Pharmacology

Introduction
PHARMACOLOGY

Greek Word

Pharmacon Logos

Drug Science
• Pharmacology: the science that deals with
drugs.

• Drug: a substance that is used for prevention,

treatment & diagnosis.
 Drugof
Names Names
Drugs
Chemical name
• The drug’s chemical composition and molecular
structure… is the name by which the chemist
knows it.

Generic name (nonproprietary name, Official)

• Name given by international organization of drug
nomenclature & independent of the manufacture.

Trade name (proprietary name, brand name)

• The drug has a registered trademark; use
of the name restricted by the drug’s owner
(usually the manufacturer)
• Pharmacologic Principles: Drug Names

• Chemical Name : N-(4-Hydroxyphenyl)acetamide

• Generic Name: Acetaminophen.

Paracetamol.

• Trade Name: Panadol®

Revanin®
Pandarin®
 Source of drugs
1. Plants: such as digitalis, vincristine.
2. Animals: insulin
1. Minerals: as iron, iodine and zinc
3. Microorganism: antibiotics
4. Synthetic and chemical substance: as sodium
bicarbonate.
5. Drugs produced by genetic engineering :
Human insulin, human growth hormone
 Drug classification
• Drugs may be classified by:
• Their effect on particular Body system.
• Their Therapeutic uses.
• Their chemical structure.

• E.g: morphine can be classified as central

nervous system depressant, a narcotic or opioid
analgesic, & as an opiate( derived from opium)
• Prescription & non prescription drugs

American consumers have 2 routes of access to

therapeutic drugs:

1.Over the counter (OTC) purchase of drugs that

do not require a prescription.
2. By prescription or order from a licensed
health care provider.

• Using prescription drugs for non therapeutic

purposes by persons who are not authorized
to have the drugs or whom they are not
prescribed , is illegal.
 Pharmacokinetic Processes
The study of what the body does to the drug:

“ADME” is key
Absorption
Absorption Metabolism
Metabolism

Distribution Excretion
Excretion
Distribution
• What is the effect of the body on the drug?
 Pharmacologic Principles
Pharmacodynamics
• The study of what the drug does to the body:
– The mechanism of drug actions in living tissues
• Routes of administration
• Selection of the best route of drug
administration depends on:

• Patient condition
• Drug property
 Definition:

A route of administration is the path by which a

drug, fluid, poison or other substance is
brought into contact with the body.
 CLASSIFICATION

Others
Enteral Parenteral LOCAL
Oral •Skin topical
•Intranasal
Sublingual Injections
•Ocular drops
Rectal Intravenous •Mucosal-throat,
Intramuscular vagina, mouth,
ear
Subcutaneous
Intra-arterial Inhalational
Intra-articular Transdermal
Intrathecal
Intradermal
 Enteral Routes

• Enteral - drug placed directly in the GI tract:

– sublingual - placed under the tongue

– oral - swallowing (p.o.)
– rectum - Absorption through the rectum
 Oral Route

• Advantages: Convenient- portable

no pain
easy to take
Cheap – no sterilization
no expert.
 Oral Routes
• Disadvantages: Variable bioavailability
Food can affect absorption
Local effect: taste,irritation
Unsuitable for Unconscious pts.
First pass effect
 First pass effect
• Drugs absorbed orally are transported to liver
by Portal circulation before reach systemic
circulation, thus are extensively metabolized in
the Liver, this is known as first pass effect.

Hepatic
Swallowed Digestive Rest of the
portal Liver
Drug system body
system
Dosage forms Syrup
Capsules, powders
Tablets
Syrup,
Suspension, elixirs
Tablets
Hard- gelatin capsule Soft- gelatin capsule
 Sublingual Medication
Administration
Place the pill between the underside of the tongue
and the floor of the oral cavity.
 Sublingual
• Advantages: No first pass effect
Rapid absorption and effect

• Disadvantages: Inconvenient
Small doses only.
Bitter tasting
can not give to unconscious patient.
 Buccal/Sublingual route (Cont.)

Applicable dosage forms:

 Tablets
 Chewable tablets
3. Rectal
Drugs are administered rectally for their local or for
systemic effect
Advantages:
• Reduced first pass hepatic effect
• Useful if the drug induces vomiting when given
orally or if the patient is already vomiting
Disadvantages:
• Absorption is often incomplete
• Chance for local irritation
• Loss of dosage form by defecation

• Applicable dosage forms:

• Suppositories
• Ointments
• Solutions, usually employed as enemas
Prepackaged enema container
 B. Parentral Route
• A drug administered parentrally is one
injected via a hollow needle into the body at
various sites and to varying depth.

• Parentral administration is used for drugs

that are:
• Poorly absorbed from GIT
• Unstable in the GIT
 Parenteral Routes

– Intravascular (IV, IA)- placing a drug directly

into the blood stream

– Intramuscular (IM) - drug injected into skeletal

muscle
– Subcutaneous - Absorption of drugs from the
subcutaneous tissues.
 Parenteral route
1. Intravenous (I.V.)
I.V. injection is the most common parentral route
Drugs may be given into peripheral vein over 1-2 min or
longer by infusion
Advantages:
• With I.V. administration the drug avoids the GIT, so
bypass the Liver
• Large volume can be given
• Used to treat acute cases as epileptic seizures,
cardiac arrhythmias
Disadvantages:

• Unlike drugs present in GIT, those that are injected

cannot be recalled by strategies such as emesis.
• Chance of infection
• More expensive.
• Require trained personnel for their proper
administration
 Parenteral route (Cont)
B-Intramuscular : (into the skeletal muscle).

suitable for injection of drug in aqueous solution (rapid

action) and drug in suspension (sustained release).
Large volume can be given 1-5 ml
Should be given at an angle of 90˚
Disadvantages:
• Trained personnel required for injection
• Painful
• Absorption is sometimes erratic
3.Subcutaneous (S.C.)
• This involves administration of a dose into the fatty
layer just under the skin
• The needle is inserted at an angle of 45 ْ

Advantages:
• Can be given by the patient.
Disadvantages:
• Can be painful
• Irritant drugs can cause local tissue damage
• Intrathecal/intraventricular: It is sometimes
necessary to introduce drugs directly into the
cerebrospinal fluid. For example, amphotericin B
is used in treating cryptococcal meningitis
 Intradermal
• Intradermal injections are delivered into
the dermis, or the skin layer underneath the
epidermis at angle 10-15˚. Mainly used for
testing sensitivity to drugs.
the position of needle for I.M, S.C, Intradermal injection
Ampules and Vials

Vials
Ampules
 Others- Topical route:
Topical: Drugs are applied topically to the skin or
mucous membranes, mainly for local action.
I Skin
cream, ointment (local action)
Lotion, paste,gel
II Mucosal membranes
• eye drops (onto the conjunctiva)
• ear drops
• intranasal route (into the nose)
 Others- Transdermal

Transdermal - absorption of drug through

skin (systemic action)
 stable blood levels
 no first pass metabolism.
 Inhalation route:
- Used for gaseous and volatile agents and aerosols.
• Delivery of drugs across the large surface area of
mucous membranes of respiratory tract.

• Local effect – Bronchodilator

• Systemic effect – General anesthesia
• Advantages: - Rapid
- No first pass effect
• Disadvantages: - Irritation
- Some particles may be
precipitated in mouth or throat
Nebulizer Inhaler
 DRUG DOSAGE FORMS

Tablets
Aerosol Capsule

Suspension Injection

Cream Infusion

Solution
 Absorption
• The passage of drug from site of administration
(from out side) to the blood stream.
• To do so the drug has to pass through cell
membranes.
• Cell membranes are of lipid bilayer and pores.
• Most drugs are absorbed by “Passive diffusion”
or simple diffusion.
 III. ABSORPTION OF DRUGS
• A. Transport of Drug
from the GIT
1. PASSIVE DIFFUSION - Does not involve a
- The driving force for carrier
passive absorption of a - Vast majority of drugs
drug is the gain access to the body
concentration gradient by this mechanism
Mechanisms of Passage Across
Membranes
ACTIVE TRANSPORT

♦ requires carrier
♦ energy consuming
♦ against a
concentration gradient
♦ saturability
♦ selectivity
• Factors influencing absorption:

1. Effect of pH on Drug Absorption

• Most drugs are either weak acids or weak bases
which disassociate in the body fluid

• Diffusion of the non-ionized form of a weak acid

through a lipid membrane. B. Diffusion of the
nonionized form of a weak base through a lipid
membrane
.
Environmental pH and Ionization
IfIfwe
weput
putananacidic
acidicdrug
drugininan
anenvironment
environmentwith
withaalot
lotofofHH+ (low
+
(lowpH)
pH)
what
whatwill
willthis
thisequilibrium
equilibriumdo?
do?

HA H+ + A-
HA
HA
HA
HA

System
H +
+fromat
Non-ionized
System
H fromat
Non-ionized
 Equilibrium
acid
formenvironment
predominates!
Equilibrium
acid
formenvironment
predominates!
 Acidic drugs are best absorbed from
acidic environments

Basic
Basic drugs
drugs are
are best
best absorbed
absorbed from
from
basic
basic environments
environments
 Factors influencing absorption:
2. Blood flow
3. Contact time at absorption site
4. Total surface area available for absorption
 Bioavailability
Definition: the fraction of the administered
dose reaching the systemic circulation
unchanged
for i.v.: 100%
for non i.v.: ranges from 0 to 100%

e.g. lidocaine bioavailability 35% due to

destruction in gastric acid and liver metabolism
 Factors that influence bioavailability:

• First-pass hepatic metabolism

• Solubility of the drug
• Chemical instability
• Drug Distribution
refers to the movement of a drug from the blood
to various tissues of the body and depend on:

1.Blood flow.
2. Capillary permeability
2. Capillary permeability
 Membranes
• Special barriers to distribution

• Blood/Brain Barrier: This barrier provides a

protective environment for the brain. Speed of
transport across this barrier is limited by the lipid
solubility of the drug and its molecular weight…

• Placental Barrier: This barrier separates two

distinct human beings but is very permeable to
small molecular weight drugs.
 Blood-Brain Barrier

The
The blood
blood brain
brain barrier
barrier consists
consists of
of cell
cell
tightly
tightly packed
packed around
around the
the capillaries
capillaries of
of
the
the CNS.
CNS. What
What characteristics
characteristics must
must aa
drug
drug possess
possess to
to easily
easily cross
cross this
this
barrier?
barrier?

Non-protein bound, non-ionized, and highly lipid soluble

Why?
Why?
3. Binding of drugs to proteins
• D + plasma protein [D-plasma protein] complex

Reversible binding to plasma proteins sequesters drugs

in a non-diffusible form & slows their transfer out
the vascular compartment

Plasma albumin is the major drug-binding protein & act

as a drug reservoir
 LOCUS OF ACTION TISSUE
“RECEPTORS” RESERVOIRS
Bound Free Free Bound

ABSORPTION Free Drug EXCRETION

Bound Drug SYSTEMIC

CIRCULATION

BIOTRANSFORMATION
 Volume of Distribution(Vd)
♦It is the volume that would be
required to contain all the drug in the
body at the same concentration as in
the plasma
♦ drugs with large volume of
distribution will have a longer
half-life and duration of action
 E lim in a tio n
o f d ru g s fro m th e b o d y

M K ID N E Y L IV E R
A
J f iltr a tio n m e ta b o lis m
O s e c r e tio n s e c r e tio n
R ( r e a b s o r p tio n )

M LU N G S O TH E R S
I
N e x h a la tio n m o t h e r 's m ilk
O s w e a t, s a liv a e tc .
R
VII. DRUG METABOLISM
 Drugs are often
eliminated by
biotransformation and
or excretion into the
URINE OR BILE.

 LIVER – the MAJOR

SITE FOR DRUG
METABOLISM
• Renal elimination
of a drug
• Effect of drug
metabolism
On reabsorption in the
distal tubule.
 Reactions of Drug Metabolism
 The kidney cannot
efficiently eliminate PHASE I
lipophilic drugs ,
therefore lipid soluble
agents must 1st be
metabolized in the liver
using 2 general sets of
reactions
PHASE II
 Phase I
• uses the P 450 system
Located within the • Its function is to convert
endoplasmic reticulum lipophilic molecules into
of hepatocytes. more polar (H2O-
soluble) molecules by
• Phase I metabolism may introducing a polar
increase, decrease, or group as –OH2 –NH2
leave unaltered the • Hydrolysis
drug’s pharmacologic • Oxidation
activity. • Reduction
 Phase II
• Consists of conjugation • Renders the
reactions metabolites INACTIVE
and more water soluble
• Uses substrates like
glucuronic acid, or an • The highly polar drug
amino acid conjugates may then be
excreted by the kidney
or bile
• Factors Affecting Drug Metabolism
• P450 activity is genetically determined:
– Some persons lack such activity  leads to higher drug
plasma levels (adverse actions)
– Some persons have high levels  leads to lower plasma
levels (and reduced drug action)

• Other drugs can interact with the P450 systems

– Either induce activity. e.g : rifampicin
– Inactivate an enzyme system. e.g: cimetidine
• Age, neonates and very old.

• Pathological factors – Liver diseases.

 Question
• The addition of glucuronic acid to a drug:

A. Decreases its water solubility.

B. Usually leads to inactivation of the drug.
C. Is an example of a Phase I reaction.
D. Occurs at the same rate in adults and
newborns.
E. Involves cytochrome P450.
 Elimination by the Kidney
• Excretion - major
1) glomerular filtration

2) tubular reabsorption/secretion
• Proximal tubular secretion
• Distal tubular reabsorption
 Clearance

♦the measure of the ability of

the body to eliminate the drug
♦the sum of hepatic metabolism
and renal excretion
• The speed of elimination is the main factor in
deciding the duration of action of the drug & is
referred plasma half-life (t½) of the drug

T½: The time required to change the plasma

concentration of the drug by one half
 Half- life (T½)

♦often used to determine

frequency of administration

♦determines the time to attain

steady-state concentration
• Factors influencing the dosage regime
• The blood level & therapeutic effectiveness
depend on the dose, distribution within the
body & speed of elimination.

• Rapidly excreted drugs with short t½ will

require frequent administration to maintain a
fairly constant concentration in the body
where as those that are eliminated slowly can
be given once or twice
• With repeated dosing, concentration in plasma
climbs until more or less steady state (SS) is
obtained.

• Steady-state occurs after a drug has been

given for approximately five elimination half-
lives.
 Steady State

♦the point where rate of drug

availability equals rate of
elimination
♦constant drug concentration
♦point where expect maximum
drug effect
♦usually attained after 4-5 half
lives
• To hasten achievement of SS & full therapeutic
effect with more slowly excreted drugs, a large
loading dose is given followed by smaller
maintenance doses
 Single dose –
Loading dose

Therapeutic
Plasma Concentration

level

Repeated doses –
Maintenance dose

Time
 Dose Response Relationships
• Loading dose
– Bolus of drug given initially to rapidly reach
therapeutic levels
• Maintenance dose
– Lower dose of drug given continuously or at
regular intervals to maintain therapeutic levels
• Pharmacodynamics
• The action of the drug on the body

• The drug interacts with a receptor:

• D+R D – R complex  effect
• This reaction is reversible & in order to occur,
an affinity between the drug & receptor
 Non-receptor Mechanisms

• Actions on Enzymes
– Drugs altering enzyme activity alter processes
catalyzed by the enzymes
– Examples
• Cholinesterase inhibitors
• Monoamine oxidase inhibitors
 Non-receptor Mechanisms
• Changing Physical Properties
– E.g:Mannitol
– Changes osmotic balance across membranes
– Causes urine production (osmotic diuresis)
 Non-receptor Mechanisms

• Changing Cell Membrane Permeability

– Lidocaine
• Blocks sodium channels

– Verapamil, nefedipine
• Block calcium channels
 Non-receptor Mechanisms
• Combining With Other Chemicals
– Antacids
– Chelation of heavy metals.

• Replacement therapy as hormones&

vitamins
 Non-receptor Mechanisms
• Anti-metabolites
– Enter biochemical reactions in place of normal
substrate “competitors”
– Result in biologically inactive product
– Examples
• Some anti-neoplastics
• Some anti-infectives
• Types of drugs:
• Agonist: a drug that interact with a receptor
followed by effect
• Antagonist: a drug that interact with a
receptor but with no effect
• Partial Agonist: a drug that bind to a receptor
followed by weak effect
PARTIAL AGONISTS - EFFICACY
Even though drugs may occupy the same # of receptors, the magnitude of
their effects may differ.

1.0
% Maximal Effect

0.8

0.6

0.4

0.2

0.0
0.01 0.10 1.00 10.00 100.00 1000.00

[D] (concentration units)

 Receptor Interactions

Lock and key mechanism

Agonist Receptor

Agonist-Receptor
Interaction
 Receptor Interactions

Competitive
Inhibition

Antagonist Receptor

Antagonist-Receptor
DENIED!
Complex
 Receptor Interactions

Non-competitive Antagonist
Inhibition

Agonist Receptor

!DENIED
Inhibited’-Receptor‘
• Dose – Response curve Graded -dose response:

• Drugs A & B have the similar efficacy but they differ

in potency
• Efficacy: The maximal response produced by the drug

• Potency: How much of the drug required to produce

a response
• More potent drug is capable to produce the desired
effect with smaller dose
• In the case of drug C it has lower efficacy than A & B
& lower potency
• Therapeutic Index
The ratio of the dose that produce toxicity to that
produce clinical response

Therapeutic index TD50/ED50

• TD50: The dose that cause toxicity in 50% of
individuals
• ED50: The dose that produce an effect in 50% of
individuals

The ratio must be large in order to be a safe drug