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MODULE AND PRACTICAL

PHARMACOKINETICS AND PHARMACODYNAMICS PROCESS

Code :MKK :BS-4, BA : L-7


SKS :3
Semester: 2

Faculty of Medicine
UNIVERSITAS BRAWIJATA
2011

PHARMACOKINETICS AND PHARMACODYNAMICS PROCESS


Code :MKK :BS-4, BA : L-7
SKS :3
Semester: 2

THE AIM:
To study the general concepts of: pharmacokinetics, pharmacodynamics in a normal
conditions and in a special considerations, the concept of autonomic nervous system, the
general properties of endogenous substances (autacoids, peptide and their analog, biogenic
amine), the general properties of antimicrobials agents and anti cancer, and the drug
development and formulation.

DESCRIPTION AND ORGANIZATION:


Pharmacokinetics and pharmacodynamics process is a 3-credit course offered for
graduate students (S1) in Faculty of Medicine. This course is divided into 9 topics
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INTRODUCTION TO PHARMACOLOGY
PHARMACOKINETICS IN A NORMAL CONDITION AND A SPECIAL CONSIDERATIONS
PHARMACODYNAMICS IN A NORMAL CONDITION AND A SPECIAL CONSIDERATIONS
NEUROTRANSMISSION: AUTONOMIC NERVOUS SYSTEM (ADRENERGIC AND CHOLINERGIC)
AUTOCOIDS AND ANTI INFLAMATION AGENTS
PHARMACODYNAMICS OF ANTIMICROBIALS AGENT
CELL CYCLE AND ANTI CANCER
SIDE EFFECTS ,TOXICOLOGY AND DRUG INTERACTION
DRUG DEVELOPMENT AND DRUG FORMULATIONS

LEARNING EXPERIENCES::
The course format will consist of lectures, practices and small group discussion

RECOMMENDED TEXTBOOK:
1. THE PHARMACOLOGICAL BASIS OF THERAPEUTICS: 11th Edition (2006) -(Goodman & Gilman).
2. BASIC AND CLINICAL PHARMACOLOGY: 10th Edition (2007)- (Bertram G. Katzung)
3. MODERN PHARMACOLOGY 6th Edition (2004) -(Craig & Stitzel)
4. PHARMACOLOGY 5th Edition (2004)- (Rang, Dale, & Ritter).
5. FARMAKOLOGI DAN TERAPI (2006), Published by UI

COORDINATOR
TEACHING STAFFS

Prof. M. Aris Widodo, dr.,MS.,PhD.,SpFK

Prof.Dr.dr.Mulyohadi Ali, SpFK


Dr.dr.Setyawati K, MKes

Dr. Nurdiana, dr.,MKes

Dr. Nur Permatasari, drg.,MSi


Dra. Diana :yrawati, Apt, MS, PhD
Sri Winarsih, Dr, Dra, Apt. Msi
Loeki Enggar Fitri, Dr. dr. MKes. SpPark
Drs. Bambang Sidharta, Apt, MS
Umi Kalsum, dr,. MKes
Husnul Khotimah, S.si, MKes
Dian Nugraheni, dr
Elly Mayangsari, dr
Bayu Lestari, dr
Hikmawan, dr

Dr. Nur Permatasari, drg.,MSi


INTRODUCTION TO PHARMACOLOGY
NEUROTRANSMISSION: AUTONOMIC
NERVOUS SYSTEM (ADRENERGIC AND
CHOLINERGIC)
FACILITATOR
DRUG DEVELOPMENT
FACILITATOR
PHARMACODYNAMICS
FACILITATOR
AUTOCOIDS AND ANTI INFLAMMATION
AGENTS
CLINICAL TOXICOLOGY
FACILITATOR
PHARMACOKINETICS
DRUGS INTERACTION AND SIDE EFFECTS
FACILITATOR
CELL CYCLE AND ANTI CANCER
FACILITATOR
PHARMACODYNAMICS OF ANTIMICROBIALS
AGENT
PHARMACODYNAMICS OF
ANTIPARASITOBIALS AGENT
DRUG FORMULATIONS
FACILITATOR
PRACTICAL
FACILITATOR
PRACTICAL
FACILITATOR
PRACTICAL
FACILITATOR
PRACTICAL
FACILITATOR
PRACTICAL
FACILITATOR
PRACTICAL

SCHEDULE OF PHARMACODYNAMICS AND PHARMACOKINETICS


SEMESTER II -2011/2012
RK. II.1

LT. 4.08
DATE
Monday
APRIL,09TH.2012
(1RD DAY)

TIME
07.00-07.50
07.50-08.40
08.40-09.30
09.30-10.00

RK. II. 2

GROUP A

GROUP B

PK (NP)

PD (SK)

10.00-10.50
10.50-11.40
11.40-12.30
12.30-13.00
13.00-13.50
13.50-14.40
14.40-15.30
15.30-16.00
Tuesday
APRIL,10TH.2012
(2RD DAY)

10.50-11.40

ANS (MAW)

PK (NP)

PK (NP)

PD (SK)

PD (SK)

07.00-07.50
07.50-08.40
08.40-09.30
09.30-10.00
10.00-10.50

GROUP C

ANS (MAW)

M1
SK

M1
NP

M1
ND

M1
DN

M1
BL

M1
HIK

CELL CYCLE (DL)

ANS (MAW)

11.40-12.30
12.30-13.00
13.00-13.50
13.50-14.40
14.40-15.30
15.30-16.00

BASIC AND CLINICAL


TOXICOLOGY (ND)

EFEK SAMPING (NP)

CELL CYCLE (DL)

07.00-07.50
Wednesday
APRIL, 11TH.2012
(3RD DAY)

07.50-08.40
08.40-09.30

BASIC AND
CLINICAL
TOXICOLOGY (ND)

CELL CYCLE (DL)

EFEK SAMPING (NP)

MIKRO (SW)

PARASIT(LE)

M1
SK

BASIC AND CLINICAL


TOXICOLOGY (ND)

MIKRO (SW)

PARASIT (LE)

AUTACOID (ND)

EFEK SAMPING
(NP)

09.30-10.00
10.00-10.50
10.50-11.40

M1
NP

11.40-12.30
12.30-13.00
13.00-13.50
13.50-14.40
14.40-15.30
15.30-16.00
07.00-07.50

Thursday
APRIL, 12TH.2012
(4RD DAY)

07.50-08.40
08.40-09.30

PARASIT (LE)

09.30-10.00

M1
SK

10.00-10.50
10.50-11.40

M1
NP

M1
ND

M1
EM

M1
BL

M1
HIK

MIKRO (SW)

11.40-12.30
12.30-13.00
13.00-13.50
13.50-14.40
14.40-15.30

AUTACOID (ND)

PRAKTIKUM

DRUG
DEVELOPMENT
(MA)

15.30-16.00
Friday
APRIL, 13TH.2012
(5RD DAY)

07.00-07.50
07.50-08.40
08.40-09.30

PRAKTIKUM

DRUG DEVELOPMENT (MA)

AUTACOID (ND)

09.30-10.00
10.00-10.50

DRUG FORMULATION AND


PRESCRIBING (BS)

10.50-11.40

M2

M2

M2

M2

M2

M2

11.40-12.30
12.30-13.00
13.00-13.50
13.50-14.40

DRUG FORMULATION AND


PRESCRIBING (BS)

DRUG DEVELOPMENT (MA)

PRAKTIKUM

14.40-15.30
15.30-16.00

Monday
APRIL, 16TH.2012
(6RD DAY)

07.00-07.50
07.50-08.40
08.40-09.30

DRUG
FORMULATION
AND PRESCRIBING
(BS)

09.30-10.00
10.00-10.50
10.50-11.40

M2
SK

M2
NP

M2
ND

M2
DN

M2
BL

M2
HIK

11.40-12.30
12.30-13.00
13.00-13.50
13.50-14.40

M2
DN

M2
BL

M3
HIK

M3
ND

M4

M4

14.40-15.30
15.30-16.00
Tuesday
APRIL, 17TH.2012
(7RD DAY)

07.00-07.50
07.50-08.40
08.40-09.30
09.30-10.00

UTS

10.00-10.50

M3
SK

10.50-11.40

M3
NP

M3
ND

M3
DN

M3
BL

M3
HIK

11.40-12.30
12.30-13.00
13.00-13.50
13.50-14.40
14.40-15.30
15.30-16.00
Wednesday
APRIL, 18TH.2012
(8RD DAY)

07.00-07.50
07.50-08.40
08.40-09.30
09.30-10.00
10.00-10.50
10.50-11.40

M3
SK

M3
NP

M3
ND

M3
EM

M3
BL

M3
HIK

11.40-12.30
12.30-13.00
13.00-13.50
13.50-14.40
14.40-15.30
15.30-16.00

Thursday

APRIL, 19TH.2012
(9RD DAY)

07.00-07.50
07.50-08.40

M4
SK

M4
NP

M4
ND

M4
DN

M4
BL

M4
HIK

08.40-09.30

09.30-10.00

M4
SK

10.00-10.50
10.50-11.40

M4
NP

M4
ND

M4
EM

M4
BL

M4
HIK

11.40-12.30
12.30-13.00
13.00-13.50
13.50-14.40
14.40-15.30
15.30-16.00

Friday

APRIL, 20TH.2012
(20RD DAY)

CAPITA SELEKTA

07.00-07.50
07.50-08.40
08.40-09.30
09.30-10.00

CAPITA SELEKTA

CAPITA SELEKTA

UJIAN

10.00-10.50
10.50-11.40
11.40-12.30
12.30-13.00
13.00-13.50
13.50-14.40
14.40-15.30
15.30-16.00

PD= PHARMACODYNAMICS (SK)


PK=PARMACOKINETICS (NP)
BCT=BASIC AND CLINICAL TOXICOLOGY (ND)
ANS=AUTONOMIC NERVOUS SYSTEM(MAW)
AUTA=AUTACOIDS (ND)
CC=CELL CYCLE(DL)
AM=ANTIMICROBE
AP=ANTIPARASIT
AD=ADVERSE DRUD, DRUG INTERACTION (NP)
DFP= DRUG FORMULATIONS AND PRESCRIBING(BS)
DD= DRUG DEVELOPMENT (MA)

Keterangan :
MA: Prof.Dr.dr.Mulyohadi Ali, SpFK
MAW : Prof.Dr.dr.Moch.ArisWidodo,MS,SpFK,PhD
SK : Dr.dr.Setyawati Soeharto,MKes
ND : Dr.dr.Nurdiana, MKes
NP : Dr.drg.Nur Permatasari,MS
UK : dr.Umi Kalsum,MKes
DL : Dra.Diana Lyrawati,Apt,PhD
BS : Drs.Bambang Sidharta,Apt
DN : dr.Dian Nugrahenny
EM : dr.Elly Mayangsari
SW: Dr.Dra.Sri Winarsih,Apt,MSi
LE : Dr.dr.Loeki Enggar Fitri,MKes,SpPark
DN : dr. Dian Nugrahenny
EM : dr. Elly Mayangsari
BL : dr. Bayu Lestari
HIK: dr. Hikmawan

M1=MODUL PK
M2=MODUL PD
M3= MODUL ANS
M4= AUTACOID & TOXICOLOGY
P = PRACTICAL AUTACOID
GROUP A=REGULER A
GROUP B= REGULER B
GROUP C= ENGLISH CLASS

Coordinator,
NUR PERMATASARI
NIP. 19601005 199103 2 001

Modul 1:
PHARMACOKINETICS I-IV

Learning Objectives
Understand the physical processes that govern the movement of drugs and other
small molecules across cell membranes
Understand the concept of bioavailability and how first-pass metabolism can
affect it
Understand the various routes of administration of drugs, and how role of the
nature of the drug and the target organ(s) play in selecting a method of
administration.
Understand the concepts of parameters are used in designing a dosage regimen
(volume of distribution, half-life, and clearance)
Understand the routes of elimination of drugs, and the that biotransformation
reactions play in this process
Understand how the biotransformation process of one drug can be affected by
another can be affected by
Understand how age, genetics, and disease state can affect pharmacokinetic
profiles
PART I: ABSORPTION OF DRUGS AND METHODS OF DRUG DELIVERY
All drugs must cross one or more cell membranes to reach their site(s) of action and to
be eliminated from the body. Drugs cross membranes either by passive or active (energydependent) processes. Other factors can influence the absorption of compounds across
cell membranes: -dissolution rate (if solid), -surface area of absorption site, -rate of
blood flow, -drugs concentration at the site of absorption.
Assignment:
1. Explain the different types of transmembrane transport
2. Explain how gastric pH, gastric emptying and intestinal motility affect drug
absorption.
3. Explain the definition of first pass effect (pre systemic elimination) and its
correlation with drug delivery and bioavailability.
PART II: DRUG DISTRIBUTION
Once a drug is absorbed into the bloodstream, it may be distributed to interstitial and
cellular fluids. Plasma protein binding influences a drugs inter-compartmental distribution
because only unbound drug may passively diffuse from plasma into tissue. Many drugs
accumulate in tissues at higher concentrations than those in the extracellular fluids and
blood.
Assignment:
1. Name the organs (2) that are able to become drug reservoir organs and explain
why that is possible.
2. Describe what possibilities may occur when giving 2 drugs that have different
protein binding strength (strong and weak).

PART III: BIOTRANSFORMATION REACTIONS AND EXCRETION


Drug is converted to another molecular form. Conversions may be anabolic (synthetic) or
catabolic (degradative), and may result in activation or inactivation.. Biotransformations: 1)
often inactivate the drug (terminate pharmacological action), and 2) often generate polar,
highly ionized metabolites susceptible to rapid kidney excretion. Some drugs, however, are
metabolized into an active or a toxic metabolite. The enzymes that play a role in
metabolism can be inhibited or induced by certain drugs.
Assignment:
1. Explain the definition of a prodrug and give its example.
2. How is the toxicity mechanism of a drug in a hepatic cell related to its metabolism?
3. Explain the possibility that may occur when giving 2 drugs where one drug is an
metabolism enzyme inducer?
The kidneys are the main organs that function in drug excretion. A drug or its metabolite
may appear in the urine as a result of: 1) glomerular filtration without tubular
reabsorption, 2) filtration with partial reabsorption (active or passive), 3) tubular
secretion, or 4) a combination of these processes. Increasing the drug excretion is one
way to handle drug poisoning, where the urinary pH would determine the drug reabsorption in the tubuli.
Assignment:
1. Explain how a change of urinary pH (to more acidic or basic) caused by certain
drugs or food can affect the drug excretion and how it correlates with the half
life of another drug (weak acidic or basic).
2. Some drugs go through the enterohepatic cycle. Explain how that occurs and its
affect on the pharmacologic activity of a drug.
PART IV: Pharmacokinetics Variability
Therapeutics would be a great deal easier if responses to the same dose of drug were
always the same. In reality, inter- and even intraindividual variation is often substantial.
Physicians need to be aware of the sources of such variation to prescribe drugs safely and
effectively. Variation can be caused by different concentrations at sites of drug action.
That pharmacokinetic variation can occur because of differences in absorption,
distribution, metabolism or excretion.
Assignment
1. Explain how the changes of age, genetics, and physiologic conditions can affect the
drug absorption, metabolism and excretion and how these factors correlate with
the drugs half life

Modul 2:
PHARMACODYNAMICS
I. DESCRIPTION
Definition and Oveview

Competency Area
Competency Component

Learning Methode
Equipment
Lecturer
Evaluation
Suggested
Refferences

Pharmacodynamics deals with the study of the biochemical and


physiological effects of drugs and their mechanisms of action.
The pharmacodynamic process (the actions of drug to the body)
cause pharmacological respons. Pharmacological responses are
initiated by molecular interactions of drugs with cells, tissues or
other body constituents.
Area of competence : 3th of the Doctor Competencies Standart
from Indonesian Medical Council
To apply the concept and principles of drug action, agonistantagonist drugs, desensitization-supersensitization of drugs,
and therapeutics index
Active learning with module task, group discussion, and expert
lecture
Classroom, worksheet, computer, LCD and screen
DR.dr.Setyawati SK, MKes
Midle exams at the end of module programmes and final exams
at the end of semester with multiple choice questions.
1. Goodman & Gilman's The Pharmacological Basis Of
Therapeutics - 11th Ed. (2006) : Chapter 1
2. Katzung Basic & Clinical Pharmacology -9th Ed.(2007) ;Chapter
2

Learning objectives :
By the end of this session, the students should be able to :

o
o

o
o
o
o
o

Describe the properties of membrane-bound drug receptors and specific vs.


nonspecific binding of drugs.
Explain the four major transmembrane signalling mechanisms and describe the
sequence of steps involved in each pathway in response to receptor stimulation.
This is particularly important for the G protein-linked pathways.
Compare these two G protein-linked transduction pathways: the calcium
-phosphoinositide pathway, and the cAMP pathway.
Explain the difference between agonist and antagonist receptors.
Compare the dose-response curve base on the graded response with quantal
response
Understand the receptors regulatory mechanism and compare homologous
desensitization with heterologous desensitization
Define factors that affecting drug response

II. OVERVIEW
Pharmacodynamics deals with the study of the biochemical and physiological
effects of drugs and their mechanisms of action. The actions of the drug on the body are
termed pharmacodynamic processes. A drug enters the body through various ways, then
goes through many changes in its journey to the target site (target cell/ target organ).
The effects of most drugs result from their interaction in target cell with
macromolecular components of the organism. These interactions alter the function of the
pertinent component and thereby initiate the biochemical and physiological changes that
are characteristic of the response to the drug. The term receptor denotes the component
of the organism with which the chemical agent is presumed to interact. Most drugs
effects by interaction with receptors and the other without receptors. Drug acting on
receptor would stimulate transduction signal mechanism which will cause cellular response
or pharmacologic effect. There are four major transmembrane signalling mechanisms. One
of this mechanism is receptor coupled to G protein to regulate generation of intracellular
second messengers (cAMP, inisitol tri phosphates, Calcium).
The drug that interacts with a receptor may be an agonist, whish has an affinity
with the receptor and also has an efficacy, or antagonist, which has an affinity with a
receptor but not has an efficacy.
Binding between drug and receptor molecules occurs according to the law of mass
action, the concentrations (dose) of drug and receptor are key variables. It is therefore
appropriate to address the question of how much drug is needed to produce a given
response in terms of "concentration (dose) -response" relationships. Based on the
occupancy theory can calculate the dose of drug and the receptor. Biological responses to
drugs are usually graded. Although many drugs produce graded responses, there are other
drugs for which the observable response can be described only as an all-or-none event
called a "quantal" response.
Receptors not only initiate regulation of biochemical events and physiological
function but also are themselves subject to many regulatory and homeostatic controls.
These controls include regulation of the synthesis and degradation of the receptor by
multiple mechanisms, covalent modification, association with other regulatory proteins,
and/or relocalization within the cell. Loss of receptor responsiveness to an agonist is
termed desensitization.
III. MODULE TASK
1. A few drugs work without an interaction to a receptor. Name those types of drugs
and how it works to create a pharmacologic effect.
2. Base on the transmembrane signaling mechanisms, the receptor is classified into 4
types. Describe those classification and the sequence of steps involved in each
pathway in response to receptor stimulation.
3. Explain the difference between the calcium phosphoinositide pathway and the
cAMP pathway. What the receptors by those pathways ?
4. Define agonist, partial agonist and antagonist in terms of receptor affinity and
efficacy. Draw graded dose-response curves for agonists of differing potency at
the same receptor. Draw graded dose-response curves for agonists of differing
efficacy at the same receptor.
5. The interaction with the receptor and the drug, whether it is with an agonist or
antagonist would cause a regulation of receptor aside from creating a
pharmacologic effect. Describe the mechanism of receptor regulation that occurs
and give an example of receptor regulation that can happen clinically.
6. Explain the difference between dose-response curve base on the graded response
with quantal response

7. How is therapeutic index determined and what does it tell you?


8. Describe the factors that can affect drug response and need a dosage adjustment.
IV. SUGESTED READING
1. Goodman & Gilman's The Pharmacological Basis Of Therapeutics - 11th Ed. (2006) :
Chapter 1
2. Katzung Basic & Clinical Pharmacology -8th Ed;Chapter 2

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Modul 3:

Pharmacology Autonomic Nerve System


Learning Objectives:
By the end of this session, the students should be able to:

o Compare and contrast the anatomy of the sympathetic and parasympathetic


o

o
o
o
o
o

divisions of the autonomic nervous system (ANS).


List and compare/contrast the physiological responses of end organs produced by
activation of the sympathetic and parasympathetic nervous systems
Explain what tone is, and apply knowledge of predominant tone to the regulation of
dually-innervated organs.
Describe the biosynthetic steps and regulation of the biosynthesis of
catecholamines
Describe the biosynthetic steps and regulations of the biosinthesis of of
acetylcholine
Explain the actions of the transmitters of the autonomic nervous system
Describe how the transmitters of the autonomic nervous system regulates vascular
and cardiac function, respiratory system and GIT system

Introduction
Sympathic and Parasympathic autonomic nerve system is centered in the
hypothalamus. Unlike the voluntary motoric nerve system, autonomic nerve system is
involuntary, meaning, it cannot be controlled like controlling a striated muscle. Autonomic
nerves innervate most visceral organs inside the body, such as in the heart, intestines,
blood vessels, lungs and glands. To communicate between the nerve cells and the visceral
organ cells, the end autonomic nerve cells, whether praganglionic or postganglionic wil
excrete a certain chemical substrate which is known as a neurotransmitter. In its journey,
the sympathic and parasympathic autonomic nerve cells will exit from the central nerve
and medulla spinalis to the visceral organs.
Assignment 1:
1. Describe the anatomical and physiological difference and also the receptor in the
effector cells which is located in the post synaptic nerve joint between the
sympathic and parasympathic nerves (make a table or a diagram).
2. There are a few exceptions to some organs or effector cells above which is
different from the usual regulations. Describe those exceptions.
It is very interesting to study neurotransmitters, because the synthesis mechanisms,
storage, and release can be used to explain a few disorders in the nerve and be used to do
a drug intervention in the diseases that is related to autonomic nerve cell
neurotransmitters. Those principles can also be used to explain physiologic and pathologic
processes which are related to gland secretion and cell mediator.
Assignment 2:
1. Describe how dopamine, noradrenaline and adrenaline is synthesized in the nerve
cells.
2. How is noradrenaline and acetylcholine metabolized in the nerve cells? What
enzymes and processes is involved in the synthesis and metabolism of
noradrenaline.
3. Mention the chemicals or drugs that affects synthesis process, storage, release,

11

uptake and metabolism of neurotransmitters. Are those substrates useable in


medicine related to neurotransmitters?
Neurotransmitters work on an organ effector through many receptors. Binding with those
receptors cause an increase of second messenger numbers inside the cells and cause the
opening of various ion channels.
Assignment 3:
1. How is the adrenegic and cholinergic receptor subtype division and name the main
specific receptor in these organs: heart, blood vessels, bronchiolus, intestinals,
liver, urogenital tract and pupil?
2. How is the pharmacodynamic mechanism of neurotransmitter bounded with a
certain receptor, and how is the biochemistry cascade inside the cell?
Inside our body, there are some vital organs which are important to maintain the
physiologic function of our body. Those physiologic functions are maintained by the
activity of the sympathic or the parasympathic nerve cell activity in the organ or system.
Those nerve activities is depends on the receptor distribution on those organs and also the
sympathic and parasympathic nerve domination on those organs.
Assignment:
1. What is the effect of autonomic nerve cell activity in the heart (SA node, AV
node, Purkinje and ventricle muscle)?
2. What is the effect of autonomic nerve cell activity on the vascular system and
blood pressure?
3. What is the effect of autonomic nerve cell activity on the respiration system
(bronchiolus)?
4. What is the effect of autonomic nerve cell activity on the gastrointestinal tract?
Autonomic nerve cell activity depends on the availability of the endogenic
neurotransmitter, such as noradrenaline and acetylcholine. However, many exogenic
substrates can be in the form of agonist, antagonist, or chemicals/drugs that can increase
the neurotransmitter in the synaptic gap which of course would effect the activity of the
organ or system inside the body.
Assignment:
1. Name and describe the mechanisms other drugs that can increase the
norepinephrine and acetylcholine concentration in the synaptic gap.
2. Based on the adrenergic receptor distribution in the cardiovascular, how does
exogenic noradrenaline and adrenaline intake affect the blood pressure and heart
(draw the effect of the drug on the blood pressure increase graphic).
3. What happens to the heart, blood vessels, and bronkhiolus if given a selective
beta-1 blocker?
4. What happens to the heart and bronchus if given a non selective beta agonist.

12

MODUL 4:
Autocoids and Anti-inflammatory Agents
Learning Objectives:
By the end of this session, the students should be able to:
o Understand the concept of local hormones or autocoids.
o Familiar with the compounds or materials that is grouped as autocoids.
o Understand the source, synthesis, storage and distribution of autocoids.
o Understand the pharmacological effects of autocoids and its mechanism.
o Understand the role of autocoids in inflammation.
o Understand the role of antiinflammaotry agents and its relation with autocoids in
inhibiting inflammatory processes.
o Understand the proinflammatory cytokines and anti-inflammatory cytokines
Introduction
Other than hormones and neurotransmitters, there are compounds with a short life span
and works in its origin of synthesis. Compounds with these characteristics are gathered
into one group and named autocoid derived from the word autos (greek, meaning alone)
and akos (greek, meaning medicinal compound or medicine). These compounds are also
known as local hormones. The study of autocoids is required because autocoids functions in
the many process in the human body, whether it is physiological or pathological. Various
organs are affected by autocoids, resulting in different effects depending on the type of
the autocoid and where it works.
Assignment:
Inflammation is affected by many mediators, among them, the autocoid. Name the types
of autocoids that play a role in inflammation.
Histamine.
Histamine is considered an autocoid. Histamine functions in many physiological and
pathological processes in the human body, such as, in urticaria, allergy, hipersensitivity,
etc. Thus, the study of its mechanism and role in those processes is needed.
Understanding its mechanism can be used to explain how those processes occur.
Assignment
1. Name the distribution of histamine and how it is synthesized, stored and
metabolized.
2. Name the regulation of histamine release and the factors that affect it.
3. Explain the mechanism of histamine in allergy
4. Name histamine subtype receptors and some organs that those receptor reside in.
5. Name some examples of the effects of histamine in some organs in the body.
6. Explain how the effects of histamine causes edema.
7. Name the groups of antihistamines and explain its mechanism and some examples
of its effect in the organs of the human body.
8. Name some antihistamine that has an local anaesthetic effect.

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Bradikynin
Bradykinin and kalidin (peptide autocoids) occurs in tissue damage, allergic reaction,
virus infection and in inflammatory events cause by other things, which activates the
proteolytic process. These peptides are autocoids which works locally in causing pain,
vasodilatation, and an increase in vascular permeability. The activity of this autocoid is
associated with mediator release stimulation such as prostaglandin, NO, or endotheliumderived hyperpolarizing factor (EDHF).
Assignment
1. Describe the formation and destruction of kinin.
2. Name the groups of bradikynin receptors.
3. Give some examples of bradikynin effects in subtype receptors and its organ
response.
5-Hydroxytryptamine (5HT, Serotonin)
5-hydroxytryptamine (5 HT, serotonin)is a regulator of smooth muscle function in the
cardiovascular and gastrointestinal tract, a regulator in platelet function and a
neurotransmitter in the central cnervous sytem (CNS). There is a high concentration of 5
HT in enterochromaffin cells in the gastrointestinal tract, it is stored in platelet granules
and widely spread in the CNS.
Assignment
1. Name the source of 5 HT.
2. Explain the synthesis and metabolism of 5 HT.
3. Name the subtype receptors of 5 HT, its distribution, post receptor mechanism
and some examples of its prototype antagonist receptor.
4. Explain how 5 HT regulates smooth muscle function in the cardiovascular system
and gastrointestinal tract.
5. Explain the mechanism of ondansetron.
Lipid derived Autocoids (Eicosanoid and Platelet Activating Factors/PAF)
The lipid cell membrane supplies substrate for the synthesis of eicosanoid and the
platelet activating factor (PAF). Eicosanoid is an arachidonic metabolite, it includes
prostaglandins, prostacyclines, thromboxane A2 and leukotriens, all are not stored in the
cell yet produced by most cells. Various induction in the cells, such as physical, chemical
and hormonal induction will activate acyl hydrolases enzymes that would eventually form
arachidonic acids. Glycerophosphocholine derivates in the cell membrane can be
enzymatically modified to produce platelet activating factors (PAF). PAF is formed by
leukocytes, platelets and endothels. Eicosanoid and PAF derived from lipids contributes in
inflammation, smooth muscle tonus change, homeostasis, thrombosis, secretion in the
gastrointestinal tract, and birth. Some medicinal groups, especially aspirine, is grouped
into traditional non-steroidal anti-inflammatory agents (tNSAID) and special
cyclooxygenase-2 (COX-2) inhibitors such as coxibs, that has the therapeutic principle of
blocking the formation of eicosanoids. To understand the therapeutic potential of a
selective inhibitor to the synthesis and function of eicosanoids, a study on the synthesis,
metabolism, and mechanism of eicosanoid and PAF is needed.
Assignment:
1. Explain the synthesis, metabolism, and mechanism of eicosanoid.
2. Explain the role of eicosanoid in inflammation.
3. Explain the synthesis, metabolism, and mechanism of PAF.
4. Explain the mechanism of tNSAID (non selective COX inhibitor) and COX specific
inhibitor and their role as an anti-inflmmatory agent.

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Cytokines

Cytokines are soluble (glyco)proteins, nonimmunoglobulin in nature, released by living cells


of the host, which act nonenzymatically in picomolar to nanomolar concentrations through
specific receptors to regulate host cell function. Cytokines make up the fourth major class
of soluble intercellular signaling molecules, alongside neurotransmitters, endocrine
hormones, and autacoids. Proinflammatory cytokines are produced predominantly by
activated macrophages and are involved in the up-regulation of inflammatory reactions.
Anti-inflammatory cytokines belong to the T cell-derived cytokines and are involved in
the down-regulation of inflammatory reactions.
Assignment:
1. Name the source of cytokine.
2. Explain the role of cytokine in inflammation.
3. Explain the mechanism of cytokine
4. Name the proinflammatory cytokines and anti-inflammatory cytokines and explain
the mechanism.

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PRACTICAL GUIDANCE
Introduction of the practical
The teaching of pharmacology given to medical faculty students is incomplete,
whether using the classical methodology or the more newer Problem Based Learning
(PBL) methodology, without a conducting a pharmacological practice.
This practice isn't aimed to increase the practical skill of the students its
purpose is to help the participants obtain a direct explanation from observing the
effects and responses of a drug in various levels of an organisms: organs, tissues and
even towards cell cultures.
The participants would actively give a predetermined treatment to the organs or
tissues, observe and not the changes or responses that occur, report in groups and in
class, and, more importantly, conduct an analysis an discuss any results found deviating
from the existing theories.
For that purpose, and also as a guide in completing the
practice and a practice report, is this module
As for the practice itself, participants are expected to prepare and learn
beforehand the pharmacological effects of the certain drug used in the forthcoming
practice, as it would ensure that the practice runs smoothly. Participants should work
earnestly, seriously, with discipline and peacefully, so the practice would give benefit to
the teaching of pharmacology.

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PRACTICAL 1A: THE EFFECTS OF DRUGS ON THE BLOOD VESSELS


INTRODUCTION
Blood vessels disorders are mostly found in the pathomechanisms of several
diseases, such as hypertension, vascular angiopathy on diabetes, etc. In order to solve
this problem, many drugs have been developed - some target the smooth muscle of the
blood vessels (alpha-1 blocker, isosorbide dinitrate), others the endothelial cells
indirectly (help to maintain/increase the quantity and quality of the endothelial cells). To
observe or develop drugs and even explain the pathomechanism of the blood vessel
disorder, an experimental method takes place, in which is used a separated blood
vessels. The blood vessels used are artery and aorta with or without endothelial cell.
OBJECTIVES:
1) Observe the vasoconstriction and vasodilatation effects from the separated
aorta with and without endothelial cell.
2) Understand the mechanism of a drug that has a vasodilatation effect which
works at the smooth muscle of blood vessels or endothelial cell.
METHODS:
1. Experiment Animal: Marmot
2. The drugs used are: Phenylephrine 0,5 ml 10 -4M Phenylephrine followed by
isosorbide dinitrate 0,5 ml 10-4M Phenylephrine followed by acetylcholine 0,5 ml
10-4M
3. Equipment: organ bath, Mac-lab computer
4. Experimental methods:
Isolate the marmot's aorta from it's thorax cavity
Prepare the whole blood vessel with and without endothelial cell (after
wiped with a cotton) in a length of more than 1 cm long.
Fixate the aorta with 2 hooks in to the organ bath with Krebs solution
inside, and maintain the temperature at 37oC.
Ensure the organ bath content is more or less 5 ml
Ensure the weight of aorta is 1 g, and connect to an isotonic contraction
recorders using isotonic transducers.
Insert the drugs in the organ bath and observe the response from the
recorder.
Figure: A technique diagram of an Aortic ring preparation
Details:
a) Tissue/ Organ
b) Henselheit Kreb's Solution
c) Double Jacketed Chamber
d) Transducer
DISCUSSION AND ASSIGNMENT
Phenylephrin's effect on the blood vessels
a) What effect did you observe after phenylephrine was administered to the
stock?
b) How is the mechanism of action?
c) Name the same type of drugs which has the same effect.
d) Based on the effect, what are the side-effects of this drug?
2. Isosorbid's effect on the blood vessels
a) What effect did you observe after isosorbid was administered to the stock?
b) How is the mechanism of action?

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c) Name the same type of drugs which has the same effect.
d) Based on the effect, what are the side-effects of this drug?
3. Acetylcholine's effect on the blood vessels
a) What effect did you observe after acetylcholine administered to the stock?
b) How is the mechanism of action?
c) Name the same type of drugs which has the same effect
d) Based on the effect, what are the side-effects of this drug?

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PRACTICAL 1B: THE EFFECT OF HISTAMIN AND ISOPRENALIN TO THE


SEPARATED TRACHEA STOCK
INTRODUCTION
Bronchus spasm in asthma is a result of an inflammation process and a hyperactive
bronchus. Asthma therapy, besides using anti-inflammation drugs to manage the
underlying process of asthma also uses bronchodilators which functions mainly as a
symptomatic drug.
To observe or develop drugs which would function as a bronchodilator or
bronchoconstrictor, an experimental method takes place in which a separated trachea
stock is used. In this isolated tissue method, the trachea is more often used than
bronchus smooth muscle because it is structurally and functionally (the distribution and
number of receptors) similar to bronchus smooth muscles, but it is easier to prepare.
OBJECTIVES:
1. To observe the bronchocontriction and bronchodilatasi effects on the separated
stock of respiratory tract smooth muscles.
2. To understand the mechanism of bronchocontriction and bronchodilatation.
METHOD:
1. Experiment Animal: Marmot
2. Drugs used: histamine and isoprenaline
3. Equipment used: organ bath, Mac-Lab computer
4. Experimental method:
a) Isolate the trachea of the marmot from the thorax, and make a connected
ring stock.
b) Fixate stock using two strings with one end hooked with an isotonic
transducer.
c) Use Kreb's solution as the media solution, with the volume of the organ bath
up to 25 ml.
d) The trachea load is about 0.500 grams.
e) Insert the drugs in to the organ bath and observe the response on the
recorder.
5. Drugs used:
a) 10-5 M histamine (it would give 80% of the maximum effect which is 0.1 ml
2.5x10-3).
b) After the effect of histamine reaches maximum, administer isoprenalin with
succesive concentration 10-8 M, 10-7 M, 10-6 M, and 10-5M.
6. Observe the changes of contraction on the recorder following the administration
of drugs
Figure: Technique Diagram of Separated Trachea Preparation
DISCUSSION:
1. The effect of histamine on the respiratory tract smooth muscle
a) What effect did you observe after histamine is administered to the stock?
b) How is the drugs mechanism of action?
c) Name the same type of drugs with the same effects.
d) Based on the effect, what are the side effects of this drug?
e) Explain the mechanism of histamine release following an allergic reaction.
2. The effect of Isoprenalin on the respiratory tract smooth muscle
a) What effect did you observe after isoprenalin is administered to the stock?
b) How is the drugs mechanism of action?
c) Name the same type of drugs with the same effects.
d) Based on the effect, what are the side effects of this drug?

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