FARMAKOLOGI

PENDAHULUAN
Farmakologi dapat di rumuskan sbg kajian
bhn2 yg berinteraksi dg sistem kehidupan
melalui proses kimia, khususnya mll
pengikatan molekul regulator dan
pengaktifan atau penghambatan proses2
tubuh yang normal.
 SIFAT DASAR OBAT
Obat : bhn yg menyebabkan perubahan
dlm fungsi biologis melalui proses kimia.
Molekul obat berinteraksi dg molekul
khusus dlm sistem biologis yg berperan
sbg regulator, yaitu molekul reseptor.
Obat dpt berasal dari bhn yg disentesis
tubuh atau bhn sintetik.
 SIFAT DASAR OBAT
Sifatdasar fisik obat (padat : aspirin, cair :
etanol, gas : nitrogen)
Ukuran obat, agar dpt cocok dng satu
reseptor molekul obat hrs mmpunyai
bentuk dan muatan listrik.
Bentuk obat, bentuk molekul obat hrs
dibuat begitu rupa spy terikat pada situs
reseptornya.
 INTERAKSI OBAT-TUBUH
Farmakodinamika : kerja obat pd tubuh
manusia.
Farmakokinetik : apa yang dilakukan
tubuh terhadap obat.
 Perembesan obat
Melalui empat mekanis :
1. Difusi dlm medium air
2. Difusi lemak
3. Pembawa khusus
4. Endositosis dan eksositosis
 ABSORPTION OF DRUGS
Routes of administration:
To enter the bloodstream, a drug must be absorbed from its site of
administration
1. Oral (swallowed)
2. Intravenous
3. Intramuscular
4. Subcutaneous
5. Buccal and lingual
6. Rectal (suppositoria)
7. Inhalation
8. Topical
9. transdermal
 DISTRIBUTION OF DRUGS
Distribution of drugs to the tissues depends
on :
1. Size of the organ
2. Blood flow
3. Solubility
4. Binding of the drug to macromolecules in
the blood
 METABOLISM OF DRUGS
Drug metabolism occurs primarily in the liver
Drug metabolism as a mechanism of termination
of drug action
the action of many drugs is terminated before they are excreted
because they are metabolized to biologically inactive derivatives
Drug metabolism as a mechanism of drug
activation
prodrugs are inactive as administered and must be metabolized to
become active
Drug elimination without metabolism
some drugs are not modified by the body, they continue
to act until they are excreted
 ELIMINATION OF DRUGS
Dissapearance of the active molecules
from the bloodstream or body
Drug elimination is not the same as drug
excretion
The excretion of most drugs and
metabolites is primarily by way of the
kidney, except anesthetics gases
(excreted by the lungs)
 ELIMINATION OF DRUGS
First-Order Elimination : the rate of elimination is
proportionate to the concentration.
The drugs concentration in plasma decreases
exponentially with time.
Most drugs in clinical use demonstrate first-order kinetics
Zero-order Elimination : the rate of elimination is
constant regardless of concentration.
The concentrations of these drugs in plasma decrease in
a linear fashion over time.
Ethanol and phenytoin & aspirin (at high therapeutic or
toxic concentration) show this elimination
 PHARMACODYNAMICS
Effects of drugs on biologic systems
The most important principles in
Pharmacodynamic concepts :
Receptors are the spesific molecules in a
biologic system with which drugs interact to
produce changes in the funtion of the system
Efectors are molecules that translate the drug-
receptor interaction into a change in cellular
activity (ex; enzymes such as adenylyl cyclase
 PHARMACODYNAMICS
Efficacy is the maximal effect (Emax) an
agonist can produce if the dose is taken to
very high levels.
It can be measured with a graded dose-
response curve.
Potency is the amount of drug needed to
produce a given effect
 PHARMACODYNAMICS
Agonist and Partial Agonist
Agonist a drug capable fully activating
the effector system when it binds to the
receptor
Partial Agonist produces less than the
full effect, even when it has saturated the
receptor
 PHARMACODYNAMICS
Antagonists
Competitive & Irreversible Pharmacologic
Antagonists
Competitive Antagonists are drugs that binds to
the receptor in a reversible way without
activating the effector system for that receptor
the log dose-curve is shift to the higher doses
but the same max effect is reached
An irreversible antagonist causes a downward
shift of the max, with no shift of the curve on the
dose axis unles spare receptors are present
 PHARMACODYNAMICS
Physiologic Antagonists
Physiologic antagonist is a drug that binds to a
different receptor, producing an effect opposite
to that produced by the drug it is antagonizing.
Differs from a pharmacologic antagonist, which
interacts with the same receptor as the drug it is
inhibiting
Chemical Antagonists
A chemical antagonist is a drug that interacts
directly with the drug being antagonized to
remove it or to prevent it from reaching its target
 PHARMACODYNAMICS
Therapeutic Index is the ratio of the TD50
(or LD50) to the ED50, determined from
quantal dose-response curves
represent an estimate of the safety of a
drug
 PHARMACOKINETICS
Def : the effects of biologic systems on drugs
Effective drug concentration is the concentration
of a drug at the receptor site
The plasma concentration is a function of the
rate of input of the drug (by absorption) into the
plasma, the rate of distribution to the peripheral
tissues, & the rate of elimination or loss from the
body
well described by 2 parameters : volume of
distribution and clearance
 PHARMACOKINETICS
Bioavailability of a drug is the fraction (F)
of the edministered dose that reaches the
systemic circulation
After administration, bioavailability is
generally reduced by incomplete
absorption, first-pass metabolism, & any
distribution into other tissues before the
drug enters the systemic circulation.
(except: IV adm=100%)
 DRUG METABOLISM
Types of Metabolic Reactions
A. Phase I Reaction
include : oxydation (especially by the
Cytochrome P450 group of enzymes),
reduction, deamination, & hydrolysis
B. Phase II Reaction
Synthetic reactions that involve addition
(conugation) of subgroups to OH, -NH, and
SH functions on the drug molecules
(glucoronate, acetate, glutathione, sulfate, &
methyl groups)
 DRUG METABOLISM
Sites of Drug Metabolism
Most important organ : Liver
Kidney play an important role in the
metabolism of some drugs
 DOSIS
Adalah besarnya jumlah bahan dalam satuan
tertentu yg diberikan pada waktu tertentu.
Digunakan untuk menentukan jumlah dari :
1. Obat atau bhn obat
2. Bhn racun/kimia
3. Toksin atau antitoksin bakteri

Yg diberikan atau masuk kedalam tubuh

manusia atau hewan pada pengobatan atau
prcobaan yg menimbulkan gejala atau tidak
pada manusia atau hewan tersebut.
 MACAM-MACAM DOSIS DAN ISTILAH

Dosis efektif : jumlah obat dalam satuan

tertentu yg dapat menimbulkan efektifnya
terhadap individu tertentu.
Dosis lethalis dosis mematikan : jumlah
zat dalam satuan tertentu, yg dapat
menimbulkan kematiaan.
Dosis pengobatan : dosis yang digunakan
untuk mendapatkan efek pengobatan.
Dosis lazim usul dosis : dosis obat yg
digunakan pada pengobatan dalam batas-
batas dosis biasa, dikenal juga dosis
normal.
 TINGKAT2 DOSIS DALAM
SUATU PENGOBATAN
Dosis awal, dosis dari suatu obat yg diberikan
pertama kali pada penderita, dg tujuan :
1. Pendapatan kerja obat yg maksimal dikenal
juga sebagai stoot dosis dg pemberian dosis
tinggi pertama kali.
2. Mendapatkan atau mengetahui respon obat
pada dosis rendah, sampai dimana efek obat
dapat dicapai, sehingga perlu penambahan
atau pengurangan dari dosis agar sampai
ketingkat tertentu, misalnya pada pemberian
obat oral hipoglikemia.
Lanjutan dari dosis awal dikenal dosis
penyesuaian
 Dosis penyesuaian, setelah dosis awal diketahui
sampai dimana, efektifitasnya dapat dicapai,
maka perlu ditingakatkan atau dikurangi dosis
selanjutnya dg bertahap sampai efek yg diingini.
Dosis pemeliharaan maintenance dose, tingkat
besarnya dosis yang dapat memberikan efek
kerja obat yang stabil seperti diharapkan, norma
atau meningkatkan yg sesuai dan perlu
dipertahankan, baik dalam jangka panjang atau
jangka sedang.
 Dosis maksimum, dosis tertinggi yg masih
dapat diberikan kepada penderita tanpa
menimbulkan efek yang membahayakan.
Dosis toksis, sejumlah obat terapi yg
dapat menimbulkan gejala keracunan