merusak membran sel
E. Menghambat sintesis dinding sel
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Latihan 6
Seorang bapak, berusia 45 tahun, menjalani perawatan di
sebuah Rumah Sakit akibat infeksi saluran kencing. Dokter
memberikan kotrimoksazol untuk pengobatan. Apakah target
aksi dari obat tersebut?
A. Metabolisme sel
B. Replikasi DNA
C. Transkripsi
D. Translasi
E. Pembelahan sel
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Latihan 7
Seorang pria, 40 tahun, positif terinfeksi HIV. Berdasarkan data
hematologi, jumlah sel T tipe CD4+ turun signifikan. Pria tersebut
dirujuk berobat ke dokter spesialis bedah onkologi. Dokter
tersebut memberi pasien tersebut injeksi obat untuk
menghambat aktivitas enzim dalam virus. Apakah obat yang
diinjeksikan oleh dokter tersebut?
A. Asiklovir
B. Gangsiklovir
C. Zidovudin
D. Valgansiklovir
E. Desiklovir
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Latihan 8
Seorang bapak, berusia 45 tahun, dibawa ke IGD sebuah Rumah
Sakit karena sesak nafas akibat COPD. Dokter memberikan injeksi
salmefamol, suatu agonis reseptor adrenergik, pada pasien
tersebut. Apa reseptor tipe apakah obat tersebut bekerja?
A. 1
B. 2
C. 1
D. 2
E. 3
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TERIMA KASIH
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