Pharmacology
Pharmacology
Pharmacology is the science of
Drugs.
It encompasses all aspects of
knowledge about drugs, but
most importantly those that are
relevant to effective and safe
use for medicinal purposes.
Pharmacology:
Pharmacology: History
History
Forthousands of years, most
drugs were crude natural
products of unknown
composition.
Pharmacology
Pharmacology is
is one
one of
of the
the
oldest
oldest branches
branches of
of medicine
medicine
Ancient Egyptians Medievalphysicians
treated diseases with prescribed opium and
frog’s bile, sour milk, gold as well as herbs.
lizard’s blood, etc.
The ancient
Egyptians applied
moldly bread to
abrasions.
Pharmacology:
Pharmacology: History
History
For thousands of years, most drugs were
crude natural products of unknown
composition.
Over the past 100 years, crude drugs
have been purified, chemically
characterized and a vast variety of highly
potent and selective new drugs have
been developed.
Pharmacology
Pharmacology
This improvement has been possible
due to prolific growth of
PHARMACOLOGY.
Pharmacology forms the backbone
of Pharmacy practice and rational
therapeutics.
Pharmacology
Pharmacology
The classical Greek word pharmakon, on
which the term pharmacology is based, had
three related meanings:
Charm
Poison
Remedy
Pharmacology
Pharmacology
Pharmacology is the study of drugs
and their interactions with living
organisms.
Pharmacology is concerned with the
nature of drugs and medications, their
actions in the body, drug dosages, and
side effects.
Definitions
Definitions
Pharmacology:
the
scientific study of the origin, nature,
chemistry, effects, and use of drugs
Toxicology:
thescience that investigates the adverse
effects of chemicals on health
.
Pharmacology
Pharmacology
This improvement has been possible
due to prolific growth of
PHARMACOLOGY.
Pharmacology forms the backbone
of Pharmacy practice and rational
therapeutics.
Pharmacology:
Pharmacology: Division
Division
Two main divisions of pharmacology-
Pharcodynamics.
Pharcokinetics
Pharmacodynamics
Pharmacodynamics
What the drug does to the body. This
includes -
“The study of the Physiological and
biochemical effects of drugs and their
mechanism of action”
Objective is identification of the primary
actions of a drug
Pharmacokinetics
Pharmacokinetics
What the body does to the Drug. This
refers to movements of drugs in and
alteration of drug by the body. This
includes-
Absorption
Distribution
Metabolism/ biotransformation
Excretion of drugs
General
General Pharmacological
Pharmacological terms
terms
Drug: It is the single active chemical entity
present in a medicine that is used for diagnosis,
prevention, treatment or cure of a disease.
In the Year 1966, WHO has defined drug in a
more comprehensive way-
Drug is a any substance or product that is used or
intended to be used to modify or explore
physiological systems or pathological states for
the benefit of the recipient.
General
General Pharmacological
Pharmacological terms
terms
Drugs can be divided into -
Pharmacodynamic agent: These are
designed to have pharmacodynamic
effect in the recipient. (Cholinergic drugs)
Chemotherapeutic agent: These are
designed to inhibit or to kill invading
parasites or malignant cells having no or
minimal pharmacodynamic effects in the
recipient. (Sulfa drugs, Antibiotics)
Origin
Origin of
of Drugs
Drugs
Animals
Plants
Syntheticallyproduced in
the laboratory
Drugs
Drugs Derived
Derived from
from Plants
Plants
Ephedrine is present in the leaves of a
bushy shrub (species name Ephedra),
which, when burned were used by the
ancient Chinese to treat respiratory
ailments. Today, it is a bronchodilator.
The belladonna plant – source of
atropine, which is still used to dilate the
pupils.
Drugs
Drugs Derived
Derived from
from Animals
Animals
Thyroid
supplement tablets
are derived from
dried thyroid gland
tissue taken from
animals.
Drug
Drug Nomenclature
Nomenclature
A Drug generally has three categories of
names -
Chemical name
Non-proprietary name
Proprietary name
Drug
Drug Nomenclature
Nomenclature
Chemical name: It describes the drug
substance chemically. This name is usually
big and not suitable for using in prescribing.
e.g. Acetyl Salicylic acid.
Non-proprietary name: It is the name
accepted by a competent scientific body such
as USAN Council. The Non-proprietary name
of newer drugs are uniform all over the world
by an international agreement through WHO.
Drug
Drug Nomenclature
Nomenclature
Until the drug is included in a
Pharmacopoeia,the nonproprietary name may
also be called the approved name. After its
appearance in the official publication, it
becomes the official name. In common
practice generic name is used in place of
nonproprietary name.
Proprietary (Brand) name: It is the name
assigned by the manufacturers and is his
property or trademark.
Routes
Routes of
of drug
drug
administration
administration
most drugs can be administered by a
variety of routes. The choice of
appropriate route in a given
situation depends both on drug as
well as patient related factors.
Mostly feasibility and convenience
dictate the route to be used.
Routes
Routes of
of Drug
Drug Delivery
Delivery
Parenteral Inhaled
(IV)
Oral
Transdermal
Parenteral
Topical (SC, IM)
Rectal
Types
Types of
of routes
routes
Routes can be broadly divided into
those for -
1. Local action
2. Systemic action
Local
Local routes
routes
These routes can only be used for localized
lesions at accessible sites. Systemic
absorption of the drug from these routes
is minimal or absent .
Thus, high concentration are attained at the
desired site without exposing the rest of
the body . Systemic side effects or toxicity
are consequently absent or minimal.
Local
Local routes
routes
The local routes are
1.Topical – This refers to external
application of the drug to the surface
for localized action . It is often more
convenient as well as encouraging to
the patient.
a. Skin: drug is applied as ointment,
cream, lotions, paste, powder, dressing
etc
Local
Local routes
routes
b. mucous membranes – The dosage forms
depend on the site –
Mouth and pharynx- As lozenges ,mouth
washes , gargles .
Eyes, ear and nose – As drops, ointment ,
irrigation, nasal spray .
Gastrointestinal track – As non absorbable
drugs given orally e.g. aluminium hydroxide,
kaolin .
Bronchi and lungs –as inhalation , aerosols
e.g. salbutamol, cromolyn sod.
Local
Local routes
routes
Urethra – As jellys e.g. lidocaine ,
irrigating solutions.
Vagina – As pesseries, vaginal tablets ,
inserts , cream , powders.
Anal canal – As ointment,
suppositories .
Local
Local routes
routes
2.Deeper tissues– Certain deep areas
can be approached by using a syringe
and needle , but the drug should be
such that systemic absorption is very
slow, e.g. intra – articular injection
(hydrocortisone acetate) ,intrathecal
injection (lidocaine , amphotericin B).
Local
Local routes
routes
3. Arterial supply – close intra arterial
injection is used for contrast media
in angiography , anticancer drugs
can be infused in femoral or
brachial artery for limb
malignancies .
Systemic
Systemic routes
routes
The drug administered through systemic
routes is intended to be absorbed into blood
and distributed all over , including the site of
action, through circulation .
1.Oral—oral ingestion is the oldest and
commonest mode of drug administration . It is
safer, more convenient , does not need
assistance, noninvasive , often painless, the
medicament need not be sterile and so is
cheaper .
Systemic
Systemic routes
routes
Both solid dosage forms ( powders,
tablets , capsule, moulded tablet,)
and liquid dosages forms (elixirs ,
syrups , emulsion, mixture ) can be
give orally .
Systemic
Systemic routes
routes
Limitation of oral route of
administration -
Action is slower and thus not suitable
for emergencies
Unpalatable drugs are difficult to
administer , drug may be filled in
capsules to circumvent this.
May cause nausea and vomiting .
Systemic
Systemic routes
routes
Cannot be used for uncooperative /
vomiting patient .
Certain drugs are not absorbed
( streptomycin )
Others are destroyed by digestive juices
(penicilline G , Insulin ) or in liver
( Nitroglycerine , testosterone ,
lidocaine ).
Systemic
Systemic routes
routes
2. Subligual or buccal – The tablet or pellet
containing the drug is placed under the
tongue or crushed in the mouth and spread
over the buccal mucosa . Only lipid soluble
and non- irritating drugs can be so
administered .
3.Rectal – certain irritant and unpleasant drugs
can be put into rectum as suppositories or
retention enema for systemic effect .
Systemic
Systemic routes
routes
this route can also be used when the
patient is having recurrent vomiting .
However it is rather inconvenient and
embarrassing , absorption is slower ,
irregular and often unpredictable .
Drug absorbed into external haemorrhoidal
veins ( about 50%) by passes liver , but
not that absorbed into internal circulation
veins.
Systemic
Systemic routes
routes
rectal inflammation can result from
irritant drugs . Aminophylline ,
indomethacin , paraldehyde , diazepam ,
ergotamine and few other drugs are
some times given rectally .
4.cutaneous—highly lipid soluble drugs
can be applied over the skin for slow and
prolonged absorption .
Systemic
Systemic routes
routes
the liver is also by passed . The drug can be
incorporated in an ointment and applied
over specified area of skin .
Transdermal therapeutic systems (TTS) these
are recently developed devices in the form
of adhesive patches of various shapes and
sizes (5-20 cm2)which deliver the contained
drug at a constant rate into systemic
circulation via the stratum corneum .
Systemic
Systemic routes
routes
Systemic
Systemic routes
routes
the drug (in solution or bound to a polymer ) is
held in a reservoir between an occlusive
backing film and a rate controlling micropore
membrane , the under surface of which is
smeared with an adhesive impregnated with
priming dose of drug that is protected by
another film to be peeled off just before
application .
Systemic
Systemic routes
routes
5. Inhalation –volatile liquids and gases
are given by inhalation e.g. general
anaesthetics , amylnitrite .
Absorption takes place from the vast
surface of alveoli – action is very rapid .
When administration is discontinued the
drug diffuses back and is rapidly
eliminated in expired air .
Systemic
Systemic routes
routes
Thus controlled administration is
possible with moment to moment
adjustment . Irritant vapours cause
inflammation of respiratory tract and
increases secretion .
6. Nasal – the mucous membrane of the
nose can rapidly absorb many drug ,
digestive juices and liver are by passed .
Systemic
Systemic routes
routes
However , only certain drugs like
posterior pituitary powder and
desmopressin , applied as a snuff or
spray or nebulized solution have
been used by this route .
This route is being tried for some
other peptide drugs like insulin ,
GnRH agonists etc .
Systemic
Systemic routes
routes
7.Parenteral – This refers to administration
by injection which takes the drug
directly into the tissue fluid or blood
without having to cross the intestinal
mucosa . The limitation of oral
administration are circumvented . Action
is faster and surer( Valuable in
emergencies ) .
Systemic
Systemic routes
routes
gastric irritation and vomiting are
not provoked . It can be employed
even in unconscious, vomiting
patient. There are no chances of
interference by food or digestive
juices . Liver is bypassed .
Systemic
Systemic routes
routes
i) Subcutaneous (sc): the drug is
deposited in the loose
subcutaneous tissue which is richly
supplied by nerves but less
vascular.
ii) Intramuscular (i.m.): The drug is
injected in large skeletal muscle –
Deltoid, triceps.
Systemic
Systemic routes
routes
iii) Intravenous (i.v.): the drug is
injectedas a bolus or infused slowly
over hours in one of the superficial
veins. Drugs directly reaches into blood
and effects are produced immediately.
ii) Intradermal injection: The drug is
injected into the skin raising a bleb, e.g.
BCG vaccine, small pox vaccine.
Factors
Factors governing
governing choice
choice of
of
route
route
1.physical and chemical properties of drug.
2.site of desired action –located and
approachable or generalized and not
approachable .
3.Rate and extent of absorption of the drug
from different routes.
4. Effect of digestive juices and pass
metabolism of drug.
Factors
Factors governing
governing choice
choice of
of
route
route
5.Rapidly with which the response is
desired .
6.Accuracy of dosages required .
7.Condition of the patient .
Reference
Reference
Essentials of medical Pharmacology
(4th Edition)
Author: K D Tripathi
Pharmacokinetics
Pharmacokinetics and
and Pharmacodynamics
Pharmacodynamics
Passive
Passive diffusion
diffusion
c. basic drugs attain higher concentration
intracellularly (pH7 vs 7.4 of plasma ) .
d. acidic drugs are ionized more in alkaline
urine – do not back diffuse in the kidney
tubules and are excreted faster . Accordingly ,
basic drugs are excreted faster if urine is
acidified .
Passive
Passive diffusion
diffusion
Lipid soluble non electrolytes
( e.g. ethanol ) readily cross biological
membranes and their transport is pH
independent .
Filtration
Filtration
Filtration is passage of drugs so aqueous
pores in the membrane or through paracellular
spaces . This can be accelerated if
hydrodynamic flow of the solvent is occurring
under hydrostatic or osmotic pressure
gradient , e.g. in most capillaries including
glomeruli .
Filtration
Filtration
lipid insoluble drugs cross biological
membrane by filtration if their molecular size
is smaller than the diameter of the pores
.majority of cells( intestinal mucosa , RBS etc)
have very small pores and drugs with MW>100
or 200 are not able to penetrate .
Filtration
Filtration
However capillaries (except those in brain ) have
large pores and most drugs ( even albumin )
can filter through these . As such diffusion of
drugs across capillaries is dependent on rate
of blood flow through them rather then on lipid
solubility of the drug or pH of the medium .
Specialized
Specialized transport
transport
This can be carrier mediated or by pinocytosis.
Carrier transport- the drug combines with a carrier
present in the membrane and the complex then
translocates from one face on the membrane to the
other . The carriers for polar molecule appear to form
a hydrophobic coating over the hydrophilic groups
and thus facilitate passage through the membrane .
Specialized
Specialized transport
transport
Substances permitting transit of ions across
membranes are called ionophores .
Carrier transport is specific , saturable and
competitively inhibited by analogues which
utilize the same carrier .this is two types –
a. active transport – movement occurs
against the concentration gradient , needs
energy and is inhibited by metabolic poisons .
Specialized
Specialized transport
transport
it results in selective accumulation of the
substance on one side of the membrane .
Drugs related to normal metabolites , e.g.
levodopa and methyldopa are actively
absorbed from the gut by aromatic amino acid
transport process .
Specialized
Specialized transpor
transpor
b. Facilitated diffusion – this proceeds more
rapidly than simple diffusion and even
translocates nondiffusible substrates , but
along their concentration gradient , therefore
does not need energy .
Specialized
Specialized transport
transport
Nonspecific active transport of drugs , their
metabolities and some endogenous products
occurs in renal tubules and hepatic sinusoids
which have separate mechanisms for organic
acid and organic bases . Certain drugs have
been found to be actively transported in the
brain and choroid plexus also .
Specialized
Specialized transport
transport
Pinocytosis – it is the process of transport
across the cell in particulate form by formation
of vesicles . This is applicable to proteins and
other big molecules and contributes little to
transport of most
drugs .
Affinity,
Affinity, Efficacy,
Efficacy, and
and Potency
Potency
Ligand
+
Receptor I
AFFINITY
Kd
Ligand-
Receptor I
INTRINSIC POTENCY
EFFICACY EC50
Ligand-
EFFICACY
Receptor A
KE
TISSUE
COUPLING
RESPONSE
Hestermann et al. 2000
Dose
Dose
Pharmacology:
Dose refers to the amount of a drug
absorbed from an administration.
Toxicology:
Dose refers to the amount of a chemical
absorbed into the body from an exposure.
Key
Key Factors
Factors Related
Related to
to Dose
Dose
In pharmacology, we have good control over
who receives what dosage of what substance.
In environmental health, it is usually difficult to
control or determine who receives what dose
of which toxin(s).
Administration/Exposure
Administration/Exposure
Pharmacology:
Administration regimen: A drug can be administered
one time, short-term, or long-term.
Toxicology:
Exposure is the actual contact that a person has with a
chemical. It can be one-time, short-term, or long-term.
Key
Key Factors
Factors Related
Related to
to
Administration/Exposure
Administration/Exposure
Drugs are taken voluntarily.
Hazardous chemical exposures are often
involuntary.
With both drugs and hazardous chemicals,
children’s behavior entails special exposure
risks.
Routes
Routes of
of
Administration/Exposure
Administration/Exposure
Pharmacology:
Routes of administration: oral, IM, IV,
subcutaneous, topical
Toxicology:
Routes of exposure: ingestion, inhalation,
dermal, conjunctival
Key
Key Factors
Factors Related
Related to
to
Routes
Routes of
of
Administration/Exposure
Administration/Exposure
In administration of medication, different routes are
used based upon the efficacy of absorption of drugs
from each route.
In environmental health, different toxins are absorbed
through different routes of exposure, which results in
variations in toxicity.
Distribution,
Distribution, Metabolism
Metabolism
and
and Excretion
Excretion
Pharmacology and Toxicology:
Distribution, metabolism and excretion describe
what happens to the drug or toxin in the body.
Distribution: organs that are reached
Metabolism: chemical transformation
metabolites
Excretion: elimination
.
Dose-Response
Dose-Response Curve
Curve
Pharmacology:
Dose-response curve
graphically represents
the relationship
between the dose
of a drug and the response elicited
Dose-Response
Dose-Response Curve
Curve
Toxicology:
Dose-response curve
describes the
relationship of the
body’s response to
different amounts of
an agent
