Pharmacology – I

PHL-313 Chapter 1:

Introduction and Basic Principles

in Pharmacology

By

Majid Ahmad Ganaie M. Pharm., Ph.D. Assistant Professor Department of Pharmacology E mail: majidsays@gmail.com

B. Basic concepts in Pharmacology - Drug-Body Interactions

- Drug Receptors

- Drug Receptor Interactions

- Dose Response Functions

Overview

A. Introduction

- Pharmacology, Scope & link to other biomedical principles

- Basic terms and Definitions

- Drug Nomenclature

- Drug sources

Introduction

• What is Pharmacology?

• Why do we need to take Pharmacology?

• Significance of Pharmacology to Pharmacy

Pharmacology, Scope & link to other biomedical principles

FOUR BASIC TERMS

DRUG: A drug is defined as any chemical that can affect living processes.

PHARMACOLOGY: The study of drugs and their interactions with living systems.

Encompasses the study of the physical and chemical properties of drugs as well as their biochemical and physiologic effects, Includes knowledge of the history, sources, and uses of drugs

CLINICAL PHARMACOLOGY:

Defined as the study of drugs in humans

THERAPEUTICS:

The use of drugs to diagnose, prevent, or treat disease.

(The medical use of drugs.)

Receptor

“A specific protein in either the plasma membrane or interior of a target

cell with which the drug combines”

Pharmacology, Definitions

Pharmacology ( Pharmakon “Greek” : Drug )

“ The effect of a drug (chemical) on the body (living system).

Dose

“The amount of a drug to be administered at one time”

Mechanism of Action

“How the drug exerts its action”

Indications

“The reasons for administering a medication or performing a treatment”

Contra-indications

“Factors that prevent the use of a medication or treatment (e.g., allergies)”

Pharmacology, Definitions

Effects (therapeutic effects)

“The desired results of

administration of a medication”

Side Effects (adverse effects)

“Effects that are harmful and

undesired, and that occur in

addition to the desired therapeutic

effects”

Brand or trade name (proprietary) is developed by the company requesting

approval for the drug and identifies it as the exclusive property of that company.

Example 1: Metrogyl® is the trade name for metronidazole.

Example 2: Reglan® is the trade name for metoclopramide.

Example 3: Amoxil® is the trade name for amoxycillin.

Example 4: Celebrex® is the trade name for celecoxib.

Drug Nomenclature

Chemical name represents the exact description of the drug’s chemical

composition

Example 1: the chemical name 2-methyl-5-nitroimidazole-l-ethanol is condensed

to the generic name metronidazole. The word methylnitro is condensed to

metroni and dazole is due to its imidazole ring

Example 2: Metoclopramide is the condensed form of the word

methoxychloroprocainamide: where Me is retained and th is written as t; chloro

is written as clo: and procainamide is written as pramide

Generic name (non-proprietary)

- derived from the chemical name itself

- simpler than the chemical name and

- easier to remember

Drug Sources

1. Plant Sources: Obtained from plant parts or products. Seeds, stem,

roots, leaves, resin, and other parts yield these drugs. Examples include digoxin from digitalis and morphine from opium.

4. Mineral Sources: Some drugs are prepared from minerals, for example,

lithium carbonate (an antipsychotic), MgSO4 (a laxative)

2. Animal Sources: Glandular products from animals are used, such as

insulin and thyroid.

5. Synthetic Sources: Laboratories duplicate natural processes, and may

modify the products. Frequently this can eliminate side effects and

increase the potency of the drug. Examples include sulfonamides, and aspirin.

6. Recombinant proteins: Proteins that are synthesized by expression of

cloned genes in recombinant cells, such as interferons, antibodies

3. From micro-organisms (fungi, bacteria) Penicillin was discovered by

Alexander Fleming in 1928 as a product of penicillium notatum (a mold

growing in his lab)

B. Basic concepts in Pharmacology - Drug-Body Interactions

- Drug Receptors

- Drug Receptor Interactions

A. Introduction

- Pharmacology, Scope & link to other biomedical principles

- Definitions

- Drug Nomenclature

Pharmacokinetics (in Greek: "pharmacon" meaning drug, and

"kinetikos" meaning putting in motion)

The study of the movement of drugs in the body, including the

processes of absorption, distribution, localization in tissues,

biotransformation and excretion

Pharmacokinetics

Pharmacodynamics The study of the actions or effects of drugs on living organisms

Pharmacokinetics vs Pharmacodynamics

What the drug does to the body What the body does to the drug

Drug-Body Interactions

Receptor/Binding site

“A specific protein in either the plasma membrane

or interior of a target cell with which a ligand/drug

combines”

It must be selective in choosing ligands to bind

To avoid constant activation of the receptor by promiscuous binding of many different ligands

It must change its function upon binding in such a

way that the function of the biologic system (cell,

tissue, etc) is altered This is necessary for the ligand to cause a pharmacologic effect

Drug Receptors

Drug Receptors

Receptor/Binding site

“A specific protein in either the plasma membrane

or interior of a target cell with which a ligand/drug

combines”

It must be selective in choosing ligands/drugs to

bind To avoid constant activation of the receptor

by promiscuous binding of many different ligands

It must change its function upon binding in such a

way that the function of the biologic system (cell,

tissue, etc) is altered This is necessary for the

ligand to cause a pharmacologic effect

Drug Receptors

Receptor/Binding site

“A specific protein in either the plasma membrane

or interior of a target cell with which a ligand/drug

combines”

It must be selective in choosing ligands/drugs to

bind To avoid constant activation of the receptor

by promiscuous binding of many different ligands

It must change its function upon binding in such a

way that the function of the biologic system (cell,

tissue, etc) is altered This is necessary for the

ligand to cause a pharmacologic effect

Drug

Orphan receptors

“Receptors for which no ligand has been discovered but they have a similar structure to other identified receptors and whose function can only be presumed” If a ligand for an orphan receptor is later discovered, the receptor is referred to as "adopted

orphan receptor"

In order to interact chemically with its receptor, a drug molecule must have the appropriate size, electrical charge, shape, and atomic composition

Receptor Down-Regulation

“A decrease in the total number of target-cell receptors for a given messenger/ligand in response to chronic high extracellular concentration of the messenger/ligand”

Drug Receptors, contd.

Supersensitivity

“The increased responsiveness of a target cell to a given messenger/ligand,

resulting from receptor up-regulation”

Receptor Up-Regulation

“An increase in the total number of target-cell receptors for a given

messenger/ligand in response to a chronic low extracellular concentration of

the messenger/ligand”

Desensitization

“The loss of a drug’s effect, when it is given continuously or repeatedly, on a

short time-scale”

Often results from receptor down-regulation

Drug Receptor Interactions

Agonist

“A chemical messenger (or drug) that binds to a receptor and triggers the cell‟s

response; often refers to a drug that mimics a normal messenger’s action”. For example, pilocarpine is a muscarinic receptor agonist because it can bind to and

activate muscarinic receptors

Antagonist

"A molecule that competes for a receptor with a chemical messenger normally

present in the body. The antagonist binds to the receptor but does not trigger the cell‟s response” For Example, atropine is a muscarinic receptor antagonist because it can bind to

muscarinic receptors but it does not trigger the cell’s response. In this way, it prevents binding of acetylcholine (ACh) and similar agonist drugs to the ACh receptor

The Lock and Key Model of Signal-Receptor Interaction

Ligands such as hormones, neurotransmitters or drugs (the "key") affect target cells by binding to specific receptors (the "lock”), which are often located in the cell membrane

This binding "unlocks" the cell's response, so that the hormone or neurotransmitter can exert its effects

Drug Receptor Interactions

Drug Receptor Interactions

Agonist Receptor

Agonist-Receptor

Interaction

Lock and key mechanism

Antagonist Receptor

Antagonist-Receptor

Complex

DENIED!

Competitive

Inhibition

Drug Receptor Interactions

Agonist Receptor

Antagonist

„Inhibited‟-Receptor DENIED!

Non-competitive Inhibition

Drug Receptor Interactions

Drug Receptor Interactions, contd.

Affinity

The extent to which the ligand/drug is capable of binding and remained bound to receptor.

High Affinity – the ligand binds well and remains bound long enough to

activate the receptor.

Low Affinity – the ligand binds less well and may not remain bound long enough

to activate the receptor.

High Affinity

Low Affinity

Drug Receptor Interactions, contd.

Affinity

The extent to which the ligand/drug is capable of binding and remained

bound to receptor.

High Affinity – the ligand binds well and remains bound long enough to activate

the receptor

Low Affinity – the ligand binds less well and may not remain bound long enough

to activate the receptor

Dose-Response Functions

Bio

logic

al E

ffec

t

Displays the relationship between the dose of a ligand and some

biological response to that ligand

20 30 40

Dose-Response Functions, contd.

Which drug has more efficacy? And why?

Efficacy (Emax)

The maximal response that the drug can produce. It is the effect that is

observed at saturating concentrations Agonists will have high efficacy, whereas antagonists will, generally, have zero efficacy

EC50 (ED50)

The concentration or dose of the drug that is needed to produce a 50%

maximal response

1

(A)

Red

(B)

25 -

50 -

75 -

100 -

Log Dose (mg)

1 50 100

Dose-Response Functions, contd. Potency

The amount (weight) of drug in relation to its effect. For example, if the weight-for-weight drug A has a greater effect than drug B

drug A is more potent than drug B, although the maximum therapeutic effect may

be similar with both drugs

Drugs of high potency will generally have a high affinity for the receptors and

thus occupy a significant proportion of the receptors even at low

concentrations

Dose-Response Functions, contd. Efficacy & Potency

Bio

log

ical

Eff

ect

B A

Efficacy: A=B

Potency: A>B

Which drug has more efficacy? Which drug has more potency? And

why?

Bio

log

ical

Eff

ect

B

A

Efficacy: A>B

Potency: A=B

Dose-Response Functions, contd. Efficacy & Potency

Which drug has more efficacy? Which drug has more potency? And

why?

Bio

log

ical

Eff

ect

B

A

Efficacy: A>B

Potency: A>B

Dose-Response Functions, contd. Efficacy & Potency

Which drug has more efficacy? Which drug has more potency? And

why?

THANKS