1. PHARMACOLGY I
LECTURE 1
MUTUA W. MUTHEU

2. INTRODUCTION

3. HISTORICAL BACKGROUND
 Recent branch of medical science ~ 100 y old
 World’s oldest pharmacological or therapeutic writing come from China and India
 Around the end of the 17th century, reliance on observation and experimentation began
to replace theorizing in physiology and clinical medicine
 In the late 18th and early 19th centuries, François Magendie and his student Claude
Bernard began to develop the methods of experimental physiology and pharmacology.
 Advances in chemistry and the further development of physiology in the 18th, 19th, and
early 20th centuries laid the foundation needed for understanding how drugs work at the
organ and tissue levels.

4. DEFINITIONS
 Pharmacology can be defined as the study of the effects of drugs on the function of
living systems.
 Drug - a chemical substance of known structure, other than a nutrient or an essential
dietary ingredient, which, when administered to a living organism, produces a
biological effect.
 Medicine - chemical preparation, which usually, but not necessarily, contains one or
more drugs, administered with the intention of producing a therapeutic effect.
 Toxins are usually defined as poisons of biologic origin, ie, synthesized by plants or
animals, in contrast to inorganic poisons such as lead and arsenic.
 Poisons are drugs that have almost exclusively harmful effects.

5. Bioavailability
The fraction of an administered dose of drug that reaches the blood stream.
What determines bioavailability?
• Physical properties of the drug (hydrophobicity, pKa, solubility)
• The drug formulation (immediate release, delayed release, etc.)
• If the drug is administered in a fed or fasted state
• Gastric emptying rate
• Circadian differences
• Interactions with other drugs
• Age
• Diet
• Gender
• Disease state

6. Half-life:
Plasma half-life: Time it takes for plasma concentration of a drug to drop
to 50% of initial level.
Whole body half-life: Time it takes to eliminate half of the body content
of a drug.
Factors affecting half-life
• age
• renal excretion
• liver metabolism
• protein binding

7. DRUG EFFECTIVENESS
• Dose-response (DR) curve
• Depicts the relation between drug dose
and magnitude of drug effect
• Drugs can have more than one effect
• Drugs vary in effectiveness
• Different sites of action
• Different affinities for receptors
• The effectiveness of a drug is considered
relative to its safety (therapeutic index)

8. ED50 = effective dose in 50% of population
100
50
0
DRUG DOSE
0 X
ED50
% subjects

9. Therapeutic Index
• Effective dose (ED50) = dose at which 50% population
shows response
• Lethal dose (LD50) =dose at which 50% population dies
• TI = LD50/ED50, an indication of safety of a drug (higher is
better)
ED50 LD50

10. Potency
• Relative strength of response for a given dose
– Effective concentration (EC50) is the concentration of an agonist
needed to elicit half of the maximum biological response of the
agonist
– The potency of an agonist is inversely related to its EC50 value
• D-R curve shifts left with greater potency

11. Efficacy
• Maximum possible effect
relative to other agents
• Indicated by peak of D-R
curve
• Full agonist = 100%
efficacy
• Partial agonist = 50%
efficacy
• Antagonist = 0%
efficacy
• Inverse agonist = -100%
efficacy

12. Tolerance
(desensitization)
• Decreased response to same
dose with repeated
(constant) exposure
• or more drug needed to
achieve same effect
• Right-ward shift of D-R
curve
• Sometimes occurs in an
acute dose (e.g. alcohol)
• Can develop across drugs
(cross-tolerance)
• Caused by compensatory
mechanisms that oppose the
effects of the drug

13. Sensitization
• Increased response to same
dose with repeated (binge-
like) exposure
• or less drug needed to
achieve same effect
• Left-ward shift in D-R curve
• Sometimes occurs in an
acute dose (e.g.
amphetamine)
• Can develop across drugs
(cross-sensitization)
It is possible to develop tolerance to some side effects AND
sensitization to other side effects of the same drug

14. BRANCHES/DIVISIONS OF PHARMACOLOGY

15.  Pharmacokinetics
The process by which a drug is absorbed, distributed, metabolized and
eliminated by the body
 Pharmacodynamics
The interactions of a drug and the receptors responsible for its action in
the body

17.  Pharmacogenomic
The relation of the individual’s genetic makeup to his or her response to specific
drugs—is becoming an important part of therapeutics
 Pharmacoepidemiology
This is the study of drug effects at the population level
 Pharmacoeconomics
Branch of health economics aims to quantify in economic terms the cost and benefit
of drugs used therapeutically
 Toxicology
The branch of pharmacology that deals with the undesirable effects of chemicals on
living systems, from individual cells to humans to complex ecosystems

18.  Pharmcotherapeutics
Application of pharmacological information together with knowledge of the disease
for its prevention or cure i.e. use of drugs in treatment of disease
 Clinical pharmacology
Scientific study of drugs in man
 Chemotherapy
Treatment of systemic infection/malignancy with specific drugs that have toxicity for
infecting organism with no/minimal effects on host cells

19.  Pharmacy
-Preparation, compounding and dispensing the drugs
Collection, identification, purification, isolation, synthesis, standardization and quality
control of medicinal substances
-Large scale manufacture of drugs is Pharmaceutics
 Pharmaceutical chemistry
Deals with chemical structure and chemical reactions of active principles of drugs
 Posology
Branch of medical science which deals with dose or quantity which can be
administered to a patient to get a desirable pharmacological action

20.  Pharmacognosy (Materia Medica)
Deals with source, identification, physical and chemical characteristic of drugs
obtained from plants

21. GENERAL PRINCIPLES OF PHARMACOLOGY
Nature of drugs
 In most cases, the drug molecule interacts as an agonist (activator) or antagonist
(inhibitor) with a specific target molecule that plays a regulatory role in the biologic
system.
 This target molecule is called a receptor.
 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)

22.  To interact chemically with its receptor, a drug molecule must have the
appropriate size, electrical charge, shape, and atomic composition.
 Drugs may be ;
solid at room temperature (eg, aspirin, atropine)
liquid (eg, nicotine, ethanol)
gaseous (eg, nitrous oxide).
The Physical Nature of Drugs

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

24. Drug Reactivity & Drug-Receptor Bonds
Drugs interact with receptors by means of chemical forces or bonds
These are of three major types:
Covalent
electrostatic
hydrophobic

25. Covalent Bonds
 Covalent bonds are very strong and in many cases not reversible under biologic
conditions.
 The covalent bond formed between the acetyl group of acetylsalicylic acid (aspirin)
and cyclooxygenase, its enzyme target in platelets, is not readily broken.
 The platelet aggregation–blocking effect of aspirin lasts long after free
acetylsalicylic acid has disappeared from the bloodstream (about 15 minutes) and is
reversed only by the synthesis of new enzyme in new platelets, a process that takes
several days.

28. Electrostatic bonding
 Electrostatic bonding is much more common than covalent
bonding in drug-receptor interactions
 Electrostatic bonds vary from relatively strong linkages between
permanently charged ionic molecules to weaker hydrogen bonds
and very weak induced dipole interactions such as van der Waals
forces and similar phenomena.

29.  Hydrophobic bonds are usually quite weak and are probably
important in the interactions of highly lipid-soluble drugs
Hydrophobic bonds

30. Drug Shape
 The shape of a drug molecule must be such as to permit binding to its receptor
site via the bonds just described
 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
 For example, carvedilol, a drug that interacts with adrenoceptors, has a single
chiral center and thus two enantiomers
 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.

31. Rational Drug Design
 Computer programs are now available that can iteratively
optimize drug structures to fit known receptors.
 As more becomes known about receptor structure, rational drug
design will become more common.

32. DRUG NOMENCLATURE

33. Drug has 3 names
1) Chemical Name
 According to molecular structure of drug
 Long, complicated, inconvenient and not used clinically
e.g. acetylsalicylic acid of aspirin

34. 2)Generic name (non proprietary)
 Official name or approved name
 Simple, accepted world wide and used in text books, pharmacopoeias, medical
journals and other reference books
E.g. ampicillin, aspirin

35. 3) Proprietary Name
 Brand name chosen by pharmaceutical firm
 Same drug may have different names
e.g. paracetamol (Acenol, Aminol, Atamol etc)

36. Slow Absorption
• Orally (swallowed)
•through Mucus Membranes
–Oral Mucosa (e.g. sublingual)
–Nasal Mucosa (e.g. insufflated)
•Topical/Transdermal (through skin)
•Rectally (suppository)
ROUTES OF ADMINSTRATION

37. Faster Absorption
• Parenterally (injection)
-Intravenous (IV)
-Intramuscular (IM)
-Subcutaneous (SC)
-Intraperitoneal (IP)
• Inhaled (through lungs)
•Directly into brain
–Intracerebral (into brain tissue)
–Intracerebroventricular (into brain ventricles)
General Principle: The faster the absorption, the quicker the
onset, the higher the addictiveness, but the shorter the duration

38. ANY QUESTIONS?

39. END