BASIC PHARMACOLOGY
2
SAMUEL AGUAZIM(MD)
PHARMACODYNAMICS
• Pharmacodynamics describes the actions
of a drug on the body and includes the
principles of receptor interactions,
mechanisms of therapeutic and toxic action
and dose- response relationships
How is Pharmacodynamics
related to pharmacokinetics?
• the pharmacokinetics processes of
absorption, distribution and
biotransformation and excretion determine
how quickly and to what extent a drug will
appear at a target site.
• Pharmacodynamics concept explain the
pharmacological effects of drug and
mechanism of action
Receptor Interactions
• What is a receptor?
• A macromolecule typically made up of
proteins that interacts with either an
endogenous Ligand or a drug to mediate a
pharmacologic or physiologic effect
What are two main functions
of receptors?
• 1. Ligand binding
• 2. Activation of an effectors system ( message
propagation)
What is an effectors?
• Effectors transduce drug receptor interactions
into cellular effects. There are four types of
well- know effectors mechanisms
1.Transmembrane• some ligands such as insulin bind to receptors
that have both extracellular and intracellular
component.
• Binding of the extracellular component
stimulates the intracellular component, which
is coupled to an enzyme, for example tyrosine
kinase
2. Ligand-gated ion
channels• drugs bind to these receptors, which then alter
the conductance of ion through the cell
membrane
• Example of ligand-gated ion channel drugs are
benzodiazepines and acetylcholine
3.Intracellular• thyroid and steroid hormones bind to nuclear
receptors to form complexes that interact with DNA
which causes changes in gene expression
4.Second messenger system• Drugs bind to receptors that activate second
messenger systems involving G protein
• Second messenger system allows signals form
cell surface receptors to be converted and
amplified into a cellular response
3 types of second messenger
• 1. Cyclic adenosine monophosphate (cAMP) –
produced by adenylate cyclase
• 2. Cyclic guanosine monophosphate( cGMP)
produced by guanylate cyclase
• 3. Inositol triphosphate (IP3)- produced by
phospholipase C
Mechanism of Therapeutic and Toxic
Action
What is an agonist:
a drug that binds to and activate receptors.
What is a full agonist?
A drug that when bound to a receptor, produces
100% of the maximum possible biologic response
• What are partial agonists?
• Produces the biological response but cannot
produce 100% of the biological response even at
very high dose
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• What are antagonists?
• Drugs that bind to receptors or other drugs
and inhibit a biologic response
• What does a competitive
antagonist do?
• It binds reversibly to the same active site of an
enzyme as an agonist
• How can a competitive antagonist be
overcome?
• By increasing the concentration of the
drug(agonist). The maximum efficacy of the
drug will not change in the presence of a
competitive antagonist
• What does a noncompetitive antagonist do?
• It binds irreversibly to a different site on the
enzyme than the antagonist.
• Noncompetitive agonists cannot be overcome
by increasing concentrations of the drug.
• Note: maximum efficacy will be reduced in the
presence of a noncompetitive antagonist
Dose-Response Relationships
• What is the difference between efficacy and
potency
• Efficacy is the ability to produce a biologic effect.
• Potency is related to the amount of drug
necessary to cause a biologic effect
• E.g. Two Drugs A and Drug B are both claimed to
reduce a patient’s heart rate by 25%, then they
both have the same efficacy.
• Give an example of potency.
• Only 1 mg of drug A needs to be given to
achieve a reduction in heart rate.
• Whereas 10mg of drug B are needed.
Therefore , it can be inferred that drug A is
more potent.
• What is Kd?
• The concentration of drug yielding 50% occupancy
of the receptor( dissociation constant)
• What is EC50?
• The drug concentration that produces 50% of the
maximum possible response in a graded doseresponse curve
Drug Dosing and Prescription Writing
• DRUG DOSING
• What three factors are involved in
determining an appropriate drug dose for a
patient?
• 1. type of infection or disease
• 2. patient variables( e.g. weight, liver or
kidney disease)
• 3. Plasma concentration needed to achieve
efficacy
What is volume of distribution(Vd)?
• The apparent volume into which a drug is able
to distribute
• How is Vd calculated?
• Vd= total drug in the body divide by plasma
concentration of the drug
• What is the significance of a large Vd?
• Based on the equation presented above, a large
Vd signifies that most of the drug is being
sequestered in some organ or compartment
• What is a maintenance dose?
• A dose of a drug given to achieve a
therapeutic plasma concentration over an
extended period of time
• What is the equation for calculating a
maintenance dose?
• Maintenance does= clearance multiply by
desired plasma concentration
• What is important to remember in performing
this calculation?
• You must be absolutely certain that
the units are correct.
• What is a loading dose?
• It is a single large dose of a drug that is used to
raise the plasma concentration to a therapeutic
level more quickly than would occur through
repeated smaller doses.
• What is the equation for calculating a loading
dose?
• Loading dose= Vd
concentration
x
desired plasma
• Define peak and trough concentrations?
• These are maximum and minimum plasma
concentrations, respectively, which are
observed during dosing intervals.
• these variable will fluctuate around the
steady state plasma concentration
• What is the steady state plasma
concentration?
• The point at which the rate of drug availability
is equal to the rate of drug elimination
• Frequency of dosing does not affect steady
state of concentration
• What is clearance? Is a term that indicates
the rate at which a drug is cleared from the
body.
• Clearance is defined as the volume of plasma
cleared of drug per unit of time.
• What is an excretion rate?
• The rate at which a drug is eliminated from
the body, which is measured by clearance x
plasma concentration
• What is therapeutic index? It is a measure of
drug safety.
• The ratio of a drug’s toxic to its therapeutic dose.
A safe drug will have high therapeutic index.
• How to calculate therapeutic index?
• Therapeutic index= LD 50/ED50
• LD: Lethal dose
• ED: Effective dose