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Introduction
• Pharmacology came from the Greek words “Pharmacon”
meaning drug or medicine and “logos” meaning the truth
about or a rational discussion.
• Pharmacology
>> Is the study of drugs and their interaction with living systems.
• Medicine
>> Are chemicals that alter functions of living organisms given for
the diagnosis, prevention, control or cure of disease.
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Cont’ed
• Drug names
– For written and verbal communications about drugs
– To put labels to identify the medications present in containers
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Basic Principles of pharmacology
Pharmacokinetics
- Pharmacon------------ drugs or poison
- Kinesis------------------ motion
The four major pharmacokinetic processes are:
Drug absorption
- The movement of drugs from the site of administration into
the blood.
Drug distribution
- Drug movement from the blood to the interstitial space of
tissues and from there into cells.
Drug metabolism
- Enzymatically mediated alteration in drug structure.
Drug excretion
- Movement of drugs (& their metabolites) out of the body.
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The four basic pharmacokinetic processes.
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Cont’ed
• Determine the concentration of a drug at its sites of
action.
• All phases of pharmacokinetics involve drug movement
• Factors that determine the passage of drugs across
membranes have profound influence on all phases.
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Passage of drugs across membranes
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Passage of drug
Drugs can cross cellular membranes by:
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Absorption
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Factors affecting drug absorption
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Characteristics of Commonly Used Routes of
Administration
ROA of administration affects rate of absorption.
1. Parentral
Intravenous (IV)
Advantages—Absorption is instantaneous and complete;
rapid onset; precise control over levels; can use large
volumes of fluids; used for irritating drugs.
Disadvantages—High cost; cannot self-administer; cannot
reverse injection; could cause fluid overload; increased risk of
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Intramuscular (IM)
• Advantages—Only barrier is capillary wall; used for
poorly soluble drugs; for depot preparations to
decrease number of injections.
• Disadvantages—Inconvenience; discomfort with
administration.
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Subcutaneous (SC)—Almost identical to IM for
advantages and disadvantages.
2. Enteral—Via gastrointestinal tract
Oral(PO); must cross GI tract and capillary wall; highly
variable absorption.
• Advantages—Administration is easy, convenient, and
inexpensive.
• Disadvantages—High variability, inactivated by pH and
first-pass effect; requires compliance; local irritation.
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Comparing oral administration with parenteral
administration
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Bioavailability(F)
• Bioavailability is the amount of drug which enters
the plasma or site of action.
• For an IV infusion, all the drug administered appears
in the plasma, and so bioavailability = 100%
• Bioavailability is often expressed as fractional
bioavailability, F, where
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Distribution
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Metabolism (Biotransformation)
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First-Pass Metabolism
• Following nonparenteral administration of a drug, a
significant portion of the dose may be metabolically
inactivated in either the intestinal endothelium or the
liver before it reaches the systemic circulation
• Limits oral availability of highly metabolized drugs
Types of biotransformation
Classified as phase-I & phase – II
• In phase-I reaction the drug is converted to more polar
metabolite.
– Oxidation, reduction and hydrolysis.
– Some metabolites may not be excreted and further
metabolised by phase –II reactions.
• Phase-II: Glucuronidation, sulfate conjugation, acetylation,
glycine conjugation and methylation reactions.
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Therapeutic Consequences of Drug Metabolism
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Factors affecting drug biotransformation
Genetic polymorphism
Disease conditions especially of the major drug
metabolizing sites.
Age
Predisposing factors to enzyme induction or inhibition.
• Diet :- eg. grape fruit juice (inhibit cyp3A4)
• Sex:- eg. Alcohol
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Induction & inhibition of drug metabolism
Enzyme ↑ synthesis of
microsomal ↑metabolism ↑excretion
duction enzyme
Enzyme ↓liver
enzyme ↓metabolism ↓excretion-
hibition function
toxicity
Excretion
• Drug excretion is the elimination (passage
out) of a systemically absorbed drug from the
body in the form of metabolites or unchanged
drug.
– It is a process of drug transfer from the
internal to the external environment
The kidneys are the main organ of excretion
of drugs and their metabolites.
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Renal excretion
• Principal organ for most drug removal
especially for water soluble (responsible for
excreting water soluble substances) and
non volatile drug
• The amount of drug or its metabolites
ultimately present in urine is the
cumulative effect of:
– Glomerular filtration
– Tubular secretion
– Tubular reabsorption
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Generally the rate of urinary drug excretion will
depend on:
Drug volume of distribution
Degree of protein binding
Glomerular filtration rate
Tubular fluid PH
Extent of back-diffusion of unionized form of drug
Extent of active tubular secretion of compound
Possibly, extent of tubular reabsorption
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Excretion
• Removal of drugs from the body
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Time Course of Drug Responses
A. Plasma Drug Levels
Clinical significance of plasma drug levels—there is usually direct
correlation between therapeutic and toxic responses and plasma
drug levels.
Two plasma drug levels defined
A. Minimum effective concentration (MEC) –
> Is defined as the plasma drug level below which therapeutic
effect will not occur.
B. Toxic concentration – the plasma drug level
> At which toxic effects begin is termed as toxic concentration.
Drug Half-Life - Time required for amount of drug in the body to
decrease by 50 %.
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Therapeutic range—Objective of drug dosing (between
MEC and toxic levels).
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Pharmacodynamics
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Receptor families
Action of drug
• Most drugs (free drug) act by forming chemical
bonds with specific receptor sites within the body to
stimulate and/or inhibit a response.
• Some drug act trough simple physical or chemical rxn
with out interacting with receptor
– Receptors: cimetidine + histamine receptor
– Enzyme--- eg acetylcholinesterase ---neostigmine
– Structural proteins: colchicine + tubuline
– Ion channel---Ca2+ channel ----calcium channel
blocker (verapamil)
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– Carrier molecule –proton pump inhibitor---
omeoprazole
• Site of drug action
– Extracellularly e.g osmotic diuretics
– On the cell surface e.g digitalis
– Inside the cell e.g anticancer drugs
Drug & receptor
Affinity: ability of a ligand (the drug) to bind to receptors
Intrinsic activity (efficacy): ability of a ligand to activate
(cause change in receptor conformation) upon binding
and produce the response.
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In view of binding, ligands can be
Agonists: It binds to the receptors and it will activate the
receptor.
Has both affinity and intrinsic activity (A=1 & IA=1). Eg.
morphine, epinephrine
Antagonist: binds to the receptor but it will not activate the
receptor.
Has affinity but no intrinsic activity (A=1 & IA=0). Eg :
atenolol, metoprolol, Prazosin
Partial agonist/antagonist: It activates the receptor and
produce sub maximal response.
Has affinity but with sub maximal intrinsic activity (A=142&
Dose response relation ship
Is the relationship between intensity of drug effect and
drug dosage (drug level)
Has two components
Potency
• It refers to the amount of drug needed to produce
the response.
Intrinsic activity (IA) (Efficacy)
• It refers to the maximum response of the drug.
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Drug-drug interaction
Reversible antagonism
-Is reversible since week bond b/n receptor & antagonist
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Agonist- antagonist interaction at receptors
• Competitive antagonist
– Agonist & antagonist compete for same receptor
site
– Do not produce effect by themselves but ↓
agonist potency
– ↑ dose of agonist reverse antagonist effect
– Dose-response curve shift to the right
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Agonist- antagonist interaction at receptors
• Non-competitive antagonism
– Binding site for antagonist is different from agonist
– Antagonist cannot be overcome by ↑ increasing
agonist concentration
– ↓ maximal response
• Irreversible antagonist
– Strong covalent bond
– Irreversibly inactivate the receptor
– Shift the dose response curve to right & ↓ maximal
response
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Drug adverse effects and drug toxicities
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Unexpected adverse effects
Hypersensitivity reactions: abnormal response
due to antigenic nature of some drugs
Allergy
Anaphylaxis: extreme sensitivity to antigenic
substance and subsequent circulatory collapse
Idiosyncratic reactions: an abnormal reactivity to
a chemical that is peculiar to a given individual.
General procedures in the management of
poisoning
o Life support
The first step is to recognize and treat life threatening
conditions (ABCD)
o Drug identification
More detailed evaluation to make a specific diagnosis
o Decontamination
Should be undertaken simultaneously with initial
stabilization, diagnostic assessment, and laboratory
evaluation
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Termination of exposure to the toxic substance
Allowing to fresh air
Washing of the eyes and skin
Prevention of further absorption of ingested poison
Induction of emesis
Use of adsorbent
Induction of purgation
o Specific antidotes
– e.g. Atropine antidote Anticholinesterases
o Enhancing elimination of toxins
- Hemodialysis or urinary alkalinization