PHARMACOLOGY

The Study Of Drug

Contents
• Pharmacology Overview
• Pharmacokinetics
• Pharmacodynamics
• Routes of Administration
• Enteral
• Parenteral
• Drug Dosage Forms/Drug
Delivery System
What is Pharmacology?

Pharmacology
(Pharmakon - a drug or poison, logos - word or discourse)
is the study of the therapeutic value and/or potential toxicity of
chemical agents on biological systems.
What is a Drug?

Drug a natural product, chemical substance or pharmaceutical preparation intended for

administration to a human or animal for the purpose of diagnosing or treating a disease.

A chemical agent capable of producing biological response within the body.

After a drug is administered it is called a medication.

All medicines are drug but not all drugs are medicine.
Why Study Pharmacology?
Pharmacology is crucial for:

• Understanding why individuals differ in the way they respond to certain drugs, and why some
others cause addiction

• Discovering new medicines to help fight diseases

• Improving the effectiveness of medicines

• Reducing unwanted side effects of medicines

Essentials of Pharmacology

• Pharmacodynamics is the study of the

molecular, biochemical, and physiological
effects of drugs on cellular systems and their
mechanisms of action.

• Pharmacokinetics deals with the absorption,

distribution, metabolism and excretion of drugs.
(ADME)
Pharmacokinetics
• Absorption is the process by which drugs enter the
body.

• Distribution is the process by which drugs move

around the body.

• Metabolism is the process by which drugs are

chemically altered to make them water-soluble for
excretion in urine or faeces.

• Excretion is the process by which drugs leave the

body.
 Drug Absorption
Absorption is the process by which drugs enter the body.
Unless a drug acts topically, it must first enter
the blood stream.

When a drug is administered intravenously,

absorption is not required because the drug is
transferred from the administration device
directly into the bloodstream.

A drug that is a weak acid will be absorbed

primarily in the acidic environment; whereas, a
drug that is a weak base will be absorbed in the
alkaline environment i.e. small intestines.
Hydrophilic & Lipophilic Drugs

Plasma
Membrane
 Drug Absorption
Basic
Acidic H+ Environment
-OH • Drugs that are un-ionized will be
Environment better able to cross a biologic
barrier and enter the
Acidic A- Acidic A- bloodstream (e.g. be absorbed)
Drug Drug compared to drugs that are
ionized.

• Thus, A drug that is a weak acid

will be best absorbed in an
HA A-
acidic environment (because it
(Protonated/ (Remain gains a proton and becomes un-
un-ionized) Ionized) ionized).
First pass metabolism & Bioavailability

Enzymes in liver metabolize a portion of the

drug dose before it reaches to the systemic
circulation. This is called First-pass effect.

The extent to which a drug reaches its site of

action is known as its Bioavailability.
Factors Affecting Bioavailability
 Physical properties of the drug (hydrophobicity,
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
Bioavailability According to Routes of Administration
 Drug Absorption through various Dosage forms

• Parenterally (injection) Fastest

• Inhaled (through lungs)
• Oral disintegration, Buccal
tablets
• Liquids, Elixirs and Syrups
• Suspension & Solutions
• Powders
• Capsules
• Tablets
• Coated Tablets
• Enteric coated tablets
• Topical Slowest
• Rectally (suppository)
Absorption
Distribution
 Distribution is the process by which drugs move around
the body.
 After entering the blood, drug molecules enter the
tissues, reach cell membranes and enter cells.

Volume of distribution??
Distribution
Metabolism
 Metabolism is the process by which drugs are
chemically altered to make them water-soluble
for excretion in urine or faeces.

 Metabolism occurs chiefly in the liver, gut wall,

kidney and skin.
Pharmacokinetics
(What body does to the drug)
Pharmacodynamics
Pharmaco-dynamics is the study of the relationship of
drug concentration and the biologic effect. Most drugs
exert effects on several organs or tissues and have
unwanted as well as therapeutic effects.

Therapeutic effect are the intended effects of a drug – the

effects that will treat a disease or relieve its symptoms

Non-therapeutic effects are other effects that may or may

not related to a drug’s therapeutic effects and also called
as adverse effects.
 Pharmacodynamics
(What drug does to the body)

Drug

Activated
Receptor

Biological
Response
 Definitions
Potency: The relative dose or concentration of a drug
required to produce a specific effect.

The Receptor is a chemically reactive area of the cell

on which the drug acts.

A drug, which is able to fit into a particular receptor, is

said to have Affinity for that receptor.

If a drug acts on a particular receptor and as a result Affinity

elicits a response, it is said to have Intrinsic activity.
Agonist & Antagonist
The drug having affinity as well as intrinsic activity
is called agonist (i.e. the drug combines with a
particular receptor and produces responses).

The drug having affinity, but no intrinsic activity is

called antagonist (i.e. the receptor antagonist
binds to the particular receptors but does not elicit
biological response. This binding of antagonist
prevents agonist to bind and activate the
receptors).
Definitions

Dose: The amount of drug administered

at one time.

Dosage: The frequency and amount of

drug administration.

Drug delivery system is concerned with

development of drug forms that delivers
precise and reliable doses.
Half-Life of a Drug

The half-life (t ½) is the time it

takes for the plasma
concentration or the amount of
drug in the body to be reduced
by 50%.
Efficacy of a Drug

The degree to which a drug

produces a therapeutic effect.
Tolerability
 The failure of responsiveness to the
usual dose of drug.

 Tolerance of a medicine may be

considered as the ability of the body
to endure a certain dose of a
medicine.

 In contrast, drug tolerance refers to a

decreasing response to repeated
constant doses of a medicine.
Therapeutic Window
For every drug, there exists;

 Some concentration which is

just barely effective (the
Effective Concentration) Effective Therapeutic Toxic
 Some concentration which is Concentration Window Concentration
just barely toxic (the Toxic
Concentration).

Between them is the therapeutic

window where most safe and
effective treatment will occur.
Therapeutic Index

 A ratio that compares the blood

concentration at which a drug
becomes toxic and the
concentration at which the drug is
effective is Therapeutic Index.

 The larger the therapeutic index

(TI), the safer the drug is.

 Example: Penicillin has large

Therapeutic Index while Digoxin
has much less.
Therapeutic Index

Therapeutic index is the lethal dose of a

drug for 50% of the population (LD50)
divided by the minimum effective dose for
50% of the population (ED50).

THERAPEUTIC INDEX = LD 50
ED 50

ED50 LD50
Therapeutic Index
For example, if the LD50 is 200 and the ED50 is 20 mg, the TI would be 10.
A clinician would consider a drug safer if it had a TI of 10 than if it had a TI of 3.
Cmax, Tmax, AUC
• Cmax is maximum/peak
plasma drug concentration.

• Tmax is time required to

achieve a maximal
concentration.

• AUC total area under the

plasma drug concentration-
time curve.
Side Effects & Adverse Effects
Side Effect
Unintended effect occurring at normal dose related to
the pharmacological properties.

Adverse Event
Any untoward medical occurrence which does not
necessarily have a causal relationship with the
treatment.

Adverse Reaction
All noxious and unintended responses to a medicinal
product related to any dose should be considered
adverse drug reactions.
Hypersensitivity & Idiosyncrasy

If a drug produces its usual effect at

unexpectedly low dosage, the condition is
called Hypersensitivity.

Idiosyncrasy is an apparently abnormal

reaction to a drug and for which there is no
explanation.
Routes of Administration
Enteral Route

Enteral route is through the alimentary

canal. It might be:

• Oral- By mouth

• Sublingual- Sublingual route involves

tablets placed under the tongue

• Rectal
Parenteral Route
Parenteral route includes:

• Intra venous- Into the veins.

• Intramuscular- Into the large skeletal
muscles
• Intraperitoneal- Into the peritoneal cavity
• Subcutaneous- Injected just below the
skin
• Intradermal- Into the skin, so it forms a
small bulge
• Intrathecal- Into the spinal cord
• Epidural- Near the spinal cord such that
it affects the local nerves
• Intraosseous- Into the bone marrow
Routes of Administration
Oral Drug Administration
1. Advantages:
1. Convenient
2. Safe
3. Economical
1. Disadvantages:
1. Non uniform absorption
2. Frequent gastric problems
3. Not good for all drugs (Proteins, food interaction)
4. Patient must be conscious & cooperative
Parenteral Drug Administration
Intravenous Drug Administration (IV)
Advantages:
100 % Bioavailability
 Large volume can be administered
 Useful for drugs that cause Irritation

Disadvantages:
 Can not compensate for accidental overdose
 Rapid injection may cause toxic effects
Parenteral Drug Administration
Intramuscular Drug Administration (IM)

Advantages:
 Drug suspension or oily drug may be administered
 Irritating drugs may be given

Disadvantages:
 Painful
Parenteral Drug Administration
Subcutaneous Drug Administration (s/c)
 Definition (under the skin, deeper between skin and muscle tissue)
 Suitable for some implantation of solid pellets

 Pain & infection from Irritating substances

Intra Dermal Drug Administration

 Definition (very shallow, just within the skin)
 Used for Allergy test
 Painful
Other Routes of Administration

Intra Articular Drug Administration

 Definition (are injections that are given within the joint)
 Used for Arthritis Treatment

Intra Cardiac Drug Administration

 Definition (are injections that are given directly into the heart
muscles).

 Emergency use only

Other Routes of Administration

Inhalational Route (Bronchodilators for Asthma)

Transdermal Route (Nitroglycerine Patch for Angina)

Topical Route (Antibiotic Creams)

Drug Dosage Forms
Drug Delivery System
Form Definition

1.Tablet Solid dosage form of a compressed drug and diluent (inactive

component)
Tablet with a coating that protects the drug from destruction by gastric
2. Enteric coated acids, used to delay absorption until the drug reached to small
tablet intestine
3. Capsule Dosage form in which drug is enclosed in gelatin shell
4.Suspension Finely divided drug distributed but not dissolved in a water. Must be
shaken to assure uniformity

5. Elixir Solution in a sweetened vehicle containing alcohol

Drug Delivery System

Form Definition

6. Syrup Viscous sugar solution

7.Ointment Drug in a semi-solid base, for topical administration
8. Cream Drug contained in semi-solid base less viscous than ointment
(water/oil w/v)

9. Lotion Suspension of solid drugs in water base vehicle

10.Powder Drug mixture containing inert base (talcum)

11.Aerosols Soluble drug particles suspended in air

12.Suppositories Solid base that release a drug as they soften or meld in a body
orifice
 The Four Rs of Pharmacology

Right
Dose Right
Goal Patient

Right Right
Time Drug