Pharmacodynamics Dent

Pharmacodynamics
DR. Ghada Salah

MD Pharmacology
2023
Contents
• PRINCIPLES AND MECHANISM OF DRUG ACTION
• TRANSDUCER MECHANISMS
• DOSE-RESPONSE RELATIONSHIP
• COMBINED DRUG EFFECTS

Pharmacodynamics
 It is the study of physiological & biochemical
effects of drugs & their mechanism of action at organ
system /subcellular /macromolecular levels.
 It deals with what the drug does to the body.
 Drug Patient
: Targets of drug action
1. Receptors
2. Ion Channels
3. Enzymes
4. Carrier or Transport proteins
: Receptors
Receptor
It is a macromolecular or binding site located on the
surface or within the cell that serves to recognize the signal
molecule / drug ( ligand) & initiate the response to it, but
itself has no other function.
Sites of receptors: cell membrane, cytoplasm,

nucleus
Ligand :
Any molecule that binds selectively to a specific receptor is
called ligand ( Drug , Neurotransmitters , Hormones).
Affinity :
It is the ability of the drug to bind to a receptor .
Intrinsic activity/Efficacy :
It is the ability of the drug to elicit a response after binding
with the receptor.

Drugs acting on receptors may be :
Agonists
Antagonists
• Agonist: drugs bind to and activate the receptor to
bring about the effect.
(Has both affinity and intrinsic activity( efficacy)).
• Antagonist: drugs, by binding to a receptor, compete

with and prevent binding by other molecules and they
stabilize the receptor in its inactive state.
Has affinty but no intrinsic activity (no efficacy).
• Allosteric modulator (agonist, antagonist): A drug

that binds to a receptor molecule without interfering
with normal agonist binding but alters the response to
the normal agonist
PARTIAL AGONIST:
Have affinity & submaximal intrinsic activity(efficacy).
Inverse Agonists:
These drugs have affinity but produces actions opposite to
those produced by agonist.
(have Affinity and negative Intrinsic activity)
TYPES OF DRUG-RECEPTOR INTERACTIONS
DOSE –RESPONSE CURVE
(D/RC)
• This is a graph showing dose response relation.
 Dose is plotted on X-Axis and Response is plotted on Y-Axis.
There are two types of DRC:

-Graded/simple DRC
- Log DRC
In Log DRC – dose is converted to logarithmic scale
Log DRC is more convenient and used

Simple dose
Log Dose
% Max Response
Drug Concentration
Graded Dose-Response Relationships- 1
• made when a single animal gives graded responses to

graded doses; that is, as the dose is increased, the
response increases.
• Efficacy:
often called maximal efficacy—is the greatest effect (Emax)
an agonist can produce.
• Potency:
the amount of drug needed to produce a given effect. In
graded dose-response measurements, the effect usually
chosen is 50% of the maximal effect and the dose causing
this effect is called the EC50.
Potency Efficacy
• Dose of a drug that required to • Maximum effect of the drug
produce 50% of maximal effect
(ED 50)
• Height of the curve

• More left the DRC, more potent on x-axis indicates the efficacy
the drug of the drug
•The clinical effectiveness of a drug
depends not on its potency (EC50), but on
its maximal efficacy and its ability to
reach the relevant receptors.
Quantal Dose-Response curve
• Def: A graph of the fraction of a population that shows a specified

response at progressively increasing doses
• Advantages over graded D/R curve:

1- Suitable for pharmacologic response that is all or none,
as prevention of convulsions, arrhythmia and epilepsy
•From Q/R curves we obtain:
• Median effective dose (ED50): the dose at which 50% of

individuals exhibit the specified quantal effect.
• Median lethal dose (LD50): the dose leading to death of 50%

of animals.
• Therapeutic index: the ratio of the LD50 to the ED50 for some
therapeutically relevant effect
TI = TD50 / ED50
Therapeutic index /Safety margin
• The gap between therapeutic effect DRC and toxic effect

DRC defines the safety margin or therapeutic index (TI)
• It can be calculated as ratio between LD50 and ED50
• TI = median Lethal Dose = LD50

median Effective Dose ED50
TI : indicates the safety of drug.

Greater the TI , more will be the safety of the drug
Receptor antagonism:
1-competitive antagonist:
• Competitive --- Surmountable
• Competes with agonist in reversible fashion

for same receptor site
• Necessary to have higher concentration of

agonist to achieve same response
and so the agonist concentration-effect curve
is shifted to the right.
2- irreversible antagonists:
• Some receptor antagonists bind to the receptor in an
irreversible fashion by forming a covalent bond with
the receptor for practical purposes, the receptor is
unavailable for binding of agonist
• After occupancy of some proportion of receptors by

such an antagonist, the number of remaining
unoccupied receptors may be too low for the agonist
(even at high concentrations) to elicit a response
comparable to the previous maximal response.
irreversible (noncompetitive) antagonist, reduces the
maximal effect the agonist can achieve, although it may
not change its EC50
RECEPTOR BY DR.MOHAMMED ABDUL RAOF
Types OF Drug Antagonism:
1.Physical antagonism:
• The effect of one drug is inhibited by physical property
of another drug.
• Eg: Charcoal adsorbs poisons on its surface &
useful in alkaloid poisoning
2.Chemical antagonism :
• Here two drugs interact chemically and one drug
neutralise the effect of the other.
• Eg :Antacids neutralise gastric acidity
3.Physiological antagonism
Here two drugs act on different receptors; but their
pharmacological effects are opposing each other
functionally
Examples:
• Histamine (H1) produce bronchospasm
• Adrenaline (β2) produce bronchodilation
• Insulin reduce blood sugar

• Glucagon increase blood sugar
SPARE RECEPTORS:
These are reserve receptors present in the
body, gets stimulated only at special
situations.
SILENT RECEPTORS:
These are receptors to which an agonist binds
but does not produce a response.
LIGAND GATED CHANNEL IN -1
ACTION

GPCR AND ITS EFFECT -2

Gs – Adenyl cyclase Stimulator &
Ca channel opener
Gi – Adenyl cyclase Inhibitor &

K+ channel opener
Gq – Phospholipase C activator
Go – Ca channel inhibitor

Gq
Tyrosine-kinase receptors
• Structure:
• Each has an extracellular
signal-binding site
• An intracellular tail with a

number of tyrosines.
• Receptor action is slow &

occurs in hours
& Eg: Insulin receptors, EGF

.PDGF receptors
cGMP IP3
Tyrosine kinase receptor -3

NUCLEAR RECEPTORS
• Receptors are seen intracellularly in the cytoplasm,
drug cross cell membrane and bind with receptor and
form Drug Receptor complex .
• DR complex moves to nucleus, interact with DNA, regulate gene

transcription , synthesise specific proteins which produce cellular
effects.
• Nuclear receptor action is very slow and occurs with in hours or days
Eg: Corticosteroids, Sex hormones ,Thyroxine,

Vitamin D, Vitamin A
NUCLEAR RECEPTOR -4

Tolerance
• Gradual reduction in response to drugs is called tolerance.
• Requirement of higher dose to produce a given response.
• It occurs over a period of time.
• E.g. tolerance to sedative-hypnotics.
• Many reasons for tolerance:

1. Pharmacokinetic reasons-chronic use leads to enhanced
clearance-less effective concentration.
2. Pharmacodynamic reasons (reduced number and/or affinity

of the receptors to the drugs)-downregulation
RECEPTOR-DOWN
REGULATION
Continued use & stimulation of receptors by agonist drugs

may decrease the number and sensitivity of the receptors.
This phenomenon is called down regulation
Eg: Constant use of β2 agonist (salbutamol) reduce

therapeutic response in Asthma
RECEPTOR - UP REGULATION
• Continued use and inhibition of receptors by antagonist

drugs, may increase the number and sensitivity of the
receptors.
• This phenomenon is called up regulation.
• Eg: sudden withdrawal of anti-anginal drug (Propranolol)

may precipitate angina.
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Pharmacodynamics

DR. Ghada Salah

• COMBINED DRUG EFFECTS

 It deals with what the drug does to the body.

Sites of receptors: cell membrane, cytoplasm,

with the receptor.

• Antagonist: drugs, by binding to a receptor, compete

• Allosteric modulator (agonist, antagonist): A drug

There are two types of DRC:

In Log DRC – dose is converted to logarithmic scale

Log DRC is more convenient and used

• made when a single animal gives graded responses to

• Height of the curve

• Def: A graph of the fraction of a population that shows a specified

• Advantages over graded D/R curve:

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

• Median lethal dose (LD50): the dose leading to death of 50%

• The gap between therapeutic effect DRC and toxic effect

• It can be calculated as ratio between LD50 and ED50

• TI = median Lethal Dose = LD50

TI : indicates the safety of drug.

• Competes with agonist in reversible fashion

• Necessary to have higher concentration of

• After occupancy of some proportion of receptors by

• Insulin reduce blood sugar

RECEPTOR BY DR.MOHAMMED ABDUL RAOF

RECEPTOR BY DR.MOHAMMED ABDUL RAOF

Gi – Adenyl cyclase Inhibitor &

Gq – Phospholipase C activator

Go – Ca channel inhibitor

• An intracellular tail with a

• Receptor action is slow &

& Eg: Insulin receptors, EGF

RECEPTOR BY DR.MOHAMMED ABDUL RAOF

• DR complex moves to nucleus, interact with DNA, regulate gene

Eg: Corticosteroids, Sex hormones ,Thyroxine,

RECEPTOR BY DR.MOHAMMED ABDUL RAOF

• Requirement of higher dose to produce a given response.

• It occurs over a period of time.

• E.g. tolerance to sedative-hypnotics.

• Many reasons for tolerance:

2. Pharmacodynamic reasons (reduced number and/or affinity

Continued use & stimulation of receptors by agonist drugs

This phenomenon is called down regulation

Eg: Constant use of β2 agonist (salbutamol) reduce

• Continued use and inhibition of receptors by antagonist

• This phenomenon is called up regulation.

• Eg: sudden withdrawal of anti-anginal drug (Propranolol)

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