TYPES

OF DRUG INTERACTION
•  ADDITIVE
–  The response elicited by combined drugs is EQUAL to the
combined responses of the individual drugs (1 + 1 = 2); i.e.
barbiturate+BZD (tranquilizer) to relax paJents preop.
•  SYNERGISM
–  The response elicited by combined drugs is GREATER than
Review CONT…
the combined responses of the individual drugs ( 1 + 1 =
3); drugs are of similar acJon i.e. barbiturate+alcohol
•  POTENTIATION
Leeland Anthony L. dela Luna, R.Ph, Pharm.D
–  A drug which has no effect on the system enhances the
effect of the other (0 + 1 = 2); i.e. morphine+anJhistamine
•  ANTAGONISM
–  Drug inhibits the effect of another due to opposite
pharmacological acJons (1 + 1 = 0)
 TYPES OF DRUG INTERACTION
Drugs under the
•  ADDITIVE SAME TherapeuJc
–  The response elicited by combined drugs is EQUAL to the
group…
combined responses of the individual drugs (1 + 1 = 2); i.e.
barbiturate+BZD (tranquilizer) to relax paJents preop.
Like AddiJve
•  SYNERGISM InteracJon BUT more
–  The response elicited by combined drugs is GREATER than
Effects!
the combined responses of the individual drugs ( 1 + 1 =
3); drugs are of similar acJon i.e. barbiturate+alcohol
Drugs are under
•  POTENTIATION DIFFERENT
–  A drug which has no effect on the system enhances the
therapeuJc
effect of the other (0 + 1 = 2); i.e. morphine+anJhistamine
categories
•  ANTAGONISM
–  Drug inhibits the effect of another due to opposite
pharmacological acJons (1 + 1 = 0)
 DOSE-RESPONSE RELATIONSHIP

•  “GRADED” RESPONSE
–  It is characterized by the
magnitude of resistance
increasing conJnuously with
greater concentraJon of
unbound drug at the
receptor site
 Criteria for drug selecBon and determining
appropriate doses of drug

•  POTENCY 100%
–  Refers to the concentraJon
(EC50) or dose (ED50) of a drug Emax
required to produce 50%of that
drug’s maximal response
•  EFFICACY 50%
–  The relaJonship between
receptor occupancy and its
ability to iniJate a response
–  Graded dose-response curve
indicates maximal efficacy of a ED50
drug 0%
–  A.k.a. “Intrinsic AcJvity” 0 0.1 0.2 0.3 0.4

–  Measured by Emax
 Describes how strong a
drug BINDS to its
receptor
AGONIST Describes HOW GOOD
the response to the
drug is.

•  IniJate cell funcJon producing effects of

various types
•  Potency depends on; affinity and efficacy
–  Full agonist (high efficacy)
–  ParJal agonist (intermediate efficacy)
* Potency refers to the rela1ve concentra1on required to produce a
given magnitude of effect
Types of Drug-Receptor Interactions: Agonists
100%

Full Agonist
PERCENT MAXIMUM RESPONSE

Full agonist gives

100% efficacy

50%

ParBal Agonist

ParJal agonist gives less

than 100% efficacy

0%
0 0.1 0.2 0.3 0.4
DOSE
 ANTAGONIST
•  Bind to receptor without iniJaJng changes
•  Efficacy is zero
•  Inhibits or blocks responses caused by agonist
 TYPES OF DRUG ANTAGONISM

•  COMPETITIVE ANTAGONISM
•  Equilibrium compeJJve or reversible
•  Nonequilibrium compeJJve or irreversible
•  NONCOMPETITIVE ANTAGONISM
•  PHARMACOKINETIC ANTAGONISM
•  CHEMICAL ANTAGONISM
•  PHYSIOLOGICAL ANTAGONISM
COMPETITIVE ANTAGONISM
Types of Drug-Receptor Interactions: Antagonist
100%

Agonist Alone
PERCENT MAXIMUM RESPONSE

50% Higher dose of agonist +

Reversible antagonist

“Rightward Shih”
Agonist + Reversible
Antagonist
Effects decrease

But if the dose of the agonist is

increased, it’s effects would be restored
0%
0 0.1 0.2 0.3 0.4
Lowers POTENCY but not EFFICACY
DOSE
Equilibrium Competitive (reversible) Antagonists

• Bind reversibly to receptors at the

same site as the agonist
• Competitively prevent the agonist
from binding to the receptor
causing a blockade of effects
• Graphically observed as a
rightward
shift of the dose-response
curve
• Effects can be overcome by adding
higher concentrations of the
agonist
• Lower potency but have no effect
on efficacy because they
produce the same maximum
response as agonist alone
Types of Drug-Receptor Interactions: Antagonist
100%

Agonist Alone
PERCENT MAXIMUM RESPONSE

50% Higher dose of agonist +

Irreversible antagonist

“Downward Shih”
Agonist + Irreversible
Antagonist
Effects decrease

Even if the dose of the agonist is increased, it’s

effects would sJll be reduced
0%
0 0.1 0.2 0.3 0.4
Lowers EFFICACY but not POTENCY
DOSE
 Non-equilibrium Competitive (irreversible) Antagonists

• Bind irreversibly to either the same

site as the agonist or to an
alternative site thus, causing
blockade of the effects of the
agonists
• Graphically observed as a
downward shift of the dose-
response curve with no
potential for achieving
maximum response
• Increasing concentrations of the
agonist has no effect since
interaction is irreversible
and bound drug are no
longer available for
activation
• Lowers the efficacy, but has no
effect on potency
NON-COMPETITIVE
ANTAGONISM
 NoncompeBBve Antagonism
•  The antagonist acts at a site beyond the receptor
for the agonist
•  Antagonizes agonists acting through more than
one receptor system (e.g., diazoxide)
PHARMACOKINETIC
ANTAGONISM
 PHARMACOKINETIC ANTAGONISM
Reduces
•  Antagonist effecJvely reduces the
ConcentraJon, NOT
necessarily the
concentraBon of the acJve drug at its site of
effects…

acJon
•  Example: Phenobarbital reduces anJcoagulant
effect of warfarin by acceleraJng its
metabolism
•  Affects the ADME.
CHEMICAL ANTAGONISM
 CHEMICAL ANTAGONISM
•  NeutralizaJon
•  Two substances combine in soluJon, so that
the effect of the acJve drug is lost
•  Example: Dimercaprol chelates heavy metals
and thus reduce their toxicity
PHYSIOLOGIC ANTAGONISM
 PHYSIOLOGICAL ANTAGONISM

•  InteracJon of two drugs whose opposing acJons in

the body tend to cancel each other
•  It describes the ability of an agonist (rather than an
antagonist) to inhibit the response to a second agonist
via activation of different receptors that are physically
separate
QUANTAL DOSE RESPONSE RELATIONSHIP

•  Graphically plots the percent of the

popula.on that responds to a drug versus the
drug dose
•  QUANTAL RESPONSE
–  The observable response can be described only in
terms of an all or none event.
 QUANTAL DOSE EFFECT CURVE
Ohen characterized by staJng the;
•  MEDIAN EFFECTIVE DOSE (ED50)
–  The dose at which 50% of the individual exhibit
the specified quantal effect
•  MEDIAN TOXIC DOSE (TD50)
–  The dose required to produce a parJcular toxic
effect in 50% of animals
•  MEDIAN LETHAL DOSE (LD50)
–  The dose with which the toxic effect is death to
50% of the populaJon
 Drugs with opposing effect Drugs with similar effect

Displacement
from protein
binding site
Alteration
of absorption
Drug
Interactions

Inhibitors
or facilitator
of excretion

Changes
in
metabolism

Alteration of
electrolyte levels Alteration of GI flora
 Toxic reactions
•  Is the degree or extent to which a drug can be poisonous and
thus harmful to the human body
•  Is injury or death produced by any substance when it is
absorbed by a living organism
•  Classes
–  Dose related toxicity
–  Drug-induced diseases
–  IdiosyncraJc reacJons
–  Allergic related reacJons
 Allergic Reactions
•  An anJgen-anJbody reacJon
•  An adverse reacJon that results from
previous exposure or sensiJzaJon to
a parJcular drug
•  It is not a result of the pharmacologic
effects of drug but rather, is a result
of paJent’s immune system, which
idenJfies the drug as foreign
substance that must be neutralized
or destroyed