PHARMACODYNAMIC

→ Efek obat terhadap tubuh

- mekanisme kerja obat
- ikatan obat dan reseptor
- interaksi obat dan reseptor
- dosis – respons
 STIMULATION
 DEPRESSION
 IRRITATION
 REPLACEMENT
 CYTOTOXIC ACTION
PRINCIPLE OF ACTION MODE EXAMPLE

STIMULATION Selective Enhancement of level of activity of Pilocarpine stimulates salivary glands

specialised cells Picrotoxin – CNS stimulant 
- Excessive stimulation is often followed by convulsions  coma  death
depression of that function

DEPRESSION Selective Diminution of activity of specialised Barbiturates depress CNS

cells Quinidine depresses Heart
Certain drugs – stimulate one cell type and Ach – stimulates smooth muscle but
depress others depresses SA node

IRRITATION Non-selective often noxious effect – applied to

less specialised cells (epithelium, connective Bitters – salivary and gastric
tissue) secretion
-stimulate associated function Counterirritants increase blood flow
to a site

REPLACEMENT Use of natural metabolites, hormones or their Levodopa in parkinsonism

congeners in deficiency states Iron in anaemia

CYTOTOXIC ACTION Selective cytotoxic action for invading parasites Penicillin, chloroquine
or cancer cells – for attenuating them without
affecting the host cells
 PHYSICAL/ CHEMICAL INTERACTION WITH
PROPERTIES TARGET BIOMOLECULE

• Physical mass → Bulk

laxatives ENZYMES
• Adsorptive property →
Activated charcoal ION CHANNELS
• Neutralization of gastric HCl
→ Antacids TRANSPORTERS
• Chelating agents → chelate
heavy metals RECEPTORS
• Osmotic activity →Mannitol,
Magnesium sulphate
  Catalytic proteins that increase the rate of
chemical reactions

• Some drugs bind to enzymes and inhibit enzymatic

activity.
 ----> enzyme inhibitors
• Cyclooxygenase Inhibitors for pain relief,
particularly due to arthritis (aspirin;
ibuprofen )

• HMG-CoA Reductase Inhibitors for

hypercholesterolemia
(atorvastatin ; pravastatin )

• Angiotensin Converting Enzyme (ACE)

Inhibitors for high blood pressure, heart
failure, and chronic renal insufficiency
(captopril ; ramipril )
 DRUGS THAT BLOCK ION CHANNELS
Examples:
• Calcium Channel Blockers (CCBs) for angina and
high blood pressure
(amlodipine ; diltiazem )

• Sodium Channel Blockers to suppress cardiac

arrhythmias
(lidocaine ; amiodarone)

Transport systems
  transport substances against concentration gradient
 special carrier molecules
 require metabolic energy

 DRUGS THAT INHIBIT TRANSPORTERS

• Selective Serotonin Reuptake Inhibitors (SSRIs) for
the treatment of depression
( fluoxetine ; fluvoxamine )
• Inhibitors of Na-2Cl-K Symporter (Loop Diuretics) in
renal epithelial cells to increase urine and sodium
output for the treatment of edema
( furosemide ; bumetanide )
RECEPTOR
 Molekul spesifik (protein macro-
molecule or DNA) yg mampu secara
selectif mengenali dan mengikat
obat , hormon, mediator atau
neurotransmiter, shg menghasilkan
respon seluler.
 D+R DR Complex
Affinity
Afinitas
- kemampuan obat mengikat receptor.
- ditentukan o/ konstanta disosiasi (Kd)
- (makin < Kd makin >> afinitiasnya).

 Covalent bonds are stable and essentially irreversible

 Electrostatic bonds may be strong or weak, but are
usually reversible

2004-2005
Receptor Binding
% Bound

Kd

Concentration of Ligand
The dose-response relationship (from C.D. Klaassen, Casarett and Doull’s Toxicology, 5th ed., New
York: McGraw-Hill, 1996).
 DR Complex Effect
Efficacy ( Intrinsic Activity) – kemampuan ikatan
obat dan reseptor yang dapat menimbulkan efek
maksimal
→ tgt pd : - juml kompleks obat-reseptor
- efisiensinya utk menimbulkan efek

→ beberapa obat mempunyai afinitas tp tdk

mempunyai aktifitas intrinsik → ANTAGONIS

2004-2005
 Potency:
- Ukuran dosis obat yg dibutuhkan utk
menimbulkan efek

- Makin kecil dosis obat yg dibutuhkan utk

menimbulkan efek, makin besar potensi obat
tsb.

- Ditentukan oleh :
- Afinitas reseptor thd obat
- Efisiensi interaksi obat dan reseptor → respon

Saja Hamed, Ph.D 09/10/1440 14

09/10/1440 Saja Hamed, Ph.D 15
drugs that interact with and activate
receptors; they possess both affinity
and efficacy
two types
 Full – an agonist with maximal
efficacy
 Partial – an agonist with less then
maximal efficacy
2004-2005
 Agonist Dose Response Curves

Full agonist
Partial agonist
Response

Dose
2004-2005
Antagonists interact with the
receptor but do NOT change the
receptor
they have affinity but NO efficacy
two types
 Competitive
 Noncompetitive

2004-2005
competes with agonist for receptor
surmountable with increasing
agonist concentration
displaces agonist dose response
curve to the right (dextral shift)

2004-2005
 drug binds to receptor and stays bound
 irreversible – does not let go of receptor
 produces slight dextral shift in the agonist DR
curve in the low concentration range
 this looks like competitive antagonist
 but, as more and more receptors are bound (and
essentially destroyed), the agonist drug becomes
incapable of eliciting a maximal effect

2004-2005
10

 agonist → affinity (+ ) intrinsic activity (+)

 antagonist → affinity (+) ; intrinsic activity (-)
 partial agonist → affinity (+) ; intrinsic activity <<
 competitive antagonists can be overcome

2004-2005
 Sensitization or Up-regulation
1. Prolonged/continuous use of receptor
blocker
2. Inhibition of synthesis or release of
hormone/neurotransmitter

 Desensitization or Down-regulation
1. Prolonged/continuous use of agonist
2. Inhibition of degradation or uptake of
agonist
 ED50 - Median Effective Dose 50; the dose at
which 50 percent of the population or sample
manifests a given effect; used with quantal dr
curves
 TD50 - Median Toxic Dose 50 - dose at which 50
percent of the population manifests a given
toxic effect
 LD50 - Median Lethal Dose 50 - dose which kills
50 percent of the subjects

2004-2005
Therapeutic index:
 the ratio of the dose that produces toxicity
to the dose that produces a clinically desired
or effective response
 LD50/TD50:ED50 ratio
 determined using laboratory animal
 measure of drug safety
 Warfarin
 Penicillin

Saja Hamed, Ph.D 09/10/1440 24

 TD50 or LD50
Therapeutic Index =
ED50

2004-2005
09/10/1440 Saja Hamed, Ph.D 26
 Drug A
100 sleep
death

Percent 50
Responding

0
ED50 LD50

dose
2004-2005
 Drug B
100 sleep
death

Percent 50
Responding

0
ED50 LD50
dose
2004-2005
 DRUG ANTAGONISM
 Pharmacologic antagonists → berikatan pd reseptor yg
sama
 Competitive → reversible
 Non – competitive → irreversible

 Chemical Antagonism → berikatan lgs dg obat (kimia) utk

menetralisir atau mencegah terjadinya efek

 Physiological Antagonism → berikatan pd reseptor yg

berbeda dan menimbulkan efek yg berlawanan
 CLASSIFICATION OF DRUG EFFECTS
Therapeutic Effect: efek utama / yg diinginkan
Side Effect: efek lain selain efek utama
Adverse Effect: efek samping yang berbahaya

Toxic Effect: efek samping yg berbahaya pd dosis

toksik
Idiosyncrasy: efek obat abnormal yg terjadi hanya
pada minoritas individu
→ kel. Genetik , alergi
 Efek non spesifik dan gangguan
pada membran
 Perubahan sifat osmotik (urea, manitol, MgSO4)
 Perubahan sifat asam-basa (antasida, NH4Cl,
NaHCO3)
 Kerusakan non spesifik (antiseptik-desinfektan)
 Gangguan fungsi membran (anestesi volatile)

 Interaksi dengan molekul kecil atau ion

(CaNa2EDTA- Pb2+)
 Masuk ke dalam komponen sel (obat kanker)
Faktor fisiologis
Interaksi obat
Interaksi obat-makanan
Penyakit & gangguan fungsi
organ
DOSIS OBAT : takaran/jumlah obat yang
diberikan kedalam tubuh sehingga mampu
melewati ambang aktivitas tetapi tidak
melewati ambang toksisitas.

Onset Of Action
Duration Of Action

FAKTOR2 YANG MEMPENGARUHI DOSIS :

1. Ukuran Tubuh ( BB)
2. Umur
3. Jenis kelamin
4. Waktu Pemberian
5. Keadaan patologi
6. Faktor genetik
7. Toleran
TOKSISITAS OBAT

 Cara Pemberian obat yang salah :

Tetrasiklin (I.V)  Kejang.

 Efek Utama obat berlebihan ( Dosis berlebihan

atau Over dosis, o.k gangguan pada organ
metabolisme dan organ ekskresi, Faktor
genetik, Adanya Interaksi obat.).

 Reaksi hipersensitif (Alergi) Seperti

Dermatitis, Asma, Syok anafilaktik, Kerusakan
hati dan ginjal, Kerusakan Sumsum Tulang.

 Diskrasia Darah, seperti Leukopenia, Anemia

Aplastik, Anemia Hemolitik, Trombositopenia.
 Toksisitas Hati danGinjal
 Efek Teratogenik.
PENELITIAN OBAT

1. PENEMUAN OBAT BARU 

* SECARA EMPIRIS
* SECARA RASIONAL
* SECARA KEBETULAN
* PROSES SCREENING
2. UJI PRAKLINIK 
* Uji Aktivitas dan Efek samping
Obat

* Uji Farmakokinetik dan

Farmakodinamik

* Uji Farmasi yang meliputi :

* Uji Kualitatif dan Kuantitatif
bahan
* Uji Stabilitas
* Uji Sifat Fisik dan Kimia
* Uji Formulasi obat
• * Uji Toksisitas Umum :
• - Uji Toksisitas Akut
• - Uji Toksisitas Sub Akut
- Uji Toksisitas Kronis.

* Uji Toksisitas Khusus :

- Uji Teratogenik,
- Uji Mutagenik
- Uji Carcinogenik
3. UJI KLINIK 
Dibagi 4 fase dan Uji Monitoring
Efek Samping Obat (MESO)