Modul :

PHARMACODYNAMICS

I. DESCRIPTION

Definition and Oveview 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.
Competency Area Area of competence : 3th of the Doctor Competencies Standart
from Indonesian Medical Council
Competency Component To apply the concept and principles of drug action, agonist-
antagonist drugs, desensitization-supersensitization of drugs, and
therapeutics index
Learning Methode Active learning with module task, group discussion, and expert
lecture
Equipment Classroom, worksheet, computer, LCD and screen
Lecturer DR.dr.Setyawati SK, MKes
Evaluation Midle exams at the end of module programmes and final exams at
the end of semester with multiple choice questions.
Suggested Refferences 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 Describe the properties of membrane-bound drug receptors and specific vs. nonspecific
binding of drugs.
o 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.
o Compare these two G protein-linked transduction pathways: the calcium -phosphoinositide
pathway, and the cAMP pathway.
o Explain the difference between agonist and antagonist receptors.
o Compare the dose-response curve base on the graded response with quantal response
o Understand the receptors regulatory mechanism and compare homologous desensitization
with heterologous desensitization
o Define factors that affecting drug response

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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

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 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 :

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 (energy-dependent)
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, -drug’s
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 drug’s 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).

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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 re-absorption 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 drug’s half
life

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 Modul :

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 divisions of the
autonomic nervous system (ANS).
o List and compare/contrast the physiological responses of end organs produced by activation
of the sympathetic and parasympathetic nervous systems
o Explain what tone is, and apply knowledge of predominant tone to the regulation of dually-
innervated organs.
o Describe the biosynthetic steps and regulation of the biosynthesis of catecholamines
o Describe the biosynthetic steps and regulations of the biosinthesis of of acetylcholine
o Explain the actions of the transmitters of the autonomic nervous system
o 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.

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 3. Mention the chemicals or drugs that affects synthesis process, storage, release, 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.

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