Ciprofloxacin Garamycin Doxycyclin Amikacin. Tetracyclin Cephalosporin Thiamphenicol Co-trimoxazole Cloxacillin Azithromycin Colistin

(1)

(2)

Chloramphenicol Spiramycin

Ciprofloxacin

Garamycin Doxycyclin Amikacin

Streptomycin

Tigecyclin Amoxicillin

Tetracyclin Cephalosporin Thiamphenicol

Co-trimoxazole

Cloxacillin Azithromycin Colistin

(3)

Antibiotik

(4)

Antibiotik

:

* Bahan / zat yg dihasilkan oleh mikroba

/ sintetiknya

*

Membunuh /menghambat

pertumbuhan

mikroba lainnya

Obat anti infeksi

(5)

Host

(6)

Gejala infeksi

Host

(7)

Ku

Gejala infeksi

Host

(8)

Antibiotik

Sawar darah otak Kapsul sendi Mata

Dinding abses

Kuman

Antibiotik .... Absorpsi GI tract <<<

(9)

kinetik

dinamik

manusia

farmakologi klinik

Antibiotik

Penyakit infeksi

efek

utama

samping

Hamil Gg ren /hpr Bayi/dws/tua Pria/ wanita

(10)

Obat

Sembuh

berjasa

(11)

Prinsip pemberian antibiotik :

1. Pastikan diagnosa ok Infeksi ( panas blm tentu ok kuman ) 2. Infeksi serius ..pemeriksaan culture

3. Bila dilakukan culture,

sambil menunggu hasil , beri  Antibiotik empirical

4. pemilihan Antibiotik yg rasional - Kuman - Host

5. Monitoring keberhasilan terapi  culture

6. Kombinasi antibiotik

- infeksi campuran - Synergis

- Penyebab tidak tahu - Mencegah resistensi

(12)

Klasifikasi :

Struktur kimia

Spektrum Titik tangkap kerja * Penicillin * Cephalosporin *Tetracyclin *Chloramphenicol * Macrolid * Aminoglycoside * Quinolon * Broad * Narrow * Dinding sel * Membran sel * Sintesa protein * Asam nukleat

(13)

Titik tangkap kerja

: Dinding sel Membrane sel Sintesa protein Asam nukeat Peinicilin Cephalosporin Carbapenam Monobactam Fosfomycin Aztreonam Meropenam Ertapenam Vancomycin Bacitracin Cycloserin Colistin Polimixin-B Chloramphenicol Tetracyclin Macrolide Ketolide Lincomycin Streptogramin Oxazoladinone Aminoglycosid Rifampicin Quinolon

(14)

Hepatotoksik

>>>

<

t½ >>

Tetracyclin Erythromycin Penicilin Cephalosporin

Chloramphenicol

Rifampicin

Lincomycin

As-Nalidixin

Sulfonamid

Nitrofurantoin

(15)

Nefrotoksik

>>

<<<< / -

Aminoglycoside

Polymixin

Colistin

Cephaloridin

Cephalotin

Chloramphenicol

Chlortetracyclin

Doxycyclin

Minocyclin

Rifampicin

Lincomycin

As-Nalidixin

Sulfonamide

(16)

Kadar di CSF

Inflamasi Pen / Ceph - + Tetracyclin - Chloramphenicol + Aminoglycoside << < Macrolide - Quinulon < Clindamycin - Rifampicin +

(17)

Bacterosid

Bacteriostatik

Penicilin

Cephalosporin

Gentamicin

Rifampicin

Polymycin

Bacitracin

Streptomycin

Tetracyclin

Chloramphenicol

Erythromycin

Lincomycin

Sulfonamide

Dosis >>

Bac-sid

(18)

Tx Antibiotika kombinasi

Sinergis

………

Bac-sid

+ bac-sid

Aditif ………… bac-statik + bac-statik

(19)

Resistensi

AB

Ku Ku

Ku resisten

Natural drug resisten

Aquired Transferred/ “infectious” *Transformation *Transduction *Conjugation

(20)

Cross resisten : Struktur kimia

sama : der Tetracyclin

Polymyxin B ~ Colistin

Neomycin ~ Kanamycin tak sama : Erythromycin ~ Lincomycin

Reaksi yg merugikan :

*Superinfeksi ( broad > narrow ) *Hipersensitifitas ( allergi )

(21)

Perlu diketahui pengobatan dengan Antibiotik

sama

dengan obat lain

……….. 

Ada istilah MIC

( Minimum Inhibitory Consentration )

(22)

Titik tangkap kerja

: Dinding sel Membrane sel Sintesa protein Asam nukeat Penicilin Cephalosporin Carbapenam Monobactam Fosfomycin Aztreonam Meropenam Ertapenam Vancomycin Bacitracin Cycloserin Colistin Polimixin-B Chloramphenicol Tetracyclin Macrolid Ketolid Lincomycin Streptogramin Oxazoladinone Aminoglycosid Rifampicin Quinolon

(23)

Antibiotik penghambat sintesa dinding sel

Penicillin Cephalosporin miscellaneous Narrow spectrum Broad

spect Extend ed Spect Narrow spectrum Broad spectrum Carbapenam - Imipenam - Meropenam Monobactam - Aztreonam Fosfomycin Ertapenam Vancomycin Bacitracin Cycloserin Penicilin ase suscep tible Penicil G Penicil V Penicilin ase resistant ( Anti- Stapyloco cal ) ? Ampi Amox Carbeni cilin, Pipera cilin Mezlo cillin, Azlocillin 1st_{gene 2}nd ,_3nd 4th Gene

(24)

Penicillin

Narrow spectum Broad

spectrum Extended Spectrum Generasi- 1 : Penicillin G , Penicillin V Antistapylococal : Methicillin, Nafcillin, Isoxazolyl penicilin: oxacillin, cloxacillin, dicloxacillin Generasi- 2 : Ampicillin , Amoxicillin, Bacampicillin Generasi- 3 : Carbenicilin, Piperacillin ( pseudomonas +proteus) Generasi- 4 : Mezlocillin, Azlocillin ( pseudomonas +proteus)>> (6)

(25)

Penicillin

(26)

Penicillin

*Alami : jamur Penicilinum Notatum/ Chrysogenum *Semi sintetik

*Sintetik : rumus bangun : 6-Aminopenicillanic acid

S C C C C N C



-lactamase / penicilinase amidase

(27)

Penicillin

Farmakokinetik :

Abs : Pe cepat / Po bervariasi

Dist : seluruh jar tb ( serum ~ jar ) kadar (<) mata, prostat, CNS

( kec. Inflamasi ….. Meningitis )

Eks : * urine ( >> ) : 90 % sekrs tubulus

10 % filtrasi glomerulus * sputum / ASI

(28)

Penicillin

Farmakokinetik :

Probenicid dapat menghambat sekresi Penicillin di tubulus

(29)

Penicilin

Generic name spectrum PO Pen-ase Res

1.Pen-G 2. Pen-V 3. Methicilin 4. Nafcillin 5. Isoxazolyl – Penicilin Oxacillin Cloxacillin Dicloxacillin Flucloxacillin GR+>> Idem+GR-< Idem idem Idem Idem Idem idem - + - - + + + + - - + + + + + +

(30)

Penicillin

Generic name spectrum PO Pen-ase Res

6. Ampicillin 7. Amoxycillin 8. Carbenicillin Carbenicillin- indanyl 9. Piperacillin 10.Mezlocillin 11.Azlocillin GR-/+ (BS) Idem GR- > Idem Idem Idem Idem + + - + - - - - - - - - - - - -

(31)

Penicillin

Narrow spectum Broad

spectrum Extended Spectrum Generasi- 1 : Penicillin G , Penicillin V Antistapylococal : Methicillin, Nafcillin, Isoxazolyl penicilin: oxacillin, cloxacillin, dicloxacillin Generasi- 2 : Ampicillin , Amoxicillin, Bacampicillin Generasi- 3 : Carbenicilin, Piperacillin ( pseudomonas +proteus) Generasi- 4 : Mezlocillin, Azlocillin ( pseudomonas +proteus)>> (6)

(32)

Kuman-kuman yg sudah membentuk



-lactamase Staphylococcus H. Influenzae N. Gonococcus E. Colli ????????

Beta-lactamase

(Penicillinase)

(33)

Beta-lactamase inhibitor:

Clavulanic acid Sulbactam / Tazobactam ( penicillinic acid sulfon ) Streptomyces semi sintetik

clavigerus ( inti pen ) cara kerja Mengikat beta-lactamase ( anti bacteria <<< ) + Amoxycillin + Ampicillin ( Augmentin ) ( Unasyn )

(34)

Penicillin

Klinis:

* First choice drug



bac meningitis,

inf bone, joints, skin, soft tisssue,

throat, bronchi, tr UG.

*

Gonorrhoea, syphilis

( banyak kuman yg sudah resistens

(35)

Alergy Penicillin

Skin test



alergy ( + /- )

( pen G dosis <<<< IC )

( unreliable / berbahaya )

Penicilloyl polylysin

( PPL, Pre Pen )

(36)

(37)

Cephalosporin

Jamur Cephalosporium acremonium semi sintetik Cara kerja / struktur kimia ~ Pen

rumus bangun : 7 aminocephalosporanic acid

S ( relatif tahan pen-ase )

C C C C N C C



-lactamase amidase

Cross alergy ~ Pen ( Jarang 5-10 % ) Kinetik ~ Pen

(38)

Cephalosporin

G e n e r a s i

I II III IV

Spektrum

~ Pen > >>

Stabil Pen-ase

> Pen > >> >>>

(39)

Cephalosporin

Genersi

I II III IV Cefadroxil Cefazolin Cefradin Cefalexin Cefuroxim Cefaclor Cefoxitin Cefotetan Cefotaxime Ceftriaxone Ceftazidime Cefipim

(40)

Klinis : (cephalosporin)

* Bacteriemia ( + aminolgycosida )

* Surgical prophylaxis ( Pre / post OP ) * Mixed infection ( + anaerobes )

* Pen-ase producing N.gonorrhae * Bac- gram (- )

Reaksi yg merugukan :

* Pemberian Po.. N / V / D , IM …iritasi/pain

IV… thromboplibitis *Allergy

(41)

Antibiotik

(42)

Bacterial

protein synthesis

inhibitors

( A-B menghambat

sintesa protein

)

Broad spectrum Moderate spectrum Narrow spectrum Chlor amphe nicol Tera cyclin Macro lide Ketolid Linco samide Strepto gramin Oxazo ladino ne (Line zolid) Amino glycocide

(43)

Subclass Prototype Other agents

Chloramphenicol Chloramphenicol

Tetracyclin Tetracyclin Demeclocyclin, Doxycyclin,

Minocyclin, Tigecyclin

Macrolid Erythromycin Clarithromycin,

Azithromycin

Ketolid Telithromycin

Lincosamide Lincomycin Clindamycin

Streptogramin Quinupristin-Dalfopristin Oxazoladinone Linezolid Aminoglycosides - Systemic - Local - Aminocyclitol Gentamicin Neomycin Spectinomycin Amikacin,Netilmicin, Tobramycin,Streptomycin Gentamicin,Kanamycin

(44)

Chloramphenicol

(45)

Chloramphenicol

Sintetik

Sintesa protein <<

Broad spct ~ Tetra

( Gram +/- , Ricketsia, Salmonella, H.influenzae )

Penggunaan jarang ?

Depressi bone marrow



(46)

Chloramphenicol



glucoronyl transferase ( hepar )

Chloramphenicol

glucoronide

new borne (-) ( hepar <<< )

Chloramphenicol >>>>

( Gray - sindrom )

t-tbh < , muntah

Kulit kelabu

Circulatory failure

Shock… mati

(47)

Klinis :

* inf Salmonella

* inf pneumococc / meningococc ( meningitis ) * inf H. influenzae

* salep mata

Drug interaction :

* Menghambat metb obat lain

( phenytoin, tolbutamid, warfarin )

* Pemberian bersama Phenobarbital, Rifampicin  memperpendek waktu paruh Chloramphenicol.

(48)

Thiamphenicol

~ Chloramphenicol

( - NO2 diganti –CH2So2 ( sulfomethyl ) )

Anti bac < ( kec :Bordetella pertusis /

Shigella sonnei )

Depresi bone marrow <<

Klinis : - Bronchitis - GO

- inf sal empedu

(49)

Tetracyclin

(50)

Tetracyclin

:

* Oxyteteracyclin * Tetracyclin * Doxycyclin * Minocyclin

* Tigecycline (iv)

Basa sukar larut air ( bentuk garam mudah larut ) Stabil pH asam

Cara kerja : Sintesa protein << Bacteriostatik

(51)

F.Kinetik :

Abs : Po tak lengkap

Chelasi dg ion

Ca , Mg , Al

membentuk

ikatan komplek

: - tak larut

- sukar di abs

Makanan mengurangi Abs ( kec : Doxy / Mino )

Dist : seluruh jar

Doxy / Mino : lipid sol >>

Oxytetra : lipid sol <<

(52)

Disimpan di

tulang / gigi ( gigi coklat ) ( < 8-9 th )

Menembus sawar uri … discoloration gigi

Eks : Ren ( >>> )

Bile ( < )

Doxycyclin

: eks bile >>>

(53)

Use:

1. Inf Mycoplasmapneumoniae, Chlamydia, Rikettsia, Vibro species

2. Alternative drug Syphilis, inf tract resp,

prophylaxis inf chronis bronchitis, Eptospirosis, Acne. 3. Selective ulcus ok Helibacter pylori (tetracyclin ), prevensi Malaria (Doxycyclin ), pengobatan amebiasis 4.

Tigecyclin

( der Minocyclin ) broad spectrum (iv)

 efektif pd ku yg sudah resisten Tetra,Methicillin, Vancomycin, ku yg produksi betalactamase,

(54)

ES :

( tetracyclin )

* Iritasi lambung ( > Oxytetra )

* Superinfeksi

* Hepatotoksik ( < Oxy / Tetra )

* Discoloration gigi / pertumbuhan tl ( < Oxy / Doxy )

* Antianabolik

* Photosensitif ( Demeclocyclin )

* Vistibular  dizziness/vertigo(reversble): doxy/mono

* waktu perdarahan >>

(55)

Macrolide

(56)

Macrolide

:

*

Erythromycin

*

Spiramycin

*Roksitromycin

*Claritomycin

*Azithromycin

(57)

Erythomycin

( dari streptomyces erythreus)

sintesa protein <<

Bacteriostatik…side (~ dosis )

Spectrum :

-

Gram + cocci - Spirochetes

- Neisseriae - Ent-histolityca

- Coryn- diphteriae - Mycopl-pneumoniae

(58)

Resistensi antar Macrolide

Klinis :

inf Upper resp Diphteri carrier

*G (+) Pen-resisten

lues Pen allargy Acne

ES :

Po: N / V/ D /

(59)

Spiramycin

Cara kerja ~ Erythromycin

Spectrum :

gram + / -

clamydia trachomatis

Toxoplasma gondii

Cryptosporidum muris ( AIDS

)

F-kinetik :

Abs : po baik

(60)

Eks : - urine

- bile

t ½ : 4 -8 jam

ES : GI tract



N / V / mulut kering

skin rash / asma / colitis

Klinis : Inf staphylococc / streptococc / pneumococc

GO ( resisten )

Toxoplasmosis

Trachoma

(61)

Roksitromycin ~

Erythromycin

* iritasi lambung <<

* kadar jar >

* t½ 10 jam ( 2dd )

(62)

(63)

Telithromycin

( stuktur ketolid ~ Macrolid ) - Cara kerja / specrtum ~ Erythromycin

( sensitif pada kuman yg sudah resisten thdp Macrolid ok terikat kuat pada ribosome ) - Pemberian oral once daily

- Eliminasi bile dan urine

- Penggunaan terbatas ok efek sampingnya

Hepatotoksik, gangg penglihatan

(64)

Lincosamide

(

Lincomycin

/

Clindamycin )

(65)

Lincomycin

/

Clindamycin

larut air

acid stable

bacterioside

toksisitas

: liver damage / CV collaps

Digeser

Clindamycin

:

(66)

Clindamycin

ES

: iritasi GI… N / V

superinfeksi

pseudomembrane colitis

bad-taste … penetrasi saliva

Klinis

:

- infeksi kulit ( G + )

- Inf- tract Resp ( H. influenzae )

- Acne

(67)

(68)

Quinopristin-dalfopristin

* Kombinasi dari 2- Streptogramin * Bacteriocid

* Efektif thdp kuman yg sudah resisten penicillin, methicillin, vancomycin * Pemberian iv

* ( menyebabkan arthralgia-myalgia sindrom ) * Streptogramin adalah inhibitor CYP3A4

Menyebabkan kadar bbp obat meningkat

(69)

Oxazoladinone

(70)

Linezolid

( Zyvox )

- Antibiotik pertama dari oxazolidinone - Menghambat sintesa protein

- Efektif thdp ku yg sudah resisten (gram +) cocci ( penicillin, vancomycin) - Pemberian peroral / parentral

- Metabolisme mel hepar

- Eliminasi half life 4 -6 jam

- Efek samping throbositopenia , neutropenia

(71)

(72)

Subclass

Prototype

Other agents

Aminoglycosides - Systemic - Local Gentamicin Neomycin Amikacin, Netilmicin, Tobramycin Streptomycin Gentamicin, Kanamycin Aminocyclitol Spectinomycin

(73)

Aminoglycosida

Streptomycin

Neomycin

Kanamycin :

( Amikasin / Dibikasin)

Tobramycin

Gentamicin

Netilmicin

Spectinomycin

Abs : Po <<<

Ik-protein <

Eliminasi di glo

Tox: -Ototoksik

-Nephrotoksik

-Curare like

-Skin reaction

(74)

Farmakokinetik

:

* Poorly lipid soluble ( parentral )

* Unable to enter the CNS

* Not metabolised

(75)

Clinical uses:

( Aminoglycoside )

* Terutama gram (-) ( garamicin, tobramycin, amikacin ) * Sering dikombinasi dg beta-lactam antibiotik (penicillin )  untuk inf ku gram (+ )

* Streptomycin + Penicillin  entrococcal carditis

* Mycobac-tbc resisten Streptomycin ( penggantinya Amikacin )

* Neomycin, kanamycin  topical dan oral

* Spectinomycin ( der – Aminocyclitol) - Single dose

- intra muscular

(76)

Gentamicin ( Garamicin )

Abs : Po <<

Eks : …glo ( bentuk tak berubah )

renal failure .. Akumulasi obat ES : gg keseimbangan / pendengaran

* keseimbangan  garamcin, tobramycin * pendengaran  amikacin, kanamycin

Tak dianjurkan ibu hamil / neonatus ( ? )

Klinis : sistemik ( Gram - )

(77)

Resistensi Aminoglycosida

- Terutama pada ku gram negatif

- gram postif streptococc ( s-pneumoniae ), entrococci resisten thdp garamicin dan aminogylosida lain



Ok enzym transferases

 Inactivasi Amikacin, garamicin, tobramycin ( tidak pada streptomycin ) Netilmicin kurang sensitif thdp transferase

(78)

(79)

Rifampicin

* Semi sintetik

* Broad spct : gram (+) cocci gram (-) bacilli

Tuberculosa / lepra * ES : GI  Nausea / vomiting

Hepar ( terutama kel - hepar )

* Enzym inducer

* Use : TBC / Lepra

(80)

Polymyxin

(81)

Polymyxin

A /

B

/ C / D /

E

/ M

colistin

Bacterioside



G (-)

Inf trct UG / telinga / kulit

Use



Topikal ( aman ) , sistemik (gg Ren / CNS)

Potensiasi dg obat neuro-muscl paralysis



kelemahan otot

Lysis mast sel



histamin

(82)

Colistin

Spectrum / cara kerja ~ Polymyxin-B

Potensi <

Abs Po : < 5 th (+) , dewasa (-)

Menembus placenta barrier

ES ~ Polymyxin-B

CI : myasthenia gravis

Use :

topikal (

+ neomycin + corticostroid )

GI tract ( E.colli yg resisten neomycin )

(83)

Quinolon

(84)

Quinolon /

Fluroquinolon

Generasi I Generasi II Generasi III

Nalidixic acid*

Pipemidic acid*

Cinoxin

Norfloxacin .

Ciprofloxacin

Ofloxacin .

Pefloxacin .

Sparfloxacin.

Levofloxacin .

Moxifloxacin .

Gemifloxacin

Getifloxacin

( ? )

(85)

quinolon

Cara kerja :

Menghambat

DNA girase

( enzym supercoiling DNA )

Spektrum :

Quinolons



Gram (-) ( trct UG )

Fluoroquinolons



Gram (-) >>

GO / Chlamydia

Staphylococc

Pseudomonas A

(86)

F. Kinetik :

Abs : Po ( 50 – 90 % )

Dist : luas  const Ren / Pulmo > serum CSF < serum

Sekrs : ren : F-quinolon

non renal : Quinolon + Pefloxacin

Hepatic failure : F-quinolon (+) ( kec. Pefloxacin )

(87)

F. Kinetik :

Abs : peroral

Peroral : Nalidixic acid +

Norfloxacin . ++ Ciprofloxacin . ++ Ofloxacin . ++ Sparfloxacin. ++ Levofloxacin . ++ Pefloxacin . +++ Moxifloxacin . ++ / entral Gemifloxacin ++ / entral Getifloxacin. ( ? ) ++ / entral

(88)

Quinolon

(Asam Nalidiksat ) Abs per oral ( cepat ) ...

Ekskresi ( cepat )…….ren ( jadi kurang manfaat utk infeksi sistemik )

Norfloxacin

~ asam Nalidiksat - kadar urin tinggi ,

- kadar serum rendah

(89)

Klinis

:

( f-quinolon )-

**• Infeksi : * saluran kemih**

( cipro / nor / of )

* saluran cerna

( cipro / of / pe )

* saluran napas

( ciporo / of / levo / moxi / gemi / gati ? )

* tulang- sendi

( cipro )

* kulit - jar lunak

( cipro ? )

(90)

Klinis :

( f-quinolon )

*

Complicated urinary tract infection

* Gonorrhae

* Cervisitis

* Prostatitis

* Typhoid fever

* Septicemia ( thdp ku yg sensitive )

* Resp tract infection( bukan ok pneumococci )

(91)

Adversed reaction :

( f-quinolon )

- Gangg GI tarct

- Skin rashes

- Joint pains

- Allergy

- Menghambat ikatan

GABA

dg reseptornya



convulsi

- Gangg pertumbuhan tulang / cartilage

(

ibu hamil / anak

masa pertumbuhan (-) )

(92)

Co-trimoxazole

(93)

Sulfonamides

& Trimethoprim

Sulfadiazine

Sulfisoxazole

Sulfamethoxazole +

Trimethoprim



Co-trimoxazole

( Bactrim )

Sulfacetamide

(94)

Co-trimoxazole

:

( bacterioside )

Trimethoprim ( 1) + Sulfamethoxazole (5)

( bacteriosatik ) ( bacteriostatik)

(95)

Pteridine precursor + PABA Pteridine + PABA + glutamic acid Folic acid Dihydrofolic acid

Dihydrofolic acid reductase

Tetrahydrofolic acid 

DNA  Bacterial growth sulfonamid

(96)

Klinis :

(Co-trimoxazole )

* Inf-systemic

* Inf chronis - trct UG

* Inf-ku gram (-) bacilus

* Inf-trct Resp (

bronchitis ok S.pneumoniae, H.influenzae )

* Otitis media

( S.pneumoniae, H.influenzae )

* Typhoid fever

( resisten Chloramphenicol, Ampicilin )

Drug of choice Tx / Px :

Pneumonia ( ok. Pneumocytsis carinii )

(97)

Adverse effects

( co-trimoxazole )

Sulfonamide

Trimethoprim

Alergy-rash, fever, Stevens-johnson synd Agranulocytosis Kristal uria Haemolysis

Inhibit metab- obat

Macrocytic anemia Trombocytopenia

Aplastic anemia (elderly)

(98)

Faktor kegagalan

tx. Antibiotik

(99)

Faktor kegagalan Tx. Antibiotik

01 _{Indikasi kurang tepat}

02 _{Dosis <}

03 _{Daya tahan tubuh <}

04 _Resistensi 05 _Superinfeksi 06 _{Infeksi campuran} 07 _{Tindakan bedah} 08 _{R. hipersensitif} 09 _{Interaksi obat} 10 _{Farmakokinetik}

(100)

Buku acuhan

1.The farmacological basis of therapeutics (Goodman & Gilmans) 2. Basic clinical pharmacology ( Bertram G Katzung)

3. Pharmacology -Examination & broad review

Katzung & Trevor’s (2008 )

4 Medical Pharmacology ( Peter winstanley & Tom Walley (2002 ) 5.WHO Model Formulary (2002 )

6.Pharmacology Principles and applications ( 2009 )

Eugenia M.Fulcher, Robert M.Fulcher,Cathy Dubeansky S 7. Farmakologi dan terapi ( UI -2008 )