This document discusses various concepts related to pharmacodynamics including: - Agonists bind to receptors and induce a response, while antagonists bind but do not activate the receptor. Full agonists produce maximum response even at low receptor occupancy, while partial agonists cannot elicit full response. - Antagonists can be competitive and reversible or non-competitive and irreversible. Allosteric antagonists bind elsewhere and prevent receptor activation. - Drugs can have additive or potentiating effects when given together. Potency refers to amount needed for effect, while efficacy is the capacity to induce response. Therapeutic index measures safety. - Doses include therapeutic, toxic, loading and maintenance amounts.

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PHARMACODYNAMICS
By
Dr. Faraza Javaid

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AGONIST
When a drug binds to a receptor, there is
conformational change which initiates chain
of chemical events, leading to response, the
drug is said to be AGONIST.

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Antagonist
The drug binds to receptor but does not activate
it, don't induce a conformational change, it has
no intrinsic activity.

4. Types of Agonists
FULL AGONIST: have a high efficacy and
are able to produce maximum response,
while occupying only small percentage of
receptors.
It has affinity and efficacy (activity) both.
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5. For example, phenylephrine is a full agonist at
α1-adrenoceptors, because it produces the
same Emax as the endogenous ligand,
norepinephrine.
Upon binding to α1-adrenoceptors on vascular
smooth muscle, both norepinephrine and
phenylephrine stabilize the receptor in its
active state, thereby increasing Gq activation.
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PARTIAL AGONIST: Have low efficacy and
are unable to elicit maximum response, even if
they occupy all available receptors, regardless
of concentration
e.g. Pindolol ( β-adrenoceptor blocker)
For example, aripiprazole, an atypical
antipsychotic, is a partial agonist at selected
dopamine receptors. Overactive dopaminergic
pathways tend to be inhibited by aripiprazole,
whereas underactive pathways are stimulated.

7. Inverse Agonist: is a drug that binds to a
same receptor as an agonist but induces a
pharmacological response opposite to that of
an agonist.
e.g. β-carbolines (at Benzodiazepine
receptor)
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Types of Antagonist
Competitive antagonist
They bind to receptor reversibly.
The effect can be overcome by increasing
the concentration of agonist.
For example, the antihypertensive drug terazosin
competes with the endogenous ligand
norepinephrine at α1- adrenoceptors, thus
decreasing vascular smooth muscle tone and
reducing blood pressure.

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Non-Competitive Antagonists
(Irreversible)
Bind covalently to the active site of receptors,
thereby reducing the number of receptors
available to the agonist.
The effect cannot be overcome by increasing
the concentration of drug.
E.g Phenoxybenzamine (alpha blocking drug)

11. Allosteric Antagonists
An allosteric antagonist binds to a site
(allosteric site) other than the agonist-binding
site and prevents receptor activation by the
agonist.
An example of an allosteric agonist is
picrotoxin, which binds to the inside of the
GABA controlled chloride channel.
When picrotoxin binds inside the channel, no
chloride can pass through the channel, even
when GABA fully occupies the receptor.
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Spare Receptors
Many full agonists are capable of eliciting
maximal response at very low occupancies,
often less than 10%, such system is said to
be possess spare receptors.
This means response can be achieved with a
lower concentration of hormone or
neurotransmitter, than if fewer receptors
were present.

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ANTAGONISM
When two drugs are give together, the
action of one drug opposes the action of
other drug.
Types of antagonism
Chemical antagonism
 Simple chemical interaction b/w two
drugs
 No receptor involved
e.g. Antacids and tetracycline given
together form unabsorbed solutes.

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Physiological Antagonism
Drugs act on different receptors antagonizes
the physiological effect
Histamine H1-receptors relaxes vascular
smooth muscles producing hypotension
e.g. adrenaline α1-receptor VC, ↑ B.P

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Synergism
Correlated action or cooperation on the part
of two or more drugs
ADDITIVE EFFECT (Summation):
When effect of two drugs having the similar
action are additive i-e 2+2=4
eg. β-adrenocptor blocker plus a thiazide
diuretics have an additive
antihypertensive effect.

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POTENCIATION( to make more powerful)
when one drug increases the action of
other drug, i.e 2+2=5
e.g trimethoprim plus sulphonamide
or when one drug have no effect as own
but increases the effect of other drug
i.e 2+0 =5
eg. levodopa and carbidopa

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POTENCY
It is a measure (in weight) of how
much drug is required to elicit a given
response.
Drug of high potency will generally
have a high affinity for the receptors
.

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EFFICACY
Ability of the drug to produce maximum
response is called Efficacy
The capacity of the drug to activate the receptor
and response produced by a drug called
Intrinsic activity

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THERAPEUTIC INDEX
This is related to safety of drug
It is the ratio between lethal dose and
effective dose.
Therapeutic index = Lethal dose
Effective dose
If therapeutic index is more than one the
drug is safe. If it is one or less it is not safe
e.g Digoxin

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Dose:
It represents the amount of a drug to produce an effect
Therapeutic dose:
A dose which is required to produce a therapeutic effect
Toxic dose:
The dose which produces a toxic effect
Loading dose:
A large initial single or multiple doses are given for some
drugs to achieve a rapid steady state concentration

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Maintenance dose:
The dose which is used to maintain the steady
– state concentration or to maintain the
therapeutic effect of a drug. It is given at a
fixed interval time

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ED50 (Effective dose 50)
The dose or concentration which produces effect in
50% of the population in a group.
TD50 (Toxic dose 50)
The dose or concentration which produces toxic
effects in 50% of the population in a group.
LD50 (Lethal dose 50)
The dose or concentration which kills 50% of the
animals in a group

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Pro-Drug
 It is a drug which is pharmacologically
inactive after administration, by the action
of enzymes, it is chemically altered
To active form in the body.
e.g Enalapril to Enalaprilat
Aspirin to Salicylates
Levodopa to Dopamine
Valciclovir to Acyclovier

25. THANK YOU
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