Prelim Grading Period

Unit 1: General principles of

Pharmacology
a. Introduction
b. Terminologies
c. Nature of drugs
d. Physical and Chemical Properties of
drug
e. Dosage Form and Dosage regimen
f. Various Drug Preparation

Prelim Grading Period

Unit 2: Principles of Pharmacokinetics
a. Absorption
-mechanism in drug absorption
- factors that affects drug
Absorption
- Routes of drug absorption
- Bioavailability and its factors

Introduction to
Pharmacology
Zyra Z. Del Rosario RPh.

PHARMACOLOGY
It is the study of drugs and their
effects on life processes

PHARMACOLOGY
It is the study of chemicalsdrugs
on living tissues and how those
chemicals help diagnose, treat,
cure, and prevent disease or
correct the pathophysiology of living
tissues
Derived: pharmakon, the Greek word
for drugs, and logos, the Greek word
for science.

PHARMACOLOGY
The GOAL is to understand the
mechanisms by which drugs interact
with biological systems to enable the
rational use of effective agents in
the diagnosis and treatment of
disease.

HISTORY OF
PHARMACOLOGY

Herbal medicine
Belief in the curative powers of
plants and certain substances rested
exclusively upon traditional
knowledge

Claudius
Galen

First attempted to
consider the
theoretical
background of
pharmacology.
Both theory and
practical experience
were to contribute
equally to the rational
use of medicines
through interpretation
of observed and

Paracelsus

Theophrastus von
Hohenheim
Gives importance on
knowledge of the
active ingredient(s)
in prescribed
remedies, while
rejecting the irrational
concoctions and
mixtures of medieval
medicine

Paracelsus

He prescribed chemically
defined substances with
such success that
professional enemies
had him prosecuted as a
poisoner.
Poisons are drugs that
have almost exclusively
harmful effect
The dose makes the
poison

Johann Jakob
Wepfer

first to verify by
animal
experimentation
assertions about
pharmacological or
toxicological actions.
Toxicology it is a
branch of
pharmacology that
deals with the
undesirable effects of
chemicals in living

Rudolf
Buchheim

founded the first

institute of
pharmacology at the
University of Dorpat
(Tartu, Estonia)
He strove to explain
the chemical
properties of drugs.


founded the first
Oswald
journal of
Schmiedeberg
pharmacology,

MAJOR AREAS OF STUDY

IN PHARMACOLOGY

DRUG

DRUG
An agent intended for use in the:
Diagnosis
Mitigation
Treatment
Cure
Prevention of disease
in humans and animals

SOURCES OF DRUG

PLANTS

ANIMALS
Humans and animals contains
hormones
ESTROGEN

urine

INSULIN
level

regulate blood sugar

SYNTHETIC/CHEMICAL DERIVATIVES
Synthetic drug is produced using
chemical synthesis, which rearranges
chemical derivatives to form a new
compound.
Ex: Sulfonamides - used to treat
many infections including bronchitis,
pneumonia, and meningitis

Drug development

Drug development

Synthesis of novel
chemical compounds

Synthesis the
production of a
substance by
combining substances
through a chemical
process

Pre-Clinical
Testing

Yields information on
the biological effects
of new substances.
Effects on body
functions
Mechanism of action
Toxicity

PHASE 1
Clinical Testing

Studies on healthy
subjects
Seeks to determine
whether effects
observed in animal
experiments also
occur in humans.
Dose-response
relationships are
determined

PHASE 2
Clinical Testing

Potential drugs are

first tested on
selected patients for
therapeutic efficacy in
those disease states
for which they are
intended.

 Involving a larger
PHASE 3
group of patients
Clinical Testing
New drug will be
compared with
standard treatments
in terms of
therapeutic outcome

Approval of a
new drug

The decision is made by a

national regulatory body
(FDA)
Manufacturers are
required to submit their
applications
Applicants must
document by means of
appropriate test data
Following approval, the
new drug may be
marketed under a trade
name

Phase 4 Clinical Trial

Regulatory surveillance continues in
the form of post-licensing studies
Only on the basis of long-term
experience will the risk: benefit ratio
be properly assessed and, thus, the
therapeutic value of the new drug be
determined.

Definition
Trade name/Brand
name

This restricts the use

of this name to that
particular company

Generic name
is the universally
accepted name and
considered the official
proprietary name for
the drug
The pharmaceutical
company that patents
a drug has exclusive
rights to sell it until
the patent expires

DRUG DOSAGE AND

TERMINOLOGY

NATURE OF DRUGS

Nature of drugs

Agonist-Antagonist
Types of binding process
Enantioselectivity of Drug Action
Drug size

Drug
Any substance that brings about a
change in biological function through
its chemical action.
Agonist
Antagonist

Receptor
The component of a cell or organism
that interacts with a drug and
initiates the chain events leading to
the drugs observes effects.

Receptor
1. Receptors largely determine the
quantitative relations between dose or
concentration of drug and
pharmacologic effects.
2. Receptors are responsible for selectivity of
drug action.
3. Receptors mediate the actions of
pharmacologic agonist and antagonist

AGONIST
affinity (binding avidity) for its receptor
generate a stimulus that elicits a change in cell
function
intrinsic activity.

agonists attain a maximal effect even when

they occupy only a small fraction of receptors
(FULL AGONIST)
agonist that posses equal affinity for the
receptor but lower activating capacity
(PARTIAL AGONIST)

The potency of an agonist can be expressed in terms of the

concentration (EC50) at which the effect reaches one-half
of its respective maximum.

ANTAGONIST
They bind to receptors but do not
activate them
It reduces the effects of agonist
(other drugs) that activate receptors
Competitive Antagonist
Non-competitive Antagonist

Competitive Antagonist

In increasing amount of CA , it
progressively inhibit the agonist response
( CA prevent response completely)
High concentration of agonist can
surmount
The effect of a given conc. of antagonist
The concentration-response curve of the
agonist is shifted to higher concentrations
(rightward shift).

Non-competitive Antagonist
Once NCA is bound by such a drug,
agonist cannot surmount the
inhibitory effect irrespective of their
concentration.
NCA bind to a receptor in an
irreversible fashion.

Types of Binding Process

Drugs interact with receptors by
means of chemical forces or bonds
Covalent bond
Electrostatic bond
Hydrophobic bond

Covalent bond
The covalent bond is firm, that is,
not reversible.
The bond, and possibly the effect,
persist for a long time after intake
of a drug has been discontinued,
making therapy difficult to control.
Ex: Aspirin and Cyclooxygenase
(enzyme target in platelets)

Electrostatic bond
The bond is reversible and typical of
most drug-receptor interactions.
Electrostatic bonds are weaker that
covalent bonds,

Hydrophobic bond
Important in the interactions of
highly-lipid soluble drug with the
lipids of cell membranes

DRUG SIZE & SHAPE

DRUG Size
To have a good fit to only one type
of receptor, a drug molecule must be
sufficiently unique in shape, charge
and other properties, to prevent its
binding from other receptors.
Drugs ranges from 100-1000 MW
The drug must be able to move
inside the body

Identification

1.Deals with the absorption,

distribution, and elimination of
drugs
2.Concerns with the action of the
chemical on the organism
3.It is a branch of pharmacology
that deals with the undesirable
effects of chemicals in living
system.

4. The amount administered to

protect the patient from
contracting the illness

5. Component of a cell or
organism that interacts with a
drug that leads to drugs
observable effects

6. The type of bond that persist

for a long time resulting to
longer effect of drugs
7. It is defined as the ration
between a drugs median
toxic dose and its median
effective dose.

Identify the phase in

drug development:
8. New drug will be
compared with standard
treatments
9. Post-marketing
surveillance
10. Studies on healthy
subjects

ROUTE
SITE
11._________

MOUTH

SUBLINGUAL
_________

12.

INTRAURAL
________

13.

TRUE OR FALSE
14. The lower the THERAPEUTIC INDEX
the GREATER margin of safety of the
drug.
15. ANTAGONIST generates a stimulus
that elicits a change in cell function

Quiz
IDENTIFY WHAT TYPE OF DOSAGE
FORM:

1. Type of tablet that releases

carbon dioxide with the
presence of water. It is
intended for very rapid tablet
dispersion and dissolution.

IDENTIFY WHAT TYPE OF DOSAGE

FORM:

2. It is placed on the skin

to deliver a specific dose
of medication through
the skin and into the
bloodstream

IDENTIFY WHAT TYPE OF DOSAGE

FORM:

3. Type of dosage form that

consists of acetic acid and
salicylic acid in an acetone
used in Treatment of warts.
4. Dosage form that is
intended for insertion in the

IDENTIFY WHAT TYPE OF DOSAGE

FORM:

5. They may be alcoholic or

oily solutions or emulsions.
Most are massaged into the
skin (e.g. counter-irritant).

IDENTIFY WHAT TYPE OF DOSAGE FORM:

6. A tablet form intended to be

placed in the empty socket
following a tooth extraction, for
preventing the local
multiplication of pathogenic
bacteria associated with tooth
extractions.

IDENTIFY WHAT TYPE OF DOSAGE FORM:

7. Type of capsule which are

normally used for dry,
powdered ingredients
8. Type of tablet designed for
administration to children e.g.
vitamin products.

IDENTIFY WHAT TYPE OF DOSAGE FORM:

9. Tablet that is placed between

the gum and the cheek
10. A device used to administer
medication to people in forms of
a liquid mist to the airways

IDENTIFY WHAT TYPE OF DOSAGE FORM:

11. A device used to introduce a

stream of water into the body cavity
for medical or hygienic reasons
12. A device used to contain
solutions, suspensions or emulsion
of drugs in a mixture of inert
propellants held under pressure in
an aerosol dispenser.

IDENTIFY WHAT TYPE OF DOSAGE

FORM:

13. It is used to medicate the

mouth and throat for the slow
administration of indigestion
or cough remedies.
14. It is a concentrated aqueous
solution of a sugar used for
masking disagreeable tastes.

IDENTIFY WHAT TYPE OF DOSAGE

FORM:

15. A type of enema

used as a bowel
stimulant to treat
constipation.

UNIT 1

INTRODUCTION TO
BIOPHARMACEUTICS AND
PHARMACOKINETICS

Areas of Study
Pharmacokinetics
Pharmacodynamics
Biopharmaceutics

PHARMACOKINETICS
Deals with the changes of drug
concentration in the drug product and
changes of concentration of a drug
and/ or its metabolites in the body
following administration
Explains the time course of the drug in
the body and the quantifying of the
drug concentration pattern

PHARMACOKINETICS
It explains what happens to the drug
prescribed and administered to a
patient
(Body to the Drug)

PHARMACOKINETICS
What does the body
do to the drug?

A-D-M-E

PHARMACODYNAMICS
Deals with the drugs action and
effect within the body
What does the drug do to the
body after administration?

BIOPHARMACEUTICS
Deals with the physical and
chemical properties of the drug
substance, the dosage form, and
the body and the biological
effectiveness of a drug and/ or
drug product upon administration

THE

LADMER SYSTEM
DRUG ACTIVITY WITHIN THE BODY

*****

LIBERATION, DISINTEGRATION
DISSOLUTION

Liberation
The liberation of the drug from the
dosage form entails the release and
dissolution of the drug.

Liberation
Primary concern
The dosage form will be able to
release the active pharmaceutical
ingredient
Secondary concern
To be able to have the drug dissolve
in the GIT fluid and be in solution at
the site of absorption

BETWEEN SOLUTION AND TABLET,

WHICH OF THE TWO ABSORBS FASTER
BY THE BODY?

Drug in drug
product
Disintegration/ Release

Solid drug
particles

Dissolution (aqueous medium

Drug in
solution
Absorption

Drug in
body

BIOAVAILABILITY

COMPLETE DISINTEGRATION

State in which any residue of

the tablet, except fragments
of insoluble coating,
remaining on the screen of
the test apparatus in the soft
mass have no palpably firm
core (USP, 27th ed, 2004)

DISSOLUTION
Process by which a solid
drug substance becomes
dissolved in a solvent

The

more soluble and

permeable the drug, the
faster will be the
absorption thus greater
bioavailability and hence,
faster response from the
body

PHYSICAL AND CHEMICAL

PROPERTIES OF DRUG THAT AFFECTS
SOLUBILITY

Physical Forms of Solid Compounds

Crystalline Form

Amorphous Form
(non crystalline
form)

Molecules packed
together in a
regularly, orderly
repeating pattern

Molecules in random
arrangement

Thermodynamically
stable

More stable

Less stable
(metastable)
Prone to
crystallization and
degradation

Free energy

Lower free energy

Higher free energy

Solubility (Aqueous)

Lower solubility

Higher solubility

Stability

More stable

Less stable

 In the manufacture of drugs,

although the AMORPHOUS form in
MORE SOLUBLE than the
CRYSTALLINE, it cannot be used
often because of its STABLITY issues.
The amorphous form usually
converts to one or more crystalline
forms

Polymorphism
The ability of a drug substance to
exist as two or more crystalline
forms that have different
arrangement of the molecules.
Most stable form slower
dissolution rate
Least stable form rapid
dissolution rate

 The stable polymorph is the crystal

species with the greatest chemical
stability, highest melting point but
with the lowest solubility
The metastable polymorph has the
lowest melting point but has the
highest solubility.

Dosage Form
Increased or Decreased Dissolution
Rate??

Particle Size
particle size : surface area :
dissolution rate
Increased in dissolution rate = Faster
absorption in the GIT = better
bioavailability
Bioavailability the degree and rate at
which a substance (drug) is absorbed
into a living system or made available
in the circulation

Enantioselectivity of Drug Action

Chirality
Amoleculeis consideredchiralif
there exists another molecule that is
of identical composition, but which is
arranged in a non-superposable
mirror image.

Enantioselectivity of Drug Action

Many drugs are racemates
A racemate consists of a molecule
and its corresponding mirror image
which, like the left and right hand,
cannot be superimposed.
Chiral(handed) pairs of molecules
are referred to as enantiomers.

 Enantiomers rotate the wave plane

of linearly polarized light in opposite
directions; hence they are refered to
as dextro- or levo-rotatory,
designated by the prefixes d or (+)
and l or (-), respectively

 Dexetimide displays an affinity at

the muscarinicrinic ACh receptors
almost 10000 times that of
levetimide

Enantioselectivity of Drug Action

For example, the (S)(+) enantiomer of
methacholine, a parasympathomimetic drug, is
over 250 times more potent than the (R)()
enantiomer.
If one imagines the receptor site to be like a
glove into which the drug molecule must fit to
bring about its effect, it is clear why a "leftoriented" drug will be more effective in binding
to a left-hand receptor than will its "rightoriented" enantiomer.

 The mode of attachment at the

receptor also determines whether an
effect is elicited and whether or not a
substance has intrinsic activity, i.e.,
acts as an agonist or antagonist. For
instance, (-) dobutamine is an
agonist at adrenoceptors
whereas the (+)-enantiomer is
an antagonist.

Conclusion: The enantiomers of a

racemate can differ sufficiently in
their pharmacodynamic and
pharmacokinetic properties to
constitute two distinct drugs.

ADME PROCESS

ADME Process
Blood concentration of a drug are the
result of four simultaneously
occurring processes:
Absorption
Distribution
Metabolism
Excretion
Besides the ADME process, an important
factor of drug concentration is how
drugs move through biological
membranes by diffusion.

Absorption
Once a drug is released from its dosage
formulation, the process that transfers it into
the blood is called absorption.
One of the primary factors affecting oral drug
absorption is the gastric emptying time.
This the time that the drug remains in the stomach
before it is emptied into the small intestine
Most absorption occurs in the small intestine.
Some factors increase the gastric emptying time,
but most slow it.
If a drug remains in the stomach too long, it can be
degraded or destroyed, and its effect decreased.

Absorption
Gastric emptying time can be
affected by:
Amount and type of food in the stomach
The presence of other drugs
The persons body position
The persons emotional state

Distribution
Blood carries the drug throughout
the body and to its sites of action.
Drugs are rapidly distributed to
organs having high blood flow rates
such as the heart, liver and kidneys.
Distribution to the muscle, fat, and
skin is slower because they have
lower blood flow rates.

Metabolism
Drug metabolism refers to the bodys
process of transforming drugs.
The transformed drug is called a
metabolite.
The primary site of drug metabolism is in
the liver.
When transformed in the liver a drug is
broken down into inactive or active
molecules. Inactive are excreted through
the kidneys and active produce effects and
excreted later.

Excretion
Most drugs are excreted in the urine
by the kidneys. The functional unit of
the kidney is the nephron.
Some oral drugs that are difficult to
break down can be excreted in the
feces (poop).
The job of the kidney is to filter the
blood and remove waste products.

ABSORPTION

ABSORPTION
The process of movement of
unchanged drug from the site of
administration to systemic
circulation.
Absorption can also be defined as the
process of movement of unchanged
drug from the site of administration
to the site of measurement. i.e.,
plasma

 For a drug to exert pharmacological

action it first has to be ABSORBED
from the site of administration.
For ORAL ROUTE
GASTROINTESTINAL TRACT (SITE)

Requirements for a successful

absorption
The drug should be released from the
formulation or dosage form
(LIBERATION)
The drug should be dissolved in the
GIT FLUID
The drug must be present as
aqueous solution in the absorption
site
The drug must be in non-ionized
form

FACTORS THAT AFFECT

ABSORPTION

 Pharmaceutical factors - physico-chemical

properties of the drug
Physiologic factors age, site of
absorption, circulation at the absorbing
surface, GIT content, GIT mobility, GIT pH,
transport mechanism at the site of
absorption, age
Pharmacologic factors interaction of
different drugs
Pathologic factors diseases that increases
or decreases drug absorption

PHYSIOLOGIC FACTORS

Transport Mechanism across

Biological Membrane
CELL MEMBRANE

GIT MOTILITY
TRANSIT TIME the time it takes
for indigested object to travel
through the entire gastrointestinal
pH
pH
tract. Surface Transit
Area

time

Buccal
cavity

(fasting)
7

Esophag
us

5-6

Stomach

0.1 sq. m.

0.5-3.5
hours

1.4-2.1

Duodenu
m

120 sq.m.

3-4 hours

6-6.5

Jejenum
Ileum

(fed
state)

3-7

4.4-6.6

5.2-6.2

6.8-8

6.8-8

GIT MOTILITY
INCREASE in GIT MOTILITY , will
result to LESSER time of drug
exposed in the GIT epitheliaabsorbing surface and LESSER
TRANSIT TIME Therefore LOWERING
the extent of absorption.
Long intestinal transit time is
desirable for the complete absorption
of drugs.

Gastric Emptying Rate

(GER)
Gastric emptying is the passage from
stomach to small intestine.
INCREASE in GER = FASTER
ABSORPTION of the drug to the
SMALL INTESTINE
DECREASE in GER = = SLOW
ABSORPTION of the drug to the
SMALL INTESTINE
It is faster in case of solution and
suspension than solid dosage form.

FACTORS THAT AFFECT GER

VOLUME OF
MEAL

indigested food = initially

rate then
GI

GI emptying
emptying rate

Liquids emptied rapidly than solid

Meal Type
Viscosity
Osmotic
pressure
DRUGS

Fats DECREASE emptying rate

Carbohydrates DECREASE emptying rate
viscosity =

emptying rate

osmotic pressure =

emptying rate

RATE: aniticholinergic (atrophine),

narcotics (morphine sulfate) , analgesics
(aspirin), ethanol, bile
salts, acidification
RATE: glycerol, Sodium bicarbonate

FACTORS THAT AFFECT GIT

MOTILITY

FACTORS THAT AFFECT GIT

MOTILITY
Anxiety INCREASES transit time
Depression DECREASES transit time
Anticholinergics, anti-histamine,
narcotics DECREASE motility of the
GIT.
Domperidone,Erythromycin,
metoclopramide INCREASE motility
of the GIT.

FOOD AND DRUG

INTERACTION

FOOD and DRUG

HIGH FAT DIET INCREASES the
absorption of LIPOPHILIC DRUGS ( fat
soluble vitamins, Vit A, D, E, K)
HIGH FAT DIET DECREASES the
absorption of some drugs
(Rapamycin, Sirolimus, Isoniazid,
Rifampicin

FOOD and DRUG

Tetracyline and Milk
The calcium in milk reacts with
tetracycline to form complex that
INHIBIT the absorption of tetracylcine.
COFFEE
In can interact with phenothiazines and
butyrophenones.
COFFEE can also ANTAGONIZE the effects
of tranquilizers

FOOD and DRUG

Spinach or broccoli
These vegetables are rich in VITAMIN
K. It interacts with WARFARIN (anticlotting drug)
Spinach and broccoli can COUNTERACT
the effect of WARFARIN.

FOOD and DRUG

If there is is an interaction between
the food and the drug, instruct the
patient to take the medication with
an empty stomach or 1 before
meals and 2 hours AFTER MEALS

DRUG AND DRUG

INTERACTION

DRUG and DRUG

INTERACTION
MULTIVITAMINS and DOXYCYCLINE
Multivitamins contains iron or calcium
forms a chelate that decreases the
bioavailability of both drugs.
SUCRALFATE (treatment of ulcer)
Reduces the absorption of digoxin,
ketoconazole, levothyroxine, phenytoin,
quinidine, ranitidine, tetracycline,
theophylline.

DRUG and DRUG

INTERACTION
Cholestyramine and Cholestipol
Interacts with warfarin, tetracycline,
penicillin G, phenobarbital, thyroid
drugs, estrogen, progesterone
It produces steatorrhea, resulting to
malabsorption.
ORLISTAT (XENICAL) for lipophilic
drugs, it can DECREASE the
bioavailability of the drug

DRUG and DRUG

INTERACTION
KAOLIN AND PECTIN it is an
adsorbent drug that can DECREASE the
availability of drug in the absorption site.
Psyllium (laxative) it can bind with
digoxin, nitrofurantoin and salicylates.
Attapulgite + Promazine
Charcoal + Promazine
Kaopectate + Lincomycin
Talc + Vitamin B12

BILE

BILE
It is a surface active agent that
facilitates the absorption of lipophilic
drugs or water-insoluble drugs
The absorption of some drugs would
require the presence of bile
Bile is secreted after a fatty meal and
administering the drug at the meal
will FACILITATE ABSORPTION

EFFECTS OF BILE
Saquinavir, Carbamazepine,
Halofantrine INCREASE absorption.
Aminoglycosides (Kanamycin,
Streptomycin, and Nystatin) forms
an INSOLUBLE COMPLEX with bile,
preventing drug absorption
Cholescystectomy (removal of gall bladder
can affect the bioavailability of drugs

GASTROINTESTINAL
DISEASE

GASTROINTESTINAL Disease
Diarrhea increase in intestinal
motility, decreases absorption of drug,
lower levels of plasma concentration
Celic sprue villous atrophy and
malabsorption. It reduces the effective
surface are for absorption
Achlorhydria no gastric secreations,
decrease absorption

 Renal impairment may cause

malabsoption
Liver disease
Thyroid disease.