Farmakodinami

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M ARIS WIDODO PHD
DEPT FARMAKOLOGI
DEFINSI FARMAKODINAMI
• CABANG ILMU FARMAKOLOGI YANG MEMPELAAJARI EFEK BAHAN
KIMA PADA ORGANISME, SISTENM, SEL MOLEKULER DAN DNA

• BAGAIANA DENGAN FARMAKOKINETIKRA

• ADA UNSUR IKATAN LIGAD DENGAN RESEPTOR AKTIVASI SGNAL

TRANSDUKSI DAN RESPON FARMAKOLOGU
Definitions
• Efficacy
• Degree to which a drug is able to produce the desired response
• Potency
• Amount of drug required to produce 50% of the maximal response the drug is
capable of inducing
• Used to compare compounds within classes of drugs
Figure 11.4
Plasma membranes

Gap junctions Plasmodesmata

between animal cells between plant cells
(a) Cell junctions

(b) Cell-cell recognition

Figure 11.5

Local signaling Long-distance signaling

Target cell Electrical signal Endocrine cell

along nerve cell Blood
triggers release of vessel
neurotransmitter.

Neurotransmitter
Secreting Secretory diffuses across
cell vesicle synapse.
Hormone travels
in bloodstream.

Target cell
Local regulator specifically
diffuses through Target cell binds
extracellular fluid. is stimulated. hormone.

(a) Paracrine signaling (b) Synaptic signaling

(c) Endocrine (hormonal) signaling

Figure 11.5a

Local signaling

Target cell Electrical signal

along nerve cell
triggers release of
neurotransmitter.

Neurotransmitter
Secreting Secretory diffuses across
cell vesicle synapse.

Local regulator
diffuses through Target cell
extracellular fluid. is stimulated.

(a) Paracrine signaling (b) Synaptic signaling

Figure 11.5b
Long-distance signaling

Endocrine cell
Blood
vessel

Hormone travels
in bloodstream.

Target cell
specifically
binds
hormone.

(c) Endocrine (hormonal) signaling

SOURCES

LIPID DERIVED MNEDIATOR

DIACYL GL8ICEROLS
INOSITOL PHOSPHAT 3
PROTEIN DEVED MEDIATORS
HISTAMINE
SEROTONIN
INTERLEOIBNE ETC
CYTOKINE
 MOLEKUL SIGNAL EKSTRA SEL

HYDROPHILIC SIGNAL
SECOND MESSENGER

HYDROPHILIC SIGNALING
MOLEKUL
NON GENOMIC EFFECT
CELL SURFACE
RECEPTOR

HYDROPHOBIC SIGNALING
MOLECULE
GENOMIC EFFECT

CARRIER PROTEIN
IN THE BLOOD

HYDROPHOBIC SIGNAL
Speed of responses
AGONIS ANTAGONIS
• RESETOR ADA DALAM TBUH MANUSIA
• SUDAH MEMPUYAI LIGAND SPESIFIK
• AKIBAT IKATAN LIGAND RSEPTOR EFEK VOUNTER DAN NON
VOLUNTER
• AGONIS ADALAH BAHAN DARI LUAR YANG MEMPUNYAI KARATER
SBAGAI LIGAND
• ANTAGONIS ADAAH BAHAN DAR LUAR YANG BERIKATAN DENGAN
RESEPTOR TIDAM MENIMBULKAN EFEK FARMAKOLOGI TEAPI
MENGHAAMBAT EFEK AGONIS
Figure 11.10

Signaling molecule

Receptor
Activated relay
molecule

Inactive
protein kinase
1 Active
protein
kinase
1

Inactive
protein kinase ATP
2 ADP P
Active
protein
PP kinase
Pi 2

Inactive
protein kinase ATP
3 ADP P
Active
protein
PP kinase
Pi 3
Inactive
protein ATP
ADP P
Active Cellular
PP
protein response
Pi
MEKANISME FARMAKODINAMI NEROTRANSMITER ADRENERGIK

ATP

G-protein  adenyllate siklase

NOR ADRE cAMP
EPINEPRNE + reseptor Ca++
DOPAMIN DAG
Pospolipase  pospolipid
IP3
Drug Receptor
• Affinity
• Refers to the strength of binding between a drug and
receptor
• Number of occupied receptors is a function of a balance
between bound and free drug
• Dissociation constant (KD)
• Measure of a drug’s affinity for a given
receptor
• Defined as the concentration of drug
required in solution to achieve 50%
occupancy of its receptors
Drug Receptors
• Action occurs when drug binds to receptor and
this action may be:
• Ion channel is opened or closed
• Second messenger is activated
• cAMP, cGMP, Ca++, inositol phosphates, etc.
• Initiates a series of chemical reactions
• Normal cellular function is physically inhibited
• Cellular function is “turned on”
 Cell surface receptors

ion-channel-linked enzyme-linked G-protein-linked

guanylyl tyrosine tyrosine kinase tyrosine serin/threonine

cyclases kinases associated phosphatases kinases
HOW DO DRUGS WORK BY ACTIVATING
ENDOGENOUS PROTEINS?

• Agonists of Cell Surface Receptors

(e.g. alpha-agonists, morphine agonists)

• Agonists of Nuclear Receptors

(e.g. HRT for menopause, steroids for inflammation)

• Enzyme Activators
(e.g. nitroglycerine (guanylyl cyclase), pralidoxime)

• Ion Channel Openers

(e.g. minoxidil (K) and alprazolam (Cl))
SECOND MESSENGER
ADALAH BAHAN KIMIA DALAM SEL
YANG MENINGKAT KADARNYA
APABILA ADA IKATAN ANTARA
LIGAND DAN RESEPTOR

CYCLIC AMP

CYCLIC GMP

DYACYL GLYCEROL

INOSTOL (145) PHOSPHAT

ION KALSIUM
Receptor Regulation
Sensitization or Up-regulation
1. Prolonged/continuous use of receptor blocker
2. Inhibition of synthesis or release of
hormone/neurotransmitter - Denervation
Desensitization or Down-regulation
1. Prolonged/continuous use of agonist
2. Inhibition of degradation or uptake of agonist

Homologous vs. Heterologous

Uncoupling vs. Decreased Numbers
From Nies A and Speilberg SP. Principles of Therapeutics. in Goodman and Gilman’s The Pharmacological
Basis of Therapeutics. 9th edition, 1996. Pages 43-62.McGraw Hill,
 REMEMBER
No drug produces a
single effect!!!