Documente Academic
Documente Profesional
Documente Cultură
PHARMACOLOGY
Leeland Anthony L. dela Luna,
Pharm.D, R.Ph
PROCEED
VERIFY
REMEMBER
UNDERSTAND
THINK
READ
PROFESSION
Science of drugs
PHARMACY
Science of:
Identification
Selection CHEMISTRY!
Preservation
Standardization
Compounding
Dispensing
OF MEDICINAL SUBSTANCES
How drugs
WORK!
PHARMACOLOGY
Science about:
Effects of drugs on
the body
BIOLOGY +
CHEMISTRY
Something that is
Produced
SYNTHETIC
Molecules in
RESEARCH are
still drugs
Which means.
All CHEMICALS that are
Vaccines
Diagnostic agents
Cures diseases
Relieves symptoms
Prevents conception
PHARMA COGNOSY
About DRUGS
To KNOW
CLINICAL PHARMACY
Related to interaction between
DOCTOR and PATIENT
PHARMACO KINETICS
About DRUGS
About MOVEMENTS
Absorption
Distribution
Metabolism
Excretion
PHARMACO DYNAMICS
About DRUGS
Dynamo = POWER
THERAPEUTICS
Deals with:
CURE of the disease (i.e. TB, Malaria)
RELIEF of the symptoms (i.e. Fever, Breathlessness)
It INVOLVES both:
PHARMACOLOGIC Tx (with drugs)
NON PHARMACOLOGIC Tx (i.e. exercise, life style
modification, diet modification, etc.)
TOXI COLOGY
About POISONS
To STUDY
QUALITATIVE ASSESSMENT
Finding the NATURE of the
poison
QUANTITATIVE ASSESSMENT
Finding the AMOUNT of the
poison ingested
CHEMOTHERAPY
Effects of drugs on the cell division / on the
cells of:
NORMAL HOST CELL
MICROORGANISMS
MALIGNANT CELLS
PHARMACOEPIDEMIOLOGY
It is the study of effects and uses of drugs in
large number of people
PHARMACO-ECONOMICS
It is the analysis of the cost of drug therapy to
the healthcare system and the society.
PHARMACOGENOMICS
Science that examines the:
Variation in genes that dictates the drug response
of:
Humans
Microbes
Tumors
DRUG NOMENCLATURE
CHEMICAL NAME
It says something about the chemical composition
Paraacetyl amino phenol
GENERIC NAME
Name assigned by a SCIENTIFIC BODY/AUTHORITY
Paracetamol
BRAND/TRADE NAME
Name assigned by the MANUFACTURER
Biogesic / Calpol
Pharmacology
Pharmacodynamic Principles
Levels of Drug
Action
Molecular
Cellular
Tissue
System
Molecular Targets
Hormones and
neurotransmitter
receptors
Enzymes
Carrier molecules
Ion channels
Idiosyncratic targets
Nucleic acids
Propranolol
Rifampin
Molecular
Cellular
Inhibits mycobacterial
RNA synthesis and
thereby kills the
mycobacterium
Tissue
System
Receptor
RECEPTORS
AGONIST
EFFECTS!!!
Receptor
RECEPTORS
ANTAGONIST
AGONIST
Blocks the active site
of the receptor
Receptor
The agonist will be
deflected; will not
bind to the active site,
thus NO EFFECT
Ion Channels
DRUG
Receptor
Ion Channels
DRUG
Receptor
Ion Channels
DRUG
Receptor
Ion Channels
Permeation of the
channel is blocked.
Enzymes
DRUG
Enzymes
Enzymes
DRUG
Enzymes
Produce an ABNORMAL
metabolite
DRUG
Produce an ACTIVE metabolite
Enzymes
Types of Receptor-Effector
Linkage
(Signaling Mechanisms)
milliseconds
Nicotinic
ACh receptor
seconds
Muscarinic
ACh receptor
Kinase-linked
receptors
Receptors linked to
gene transcription
(nuclear receptor)
minutes
hours
Insulin
receptor
Estrogen
receptor
DRUG
Receptor
Happens in a matter or
MILLISECONDS
Inotropic
Ion channels
Activation generates action potentials
EPSP (excitatory post synaptic potentials) are
initiated when excitatory neurotransmitter activates
Na+ or Ca+2 channels
IPSP (inhibitory post synaptic potentials) are
initiated when an inhibitory neurotransmitter open
Cl and K+ channels and membrane becomes
hyperpolarized
Ion Channels
Ligand gated or receptor operated ion channel (ROC)
activated when a drug or an endogenous substance
(neurotransmitter) binds with a specific receptor
thus increasing transmembrane conductance of the
relevant ion and thereby altering the electrical
potential across the membrane
VOC when a drug or an endogenous substance
(neurotransmitter) do not bind directly but are
activated by membrane potential
RECEPTOR
as the G-PROTEIN
G-Protein(Second
Messenger)
GDP Molecule
The binding caused
a phosphorylation
to the GDP, making
it to GTP (Active)
RECEPTOR
G-Protein(Second
Messenger)
GTP
ATP
ATP will be processed
by adenylyl cyclase
and be converted to:
2 Phosphate molecules
G-Protein(Second
Messenger)
GTP
GTP
G-Protein(Second
Messenger)
RECEPTOR
G-Protein(Second
Messenger)
Gi inhibit
adenylyl cyclase
Gs activate
adenylyl cyclase
Gq activate
Phospholipase C
RECEPTOR
(i.e. Insulin)
RECEPTOR
ATP
tyr
tyr
tyr
tyr
tyr
tyr
Activated
Proteins
CELLULAR EFFECTS!!!
Carrier Molecules
Energy-independent carriers
Energy-dependent pumps
Uniporters
Symporters
Antiporters
Uniporter
Symporters
are transport proteins that simultaneously transport two
substances across the membrane in the same direction
Antiporters
are transport proteins that transport one substance across the
membrane in one direction while simultaneously transporting a
second substance across the membrane in the opposite
direction e.g. Na+/Ca2+- exchanger
SYNERGISM
POTENTIATION
ANTAGONISM
DOSE-RESPONSE RELATIONSHIP
GRADED RESPONSE
It is characterized by the
magnitude of resistance
increasing continuously with
greater concentration of
unbound drug at the
receptor site
EFFICACY
The relationship between
receptor occupancy and its
ability to initiate a response
Graded dose-response curve
indicates maximal efficacy of a
drug
A.k.a. Intrinsic Activity
Measured by Emax
100%
Emax
50%
0%
ED50
0
0.1
0.2
0.3
0.4
AGONIST
Full Agonist
Full agonist gives
100% efficacy
50%
Partial Agonist
Partial agonist gives less
than 100% efficacy
0%
0
0.1
0.2
DOSE
0.3
0.4
ANTAGONIST
Bind to receptor without initiating changes
Efficacy is zero
Inhibits or blocks responses caused by agonist
NONCOMPETITIVE ANTAGONISM
PHARMACOKINETIC ANTAGONISM
CHEMICAL ANTAGONISM
PHYSIOLOGICAL ANTAGONISM
Competitive antagonism
Agonist Alone
50%
Rightward Shift
Agonist + Reversible
Antagonist
Effects decrease
But if the dose of the agonist is
increased, its effects would be restored
0%
0
0.1
0.2
DOSE
0.3
0.4
Agonist Alone
50%
Downward Shift
Agonist + Irreversible
Antagonist
Effects decrease
Even if the dose of the agonist is increased, its
effects would still be reduced
0%
0
0.1
0.2
DOSE
0.3
0.4
Non-Competitive
antagonism
Noncompetitive 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
Antagonist effectively reduces the
concentration of the active drug at its site of
action
Example: Phenobarbital reduces anticoagulant
effect of warfarin by accelerating its
metabolism
Chemical antagonism
CHEMICAL ANTAGONISM
Neutralization
Two substances combine in solution, so that
the effect of the active drug is lost
Example: Dimercaprol chelates heavy metals
and thus reduce their toxicity
Physiologic antagonism
PHYSIOLOGICAL ANTAGONISM
Interaction of two drugs whose opposing actions 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
Example: Histamine stimulates GI acid secretion, while
Omeprazole inhibits proton pump thus blocking this
effect
Displacement
from protein
binding site
Drug
Interactions
Alteration
of absorption
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
May result from the local accumulation of a drug or drug
overdose thus, toxic levels may build up before enough
drug is eliminated to reach steady state in the
therapeutic range
Drug-induced Diseases
Toxicity causing damage to tissues and organs which may
either be reversible or irreversible depending on the
toxicity and the tissues or organs involved
Idiosyncratic Reactions
An unexpected reaction to a drug which is a result of a
genetically determined abnormality
Allergic Reactions
An antigen-antibody reaction
An adverse reaction that results from previous
exposure or sensitization to a particular drug
It is not a result of the pharmacologic effects of
drug but rather, is a result of patients immune
system, which identifies the drug as foreign
substance that must be neutralized or
destroyed