8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
1/40
InteraksiFarmakodinamik
Dep. Farmakologi & Terapeutik,
Fakultas Kedokteran
Universitas Sumatera Utara
30 September 2009, FKG USU, Medan
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
2/40
DEFINITION :
Drug interaction means modification of
the effect of a drug by concurrent
administration of other drugs.
Basic principles:
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
3/40
Definition of drug Interaction
Alteration either in the pharmaco-
dynamics and/or kinetics of a drug, caused
by concomitant drug treatment, dietary
factors or social habits such as tobacco
and alcohol
B ?A +
Object DrugPrecipitant Drug
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
4/40
Precipitant Drug dan
Object Drug
Precipitant Drug
(Obat yang Mempengaruhi):
Contoh:
- aspirin
- fenilbutazon- sulfa
Object Drug
(Obat yang Dipengaruhi)
Contoh :digoksin, gentamisin,
warfarin, dilantin,
obat sitotoksik,kontraseptif oral, dan
obat-obat ssp.
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
5/40
Mechanism of drug interaction
Pharmacokinetic interactions Absorption
Distribution
Biotransformation***
Excretion
Pharmacodynamic interactions Receptor interaction
Receptor sensitivity
Neurotransmitter release/Drug transportation
Electrolyte balance
Physiological interactions
Pharmaceutical interactions
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
6/40
Pharmacokinetics Pharmacodynamics
Dosage
Regimen Effects
PlasmaConcen
tration
Site of
Action
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
7/40
INTERAKSI OBAT
INTERAKSI FARMASEUTIK INTERAKSI FARMAKOLOGIK
INTERAKSI FARMAKOKINETIK
ABSORPSI
DISTRIBUSIMETABOLISME
EKSKRESI
INTERAKSI FARMAKODINAMIK
RESEPTORFISIOLOGIS
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
8/40
Interaksi Farmakodinamik
Bila obat yg diberikan bersama:
mempunyai mekanisme kerja yangsama/mirip.
mempunyai efek farmdinamik yang
mirip atau berlawanan. Hasilnya merupakan antagonisme dan
synergisme
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
9/40
Dampak Klinis
Interaksi diperkirakan + 7% dari semua ES
obat.
Kematian + 4% dari semua kematian ES
obat.
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
10/40
Interaksi Farmakodinamik
Interaksi pada reseptor
Interaksi fisiologik
Perubahan dalam kesetimbangan cairandan elektrolit
Gangguan mekanisme ambilan amin di
ujung syaraf adrenergik Interaksi dengan penghambat monoamin
oksidasi (penghambat MAO, MAO-i)
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
11/40
Interaksi pada RESEPTOR
Reseptor SAMA Noradrenalin vs propranolol
Amphetamin vs propranolol
Acetylcholine vs atropin Succynilcholine vs atropin
Reseptor BERBEDA Noradrenalin vs dopamin
Noradrenalin vs acetylcholine Merupakan antagonisme antara agonis dan
antagonis dari reseptor yg sama
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
12/40
Histamin (agonis)
Diphenhydramine (antagonis)receptor H1
Histamin (agonis)Cimetidin (antagonis)
receptor H2
Pharmacodynamic Interaction
Asetilcholine (agonis)
Atropine (antagonis)
receptor cholinergik
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
13/40
Agonis Antagonis ReseptorAsetilkolin Atropin Kolinergik /
Muskarinik
Histamin Klorfeniramin Histamin H1
Histamin Simetidin Histamin H2
Morfin Nalorfin Opioid
Dopamin Fenotiazin Dopaminergik
Salbutamol Propranolol Adrenergik 2
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
14/40
Interaksi Fisiologik
Interaksi pd sistem fisiologik yg sama
Menghasilkan peningkatan atau
penurunan respon (potensiasi atau
antagonisme)
Dapat diramalkan atau diprediksikan
sehingga dapat dihindari bila dapat
menyebabkan efek yang tidak diinginkan
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
15/40
Physiological interactions
Drug A and Drug B bind to different receptors on the
same tissue but give opposite or similar effect
Aspirin (anti-platelet)
+Warfarin/Coumarin (anticoagulant)
Increase bleeding
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
16/40
MEKANISME
OBAT A OBAT B
EFEK EFEK
ORGAN ORGAN
INTERAKSI
PENINGKATAN/PENURUNAN EFEK
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
17/40
Interaksi Farmakodinamik Fisiologis
Obat A Obat B Efek
Sedatif/
hipnotik
Antihistamin
Analgesik NarkotikAntikonvulsi
Depresi SSP
Antihipertensi Diuretik Efek obat A
Antihipertensi Simpatomimetik Efek obat A
Antikoagulan Aspirin, NSAID Efek obat A
Antidiabetik Beta bloker Efek obat A
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
18/40
Hypnotic / sedative
Antihistamine
depresion SSP
AntihypertensionDiuretic
antihypertension
Pharmacodynamic Interaction
Aminoglycoside
Cephaloridin
nefrotoxicity
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
19/40
Perubahan Kesetimbangan
Cairan dan Elektrolit Perubahan cairan dan elektrolit
Mengubah efek obat terutama yg bekerja
pada
jantung,
transmisi neuromuskular dan
ginjal
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
20/40
Obat A Obat B Efek
Digitalis Diuretik Hipokalemi oleh obat B
toksisitas obat A
Antihipertensi(blocker)
Fenilbutazon Retensi air dan garam olehobat Befek obat A
Antiaritmia
(Prokainamid)
Diuretik Hipokalemi oleh obat B
efek obat A
Diuretik yg meretensi
K (Triamteren)
Garam K Hiperkalemia terutama pd
penderita gangguan fungsi
ginjal
Lithium Diuretik Natriuresis oleh obat B
retensi obat Atoksisitas
obat A
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
21/40
Gangguan Mekanisme Ambilan
Amin di Ujung Syaraf Adrenergik
Antagonis kompetitif
Obat A Obat B Efek
Penghambat syaraf
adrenergik (Guanitidine)
Aminsimpatomimetik
(Fenilpropanolamin)
Obat B
mengantogonisasi efek
hipotensi obat A
Bretilium Efedrin Obat B mengantagonis
efek hipotensi obat A
Betanidine Fenileferin Obat B mengantagonis
efek hipotensi obat A
Guanitidine Amfetamin Obat B mengantagonis
efek hipotensi obat A
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
22/40
Interaksi dengan
Penghambat MAO
Obat A Obat B EfekPenghambat MAO
(Moklobemid)
Fenileferin Menyebabkan pelepasan
norepinefrin >>terjadi krisis
hipertensi
Penghambat MAO Amfetamin Menyebabkan pelepasan
norepinefrin >>terjadi krisis
hipertensi
Penghambat MAO Dopamin Menyebabkan pelepasan
norepinefrin >>terjadi krisis
hipertensi
Penghambat MAO Antidepresi Trisiklik Menimbulkan hiperpireksia
dan eksitasi serebral (tremor,
konvulsi, koma)
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
23/40
Interaksi Farmakodinamik
Interaksi yang berdasarkan efek
atau aksi yang searah
Interaksi yang berdasarkan efek
yang berlawanan arah
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
24/40
Interaksi Farmakodinamik
yang searah
1. Addisiatau Sumasi
Efek obat yang merupakan
gabungan antara dua obat
2. Supra addisiBila efek obat yang diperolehlebih besar dari gabungankedua obat
= potensiasi
3. Potensiasi
Bila penggunaan satu obatakan menambah efek ataukerja dari obat yang lain
Synergism
1-Addition 2+2=4
e.g. B Blockers +Thiazide
2-Potentiation 2+2=5
e.g. Trimethoprin +
sulfmethexasol
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
25/40
synergist ic ef fects
commonly used therapeutically; examples of
synergy used therapeutically:
Parkinson's disease:L-dopa + monoamine oxidase B
inhibitor
hypertension:vasodilator + negative inotropic
problems can occur, the following show synergy:
CNS sedatives - e.g. alcohol + barbiturates
hypertension - monoamine oxidase A inhibitor +
sympathomimetic
digoxin toxicity - diurectics that cause hypokalaemia +
digoxin
Pharmacodynamic(may occur at receptor, cell or physiological level)
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
26/40
Interaksi Farmakodinamik
yang berlawanan arah
Bila penggunaan dua obat
menghasilkan efek yang lebih kecil
dari kedua obat tersebut.Antagonism (Opposing)
B-BlockersPropanolo lprevent the
bronchodilator effect of Sulbitamolor Terbutalin
Indomethacine inhibits biosynthesis of
vasodilator natruretic prostaglandins then -->inhibit diuretic effect ofLasix andThiazide
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
27/40
antagon ist ic effects
occasionally used therapeutically to reduce a side-
effect; example: benzhexol (anticholinergic) used to treat Parkinsonism
induced by chlorpromazine (tranquiliser)
problems can occur:
NSAIDs reduce antihypertensive efficacy (reduce renalsodium excretion)
Pharmacodynamic(may occur at receptor, cell or physiological level)
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
28/40
Pharmacodynamic interactions;
It means alteration of the dug action without change in its
serum concentration by pharmacokinetic factors.
EX., Propranolol + verapamilSynergistic or additive
effect
Synergism means =1+1=3
Additive means= 1+1=2
Potentiation means= 1+0=2
Antagonism means 1+1=0 or 0.5
Effect at the receptor site
Antiadrenegic
anticholinergic
On the other hand
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
29/40
Drug-Drug PD Interactions
Object Drug Interacting Drug (s)
ACE-I K+ & K+ sparing diuretics
Beta blockers Verapamil
Digoxin DiureticsMAOI SSRI, Dextromethorphan,
Pseudoephedrine, Anorexiants
Meperidine MAOI
Hydroxyine Thioridazine
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
30/40
Drug- TCA PD Interactions
Concurrent use with any other drugs with
antimuscarinic properties
Concurrent MAOI
Type I antiarrhythmics
Clonidine
Guanadrel
Guanethidine
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
31/40
Drug-NSAID PD Interactions
Object Drug Interacting Drug Outcome
Antihypertensives NSAIDs BP
Corticosteroids NSAIDs risk of PUD
Diuretics NSAIDs diuretic effect
Triamterene Indomethacin K+
Warfarin NSAIDs anticoagulanteffect
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
32/40
TRAUMA
PAINOpioids
Alpha-2 agonists
Local anesthetics
Opioids
Alpha-2 agonists
Local anesthetics
Local anesthetics
Anti-inflammatory
drugs
OPIOIDS
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
33/40
PAIN
OPIOIDS
Subs.P
Adr
ACh
GABA
Glu
M1
2
NK-1
NMDA
1
2
GABA
INHIBITION
INHIBITION
ACTIVATION
MIDAZOLAME
CLONIDINE
POST-SYNAPPRE-SYNAP
ACTIVATION
INHIBITION
PAINPAIN
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
34/40
Drug-Food/Nutrient Interactions
Drug Effect
Phenytoin Folate
Isoniazid Vit B6
Phenytoin Absorption with NG feedings
Levodopa High protein meals effect blood-brain transport
Captopril Altered taste sensation
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
35/40
* Risk factors:
1) H igh risk drugs;these are the drugs that show a narrow
therapeutic index e.g., corticosteroids, rifampin,
oral contraceptives, quindine,lidoquine
2) H igh risk patients;these are the groups of patients
that should be treated with caution due to a specific
heath condition e.g., pregnant women, malignant cases,
diabetic patients, patients with liver or kidney disorders
asthmatic patients and cardiac disorders.
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
36/40
Onset of drug interaction
It may be seconds up to weeks for example in case of enzyme
induction, it needs weeks for protein synthesis, while enzyme inhibition occurs rapidly.
The onset of action of a drug may be affected by the half
lives of the drugs e.g., cimitidineinhibits metabolism oftheophylline.
Cimitidinehas a long half life, while, theophyllinehas a short
one.
When cimitidineis administered to a patient regimen for
Theophylline, interaction takes place in one day.
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
37/40
* Prevention of drug interaction
1) Monitoring therapy and making adjustments
2) Monitoring blood level of some drugs with narrow
therapeutic index e.g., digoxin, anticancer agentsetc
3) Monitoring some parameters that may help tocharacterize the the early events of interaction
or toxicity e.g., with warffarinadministration, it
is recommended to monitor the prothrombin time
to detect any change in the drug activity.
4) Increase the interest of case reportstudies to
report different possibilities of drug interaction
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
38/40
predict and avoid if possible, that is
become familar with drug TDIs
take full drug history (including alcohol,
smoking) avoid multiple drug use when possible
if multiple drugs need to be used, select drugsto avoid TDIs
if unavoidable, carefully monitor drugresponse
Clinical approach to drug-drug
interactions
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
39/40
Apa solusi-nya ?
Nyeri yang hebat
Nyeri berkepanjangan
Hipertensi berat
Hipertensi membandel
8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik
40/40