Farmakodinami Kh

7/27/2019 Farmakodinami Kh

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FARMAKODINAMI

Dr. dr. nurdiana, Mkes

Lab. Farmakologi FKUB



DOSIS (R/)

DOSIS YG DIMINUMFaktor-2 FKA D M E

KONSENTRASI OBAT

DI TEMPAT KERJA

FisiologikPatologik

GenetikUmurInteraksi

Faktor-2 FDreseptorhomeostatik

EFEK / RESPON Px

terapeutik toksik



Food-Drug Interaction

For example, a drug that causes chronic nausea ormouth pain may result in poor intake and weightloss



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 denganproses 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, seringmerugikan, dapat berupa efek farmakologi yang lain atau reaksihipersensitif (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 efeknyamerupakan efek penambahan obat

tersebut (mis. 1+1=2)

Potensiasi : Bentuk sinergisme obat dimanaefeknya lebih besar dari efek penambahan masing-masing obat

(mis. 1+1>2) Antagonis : Efek 2 macam obat yang berlawanan



Bound Free Free Bound

LOCUS OF ACTION

“RECEPTORS”

TISSUE

RESERVOIRS

SYSTEMICCIRCULATION

Free Drug

Bound Drug

ABSORPTION EXCRETION

BIOTRANSFORMATION



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) padasistim biologik serta mekanisme kerjanya

Efek obat :

Sebag besar ok interaksi obat dgreseptor, sebagian lagi tdk melalui resept

Reseptor obat :

Makromolekul (protein) pada sistimbiologik yang dapat merubah fungsi sistimtsb ok interaksinya dg obat



Definisi

Efficacy

Derajat kemampuan obat menghasilkan responyang diinginkan

Potency

Jumlah obat yang dibutuhkan untuk menghasilkan respon terhadap obat

Digunakan untuk membandingkan komponenkandungan di dalam golongan obat



Definisi Effective Concentration 50% (ED50)

Concentration of the drug which induces aspecified 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 lethaldoses 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 ikatan dg reseptor dpt

digeser oleh agonis

(Emax sama, ED50 beda)

Antagonis ireversibel 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 frombinding its receptor.

A chemical antagonist does not depend on interaction with theagonist’s 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

Polar

Nonpolar



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

Transduction Mechanisms1. Ion channel linked receptors e.g. Ach nicotinic

(Na+) and GABA (Cl-)

2. G protein & second messenger generation,adenylate cyclase stimulation or inhibition - cAMP,

guanylate cyclase - cGMP, phospholipase C -IP3,DAG

3. Some receptors are themselves protein kinases4. Intracellular receptors (e.g. corticosteroids,

thyroid hormone)



Transmembrane Signaling

Mechanisms = drug

Out

In

gene

P

G

X Y





Receptor activation

of a G protein

G prot regulation

of an enzyme or

ion channel

Change in the

cons.of second

messenger

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)

Ob t d Ef k



Obat dan Efek

D + R DR Efek

agonis

adrbeta

GDP GTP GDP

Gs

GTP

Adenilat

siklase

ATP cAMP

Enzim

Enzim-PO4

EFEK

R2C2

Protein kinase 2C

2R

ATP

ADP

Mechanism of beta 1 receptor activation in



Mechanism of beta-1 receptor activation in

cardiac muscle

Effect of beta 2 receptor activation

http://www.mc.uky.edu/pharmacology/instruction/decor/ar/beta%20receptor%20activation.pps

http://www.mc.uky.edu/pharmacology/instruction/decor/ar/beta%20receptor%20activation.pps



Effect of beta-2 receptor activation

on smooth muscle

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

http://www.mc.uky.edu/pharmacology/instruction/decor/ar/beta%20_smooth.pps



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

of smooth muscle contraction

http://www.mc.uky.edu/pharmacology/instruction/decor/ar/alpha_smooth.pps





Intracellular Mechanism: Steroid

Plasma

R

Nucleus

XXXXXXXXXXXXX

RNA

mRNAProtein

Effects

drug



Speed of responses



Agonist vs antagonist

Ag

K +1

K -1 Ag

Ant

K +1

K -1

+

+

Response

Ant

R

R



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 mempengaruhiFarmakokinetik & Farmakodinamik

Umur :

bayi, lansia

Interaksi :

makanan, obat

Farmaseutik

Farmakokinetik

Farmakodinamik



Individual patient variations indrug responses

Body weight andcomposition

Age of client(youngand old)

Diet and Nutrition

Ethnic origin

Genetics

Pathophysiology(eg.Kidney disease, liverdisease etc.)

Immunity

Psychology

Environment



OBAT YANG BEKERJA MELALUI RESEPTOR :

Contoh : OBAT YANG BEKERJA PADA SISTEM SARAFOTONOM

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 1PROPRANOLOL 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

Full agonist

Agonist concentration [A]

R e s p o n s e

One tissue/organ can yield the full response range



•Emax & ED50

Log concentration [A]

R e s p o n s e

Emax

½ Emax

ED50 ED100 I I I I I I I I



Therapeutic and Toxic Effects are

Dose-Related: Phenobarbital

Sleep Death

Dose of Phenobarbital

ED50 LD50





Autonomic Pharmacology

Central Nervous System (CNS)

Peripheral Nervous System

Somatic Nervous System

Autonomic Nervous System (ANS)

Sympathetic Branch Parasympathetic Branch





Autonomic Nervous SystemCharacteristics

“ F i g h

t o r F l i g h t ”

“ F e

e d or B

r e e d ”



ANS Anatomy & Physiology

The nerves of the ANS exit the CNS andsubsequently enter specialized structurescalled “autonomic ganglia” Preganglionic fibers

Pass between the central nervous system and the

ganglia Postganglionic fibers

Pass between the ganglia and the effector organ



Sympathetic versusParasympathetic

Sympathetic ganglia

Located close to the spinal cord or midwaybetween the spinal cord and the effectororgan

Parasympathetic ganglia Located close to or within the walls of the

target organs





Cholinergic and AdrenergicFibers

Cholinergic Fibers that release acetylcholine

All preganglionic and postganglionic of theparasympathetic division

Adrenergic Fibers that release norepinephrine

Most postganglionic fibers of the sympatheticdivision are adrenergic, but some arecholinergic



Neurochemical Transmission

No actual physical connection exists between

two nerve cells or between a nerve cell and theorgan it innervates Synapse

Space between nerve cells

Neruroeffector junction 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



< <

<

<

<

<

<

<

<

<

MEDULLA

SPINALCORD

ACH NIC

ACH NIC

ACH NIC

ACH NIC

ACH NIC

ACH NIC

ACH MUS

ACH MUS

ADRENAL MEDULLA

VOLUNTARY MOTOR NERVE

PREGANGLION POST GANGLION

EPINEPRINE

PARASIMPATIS

Otot jantung

Otot polos

Glandula

SIMPATIS

Kel. Keringat

SIMPATIS

Otot jantungOt.polos p darah

SIMPATIS

Pemb. Darah

Ginjal

SOMATIC

Otot rangka

D1 D

NE alphabeta





Neurotransmission



Neurotransmitters

Acetylcholine

Preganglionic nerves of sympathetic nervoussystem

Preganglionic and postganglionic nerves of the parasympathetic nervous system

Norepinephrine

Postganglionic nerves of the sympatheticnervous system



Acetylcholine

For cholinergic synapses acetylcholinemolecules combine with cholinergicreceptor molecules

Nicotinic Receptors

Produces an excitatory response Muscarinic Receptors

Produce an excitatory or inhibition, depending onwhere the target receptors are found





Norepinephrine

For adrenergic synapses norepinephrinemolecules combine with adrenergicreceptor molecules

Alpha Receptors

Blood vessels Beta Receptors

Heart

Lungs



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