pharmaceutic interaction 2
TRANSCRIPT
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INTERAKSI OBAT (Farmasetik)
dr.Rul Afiyah S, M.Kes.Bagian Farmakologi dan Terapi
Fak.Kedokteran UGM
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• Kepentingan pemahaman interaksi farmasetik oleh dokter
Dalam praktek klinis, kasus emergency?
Banyak obat injeksi yang tidak dapat dicampur dalam 1 syringe atau
infus IV
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Objectives
• Memahami prinsip-prinsip pemilihan obat dan penggunaannya di dalam klinis– Memahami pengertian interaksi farmasetik– Memahami penyebab/mekanisme, tanda, dan
pencegahan interaksi farmasetik
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REFERENCE
• DGAFMS Medical Memorandum No 113. Care in Mixing Drug with intravenous Infusion.
• Hoover,J.E. 2000. Remington’s Pharmaceutical Sciences. Mack Publishing company
• King Guide Publication. 2005. King Guide to Parenteral Admixture. • Parfit K.1998. Martindale The Extra Pharmacopea. Pharmaceutical
Press.• Wicharn Junwitayanuchit. Physicochemical factors Involving drug
Incompatibilities. Faculty of Pharmaceutical Sciences, Huachlew Chalermprakiat University, Thailand.
• Sinha et al, 2004. Physical Incompatibility of Injection Diclofenac Sodium eith Isolyte P. Anesth Analg, 98:870-8
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INTERAKSI OBAT
• Efek suatu obat diubah oleh obat yang diberikan sebelumnya atau yang diberikan pada waktu yang sama– Object drug – Precipitant drug
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MEKANISME KERJA INTERAKSI
1. Interaksi farmasetik
2. Interaksi Farmakokinetik
3. Interaksi Farmakodinamik
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TEMPAT BERLANGSUNGNYA INTERAKSI
• Invivo– Di dalam tubuh– Interaksi farmakokinetik dan farmakodinamik
• Invitro– Di luar tubuh– Peracikan/penyusunan, dispensing, penyimpanan
atau pemberian obat– Interaksi farmasetik
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INTERAKSI FARMAKOKINETIK
• Suatu obat mengubah– Absorpsi– Distribusi– Metabolisme– Ekskresi obat lain
• ContohAntacids + Tetracyclin chelated complex
• Peningkatan/penurunan konsentrsai obat di tempat kerja khasiat obat
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INTERAKSI FARMAKODINAMIK
• terjadi di tingkat reseptor • Perubahan respon pasien terhadap suatu
obat karena adanya obat lain• Penggunaan 2 atau lebih obat secara
bersamaan, berefek sinergis atau antagonis
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Berdasar bahan-bahan obat yang berinteraksi : Interaksi antar komponen aktif Interaksi komponen aktif - bahan tambahan Interaksi antar bahan tambahan
Bahan tambahan : pembawa, cosolvent, surfactant, pemanis, pengawet
INTERAKSI FARMASETIK(DRUG INCOMPATIBILITY)
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• Hasil reaksi fisikokimia dalam bentuk perubahan yang terlihat atau tidak terlihat
• Bisa menurunkan potensi, peningkatan toksisitas, atau efek yang tidak diharapkan
• Type :1. Physical or visual incompatibilities 2. Chemical or invisible incompatibilities3. Combination
DRUG INCOMPATIBILITY in PARENTERAL ADMIXTURE
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PHYSICAL INCOMPATIBILITIES
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PHARMACEUTICAL INTERACTION
• Berdasar cara pemberian– Non parenteral incompatibility apoteker– Parenteral incompatibility dokter
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PHYSICAL INCOMPATIBILITIES
• Tanda-tanda physical incompatibility
• Penyebab1. Perbedaan pH untuk kelarutan obat
2. Perubahan konsentrasia) Pengenceran kosolven
b) Pengenceran surfaktan
3. Pembentukan garam tidak larut
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– Pengkabutan/kekeruhan/ – Kristal– pengentalan/gel– Precipitate– Timbul gas– Perubahan warna
Tanda-tanda Inkompatible secara fisik
Terdeteksi mata
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Penyebab Physical incompatibilities
1. Perbedaan pH untuk kelarutan obatObat larut dalam lingkungan pH basa tidak larut dalam
pH asam, dan sebaliknya
Contoho Epinefrin + Asyclovir –Na (pH = 11) quinon (pink
kemudian coklat)o Acyclovir-Na + Diltiazem-HCl Acyclovir (precipitate)o Aminophillyne + Dyphenhydramin-HCl precipitateo Phenytoin-Na (pH 12) + Glucosa 5% infusion (pH 4 )o Furosemide (pH 8-9,3) + media asam atau D5% sol.
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2. Perubahan konsentrasia) Pengenceran kosolven
obat mengandung kosolven + obat bermedia air atau saline
Table. Obat yang diramu dalam kosolven
Chlordiazepoxide propylene glycol 20%
Diazepam propylene glycol 20%, alcohol 10%
Digoxin, Phenytoin-Na
propylene glycol 40%, alcohol 10%
Dimenhydrinate propylene glycol 50%
Multivitamins propylene glycol 30%
Phenobarbital sod. propylene glycol 67,8%, alcohol 10%
Source : Handbook of Injectable Drugs, 11th ed., L.Trissel
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• Phenobarbital-Na (ph 8,5-10) + Na bicarbonat (pH 8,6) 2 lapis cairan
Obat bermedia air benzyl alcohol penicillin gentamycin
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b) Pengenceran surfaktan
Obat mengandung sejumlah surfaktan + obat dalam media air
Amphotericin B ( surfaktan : deoxycholate)
+ NaCl sol.
+ Electrolytes sol. Cholate (precipitate)
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Contoh obat mengandung surfaktan
Amphotericin B Deoxycholate
Chlordiazepoxide Polysorbate 80
Phytomenadion (Vit.K) Polysorbat 80
Vitamin A Polysorbate 80
Source : Handbook of Injectable Drugs, 11th ed., L.Trissel
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3. Pembentukan garam tidak larut• Garam dari kation monovalen (Na danK), umumnya lebih larut daripada
bivalen (Ca dan Mg)
• Dengan jumlah kation yang sama, garam karbonat dan fosfat : kurang larut daripada garam Chloride dan acetate
Inj. Mengandung fosfat + solution mengandung garam Calcium
NaH2PO4/Na2HPO4 buffer + CaCl2 Ca3(PO4)2
NaHCO3 + Ca-gluconat CaCO3 (precipitation)
Codein H3PO4,clindamycine phosphat,
dexamethasone-Na phosphat
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PHYSICAL INCOMPATIBILITY
• Pelepasan gas– Interaksi antara obat bersifat asam dengan
bicarbonat (HCO3-) atau carbonat (CO3-2)pelepasan CO2
– inj. Obat asam + NaHCO3 inj.
(Dopamin-HCL) cephalosporin dibuffer barbiturat dengan carbonat
CO2
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CHEMICAL INCOMPATIBILITIES
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CHEMICAL INCOMPATIBILITIES
– Degradasi secara kimia– Menghasilkan obat tidak aktif atau toksik– Tidak ada tanda-tanda yang dapat dilihat– Jenis degradasi
1. Hidrolisis
2. Oksidasi
3. Fotolisis
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1. Hidrolisis Reaksi senyawa (misal : laktam) dengan air
Ampicilin, Penicilline
Antibiotik ß-lactam (ampicillin-Na, Penicillin)
+obat bersifat asam (Dopamin-HCl)
degradasi Penicilline dipercepat
Penicillin inactive
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2. Oksidasi Mendapat O2 atau kehilangan H atau elektron
Contoh : Gentamycin sulphat teroksidasi lambat pada pH <4
Gentamycin sulphat + obat ber pH tinggi
(chloramphenicol, all penicillin)
pH > 4Degradasi gentamycine lebih cepat
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3. Fotolisis/foto-oksidasi Peningkatan pH meningkatkan kecepatan
fotolisis/foto-oksidasi pH < 4 : foto-oksidasi berlangsung lambat i.e : amphotericin B
Dopamin-HCl
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INFUSION FLUID CHARACTERISTICS AND COMMON INCOMPATIBILITIES
Infusion Fluids Characteristics Incompatible with
Dextrose Acidic (pH may be as low as 3.5)
Benzyl penicillin, aminophyllin, barbiturates, ampicillin, vit B-12, hydrocortisone, heparin, phenytoin-Na
Isotonic saline Neutral or slightly acidic. Suitable vehicle for most drug
Noradrenalin, amphotericin B
Electrolytes (Na,K,Ca,Mg,Cl,Lactat)
Sligthly acidic or neutral
Ringer lactat incompatible w amphotericin B, tetracyclin succinyil cholin
Dextrans Slightly acidic pH Ampicillin, ascorbic cid, chlorpromazine, barbiturates, promethazine
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INCOMPATIBLE DRUG MIXTURES
Drug Incompatible with
Aminophyllin (pH 8-9) Any strong acidic solution, vit C, dyphenhydramin-HCl, papaverin-HCl, chlorpromazine,penicillin G, opioid analgesics, phenytoin
Ampicillin (pH 8.5-10) Adrenaline, atropine, chlorpromazine, dopamin
Ascorbic acid Aminophyllin, dextran, sodium bicarbonat,
Calcium gluconat (pH 6-8.2) Oxytetracyclin, phenytoin, sodium bicarbonat, carbonat
Chlorpromazine Chloramphenicol, aminophyllin, ampicilin
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• Pencampuran obat parenteral tidak dianjurkan, kecuali– jumlah IV lines yang tersedia terbatas , untuk
pemberian secara kontinyu multipel obat– multiple obat yang harus diberikan dalam
jangka waktu yang pendek– Pasien rawat di rumah memerlukan multipel
obat yang diberikan secara bersamaan lewat continuous infusion sedangkan multiple IV lines tidak memungkinkan
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PENCEGAHANHindari pencampuran obat bila beda pH > 1Hindari mencampur obat mengandung kosolven atau surfaktan dengan obat berpelarut air
hindari mengkombinasikan obat bersifat asam dengan obat ber buffer karbonat atau bikarbonat
Bila obat IV diberikan secara berturutan lewat pipa infus, bersihkan pipa infus dengan larutan yang kompatible diantara 2 pemberian obat Ikuti instruksi pabrik obat berkaitan dengan pembuatan, media, pencampuran dan pencegahan inkompatibilitas
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Case report• A 7-year-old boy diagnosed to have an
intracranial mass with the features of obstructive hydrocephalus, was scheduled for endoscopic third ventriculostomy under endotracheal anesthesi. He received Isolyte P, a pediatric maintenance fluid through infusion set. As soon as the doctor started injecting diclofenac sodium via infuse set they noticed white precipitation along the tubing distal to infusion set.
Source : Sinha et al, 2004. Physical Incompatibility of Injection Anesth Analg, 98:870-8
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• In the case :– Isolyte P contains the salts of K and Na (the Na-
metabisulphite)– Diclofenac Na injection contains propylene glycol
• In vitro test :• Salts of K and Na + Na-diclofenac (contains propylene
glycol) no precipitation• Diazepam inj. (contains propylene glycol) + Isolyte P
white precipitates• Diclofenac Na (without propylene glycol) + Isolyte P
No precipitation
• Na-metabisulphite and propylene glycol have interacted and caused physical incompatibility
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