BASICS OF

PHARMACOLOGY

SPEAKER –
DR.SANTOSH
 Introduction & Definition

•Pharmacology
• Pharmacon - Drug
• Logos - Study

• It is defined as the study of the substances which

interact with living system by activating or inhibiting
normal body processes.
(In simple terms, it is study of all the aspects of drug.)
Pharmacokinetics :-
Greek word- Pharmakon means drug,
Kinein means To move

• What the body does to the drug.

It deals with-
Absorption – taken into the body
Distribution – moved into tissues
Metabolized – changed so can be excreted
Excreted – removed from the body
 ABSORPTION OF DRUG

The process by which the drug enters into the systemic

circulation from the site of administration through the
biological membrane is called absorption of drug .

• In case of intravenous or intra-arterial administration

the drug is not absorbed and it enters into the
circulation directly .
 Absorption Distribution

Route

Parenteral
Enteral Topical
IV

oral sublingual transdermal inhalation

Absorption Absorption

Systemic circulation
 Slow Absorption

• Orally (swallowed)

• through Mucus Membranes

– Oral Mucosa (e.g. sublingual)
– Nasal Mucosa (e.g.
insufflated)

• Topical/Transdermal
(through skin)
• Rectally (suppository)
• Parenterally (injection)
• Intravenous (IV)
• Intramuscular (IM)
• Subcutaneous (SC)
• Intraperitoneal (IP)

• Inhaled (through lungs)

 Fastest Absorption

• 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
Absorption: Solubility
• Water-soluble
• Ionized (have electrical charge)
• Crosses through pores in capillaries, but not cell
membranes

• Lipid(fat)-soluble
• Non-ionized (no electrical charge)
• Crosses pores, cell membranes, blood-brain-barrier
• Dissociation constant or pKa 
indicates the pH where 50% of the drug is ionized
(water soluble) and 50% non-ionized (lipid soluble)

pKeq = pH + log [X]ionized/[X]non-ionized

• This affects a drug's solubility, permeability,

binding, and other characteristics.
(hydroxyl group)

(amine group)
DISTRIBUTION OF DRUG:-
All the consequences of delivery of drug to the tissue is
called distribution of drug. Distribution of drug means
dividing and spreading of drug to the tissue.

• Selective distribution of drug: It means special

distribution of drug in the certain tissue of the body due
to special affinity between particular drug & particular
body constituents

Examples-
Ephedrine → Iris
Tetracycline → Ca++ containing tissue
(bones/teeth)
Heavy metal (arsenic) → hair and nail
Digoxin → heart
Thiopental Na+ → adipose tissue
 Distribution
Absorption
Metabolism

Factors affecting

Low albumin
Problems with:
Heart
Circulation
Diabetes

Bound drugs are pharmacologically inactive because the drug-protein

complex is unable to cross cell membranes.
Metabolism:-

• Drugs and toxins are seen as foreign to patients

bodies
• Drugs can undergo metabolism in the lungs, blood,
and liver
• Body works to convert drugs to less active forms
and increase water solubility to enhance
elimination
Drugs are metabolised in the liver, lungs,
kidneys, blood and intestines.
• In order for drugs to pass across the lipid cell
membrane they must be lipophilic
• The higher the solubility in lipids compared to
water, the more rapid the tissue entry
• Metabolic rate determines the duration of the
action of the drugs
Metabolism

• Liver - primary route of drug metabolism

• Liver may be used to convert pro-drugs (inactive) to
an active state
• Types of reactions
• Phase I (Cytochrome P450 system)
• Phase II
Phase I reactions types

• Hydrolysis
• Oxidation
• Reduction
• Demethylation
• Methylation
• Alcohol dehydrogenase metabolism
Phase II reactions

• Polar group is conjugated to the drug

• Results in increased polarity of the drug
• Types of reactions
• Glycine conjugation
• Glucuronide conjugation
• Sulfate conjugation
Drug Elimination

• Elimination = all the various processes that

terminate the presence of a drug in the body.
• Processes:
- metabolism
- renal excretion
- hepato-biliary excretion
- pulmonary excretion (inhaled anesthetics
mainly)
- other: saliva, sweat, breast milk, tears.

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Elimination

• Pulmonary = expired in the air

• Bile = excreted in feces
• enterohepatic circulation
• Renal
• glomerular filtration
• tubular reabsorption
• tubular secretion
Hepatobiliary excretion

• Drugs metabolites – excreted in the intestinal tract

with the bile.

• Majority: reabsorbed into the blood and excreted

through urine. (enterohepatic cycle).

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Pulmonary Excretion
•Volatile anesthetics and anesthetic gases: in
large part eliminated unchanged through the
lung

•The factors that determine uptake operate in

reverse manner

22
 Elimination
of drugs fromthe body

M KIDNEY LIVER
A
J filtration metabolism
O secretion secretion
R (reabsorption)

M LUNGS OTHERS
I
N exhalation mother's milk
O sweat, saliva etc.
R
PHARMACODYNAMICS

• It is a branch of Pharmacology which deals with the

effects of Drug & Mechanism of action.

• What the drug does to the body.

 Dosage Plasma Site of
Effects
Concen. Action

Pharmacokinetics Pharmacodynamics
Drug- derived from Drouge (French word) =
A Dry Herb
•Definition:
• According to the World Health Organization
(WHO),1992-
‘’ A Drug is any substance or product that is used or
intended to be used to modify or explore Physiological
system or Pathological states for the benefit of the
recipient.’’

Aim of Drugs: To improve quality of life.

Basic use of drugs:-

• Diagnosis- BaS04 →GIT lesion

• Prevention- Vaccine, Contraceptives, toxins
• Suppression/Control- Insulin for DM, Anti-
hypertensive drugs.
• Treatment- Antibiotics for infection, Diuretics for
edema, analgesic for pain.
 Posology: Deals with dosage of Drug.

Dose: Amount of drug or medicinal substance to be

administered at one time is called dose
Dosage: Determination of the amount , frequency and
number of dose for a patient is called dosage.
Therapeutic dose: Dose require to produce the optimal
therapeutic effect is called therapeutic dose.
Maximum dose: Largest dose of drug that is safe to
administration and produce no toxic effect is called
maximum dose.
Minimum dose: Smallest dose of drug that will be
effective is called minimum dose.
 POSOLOGY

• Loading dose: The “loading dose” is one or series of

doses that may be given at the onset of therapy with
the aim of achieving the target concentration rapidly.
• Maintenance dose: Dose required to maintain the
desired effect that is achieved by preceding dose.
• Test dose: Amount of drug given initially ( before giving
full therapeutic dose) to see the response of drug to
tissue is called test dose.
• Fatal dose: Amount of dose that cause death of 100%
of experimental animals.
 POSOLOGY

• ED50(Median effective dose): The dose at which 50%

of individual exhibit the specified quantal effect is
called ED50

• TD50(Median toxic dose): The dose required to

produce a particular toxic effect in 50% of test animals
is called TD50.

• LD50(Median lethal dose): The dose required to

produce death in 50% of experimental animals is called
the LD50.
 Therapeutic Index

• TI = LD50/ED50, an indication of safety of a drug

(higher is better)

ED50 LD50
 Half life:-
Definition: The time by which the effect of a drug will come
to half is called the Biological half life of that drug.

Importance:
1. Half life gives gross idea about the Pharmacokinetics
and Pharmacodynamics of a drug.
2. It gives idea about the duration of action of a drug.
3. It can guide the dosage schedules.
 Low Half life → Frequent administration
 High half life→ Should be given once or twice daily
First order kinetics
A constant fraction of drug is eliminated per unit of time.

When drug concentration is high, rate of disappearance

is high.
For a first order reaction A products , rate = k[A]:

34
Zero order kinetics
Constant amount eliminated per unit of time.
Rate of elimination is constant.

Rate of elimination is independent of drug

concentration.
For a zero order reaction A products , rate = k:

36
 Comparison

• First Order Elimination • Zero Order Elimination

• drug decreases • Drug decreases
exponentially w/ time linearly with time
• Rate of elimination is • Rate of elimination is
proportional to drug constant
• Plot of log [drug] or • Rate of elimination is
ln[drug] vs. time are independent of drug
linear • No true t 1/2
• t 1/2 is constant
regardless of drug
Clearance

• Clearance is defined as the theoretical volume of

body fluid containing drug (i.e. that fraction of
apparent volume of distribution) from which the
drug is completely removed in a given period of
time. It is expressed in ml/min or liters/hour.
 Bioavailability
• Definition: It is the amount or percentage of active drug
that is being absorbed from a given dosage form & is
made available to the site of action is called the
Bioavailability of that particular from.

• e.g. Bioavailability of Paracetamol is 50%. It means if a

patient orally takes 500 mg of Paracetamol, only 250mg
(50%) of drug will reach to the systemic circulation.
 Tolerance
• 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
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)
 Drug interaction
• Drug interaction is a phenomenon which occurs when the effects
of one drug are modified by the prior or concurrent administration
of another drug. Drug interaction may result beneficial or harmful
effects. Drug interaction may occur-
• Out side the body- Phenytoin + Infusion fluid = Precipitation
• At absorption level- Antacid + Tetracycline = Decreased absorption
of Tetracycline.
• At distribution level- Sulfonamide + Aspirin = Sulfonamide toxicity
• At bio-transformation level- Warfarin + Barbiturates = Decreased
anticoagulation.
• At excretion level- Penicillin + Probenecid = Increased penicillin
level.
Compartmental models are classical
pharmacokinetic models that simulate the kinetic
processes of drug absorption, distribution, and
elimination with little physiologic detail.
•A compartment is a hypothetical space bound
by an unspecified membrane across which drugs
are transferred.

•The concept of compartmental analysis is used

to determine what has become of the drug as a
function of time from the moment it is
administered until it is no longer in the body.
•Most drugs administered orally can be
adequately described using a one-
compartment model.

• whereas drugs administered by rapid

intravenous infusion are usually best
described by a two-compartment model
system.
•The one-compartment open model offers the
simplest way to describe the process of drug
distribution and elimination in the body.
•The simplest kinetic model that describes drug
disposition in the body is to consider that the
drug is injected all at once into a box, or
compartment, and that the drug distributes
instantaneously and homogenously throughout
the compartment.

•Drug elimination also occurs from the

compartment immediately after injection
•Uptake of drugs by various tissue organs will
occur at varying rates, depending on:
 the blood flow to the tissue
 the lipophilicity of the drug
 the molecular weight of the drug, and
 the binding affinity of the drug for the tissue
mass
Pharmacokinetic parameter of the one-
compartment model
1. Apparent volume of distribution (V D)
the apparent volume of distribution is the volume in
which the drug is distributed.
The apparent volume of distribution assumes that the
drug is uniformly distributed in the body. The V D is
determined from the preinjected amount of the dose in
the syringe and the plasma drug concentration resulting
immediately after the dose is injected.
• The apparent volume of distribution is a parameter
of the one-compartment model and governs the
plasma concentration of the drug after a given
dose.
2. Elimination rate constant (k)
•The elimination rate constant governs the
rate at which the drug concentration in the
body declines over time.

•The one compartment model that describes

the distribution and elimination after an IV
bolus dose is given in
Pharmacokinetic model for a drug
administered by rapid intravenous
injection.
D B = drug in body;
V D = apparent volume of distribution;
k = elimination rate constant.
•The one-compartment open model does
not predict actual drug levels in the
tissues.
•However, the model assumes that
changes in the plasma levels of a drug will
result in proportional changes in tissue
drug levels, since their kinetic profile is
consistent with inclusion within the
vascular compartment and the various
drug concentrations within the
compartment are in equilibrium.
• The drug in the body, D B, cannot be measured
directly; however, accessible body fluids (such as
blood) can be sampled to determine drug
concentrations.
•Several assumptions are associated with
modeling of drug behavior in the body.
1. It is assumed that the volume of each
compartment remains constant.
2. Is assumed that once a drug enters the
compartment, it is instantaneously and
uniformly distributed throughout the entire
compartment .
3. It is assumed that drug passes freely into
and out of compartments. Thus, these
compartmental systems are known as open
systems.
•In this simple one-compartment system, it
is assumed that the administered drug is
confined to the plasma (or blood) and then
excreted.
•Drugs that exhibit this behavior have small
volumes of distribution. For example, a
drug such as warfarin sodium, which is
extensively bound to plasma albumin, will
have a volume of distribution equivalent to
that of plasma water, about 2.8 L in an
average 70-kg adult.
•Typically, drug transport between compartments
follows first-order kinetics, where in a constant
fraction of drug is eliminated per unit of time and
can be described by ordinary differential equations.

•In these linear systems, the time constants that

describe the rate at which the plasma or blood
concentration curve of a drug decays are
independent of the dose, the volume of
distribution, and the route of administration.
•Some drugs, however, are initially distributed at
somewhat different rates in various fluids and
tissues.

•Consequently, these drugs’ kinetic behavior can

best be illustrated by considering an expansion of
the one-compartment system to the two-
compartment model.
•In the two-compartment system, a drug enters
into and is instantaneously distributed throughout
the central compartment.
• Its subsequent distribution into the second or
peripheral compartment is slower.

• For simplicity, on the basis of blood perfusion and

tissue–plasma partition coefficients for a given
drug, various tissues and organs are considered
together and designated either central
compartment or peripheral compartment.
•A drug that follows the pharmacokinetics of a
two-compartment model does not equilibrate
rapidly throughout the body, as is assumed for a
one-compartment model.
•In this model, the drug distributes into two
compartments, the central compartment and the
tissue, or peripheral compartment.
•1. The central compartment represents the
blood, extracellular fluid, and highly perfused
tissues. The drug distributes rapidly and uniformly
in the central compartment.
2.A second compartment, known as the tissue or
peripheral compartment, contains tissues in which the
drug equilibrates more slowly. Drug transfer between
the two compartments is assumed to take place by first-
order processes.

The peripheral compartment is usually comprises

tissues and organs that are poorly perfused by blood,
such as skin, bone, and fat.
•In contrast, a one-compartment model is
used when the drug appears to distribute
into tissues instantaneously and uniformly.
•For both one- and multicompartment
models, the drug in the tissues that have the
highest blood perfusion equilibrates rapidly
with the drug in the plasma. These highly
perfused tissues and blood make up the
central compartment.
•Multicompartment models were developed to
explain this observation that, after a rapid IV
injection, the plasma level time curve does not
decline linearly as a single, first-order rate
process.

•The plasma level time curve reflects first-order

elimination of the drug from the body only after
distribution equilibrium, or plasma drug
equilibrium with peripheral tissues occurs.

•Drug kinetics after distribution is characterized

by the first-order rate constant, b (or beta, ).
 Relationship
between tissue
and plasma drug
concentrations for
a two-
compartment
open model. The
maximum tissue
drug
concentration
may be greater or
less than the
plasma drug
concentration.
Context-Sensitive Half-Time
• Def.: context-sensitive half-time describes the time
required for the plasma drug concentration to
decline by 50% after terminating an infusion of a
particular drug.

• Calculated by using computer simulation of

multicompartmental models of drug disposition:
Context-Sensitive Half-Time

• Effect of distribution on plasma drug conc. varies in

magnitude and direction over time - depends on
the drug concentration gradients between various
compartments.
- ex.: early part of the infusion of a
lipophilic drug, the distributive factor decrease its
plasma conc. as the drug is transported to the
unsaturated peripheral tissues – later, after the
infusion is discontinued: drug will re-enter in the
central circulation
Context-Sensitive Half-Time (cont.)
• Reflects the combined effects of distribution and
metabolism on drug disposition
• The data confirm the clinical impression that as the
infusion duration increases, the context sensitive
half-time of all drugs increases. This phenomenon
is not described by the elimination half-life.
• No relationship with the Half-Life.
• For a one-compartment model: context-sensitive
half-life = elimination half-life.
• It is a useful concept because it helps to explain the
duration of action of a drug given by infusion after
stopping the infusion.

• It reflects several pharmacokinetic principles.

1. As any drug is infused into the body more of the
drug will deposit in the body’s tissues (i.e.,
accumulate) the longer the duration of infusion (or
“context” as it is known) until the body’s tissues are
completely saturated. Once the drug infusion is
stopped this stored drug will then redistribute back
into the blood and maintain its effects.

2. Every drug accumulates to differing extents, which

is largely influenced by the physicochemical
properties of the drug.
3. Drugs are removed from the blood through two
major mechanisms:

• Distribution: where the drug moves from the

blood into the tissues, e.g., fat.
• Excretion: where the drug is either metabolized
(e.g., by the liver) or excreted from the body
unchanged (e.g., in urine). Whether or not the
metabolites are active is also important.
THANK U