General principles

Pharmacokinetics and
Pharmacodynamics

Yohannes.T
Introduction
Pharmacology
• Blend of two Greek words, “Pharmakon” to mean drug
or medicine, and “Logos” to mean study.
• Is the study of how drugs exert their effects on living
systems
Pharmacology is the study of substances/chemicals
that interact with living biological systems through
chemical processes (particularly by binding to
regulatory molecules) and alter (activate or inhibit)
biologic function or response.
 in order to achieve a beneficial therapeutic effect
Introduction cont…
Pharmacology as a science encompasses the following:

 Action of natural chemicals in the body

 Origins and sources of drugs

 Chemical structure and physical characteristics

 Mechanisms of action of drugs

 Metabolism and excretion of drugs

 Studies of their action

 In Whole animals, isolated organs, tissues and cells, enzymes

 In Humans and their therapeutic uses
Introduction cont…
Sub-divisions of Pharmacology
Medical pharmacology (Pharmacotherapeutics)- Study of

substances that are used to prevent, diagnose and treat disease

Toxicology – branch which studies about the Undesirable

effects of chemicals on living systems

 Pharmacogenomics (or Pharmacogenetics) is the study of
the genetic variations among humans that cause differences in
pharmacodynamics/pharmacokinetics and lead to individual
differences in drug response.
Introduction cont…
 Sub-divisions of Pharmacology
 Neuropharmacology: The study of drugs on components of the
nervous system, including the brain, spinal cord, and the nerves that
communicate with all parts of the body.
 Cardiovascular pharmacology: Concern the effects of drugs on the
heart, the vascular system, and those parts of the nervous and
endocrine systems that participate in regulating cardiovascular
function.
 Endocrine pharmacology: Actions of drugs that are either hormones
or hormone derivatives, or drugs that may modify the actions of
normally secreted hormones.
 Molecular pharmacology: Deals with the biochemical and
biophysical characteristics of interactions between drug molecules
and those of the cell. It is molecular biology applied to
pharmacological and toxicological questions.
Introduction cont…
 Drug and medicine
Drug:- a chemical substance of known structure, other

than a nutrient or an essential dietary ingredient, when

administered to living organism, produce a biological
effect
Medicine:- a chemical preparation which usually but not

necessarily, contains one or more drugs

 Substance that have medical importance or therapeutic
values
 Mostly, Drug + additives
Introduction cont…
Sources of drugs
Plants: quinine, digoxine, morphine, atropine

Animals: insulin, hormones

Microorganisms: penicillin

Minerals: iron, iodine, mineral salts

Synthetics: lidocaine
Introduction
 Naming of drugs
cont…
 Chemical name - interest of chemists, indicate the chemical
entity present in the drug, only one chemical name for a
drug. E.g N-acetyl-p-aminophenol
 Generic name - non proprietary name , accepted
internationally, only one generic name for a drug, most
commonly used in prescriptions. E.g. paracetamol
• Trade name(s), Brand or proprietary name(s) - name by
manufacturer company, several name for single drug may
occur, have letter ®, expensive
• The difference b/n generic product and brand product is
only the additives but not active ingredient. E.g. Panadol ,
paramol, adol, tylol
General principle of pharmacology
 Drug- Any substance that brings about a change in biologic function

through its chemical actions

 Interact with receptor - Majority

 Hormones or Xenobiotics

 Xenobiotic , from Gr xenos “stranger”, is any substance/chemical

that is foreign to the human body (not synthesized in the body).

A drug that is not synthesized in the body is called a xenobiotic.
 Prodrug is an ‘inactive’ form of a drug that requires metabolic
activation inside the body (bioactivation) in order to release the
‘active’ form of the drug. Once released in vivo, the active form of the
drug will then exert its pharmacological effect.
General principle of pharmacology
Poisons- Drugs that have almost exclusively harmful
effects
Paracelsus - "the dose makes the poison

Toxins - Poisons of biologic origin (plants or animals)

Receptor is the component of a cell or organism

that interacts with a drug and initiates the chain of

biochemical events leading to the drug’s observed
effects.
General principle of pharmacology
Pharmacokinetics (PK) refers to the actions of the
human body on the drug (what the body does to the
drug). It is the study of ADME properties of the drug with
respect to time
great significance in the selection and administration of
a particular drug for a particular patient.
Pharmacodynamics (PD) refers to the actions of the
drug on the human body (what the drug does to the
body).
play the major role in deciding whether that class of
drugs is effective therapy for a particular disease or
symptom.
General principle of pharmacology cont…
To interact with its receptor
Drug - appropriate size, electrical charge, shape, and atomic

composition
Necessary property to be transported

Inactivated or excreted from the body at reasonable rate

 General principle of pharmacology
Drug-body interaction
The interactions between a drug and the body
Pharmacokinetics - The actions of the body on the drug

 Involves Absorption, distribution, and elimination

(Biotransformation and excretion) - ADME

Pharmacodynamics

 The actions of the drug on the body, which is Drug-Receptor

interaction
 Pharmacokinetics
Permeation
Movement of a drug Involve passage across cell (Plasma)

membrane which is dependent on

Molecular size and shape – smaller drugs easily cross

Degree of ionization – Non-ionized drugs pass easily

Relative lipid solubility of ionized and nonionized forms –

lipid soluble drugs easily pass

Binding to serum and tissue proteins- unbounded drugs

easily cross
 Pharmacokinetics
Permeation cont…
Cell membrane
Is a Bilayer of amphipathic lipids which contains

 Hydrocarbon chains oriented inward - Hydrophobic phase

 Hydrophilic heads oriented outward
Proteins are also found in membrane and function as

Receptors, ion channels, or transporters

 They are Selective targets for drug actions
 Pharmacokinetics
Permeation cont…
Water – Bulk flow – water carry water soluble drugs
 Diffusion or osmotic difference

 Works for Small water-soluble substances

Paracellular transport
 Across most capillaries between the space found in the cells

 Is dependent blood flow

 In BBB and epithelial tissues, there is no space between the

cells
 Pharmacokinetics
Permeation cont…
Passive Membrane Transport
 Not need energy
 Along concentration gradient
 Dependent on concentration of drugs, Membrane
surface area and lipid solubility, degree of
ionization
 Major means of drug transportation
 Permeation
Passive membrane transport cont…
Most drugs are weak acids or bases, that means they exist

in Nonionized and ionized species in solution

 Nonionized is Lipid-soluble and Easily diffuse

Transmembrane passage is Determined by pH

Ion trapping - Acidic drug will accumulate on the

more basic side of the membrane and a basic drug

on the more acidic side
 Pharmacokinetics
Permeation cont…
Carrier-Mediated Membrane Transport
 Active transport
 Need energy and is Against concentration gradient
 Is carrier mediated and shows saturable, selective,
competitive inhibition nature
 Secondary active transport

 Uses the electrochemical energy stored in a gradient to move

another molecule against a concentration gradient
 E.g. Na+-Ca2+exchange, Na+-dependent glucose transporters
 Permeation
Carrier mediated transport cont…
Facilitated diffusion
 Carrier-mediated transport with no input of energy

 Specific and occurs across concentration gradient

 E.g. Glucose transporter protein GLUT4

 Protect the cell from toxic substances

Efflux transporter (P-glycoprotein) – efflux drugs and hence limits

the absorption and the action of drugs leading to resistance to drugs

 E.g. Enterocytes contain these transporter
 Pharmacokinetics
Permeation cont…
Endocytosis and Exocytosis
Endocytosis is Process by which substance is engulfed by

cell membrane and transported to inside

 Works for Large or impermeant substances
 E.g. Vit B-12 (Gut-Blood)

Exocytosis - The reverse process of endoxytosis

 Important for Secretion of many substances from cells

 E.g. Neurotransmitters
Pharmacokinetics cont…
Absorption
 Movement of a drug from its site of administration into the

blood and the extent to which this occurs

Bioavailability :- Fractional extent to which a dose of drug

reaches its site of action or systemic circulation

 It is reduced by the Metabolism or degradtion of the drug in the

GIT, problem with absorption, processing or destruction by

enzymes or acids or destruction in the liver
Pharmacokinetics cont…
First pass effect – is the processing or destruction od drugs

before reaching systemic circulation

Metabolic or excretory capacity of the liver for the drug is

known as First pass effect of the liver

 Pharmacokinetics
Absorption cont…
Factors influencing absorption
 Drug properties including Lipid solubility, size of drug

 Routes of Administration (important)

 Blood flow to the absorption site – Increased blood flow increase

absorption
 Total surface area available for absorption – Increased surface

areas leads to increased absorption

 Contact time at the absorption surface – Increases absorption
Pharmacokinetics cont…
Route of administration
 Have profound effect on the speed & efficiency of drug’s action
 Broadly seen in two ways:
I. Enteral: drugs placed in the GIT
• Oral, Sublingual, Rectal
II. Parentral: drugs delivered to the systemic circulation without
crossing intestinal mucosa
• Iv, Im, Sc, IT, transdermal, inhalational, IP etc.

 Systemic vs. local effect

 The drugs after absorption enter the systemic circulation and act on
tissues remote from the site of the drug administration
 Drugs act at or near the site of the drug administration
 Pharmacokinetics
Route of adminstration cont…
Oral routes

Advantage:- Most common, safest, most convenient, most

economical
Disadvantage
Irritation to GI(N&V)
High first pass effect because Some drug destructed by GI
flora(digoxine), enzyme(insulin), p H (penicillin)
 There is also Liver metabolism( highly enzymatic)
Not given for unconscious, uncooperative, vomiting patients
Slow onset of action
Irregular absorption (drug- food interaction)
 Better to take the food and drug In at least 30 minute
 Pharmacokinetics
Oral route cont…
Absorption from the GI tract mainly occurs in small intestine

and depend on
 Surface area → ↑ Absorption

 Blood flow → ↑ Absorption

 Physical state of the drug (solution, suspension, or solid)

 Lipid solubility → ↑ Absorption

 Drug's concentration at the site of absorption → ↑ Absorption

 Gastric emptying → ↑ Absorption

 Pharmacokinetics
Routes of administration cont…
Sublingual Administration
• Placing drugs under the tongue
• Rapid absorption, avoids first pass effect
 There is small surface area but venous drainage is to
superior vena cava
 E.g. Nitroglycerin is used by this route
 Disadvantage

 Inconvenient, useful for Small doses and not suitable for

unpleasant taste of some drugs
 Pharmacokinetics
Routes of administration cont…
Rectal Administration
 Drugs placed in the rectum
 merits
 For unconscious & children patients , For nauseas or
vomiting patients
 Can reduce first pass effect by 50%
 Good for vomiting inducing drugs
 Demerits
 Inconvenient, erratic absorption , rectal irritation
 Pharmacokinetics
Routes of administration cont…
Parenteral routes
Intravascular- I.V (intravenous), I.A(intra-arterial)-
placing a drug directly into the blood stream
Intramuscular (I.M) - drug injected into skeletal muscle

Subcutaneous (S.C)- Absorption of drugs from the

subcutaneous tissues
 Pharmacokinetics
Parenteral routes
Deliver drugs in active form

Rapid, extensive, predictable availability - Accurate

Useful In emergency therapy, in unconscious, uncooperative

patient's, or in those unable to retain anything given by mouth

Disadvantages

 Asepsis must be maintained

 Pain and
 Difficult to self-medicate
 Pharmacokinetics
Parenteral routes cont…
Absorption from S.C or I.M route occurs by Simple diffusion

from depot to plasma and occurs through either

 Capillary membranes
 Relatively large aqueous channels in the endothelial
membrane
Diffusion regardless of lipid solubility
 Lymphatic channels - Larger molecules (proteins)
 Pharmacokinetics
Parenteral routes cont…
Intravenous

Bioavailability is complete

Controlled, accurate and immediate drug delivery

 Rapid effect

Irritating solutions can be administered

 By diluting the drug in blood

Warrants close monitoring of the patient's response

 Pharmacokinetics
Parenteral routes cont…
IV route disadvantage

 Once the drug is injected, there is often no retreat

 Unfavorable reactions can occur

 Due to high concentration in plasma and tissues

 Repeated injections depend on the ability to maintain a patent vein

 Drugs in an oily vehicle, those that ppt blood constituents or

hemolyze erythrocytes, and drug combinations that cause

precipitates to form are not used
 No local action, pain occurs, expensive
 Pharmacokinetics
Parenteral routes cont…
Subcutaneous

For drugs that are not irritating to tissue since it causes Severe

pain, necrosis and tissue sloughing

Produces Constant and slow absorption resulting in Sustained

effect
Incorporating vasoconstrictor helps to retard absorption

Implanted under the skin in a solid pellet

 Absorption slowly over a period of weeks or months e.g.

contraceptives
 Pharmacokinetics
Parenteral routes cont…
Intramuscular

Drugs in aqueous solution are absorbed quite rapidly

 Depend on the rate of blood flow to the injection site

 Local heating, massage, or exercise can increase
absorption
Very obese patients exhibit Unusual patterns of absorption

Substances too irritating for s.c sometimes may be given IM

It may cause Pain

 Pharmacokinetics
Routes of administration cont…
Intraarterial
To localize its effect in a particular tissue or organ

 Diagnostic agents sometimes are administered

Avoid first-pass effects of the lung

Requires great care and should be reserved for experts

Intrathecal - Allows local and rapid effects on meninges or

cerebrospinal axis
Blood brain barrier (BBB) and blood (CSF) serve as barrier to

drugs entering into the CNS

 Pharmacokinetics
Routes of administration cont…
Pulmonary route

Gaseous and volatile drugs and Solutions of drugs (Aerosols)

are given by this route

Allows Rapid access to the circulation allowing rapid onset

since there is Large surface area, Thin membranes and High

blood flow
It avoids hepatic first-pass and Used for both local action

(asthma),and systemic action (general anesthetic)

Needs special apparatus and irritations
 Pharmacokinetics
Routes of administration cont…
Drugs administered by any route into the systemic circulation are

Subject to first pass metabolism in the lungs. The exception is

intraarterial route
Lungs serve as storage site for a number of agents (Weak

bases, nonionized)
 Filter for particulate matter that may be given IV
 Route of elimination for volatile substances
 Pharmacokinetics
Routes of administration cont…
Topical

Application into Mucosal membranes

Application into Skin which could be

Dermal which produces Local action or

Transdermal which produces systemic action

 Pharmacokinetics
Routes of administration cont…
Mucous Membranes

Adminstration ito Mucous membranes of the

conjunctiva, nasopharynx, oropharynx, vagina,

colon, urethra, and urinary bladder
Primarily used for local effects
 Pharmacokinetics
Routes of administration cont…
Transdermal Absorption

 Depends on Surface area and Lipophilicity

 In Damaged and inflamed absorption will increase

 Occlusive dressing, rubbing, using oily vehicle enhance

absorption
 It also allows to use Controlled dosage which allows slow

release of drugs
 E.g. Nicotine, Nitroglycerin, Birth controls
 Pharmacokinetics
Routes of administration cont…
The route of administration is determined by:
Physico-chemical properties of the drugs like Water or lipid

solubility, ionization, solid, liquid, gas

Therapeutic objectives whether Rapid onset is needed or there

is need for long-term administration

Condition of the patient

 No single route of drug administration is ideal for all

drugs in all circumstances

 Pharmacokinetics
Routes of administration cont…
 Pharmacokinetics
Distribution
Is the delivery of drugs from systemic circulation to
tissues
Distribution of drugs is random (every tissues have equal
chance)
Movement into interstitial and intracellular fluids

Leaves bloodstream

Drug is transported from the site of absorption to the site of

action
It Controls onset, duration of actions, efficacy and side

effects
 Pharmacokinetics
Distribution cont…
Factors affecting distribution

Cardiac output – Increase cardiac output increase distribution

Regional blood flow – The drug goes to Well perfused then to a

Less perfused organs

Capillary permeability – as the permeability increase
distribution increases
Tissue volume – As tissue size increase distribution increases

Hydrophobicity- as lipid solubility increase distribution

increases
Protein binding
 Pharmacokinetics
Distribution cont…
Protein binding :- Drugs ordinarily bind to protein in a reversible

fashion and in dynamic equilibrium

The drug exists in Bound drug and Free form

 Drug ordinarily bind with plasma protein in reversible

fashion and in dynamic equilibrium.
 Only unbound drugs can diffuse through the capillary wall,
produce its systemic effects, be metabolized and be excreted.
As free drugs leave the systemic circulation the bound drug
dissociate
 Pharmacokinetics
Distribution cont…
Binding of drugs to proteins

Weakly Acidic drugs mainly to albumin

Weakly Basic drugs- Lipoproteins and α1-acid

glycoprotein

Protein binding shows saturation and competitive

inhibition
 Pharmacokinetics
Distribution cont…
Volume of distribution

Measure of the apparent space in the body available to

contain the drug and it Gives rough estimation of overall

distribution of a drug in the body
Relates the amount of drug in the body to the

concentration of drug (C) in the blood or plasma

It is the volume in which the total amount of drug in the

body would be required to be dissolved in order to reflect

the drug concentration attained in plasma
 Pharmacokinetics
Metabolism
 Process by which drugs are inactivated and transformed
into a form that can be eliminated from the body

 Goal of chemical modification or transformation is To

get rid of the drug by changing the drug to polar drug

 It Occurs in lung, GIT, kidney, liver, blood….

 But mainly occurs in liver because of large amount of enzymes
 Pharmacokinetics
Metabolism cont…
Two phase of metabolism

Phase I Reactions: Functionalization or catabolic reactions

 Convert compound into a more polar metabolite by

adding or unmasking functional groups (-OH, -SH, -
NH2, -COOH, etc.)
Eg. Oxidation, hydrolysis, reduction
 Often the product of phase I are inactive and May be
sufficiently polar to be excreted readily
 Pharmacokinetics
Metabolism cont…
Phase II Reactions - biosynthetic or anabolic reactions

Involves Conjugation of the drug with endogenous substrate to

further increase aqueous solubility

 E.g. Glucuronidation, Sulfation , Acetylation ,Amino acid
conjugation, Glutathione conjugation
The resulting conjugate or product of phase II is almost always

pharmacologically inactive and less lipid soluble than its

precursor and is excreted in urine or bile
 Pharmacokinetics
Metabolism cont…
Consequence of metabolism

Active drug to inactive metabolites

Inactive drug to active/enhanced activity

 Pro-drug is changed into drug

Active drug to active product

Harmless or less toxic drug to toxic metabolites

 Pharmacokinetics
Metabolism cont…
Enzymes are typically involved in metabolism

Microsomal cytochrome P450 monooxygenase family

(CYP 450) of enzymes (oxidize drugs) are the Most

common ones involved in Phase I reaction
 These enzymes Act on structurally unrelated drugs and
Metabolize the widest range of drugs
 Pharmacokinetics
Metabolism cont…
CYP enzymes 450

Are Found in liver, small intestine, lungs, kidneys, placenta

They are the Major source of catalytic activity for drug oxidation

There are more than 50 different isoforms of CYP enzymes but

90% or more of drug oxidation can be attributed to 6 main

enzymes
 CYP1A2, CYP2D6, CYP2C9, CYP2E1, CYP2C19, CYP3A4
In different people and different populations, activity of CYP

enzymes differs
 Pharmacokinetics
Metabolism cont…
Examples of drugs with their metabolizing enzymes
 Pharmacokinetics
Metabolism cont…
CYP450 can be induced or inhibited by drugs

Inhibitors include drugs like cimetidine, ketoconazole,

ritonavir
 These inhibitors inhibit metabolism of drugs
Inducers include barbiturates (phenobarbitone),
carbamazepine, phenythoin
 The inducers increases the metabolism of drugs
 Pharmacokinetics
Metabolism cont…
Factors affecting metabolism
Age - children & oldies metabolize drugs in slow rate

Genetic polymorphism – because of genetic variation

metabolizing capacity is different
Disease conditions like liver problem can affect metabolism

Predisposing factors to enzyme induction or inhibition i.e.

whether the patient is taking enzyme inducer or inhibitor

Diet like e.g. grape fruit juice inhibit CYP3A4
 Pharmacokinetics
Elimination
Is a process of drug transfer from the internal to the external

environment
Process of removing a drug and it could happen in the Liver,

kidney, lung and other organs

 Liver involves removal through metabolism
(Biotransformation) or excretion through bile
 Kidney- mainly involved Clearance (unchanged form) of
drug
 Pharmacokinetics
Renal excretion
Kidney is the Principal organ for most drug removal

especially for water soluble and non volatile drug

The kidneys filter blood such that drugs and their metabolites

enter nephrons
Excretion of drug through kidney involve 3 steps
 Glomerular filtration, Tubular secretion and Tubular

reabsorption
Non-polar substances are reabsorbed but polar substances are

retained in the nephrons and excreted in urine

 Pharmacokinetics
Renal excretion
Rate depends on

 Volume of distribution – The higher the volume of distirubtion the

excretion will be………..

 Degree of protein binding. The higher the binding the excretion

will be………
 Glomerular filtration rate:- As filtration increase excretion increases

 Tubular fluid PH:- Weakly acidic drug excretion will increase when

the urine pH is ……..

 Extent of tubular reabsorption and secretion ----
 Pharmacokinetics
Excretion cont…
 GI excretion for Oral drugs as some part of the drug is not

absorbed and excreted in the feces

Pulmonary excretion occurs for Many inhalation anesthetics and

alcohol
Sweat is a minor excretion route for some drugs

Mammary excretion :- Many drugs are excreted into breast milk

Lactating mothers should be cautious about the intake of these

drugs because they may enter in to baby through milk and

produce harmful effects in the baby
 Pharmacokinetics
Half life
Half life (t1/2)

Time required to change the amount of the drug in the

body by half
5 to 6 half life is require To eliminate drug from body

4 half life – For a full effect of a drug and steady state

of the drug to occur

 Pharmacokinetics
Half-Life
Pharmacokinetics summary
 General principle of pharmacology

Pharmacodynamics
Receptors are macromolecules and Most are proteins

They are present either on the cell surface, cytoplasm or in

the nucleus
They are selective in binding to drugs

The main Function of receptor is Recognize specific ligand

molecule and to Transduce the signal into response

 General principle of pharmacology
Pharmacodynamics cont…
 Ligand is Anything that binds to a receptor and it could be

 Agonist is ligand that binds and Activate the receptor to bring effect

 Antagonist is a ligand that Prevent binding by other molecules

 It could be reversible (Competitive or non-competitive) and

Irreversible antagonist
 Partial agonist is a ligand that Activate receptors but give less

response than agonist

 It could act as an agonist (Full agonist) and Antagonist
 Inverse agonist is a ligand that produces effect opposite to that of

agonist
 General principle of pharmacology
Pharmacodynamics cont…
Receptors

Four types of receptors families

 1. Nuclear receptors or intracellular receptors – produce their

action in hours and they are the slowest

 2. Enzymatic receptors (tyrosine kinase)

 3. Ligand-gated ion channels (ionotropic receptors) – produces

their action in millisecond and are the fastest receptors

 4. G-protein coupled receptor (Metabotropic receptors)

 General principle of pharmacology
Pharmacodynamics cont…
Transmembrane signaling
 General principle of pharmacology
Pharmacodynamics cont…
Dose-response relationship

Receptors Determine the quantitative relationship between dose

and effect of a drug

Dose-response curve is a Representation of the observed effect

of a drug as a function or as relation to concentration of drug in

the receptor
 It could be of Graded dose response curve or quantal dose
response curve
 General principle of pharmacology
Pharmacodynamics cont…
Graded dose-response curve
Response of a receptor is measured against increasing

concentration of a drug
Graph of the response versus the drug dose could be

Hyperbolic or Sigmoidal curve in shape

 General principle of pharmacology
Pharmacodynamics cont…
Hyperbolic graded dose-response curve

• A curve obtained from dose versus percent of response plot

• Linear relationship exists at lower dose that is an increase in does

will produce an increase in response until it reaches maximum.

After that it remains constant despite increase in dose
 General principle of pharmacology
Pharmacodynamics cont…
Sigmoidal graded dose-response curve

Curve obtained from Log of dose versus percent response plot

The curve has a characteristic sigmoid or S-shape and it shows

Linear portion in the middle

 General principle of pharmacology
Pharmacodynamics cont…
Efficacy (Emax) is a Extent of an effect that can be achieved

and is the Maximum response of the system to the drug

Efficacy refers to the ability of the drug to
accomplish a specified effect.
Potency (ED50) is the Concentration of a drug required to

produce 50% of that drug maximal effect

Potency reflects the amount of drug (i.e., the

dose) required to cause an effect

 General principle of pharmacology


Pharmacodynamics cont…
Efficacy - Depends on number of drug-receptor complexes formed
Potency - Measures how much drug is required to elicit a given

response
The lower the dose required to elicit given response, the more

potent the drug is. A drug with low ED 50 is more potent than a drug

with larger ED50

 General principle of pharmacology
Pharmacodynamics cont…
In fig (Left), A = B = C in efficacy, A > B > C in potency

In fig (Right), A = B in efficacy

A > C > B in potency
 General principle of pharmacology
Pharmacodynamics cont…
Quantal dose response curve – Shows the Response of percent

of population to increasing dose of a drug

 Helps us to determine the Dose required to produce a
specified effect in a large number of individuals
A quantal dose-response curve represents the percentage of

individuals (or laboratory animals) under study who exhibit a

specified drug effect (a therapeutic effect, an undesirable drug
effect, a lethal effect, or any other drug effect) plotted as a
function of log drug dose.
 General principle of pharmacology
Pharmacodynamics cont…
A quantal dose-response curve illustrates the potential variability

of responsiveness to the drug among individuals in a given human

population. It tells individual variability to drug among population
It is All or none effect…that is at a given dose a patient will

respond (all effect) or will no give response to the drug

The curve is bell shaped
 General principle of pharmacology


Pharmacodynamics cont…
Quantal dose response curve helps us to determine ED50 and LD50
 Median effective dose (ED50)

 Dose at which 50% of individuals exhibit the specified effect

 ED 50:- the dose that produces response in 50% of the
individual
 Toxic dose or Lethal dose (TD50 or LD50)

 Dose required to produce a particular toxic effect in 50% of

animals
 LD 50:- the dose that cause death in 50% of the animal
 General principle of pharmacology
Pharmacodynamics cont…
Therapeutic index (TI) is the Ratio of TD50 to ED50

TI gives us information about the safety of the drug and

should be > 1
Drugs with low TI should be used with caution and needs a

periodic monitoring (less safe)

 Drugs with a large TI can be used relatively safely and does not need

close monitoring (highly safe)

 General principle of pharmacology
Pharmacodynamics cont…
The Therapeutic Window (or Therapeutic Range) of a
drug is a more clinically useful index of safety.
Therapeutic window Is the Dosage range between the

minimum effective therapeutic concentration (MEC) and

the minimum toxic concentration (MTC) and is give us
information about the safety of drug
It describes the dosage range (i.e., the difference)
between the minimum effective therapeutic
concentration/dose (MEC) and the minimum toxic
concentration/dose (MTC) of a drug in humans