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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: [email protected]
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