IKATAN OBAT DENGAN

RESEPTOR
Definisi
AGONIS
1. AGONIS
• Obat disebut sbg agonis ketika berikatan
dengan reseptor, obat tersebut
menimbulkan efek.
• Agonis mengaktifkan reseptor untuk
menghasilkan sinyal.

2. ANTAGONIS ANTAGONIS
• Obat yang berikatan dengan reseptor
namun tidak mengaktifkan reseptor untuk
menghasilkan sinyal.
• mengganggu agonis dalam mengaktifkan
reseptor
• Obat yang menghambat atau mengurangi
aksi agonis. FIG 2. Molecular basis of action of histamine and antihistamines. A, Th
FIG 2. Molecular basis of action of h
active state of the histamine H1-receptor is in equilibrium with the ac
Definisi
3. AFINITAS
àKemampuan obat untuk berikatan dengan reseptor
1. Jenis-jenis ikatan Obat-Reseptor (O-R):
Kovalen à sangat kuat, pada kebanyakan kasus bersifat
irreversible.
2. Elektrostatik à jenis ikatan O-R yg sangat umum, lebih
lemah dari ikatan kovalen.
3. Hidrofobik à ikatan lebih lemah, misalnya ikatan obat
larut lemak dengan lipid membran sel.
Definisi
Ikatan O-R yang ireversibel:
e.g :
• Ikatan antara gugus acetyl dari acetylsalicylic acid (aspirin)
dan cyclooxygenase (enzim COX). Enzim COX disintesis
kembali oleh tubuh beberapa hari kemudian
• Ikatan antara Obat PPI dengan Enzim H+ , K+ ATPase (Pompa
proton), sehingga menahan pelepasan asam lambung
selama 24-48 jam atau hingga pompa proton disintesis
22 SECTION I Basic Principles

kembali. A 1.0 B 1.0

Pada umumnya ikatan obat bersifat reversible.

Receptor-bound drug (B)

Emax Bmax

Drug effect (E)

Kekuatan O-R yg reversible diukur dengan konstanta disosiasi 0.5 0.5

(Kd).
Nilai Kd = 1/2Bmax atau konsentrasi yang diperlukan oleh EC50 Kd

ligan untuk berikatan dengan ½ konsentrasi reseptor Drug concentration (C) Drug concentration (C)
Definisi
4. POTENSI
Menunjukkan dosis relatif dari dua agonis atau lebih untuk
memproduksi kekuatan efek yang sama

4. EFIKASI
Seberapa baik sebuah obat dalam menghasilkan efek
Obat-obatan yang tidak berikatan dengan reseptor fisiologis:
1. Antasida à menetralkan asam lambung
2. Manitol à menarik air, diuresis
3. Obat-obat infeksi: Antibiotik, antivirus, antiparasit
 KURVA KUANTITATIF OBAT-RESPON
fc
% Maximal Response

A B
100 100

50 50
EC50 EC50
0 0 the
[A] Log [A] W

Figure 3–2 Graded responses. On the y axis, the response is expressed as a

percentage of maximal response plotted as a function of the concentration of
 KURVA KUANTITATIF OBAT-RESPON

1. Reseptor
sama-->kurva
parallel 1. Reseptor?
2. Afinitas A > B 2. Afinitas ?
3. Potensi A > B 3. Potensi?
4. Efikasi A=B 4. Efikasi?
JENIS INTERAKSI OBAT-RESEPTOR
6 SECTION I Basic Principles

Drug Receptor Effects

Agonist +

I
A+C II
A alone

Response
–

III
A+B
B

IV
A+D

Log Dose
Competitive
inhibitor

I: A+C
C

Allosteric
activator
II: A
III: A+B
D
IV: A+D
Allosteric inhibitor

FIGURE 1–2 Drugs may interact with receptors in several ways. The effects resulting from these interactions are diagrammed in the dose-
 AGONIS
1. FULL and PARTIAL
AGONIST
• Fullà menghasilkan respon
maksimal
• Partial agonist à
menghasilkan respon yang
kurang dari 100%
AGONIS
• Ketika full agonist + partial
agonist à Partial agonist menjadi
antagonis bagi full agonist,
berkompetisi dalam berikatan
dengan reseptor yang sama.
• Contoh obat: Aripirazol (Antipsikotik) à
Partial agonist dari reseptor dopamine.
• Skizofrenia gejala positif: kelebihan Dopamin
pada jalur mesolimbik. Penambahan Partial
dapat menjadi antagonis dopamine.
• Skizofrenia gejala negatif: kekurangan
dopamine pada jalur mesocortical.
Penambahan Partial agonis akan berfungsi
sebagai agonis fungsional
 recommendations for oral, nasal,
AGONIS mine formulations in adults, childre
nitis, allergic conjunctivitis, CHAPTER and1 urt
Int
in this article’s Online Repository
2. Inverse agonist Allergic rhinitis. The morbid
allergic rhinitis are widely undere
Beberapa reseptor
Effect

Ri
disease, oralRasecond-generation H1
menunjukkan adanya aktivitas lieve
D theD sneezing, itching, and rh
konstitutif tanpa keberadaan early response to allergen, with a sm
ligan (reseptor tetap sal congestion
Ri – D Ra – Dthat characterizes th

teraktivasi meskipun tidak Efficacy is documented Effect primaril

ada ligan yang berikatan) scores and quality-of-life asses

oral H1-antihistamines are market
e.g: reseptor histamin, with the decongestant
Ra + Da
pseudoep
serotonin, benzodiazepine dll
Full agonist
Oral H1-antihistamines are more
and montelukast; however, all the

Response
R + Dpa
less efficacious than a nasal gluco
Partial agonist
are
Ra + Ri generally ineffective in patient
Ra + Dant + Ri + Dant
Nasal
Constitutive H 1-antihistamine formulat
Antagonist
activity
action than Ri + oral
Di H1-antihistamine fo
Inverse agonist
nasal azelastineLog Dosevs 150 minutes for
with seasonal allergic rhinitis, na
FIGURE 1–3 ported A model oftodrug-receptor
be as efficacious
interaction.orThemore e
receptor
is able to assume two conformations. In the R conformation, it is
i
tamines,
inactive and produces particularly
no effect, for relief
even when combined of n
with a drug
molecule. In the Rsymptoms
a conformation,in thepatients
receptor canwho are
activate unre
down-
stream mechanisms that produce a small observable effect, even in
mines
the absence of drug and activity).
(constitutive thoseIn with vasomoto
the absence of drugs,
the two isoformsshould be considered
are in equilibrium, and the R form when
i is favored.reco
 NERAL PRINCIPLES
A Competitive Competitive antagonism
100

ANTAGONIS
Ι

% Maximal Effect
A

Ι 3 Ι 10
50 Ι
Control

0
L L L L
Log [A]

B Pseudoirreversible
Noncompetitive
A 100 antagonism

% Maximal Effect
Ι
50

0
Log [A]

C Allosteric
Ι Antagonism
A 100

% Maximal Effect
50

0
Log [A]

D Allosteric
P 100 Potentiation
A

% Maximal Effect
50

0
Log [A]
KOMBINASI: SINERGIS dan ADITIF

•Additif:
Aditif: 1+1 >2 Fenobarbital + Alkohol = meningkatkan
Sinergis : 1+1 =2 efek depresi SSP
Kompetitif: 1+1<2

•Sinergis: 𝛂-blocker + ACE inhibitor =

hipotensi sinergis
 UG ACTION
kinetics are described more thoroughly in Chapters 2, 5, 6, and 7. Most drugs are evaluated in young and m
on their use in children and the elderly ar
Drug Interactions and Combination Therapy
FAKTOR YANG MEMPENGARUHI
Drugs are commonly used in combination with other drugs, sometimes
to achieve an additive or synergistic effect, but more often because two or
age, drug pharmacokinetics and pharmacod
sibly requiring avoidance of selected drugs o
dose or dosing regimen to safely produce th
RESPON OBAT RESEP
more drugs are needed to treat multiple conditions. When drugs are used
American Geriatrics Society publishes the
Inappropriate Medication Use in Older Ad
that should be avoided in older adults, drugs
PRESCRIBED used at lower doses in patients with reduced
DOSE drug-disease and drug-drug interactions tha
older adults (Beers Update Panel, 2015).
ADMINISTERED
DOSE
Mechanisms of Drug Action
Receptors That Affect Concent
Endogenous Ligands
A large number of drugs act by altering th
CONCENTRATION transport, or metabolism of endogenous ligan
AT hormones, and other intercellular mediato
ACTION drugs acting on adrenergic neurotransmiss
(inhibits synthesis of NE), cocaine (blocks
(promotes NE release), and selegiline (inhib
(see Chapters 8 and 12). There are similar ex
mitter systems, including ACh (see Chapte
(see Chapters 13–16). Drugs that affect the
DRUG circulating mediators such as vasoactive pept
EFFECTS
Chapter 26) and lipid-derived autocoids (e.g
see Chapter 37) are also widely used in th
REFERENSI
• Goodman & Gilman's: The Pharmacological Basis of Therapeutics,
13e. Laurence L. Brunton, Randa Hilal-Dandan, Björn C. Knollmann
• Basic & Clinical Pharmacology 13th Edition by KATZUNG BERTRAM G;
• Grannell L. (2008). Stockley’s Drug Interactions. 8th ed.
• Simons FE, Simons KJ. Histamine and H1-antihistamines: celebrating a
century of progress. J Allergy Clin Immunol. 2011;128(6):1139-
1150.e4. doi:10.1016/j.jaci.2011.09.005
TERIMA KASIH