Anastesi PDF
Anastesi PDF
Abstract
Drug-drug interactions can initiate undesirable or adverse effects. This could have a clinical
implication and could also become serious health problems. Since a large number of drugs are
introduced and marketed every year, new interactions between concomitant medications might possibly
increase. The safety profile of drugs including the impacts of drug-drug interactions can be provided
from pharmacoepidemiology and pharmacovigilance data.
There are some mechanisms of drug-dug interactions, i.e. pharmaceutics interaction, pharmacokinetics
and pharmacodynamics interactions. However, only pharmacodynamic interaction can be predicted
and the effect usually applies equally to any drugs in the same class therapy. On the other hand,
pharmacokinetic interactions cannot be predicted or extrapolated to any drugs in the same class
therapy because of differences in their pharmacokinetics profiles. Information on how is the mechanism
of drug-drug interaction is needed, so the possible adverse effect due to drug-drug interactions can be
anticipated.
Keywords: drug-drug interaction, adverse effect, pharmacokinetics, pharmacodynamics
Pendahuluan.
175
176
absorpsi
177
178
179
menghambat
metabolisme
lopinavir
oleh
CYP3A4 di usus dan hati.22
Kombinasi obat-obat anti malaria dengan
mula kerja cepat tetapi waktu paruhnya singkat
(misal, artemisinin) dengan obat anti malaria lain
yang memiliki waktu paruh lebih panjang, akan
meningkatkan efktivitas obat anti malaria tersebut
dan mengurangi relaps. Kombinasi obat-obat anti
tuberkulosis diharapkan akan memperlambat
terjadinya resistensi.
SUBSTRAT
Amitriptilin
betabloker
debrisokuin
fenasetin
haloperidol
CYP2C19
CYP3A4/5
CYP1A2
180
kodein
metoprolol
metoklopramid
prokainamid
propranolol
tramadol
diazepam
flunitrazepam
heksobarbital
imipramin
klomipramin
lansoprazol
kontraseptik oral
astemizol
asetaminofen
cisapride
terfenadin
triazolam
midazolam
felodipin
karbamazepin
simva-Tlovastatin
teofilin
kofein
klozapin
warfarin
INHIBITOR
Amiodarone
celecoxib
difenhidramin
flufenazin
halofantrin
klorpromazin
kuinidin
metadon
ranitidin
ritonavir
simetidin
Fluoksetin
indometazin
ketokonazol
omeprazol
probenesid
ritonavir
simetidin
INDUKTOR
Rifampisin
Ketokonazol
Dexametazon
etanol
rifampisin
INK
itrakonazol
eritomisin
klarirromisin
grapefruit juice
ritonavir
diltiazem
siprofloksasin
fluvoksamin
Karbamazepin
fenobarbital
prednison
rifampisin
rifampisin
karbamazepin
barbiturat
asap rokok
charcoal grill-meat
Efek potensial
Waktu mula
munculnya efek
Umumnya dalam
waktu 1 minggu
Keterangan dan
Rekomendasi
Pilih/ganti antibiotika
alternative
Sedapat mungkin guna-kai
dosis asetaminofen
terendah, monitor INR
Batasi dosis asetosal
lOOmg/hari dan monitor
INR
Sedapat mungkin hindari
penggunaan obat-obat
tsb bersamaan. Jika
diperlukan penggunaan
bersama, gunakan
inhibitor Cox-2 dan
monitor INR
Beri jarak waktu
pemberian2-4jam
Warfarin dengan
siprofloksasin, klaritromisin,
eritromisin, metronidazol, atau
ko-trimoksazol
Efek warfarin
meningkat
Perdarahan
meningkat, INR
meningkat
Perdarahan
meningkat, INR
meningkat
Perdarahan
meningkat, INR
meningkat
Setiap waktu
Absorpsi
fluorokuinolon
menurun
Kadar plasma
karbamazepin
meningkat
Kadar plasma
fenobarbital
meningkat
Setiap waktu
Setiap waktu
Setiap waktu
Umumnya dalam
waktu 1 minggu
Umumnya dalam
waktu 1 minggu
Kadar plasma
fenitoin menurun
Umumnya dalam
waktu 1 minggu
Kadar plasma
fenobarbital menurun
Kadar plasma
karbamazepin
menurun
Umumnya dalam
waktu 1 minggu
Umumnya dalam
waktu 1 minggu
Setiap waktu
181
Efek potensial
Waktu mula
munculnya
efek
Setiap waktu
Keterangan dan
Rekomendasi
Keefektifan pil
kontraseptik oral
menurun
Perpanjangan interval
QT diikuti aritmia
karena penghambatan
metabolisme cisapride
Umumnya
dalani waktu 1
minggu
Perpanjangan interval
QT diikuti aritmia
Setiap waktu
Hindari !
Hipotensi berat
(dramatik)
Kontraindikasi mutla
Kadar plasma
sildenafil meningkat
Segera setelah
minum
sildenafil
Setiap waktu
Kemungkinan
rhabdomyolysis
Setiap waktu
Efek warfarin
meningkat
Kadar antidepresan
trisiklik meningkat
Setiap waktu
182
Setiap waktu
Efek potensial
Krisis hipertensi
Potensi kejang
meningkat; sindrom
serotonin
Sindrom serotonin
Sindrom serotonin
Waktu mula
munculnya efek
Segera setelah
pemberian
Keterangan dan
Rekomendasi
Hindari!
Setiap waktu
Setiap waktu
Kemungkinan
setelah
pemberian dosis
awal
Keterangan:
INR = International Normalized Ratio;
NSAID = nonsteroidal anti-inflammatory drug;
SSRI = selective serotonin reuptake inhibitor.
183
11.
12.
13.
Daftar Pustaka
1.
Ament PW, Bertolino JG, Liszewski JL.
Clinical
pharmacology:
clinically
significant drug interactions. Am Fam
Physician. 2000; 61:1745-54
2.
Peng, CC, et al. Retrospective Drug
Utilization Review: Incidence of clinically
relevant potential drug-drug interactions in
a large ambulatory populations.! Managed
Care Pharm. 2003;9 (6):513-22.
3.
Lazarou, J. et al. Incidence of Adverse Drug
Reactions in Hospitalized Patients. JAMA.
Vol. 279. April 15, 1998: 1200-05.
4.
Juurlink, DN et al. Drug-drug interaction
among elderly patients hospitalized for drug
toxicity. JAMA, Vol. 289 (13), April 2,
2003: 1652-58.
5.
Conry, JM. Significant drug interactions in
the HIV paients. J Pharm Pract 2000; 13:
499-514.).
6.
May RJ. In: Pharmacotherapy a
pathophysiologic approach. Adverse drug
reactions and interactions. DiPiro JT,
Talbert RL, Yee GC, et al. Appleton &
Lange, 1997:101-16.
7.
S. U. Mertens-Talcott, et al. GrapefruitDrug Interactions: Can Interactions With
Drugs Be Avoided? J. Clin. Pharmacol.
2006; 46; 1390-1416.
8.
Leahey EB, Reiffel JA, Drusin RE, et al.
Interaction between quinidine and digoxin
JAMA 1978;240:533-4.
9.
Ito K, Iwatsubo T, Kanamitsu S, et al.
Prediction of pharmacokinetic alterations
caused by drug-drug interactions: Metabolic
interaction in the liver. Pharm Rev 1998; 50
(3):387-411.
10. Pelkonen O, Maenpaa J, Taavitsainen P,
Rautio A, Raunio H. Inhibition and
induction of human cytochrome P450
Xenobiotica
(CYP)
enzymes.
1998;28:1203-1253.
184
14.
15.
16.
17.
18.
19.
20.
21.
22.