FARMAKODINAMI

Dr. dr. nurdiana, Mkes

Lab. Farmakologi FKUB

DOSIS (R/)
DOSIS YG DIMINUM

Faktor-2 FK
A D M E
KONSENTRASI OBAT
DI TEMPAT KERJA
Faktor-2 FD

reseptor
homeostatik

EFEK / RESPON Px
terapeutik

toksik

Fisiologik
Patologik
Genetik
Umur
Interaksi

PRINSIP KERJA OBAT

Obat tidak menimbulkan fungsi baru, tetapi

mempengaruhi/memodulasi fungsi yang
sudah ada

Tidak ada obat yang mempunyai efek tunggal

(efek terapeutik dan efek samping)
Efek obat ditentukan oleh interaksinya
dengan proses biologi di tubuh mengubah
kecepatan kegiatan faal tubuh

EFEK OBAT
(farmakologi):

Efek terapi efek obat yang dikehendaki untuk

tujuan terapi, timbul pada dosis terapi

Efek samping efek obat yang tidak dikehendaki,

timbul pada dosis terapi, sering
merugikan,
dapat berupa efek
farmakologi yang lain atau
reaksi hipersensitif (alergi)

Efek toksik efek obat yang tidak dikehendaki,

timbul pada dosis toksik/ supramaksimal

Tolerans : terjadi pada tingkat f.kinetik &

f.dinamik
Resistens

Takhifilaksis

Idiosinkrasi

Sinergisme : Efek kombinasi dari 2 (/lebih)

macam obat yang saling menunjang
Addisi : Bentuk sinergisme obat dimana
efeknya
merupakan efek penambahan
obat
tersebut (mis. 1+1=2)
Potensiasi : Bentuk sinergisme obat dimana
efeknya lebih besar dari efek
penambahan masing-masing obat
(mis. 1+1>2)
Antagonis : Efek 2 macam obat yang
berlawanan

LOCUS OF ACTION
RECEPTORS

Bound

ABSORPTION

Free

TISSUE
RESERVOIRS

Free

Bound

Free Drug
Bound Drug

SYSTEMIC
CIRCULATION

BIOTRANSFORMATION

EXCRETION

EFEK OBAT

INTERAKSI OBAT DENGAN RESEPTOR PADA

SEL SUATU ORGANISME

PERUBAHAN BIOKIMIAWI DAN FISIOLOGI

RESPON
(KHAS UTK MASING-MASING OBAT)

Farmakodinami mempelajari :
Efek obat (biokimiawi & fisiologis) pada
sistim biologik serta mekanisme kerjanya
Efek obat :
Sebag besar ok interaksi obat dg
reseptor, sebagian lagi tdk melalui resept
Reseptor obat :
Makromolekul (protein) pada sistim
biologik yang dapat merubah fungsi sistim
tsb ok interaksinya dg obat

Definisi

Efficacy

Derajat kemampuan obat menghasilkan respon

yang diinginkan

Potency

Jumlah obat yang dibutuhkan untuk

menghasilkan respon terhadap obat
Digunakan untuk membandingkan komponen
kandungan di dalam golongan obat

Definisi

Effective Concentration 50% (ED50)

Concentration of the drug which

induces a specified clinical effect in
50% of subjects

Lethal Dose 50% (LD50)

Concentration of the drug which

induces death in 50% of subjects

Definisi

Therapeutic Index

Measure of the safety of a drug

Calculation: LD50/ED50

Margin of Safety

Margin between the therapeutic and

lethal doses of a drug

Dose-Response
Relationship

Drug induced responses are not an

all or none phenomenon
Increase in dose may:

Increase therapeutic response

Increase risk of toxicity

RESEPTOR UNTUK

LIGAND ENDOGEN
OBAT
hormon
nerotransmiter

AGONIS : SUBSTANSI YANG EFEKNYA MENYERUPAI

SENYAWA ENDOGEN/LIGAND
ANTAGONIS : MENGHAMBAT EFEK SUATU AGONIS DI
TEMPAT IKATAN AGONIS
Kompetitif
Non kompetitif

Agonis

obat yang mampu berikatan

dg reseptor dan menimbulkan efek
(afinitas +, aktivitas intrinsik +)

Antagonis

obat yang mampu berikatan

dg reseptor tetapi tidak dapat
menimbulkan efek
(afinitas +, aktivitas intrinsik - )

Antagonis kompetitif
Antagonis ireversibel

ikatan dg reseptor dpt

digeser oleh agonis
(Emax sama, ED50 beda)
ikatan dg reseptor kuat,
Emax lebih rendah

FUNCTIONAL ANTAGONISTS
1.

Physiologic Antagonists

2.

Chemical Antagonist

Agonists and Antagonists

Physiologic ANTAGONIST

A drug that binds to a non-related receptor, producing

an effect opposite to that produced by the drug of
interest.

Its intrinsic activity is = 1, but on another receptor.

Glucocorticoid Hormones

Blood Sugar

Insulin

Blood Sugar

Agonists and Antagonists

Chemical ANTAGONIST

A chelator (sequester) of similar agent that interacts

directly with the drug being antagonized to remove it or
prevent it from binding its receptor.

A chemical antagonist does not depend on interaction

with the agonists receptor (although such interaction
may occur).

Heparin, an anticoagulant, acidic

If there is too much bleeding and haemorrhaging
Protamine sulfate is a base. It forms a stable
inactive complex with heparin and inactivates it.

Polar

Nonpolar

Polar

RESEPTOR
*RESEPTOR TRANSMEMBRAN
- IKT. ENZIM
- KANAL ION
- IKT. G-PROTEIN
*RESEPTOR DI SITOSOL

KOMUNIKASI SEL
INTRA SEL ANTAR SEL

TRANSDUKSI SINYAL
MOLEKUL LIGAND

1ST messenger

RESEPTOR
( TARGET SEL)
EFEKTOR

2nd messenger
(cAMP, IP3, DAG)

EFEK BIOLOGI

Komunikasi sel

Classification Receptor
1.
2.

3.
4.

Transduction
Mechanisms
Ion channel linked receptors e.g. Ach
nicotinic (Na+) and GABA (Cl-)
G protein & second messenger generation,
adenylate cyclase stimulation or inhibition cAMP,
guanylate cyclase - cGMP, phospholipase C IP3,DAG
Some receptors are themselves protein
kinases
Intracellular receptors (e.g. corticosteroids,
thyroid hormone)

Transmembrane Signaling
Mechanisms
= drug

Out

In

Y
P

gene

Change in the
Receptor activation cons.of second
messenger
of a G protein

G prot regulation
of an enzyme or
ion channel

Inactivation
mechanism

The Major Effectors and Intracellular

Second Messengers in GPCR Systems
Effector

adenylyl cyclase
phospholipase C

2nd messenger

cyclic AMP (cAMP)

calcium, DAG, and
phosphoinositide (IP3)

Obat dan Efek

D +R

DR

Efek

agonis
adr
beta

Gs

GDP

GTP

ATP

GDP

Adenilat
siklase

GTP

Enzim

ATP

cAMP

R2C2
Protein kinase

2C
ADPEnzim-PO4
EFEK

2R

Mechanism of beta-1 receptor activation in

cardiac muscle

Effect of beta-2 receptor activation

on smooth muscle

Effect of alpha-1 /muskarinik3(M3) receptor activation

of smooth muscle contraction

Intracellular Mechanism: Steroid

Nucleus
XXXXXXXXXXXXX

Effects
Protein

Plasma

RNA
mRNA

drug

Speed of responses

Agonist vs antagonist
Ag

Ant

K+1
R

K-1

Ag

K+1

R
K-1

Ant

Response

Agonist & Antagonist

Agonist & Antagonist

PENGATURAN FUNGSI RESEPTOR

BILA SUATU SEL DIRANGSANG TERUS MENERUS OLEH
AGONISNYA DESENSITISASI

BILA RANGSANGAN PADA RESEPTOR BERKURANG SECARA

KRONIK, MISAL PEMBERIAN BLOCKER JANGKA PANJANG
SUPERSENSITIVITAS (HIPERAKTIVITAS) TERHADAP AGONIS

Faktor faktor yg mempengaruhi

Farmakokinetik &
Farmakodinamik
Umur :
bayi, lansia
Interaksi :
makanan, obat
Farmaseutik
Farmakokinetik
Farmakodinamik

Individual patient
variations in drug
responses

Body weight and

composition
Age of
client(young and
old)
Diet and Nutrition
Ethnic origin
Genetics

Pathophysiology(e
g. Kidney disease,
liver disease etc.)
Immunity
Psychology
Environment

OBAT YANG BEKERJA MELALUI RESEPTOR :

Contoh : OBAT YANG BEKERJA PADA SISTEM SARAF
OTONOM
AGONIS
NOREPINEFRIN RESEPTOR ADRENERGIK 1
ADRENALIN/EPINEFRIN RESEPTOR ADRENERGIK DAN
SALBUTAMOL RESEPTOR ADRENERGIK 2
ASETILKOLIN RESEPTOR NIKOTINIK DAN MUSKARINIK
ANTAGONIS/BLOCKER
PRAZOSIN ANTAGONIS RESEPTOR ADRENERGIK 1
PROPRANOLOL ANTAGONIS RESEPTOR ADRENERGIK 1
ATROPIN ANTAGONIS RESEPTOR MUSKARINIK

OBAT YANG BEKERJA TIDAK MELALUI RESEPTOR :

PERUBAHAN ASAM BASAANTASIDA Mg(OH)2, Al (OH)3
PERUBAHAN SIFAT OSMOTIK DIURETIK OSMOTIKUREA,
MANITOL
GLISEROLMENGURANGI OEDEM
SEREBRAL
GANGGUAN FUNGSI MEMBRANANESTESI UMUMETER

HUBUNGAN DOSIS-RESPON
Graded dose-responses

One tissue/organ can yield the full response range

Response

Full agonist

Agonist concentration [A]

Emax & ED50

Response

Emax

Emax

ED50

ED100

Log concentration [A]

% Respondin g

Therapeutic and Toxic Effects are

Dose-Related: Phenobarbital

Sleep

ED50

Death

LD50

Dose of Phenobarbital

Autonomic Pharmacology

Central Nervous System (CNS)

Peripheral Nervous System

Somatic Nervous System

Autonomic Nervous System (ANS)

Sympathetic Branch
Parasympathetic Branch

Feed or Breed

Fight or Flight

Autonomic Nervous
System Characteristics

ANS
Anatomy & Physiology

The nerves of the ANS exit the CNS

and subsequently enter specialized
structures called autonomic ganglia

Preganglionic fibers

Pass between the central nervous system and

the ganglia

Postganglionic fibers

Pass between the ganglia and the effector

organ

Sympathetic versus
Parasympathetic

Sympathetic ganglia

Located close to the spinal cord or

midway between the spinal cord and
the effector organ

Parasympathetic ganglia

Located close to or within the walls of

the target organs

Cholinergic and Adrenergic

Fibers

Cholinergic

Fibers that release acetylcholine

All preganglionic and postganglionic of the
parasympathetic division

Adrenergic

Fibers that release norepinephrine

Most postganglionic fibers of the
sympathetic division are adrenergic, but
some are cholinergic

Neurochemical
Transmission

No actual physical connection exists

between two nerve cells or between a nerve
cell and the organ it innervates

Synapse

Neruroeffector junction

Space between nerve cells

Specialized synapse between two nerve cells or a
nerve cell and an organ

Neurotransmitter

Chemical messenger that conducts a nervous

impulse across a synapse

PREGANGLION

POST GANGLION
PARASIMPATIS
Otot jantung
ACH NIC ACH MUS Otot polos
<
<
Glandula

MEDULLA
ACH NIC

ACH MUS

<

SPINALCORD

SIMPATIS
Kel. Keringat

<

ACH NIC

<

<

NE alpha
beta

ACH NIC

<

D1 D
ACH NIC

<

<

EPINEPRINE

SIMPATIS
Otot jantung
Ot.polos p darah
SIMPATIS
Pemb. Darah
Ginjal

ADRENAL MEDULLA
ACH NIC

<

VOLUNTARY MOTOR NERVE

SOMATIC
Otot rangka

Neurotransmission

Neurotransmitters

Acetylcholine

Preganglionic nerves of sympathetic

nervous system
Preganglionic and postganglionic nerves
of the parasympathetic nervous system

Norepinephrine

Postganglionic nerves of the sympathetic

nervous system

Acetylcholine

For cholinergic synapses

acetylcholine molecules combine with
cholinergic receptor molecules

Nicotinic Receptors

Produces an excitatory response

Muscarinic Receptors

Produce an excitatory or inhibition, depending

on where the target receptors are found

Norepinephrine

For adrenergic synapses

norepinephrine molecules combine
with adrenergic receptor molecules

Alpha Receptors

Blood vessels

Beta Receptors

Heart
Lungs

farmako@fk.unibraw.ac.id
nurdianafarmako@yahoo.com