CHAPTER ONE

INTRODUCTION TO PHARMACOLOGY
Outlines
 Introduction
 Definitions
 Scope
 Branches of Pharmacology
 History of Pharmacology
Drug
 Definition,
 Sources
 Nomenclature
 Drug body interactions
 Pharmacodynamics processes
 Pharmacokinetics processes
Definitions
 Pharmacology:
• Blend of two Greek words, “Pharmakon” to mean drug or
medicine, & “Logos” to mean study.
• The study of substances/chemicals that interact with living
biological systems through chemical processes (particularly
by binding to regulatory molecules) & alter (activate or
inhibit) biologic function or response
• These substances may be chemicals (drugs) that are
administered to a pt (humans) in order to achieve a
beneficial therapeutic effect
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Definitions …

 Toxicology:

 Is the branch of pharmacology that t deals with the

undesirable effects of chemicals on living systems, from
individual cells to humans to complex ecosystems

 Xenobiotic: (xenos “stranger”)

 Any substance/chemical that is foreign to the human body

(not synthesized in the body)

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Definitions …

 Prodrug:

 Is an ‘inactive’ form of a drug that requires metabolic

activation inside the body (bioactivation) in order to release
the ‘active’ form of the drug. Once released in vivo, the
active form of the drug will then exert its pharmacological
effect

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Definitions …
 Receptor:
 The component of a cell or organism that interacts with a drug &
initiates the chain of biochemical events leading to the drug’s
observed effects.

 Pharmacodynamics (PD):
 Refers to the actions of the drug on the human body (what the
drug does to the body)
• Play the major role in deciding whether that class of drugs is
effective therapy for a particular disease or symptom

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Definitions …

 Pharmacokinetics (PK):

 Refers to the actions of the human body on the drug (what

the body does to the drug)

 It is the study of ADME properties of the drug with respect

to time

• Great significance in the selection & administration of a

particular drug for a particular pt

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Definitions …

 Pharmacogenomics (or Pharmacogenetics):

 The study of the genetic variations among humans that

cause differences in PD/PK & lead to individual differences
in drug response

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The nature of drugs

a) The nature of drugs

 In the most general sense, a drug may be defined as any

substance that brings about a change in biologic function
through its chemical actions

 In most cases, the drug molecule interacts as an agonist

(activator) or antagonist (inhibitor) with a specific
molecule in the biologic system that plays a regulatory
role
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The nature of drugs…

 In a very small number of cases, drugs known as chemical

antagonists may interact directly with other drugs, whereas a
few drugs (osmotic agents) interact almost exclusively with
water molecules

 Drugs may be synthesized within the body (eg, hormones )

or may be chemicals not synthesized in the body (ie,
xenobiotics, from the Greek xenos , meaning “stranger”)

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The nature of drugs…

 Poisons are drugs that have almost exclusively harmful effects

 However, Paracelsus (1493–1541) famously stated that “the
dose makes the poison,” meaning that any substance can be
harmful if taken in the wrong dosage

 Toxins are usually defined as poisons of biologic origin

 i.e. synthesized by plants or animals

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 The nature of drugs…

 To interact chemically with its receptor, a drug

molecule must have the appropriate:

 Size
 Electrical charge
 Shape, &
 Atomic composition

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The nature of drugs…
 A drug is often administered at a location distant from its intended site
of action, e.g. a pill given orally to relieve a headache

 Therefore, a useful drug must have the necessary properties to be

transported from its site of administration to its site of action

 A practical drug should be inactivated or excreted from the body at a

reasonable rate so that its actions will be of appropriate duration

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The nature of drugs…
i. The physical nature of drugs
 Drugs may be solid at room temp (eg, aspirin, atropine),
liquid (eg, ethanol), or gaseous (eg, nitrous oxide)

 These factors often determine the best route of administration

 The various classes of organic compounds—carbohydrates,

proteins, lipids, & their constituents—are all represented in
pharmacology

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The nature of drugs…

 The physical nature of drugs…

 A number of useful or dangerous drugs are inorganic
elements, eg, lithium, iron, & heavy metals

 Many organic drugs are weak acids or bases.

• This fact has important implications for the way they are
handled by the body
• B/c pH differences in the various compartments of the
body may alter the degree of ionization of such drugs

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 The nature of drugs …

ii. Drug size

 The molecular size of drugs varies from very small
(lithium ion, MW 7) to very large (eg, alteplase [t-PA],
a protein of MW 59,050)

• However, most drugs have molecular wt b/n 100 &

1000

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The nature of drugs…

 Drug size…
 The lower limit of this narrow range is probably set by the
requirements for specificity of action
• To have a good “fit” to only one type of receptor, a drug
molecule must be sufficiently unique in shape, charge, &
other properties, to prevent its binding to other receptors
• To achieve such selective binding, it appears that a molecule
should in most cases be at least 100 MW units in size

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 The nature of drugs…

 Drug size…
 The upper limit in molecular wt is determined primarily by
the requirement that drugs must be able to move within the
body (eg, from the site of administration to the site of action)
• Drugs much larger than MW 1000 do not diffuse readily
b/n compartments of the body
• Therefore, very large drugs (usually proteins) must often
be administered directly into the compartment where they
have their effect

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The nature of drugs…

iii. Drug reactivity & drug-receptor bonds

 Drugs interact with receptors by means of chemical forces
or bonds

 These are of 3 major types:

• Covalent

• Electrostatic, &

• Hydrophobic

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 The nature of drugs…

 Drug reactivity & drug-receptor bonds…

 Covalent bonds are very strong & in many cases not
reversible under biologic conditions
• Example: The covalent bond formed b/n the acetyl group of
ASA (aspirin) & cyclooxygenase, its enzyme target in
platelets, is not readily broken
• The platelet aggregation–blocking effect of aspirin lasts
long after free ASA has disappeared from the
bloodstream (about 15 min) & is reversed only by the
synthesis of new enzyme in new platelets, a process that
takes several days

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 The nature of drugs…
 Drug reactivity & drug-receptor bonds…
 Electrostatic bonding
• It is much more common than covalent bonding in drug-
receptor interactions

• Electrostatic bonds vary from relatively strong linkages

b/n permanently charged ionic molecules to weaker
hydrogen bonds & very weak induced dipole interactions
such as van der Waals forces and similar phenomena

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The nature of drugs…

 Drug reactivity & drug-receptor bonds…

 Electrostatic bonds are weaker than covalent bonds

 Hydrophobic bonds are usually quite weak & are
probably important in the interactions of highly lipid-
soluble drugs with the lipids of cell membranes &
perhaps in the interaction of drugs with the internal
walls of receptor “pockets”

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The nature of drugs…

 Drug reactivity & drug-receptor bonds…

 The specific nature of a particular drug-receptor bond
is of less practical importance than the fact that drugs
that bind through weak bonds to their receptors are
generally more selective than drugs that bind by
means of very strong bonds
• This is b/c weak bonds require a very precise fit of
the drug to its receptor if an interaction is to occur

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The nature of drugs…

iv. Drug Shape

 The shape of a drug molecule must be such as to permit
binding to its receptor site via the bonds
• Optimally, the drug’s shape is complementary to that of
the receptor site in the same way that a key is
complementary to a lock
 The phenomenon of chirality (stereoisomerism) is so
common in biology that more than half of all useful drugs
are chiral molecules; that is, they can exist as
enantiomeric pairs

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The nature of drugs…

 Drug Shape…
 Drugs with 2 asymmetric centers have 4 diastereomers,
eg, ephedrine, a sympathomimetic drug
• In most cases, one of these enantiomers is much
more potent than its mirror image enantiomer,
reflecting a better fit to the receptor molecule
• The more active enantiomer at one type of receptor
site may not be more active at another receptor type,
eg, a type that may be responsible for some other
effect

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The nature of drugs…

 Drug Shape…
 Because enzymes are usually stereoselective, one drug
enantiomer is often more susceptible than the other to drug
metabolizing enzymes
• As a result, the duration of action of one enantiomer may
be quite different from that of the other

 Similarly, drug transporters may be stereoselective

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 Fig. Major areas of study in pharmacology
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 Fig. Relationship b/n PK& PD
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PROPERTIES OF IDEAL DRUG
• Effectiveness (Efficacy)
• Safety
• Selectivity
• Reversibility
• Predictability
• Ease Of Administration
• Lack Of Drug Interactions
• Low Cost
• Chemical Stability
• Simple Name

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The History of Pharmacology
• Prehistoric people undoubtedly recognized the beneficial or
toxic effects of many plant and animal materials

• records from China and Egypt list remedies of many types,

including a few still recognized as useful drugs today

• Around the end of the 17th century, reliance on observation and

experimentation began to replace theorizing in medicine

• Thus, materia medica—the science of drug preparation and the

medical use of drugs—began to develop as the precursor to
pharmacology
 History Cont…
• In the late 18th and early 19th centuries, François Magendie, and
later his student Claude Bernard, began to develop the methods of
experimental animal physiology and pharmacology
• controlled clinical trial, were reintroduced into medicine—only
about 50 years ago—did it become possible to accurately evaluate
therapeutic claims
• introduced, information accumulated about drug action and the
biologic substrate of that action, the drug receptor
• Pharmacogenomics—the relation of the individual's genetic
makeup to his or her response to specific drugs—is close to
becoming a practical area of therapy
MEDICINE IN ANCIENT EGYPT

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 EARLY
MESOPOTAMIAN
CULTURE

PRIMITIVE AMERICAN
INDIAN CULTURES

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HIPPOCRATES: MEDICINE BECAME A SCIENCE

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Drug Nomenclature

 Several names refer to the same drug, which can be a

source of confusion for students and practitioners
alike
a) Chemical name
• It is based on a drug's chemical & molecular
constituents & structure
• They are precise but complex & cumbersome &
therefore are seldom used in medical practice

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Drug Nomenclature …
b) Generic Name (Nonproprietary, Approved)
 It is assigned by the manufacturer after approval by the
regulatory body in the country of origin
• E.g., United States Adopted Names Council
 Each drug has only one generic name, which bears some
common feature of other drugs in the same class (e.g., the
ending -artan for most members of the angiotensin receptor
type 1 antagonists)
 Once assigned & approved, the generic name is in the public
domain and is commonly used

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Drug Nomenclature …

c) Trade, Brand, or Proprietary Name

 It is assigned by the manufacturer
 It is copyrighted & therefore can be used
commercially only by the originating
pharmaceutical company

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Drug Nomenclature …

 Clinical Connection:
 Drugs can have many different names
 For example
• A prototypical CCB of the dihydropyridine class has
the chemical name 3,5-dimethyl 2,6-dimethyl-4-(2-
nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• The generic name nifedipine, &
• Available under several trade names including
Adalat, Nifedical, Procardia, nifedipine denk,

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