20100301 Kbk Cs Interaksi Farmakodinamik

8/12/2019 20100301 Kbk Cs Interaksi Farmakodinamik

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InteraksiFarmakodinamik

Dep. Farmakologi & Terapeutik,

Fakultas Kedokteran

Universitas Sumatera Utara

30 September 2009, FKG USU, Medan


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DEFINITION :

Drug interaction means modification of

the effect of a drug by concurrent

administration of other drugs.

Basic principles:


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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


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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.


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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


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Pharmacokinetics Pharmacodynamics

Dosage

Regimen Effects

PlasmaConcen

tration

Site of

Action


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INTERAKSI OBAT

INTERAKSI FARMASEUTIK INTERAKSI FARMAKOLOGIK

INTERAKSI FARMAKOKINETIK

ABSORPSI

DISTRIBUSIMETABOLISME

EKSKRESI

INTERAKSI FARMAKODINAMIK

RESEPTORFISIOLOGIS


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Interaksi Farmakodinamik

Bila obat yg diberikan bersama:

mempunyai mekanisme kerja yangsama/mirip.

mempunyai efek farmdinamik yang

mirip atau berlawanan. Hasilnya merupakan antagonisme dan

synergisme


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Dampak Klinis

Interaksi diperkirakan + 7% dari semua ES

obat.

Kematian + 4% dari semua kematian ES

obat.


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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)


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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


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Histamin (agonis)

Diphenhydramine (antagonis)receptor H1

Histamin (agonis)Cimetidin (antagonis)

receptor H2

Pharmacodynamic Interaction

Asetilcholine (agonis)

Atropine (antagonis)

receptor cholinergik


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Agonis Antagonis ReseptorAsetilkolin Atropin Kolinergik /

Muskarinik

Histamin Klorfeniramin Histamin H1

Histamin Simetidin Histamin H2

Morfin Nalorfin Opioid

Dopamin Fenotiazin Dopaminergik

Salbutamol Propranolol Adrenergik 2


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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


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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


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MEKANISME

OBAT A OBAT B

EFEK EFEK

ORGAN ORGAN

INTERAKSI

PENINGKATAN/PENURUNAN EFEK


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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


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Hypnotic / sedative

Antihistamine

depresion SSP

AntihypertensionDiuretic

antihypertension

Pharmacodynamic Interaction

Aminoglycoside

Cephaloridin

nefrotoxicity


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Perubahan Kesetimbangan

Cairan dan Elektrolit Perubahan cairan dan elektrolit

Mengubah efek obat terutama yg bekerja

pada

jantung,

transmisi neuromuskular dan

ginjal


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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


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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


Guanitidine Amfetamin Obat B mengantagonis



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Interaksi dengan

Penghambat MAO

Obat A Obat B EfekPenghambat MAO

(Moklobemid)

Fenileferin Menyebabkan pelepasan

norepinefrin >>terjadi krisis

hipertensi

Penghambat MAO Amfetamin Menyebabkan pelepasan


hipertensi

Penghambat MAO Dopamin Menyebabkan pelepasan


hipertensi

Penghambat MAO Antidepresi Trisiklik Menimbulkan hiperpireksia

dan eksitasi serebral (tremor,

konvulsi, koma)


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Interaksi yang berdasarkan efek

atau aksi yang searah

Interaksi yang berdasarkan efek

yang berlawanan arah


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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


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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)


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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


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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)


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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


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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


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Drug- TCA PD Interactions

Concurrent use with any other drugs with

antimuscarinic properties

Concurrent MAOI

Type I antiarrhythmics

Clonidine

Guanadrel

Guanethidine


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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


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TRAUMA

PAINOpioids

Alpha-2 agonists

Local anesthetics

Opioids

Alpha-2 agonists

Local anesthetics

Local anesthetics

Anti-inflammatory

drugs

OPIOIDS


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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


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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


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* 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.


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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.


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* 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


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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


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Apa solusi-nya ?

Nyeri yang hebat

Nyeri berkepanjangan

Hipertensi berat

Hipertensi membandel


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20100301 Kbk Cs Interaksi Farmakodinamik

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