1-General Pharmacology.pptx

General Pharmacology for Pharmacy
Students
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General Pharmacology

Introduction
 Pharmacology:
Greek, Pharmakon – drug/medicine & logos – study
Deals with the interaction of chemical agents (drugs) with
living systems
The study of drug kinetics & dynamics
Embraces knowledge of the sources, chemical properties,
biological effects & therapeutic uses of drugs
The basis of much of the research & dev’t of new drugs
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 Drug:
French word ‘Drogue’ means dried herb
Any substance used in the prevention, diagnosis, mitigation,
treatment, alteration of physiological processes or cure of
disease
Drugs influence (modulate) existing cellular processes &
functions but can NEVER produce new ones
 Poison: any substance that produces a harmful effect
‘The dose makes the poison’ - Paracelsus
Toxin: a poison of biological origin
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 Medicine:
 A chemical preparation usually (but not necessarily) contains
one or more drugs
 Substances that have definite form & therapeutic use for
treatment
 Medicine = API + Excipients
 The study of pharmacology requires understanding of normal
body functions (biochemistry & physiology) & the
disturbances that occur (pathology)
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Branches of Pharmacology
Pharmacokinetics
Pharmacodynamics
Pharmacotherapy
Pharmacogenetics
Clinical Pharmacology
Neuropharmacology
Molecular Pharmacology
Chemotherapy
Toxicology
General Pharmacology 6

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Relationship with other disciplines
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Sources of Drugs
 Natural:
Plants: leaves, flowers, fruits, seeds, barks, roots,…
Animals:
Drugs with cumbersome & expensive procedures of synthesis
Various organs & tissue of animals are used as source of drugs
Active principles of animal drugs are proteins, oils, fat,
enzymes and hormones
Minerals, Microorganisms, Human
8

 Semisynthetic:
When the nucleus of drug obtained from natural source is
retained but the chemical structure is altered
Semi-synthetic processes are preferable when the synthesis of
drugs is;
Difficult, expensive/uneconomical
Natural sources may yield impure compounds
Insulin, ampicillin, amoxicillin, aspirin
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 Synthetic:
Majority of drugs used in clinical practice
Advantages;
Chemically pure
Easy & cheap process of preparation
Excellent quality control of the drug
More effective & safer drugs can be prepared by modifying the
chemical structure of the prototype drug
Antipyretics, sulphonamides, antihistamines, anticonvulsants,
anti-anxiety
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 Biotechnology:
Produced by rDNA technology, cell cultures, hybridoma
technique
Human gene codes for insulin cloned into bacteria: E.coli
Hepatitis B gene w/c codes for HBs Ag is cloned into yeast, then
cultured to produce hepatitis B vaccine
Humulin, Human GH, Recombinex HB, Erythropoietin
Advantages:
Mass production, Cost effective
Less immunological reactions
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Drug Nomenclature
Is the systematic naming of drugs
A drug can have four types of names
 Code Name:
Given to a new drug at the time of development/ discovery
It consists of letters and numbers like AMG 785
Once the drug is approved, the code name is no more used
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 Chemical Name:
Scientific names, based on the molecular structure of the drug
IUPAC name used by chemists & scientists
Too lengthy & complicated to use
2-(4-{2-hydroxy-3-[(propan-2-yl) amino] propoxy} phenyl)
acetamide
atenolol
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 Nonproprietary/generic/ Name:
Internationally accepted common name: approved/official name
Constructed out of affixes & stems that classify the drugs into
useful categories while keeping related names distinguishable
Assigned by the USAN Council and the WHO INN programme
Written in lowercase
Usually indicate via their stems what drug class the drug
belongs to
propranolol, omeprazole, paracetamol, atenolol
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 Proprietary, Trade or Brand Name:
Unique name to a particular product, given by the manufacturer
Serves in establishing the identity of the product in the market
A drug may have multiple proprietary names
The first letter should be capitalized
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Drug Names: Examples

Nomenclature of Combination Drug Products
Two or more drugs combined into a single dosage form
These may have single nonproprietary names beginning with
"co-" exist in both BAN & PEN or
Two names are simply given, joined by hyphens or slashes
co-trimoxazole or trimethoprim/sulfamethoxazole
co-codamol or codeine-paracetamol (acetaminophen)
co-triamterzide or triamterene-hydrochlorothiazide
The USP ceased PENs, but "co"-prefixed BANs are still current

Categories of Drugs
Based on their legal status:
 Prescription only (Rx only) Drugs
Dispensed only by an order of registered physician
Used under medical supervision
Antibiotics
 Non-Prescription (OTC) Drugs
Can be dispensed without prescription
Vitamins, antacids, paracetamol, antihelminthics
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Dosage forms of drugs
 Dosage form:
The means by which drug molecules are delivered to sites of
action within the body
Can be classified based on: physical form, site of application,
route of administration, uses
Based on physical form:
Solid:
Tablets: conventional, chewable, sublingual, extended release
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Capsules: hard gelatine & soft gelatin
Powders: powder for injections, (vials)/reconstitution,
insufflations, dentifrices
Granules: effervescent granules
Suppositories
Pessaries
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Liquid: solutions, suspensions, emulsions
Solutions: homogenous/one phase preparations
Injectables: IV fluids, ampoules
Orally: syrups, elixirs, tinctures, linctuses
In mouth & throat: mouth washes, gargles, throat sprays &
paints
In body cavities: douches, enemas, ear drops, nasal sprays,
nasal drops, eye drops
Applied to the skin: lotions, liniments, collodions, paints
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Suspensions:
Heterogeneous
Insoluble powder in a vehicle
Need shake before use
Emulsions:
Heterogeneous
Two immiscible liquids
Need shake before use
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Semisolids: ointments, creams, pastes, gels (jellies)
Gases (pressurized): oral/nasal aerosols

Routes of Drug administration
The path by which a drug, fluid, poison or other substance is
brought into contact with the body
Generally classified by the location at which the substance is
applied
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Factors governing choice of Route
Drug characteristics
Ease of administration
Site of action
Onset of action
Duration of action
Quantity of drug administered
Liver and kidney diseases
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Enteral Routes
Enteral: drug placed directly in the GI tract
Sublingual: placed under the tongue
Oral: swallowing (p.o., per os)
Rectal: absorption through the rectum
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 Oral Route
 Advantages
Safe
Convenient
Economical
Usually good absorption
Can be self administered
 Disadvantages
Slow absorption & action
Irritable, unpalatable drugs
Uncooperative & unconscious pts
Some drugs destroyed
First-pass effect
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 Sublingual Route
 Advantages
Economical
Quick termination
First-pass avoided
Quick absorption
Can be self administered
 Disadvantages
Unpalatable & bitter drugs
Irritation of oral mucosa
Large quantities not given
Few drugs are absorbed
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 Rectal route
Advantages:
For unconscious & vomiting patient
To produce local effect
GI irritant drugs: indomethacin suppositories
For children: APAP suppositories
Less first pass metabolism than oral route
Superior rectal vein drains into the portal vein
The inferior & middle rectal veins drain into inferior vena cava
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Disadvantages:
Inconvenience of administration
Slow absorption of drugs
Superior rectal vein drains into the portal vein: 1st pass effect
Irregular and incomplete absorption
Many drugs can cause irritation of the rectal mucosa
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Vaginal Route
 Advantages:
Easiness of administration
Possibility of auto-administration
Bypass hepatic first pass-effect
Low systemic drug exposure for local conditions
Increased permeability for proteins and peptides versus the
oral or other routes
Antifungal vaginal pessaries
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 Disadvantages:
Social taboos, unawareness & gender-specificity
Menstrual cycle-associated vaginal changes
Genital hygiene issues
Local side effects
Coitus interference
Variable drug permeability
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First-pass Effect
Hepatic metabolism of a pharmacological agent when it is
absorbed from the gut and delivered to the liver via the portal
circulation
The greater the first-pass effect, the less the agent will reach
the systemic circulation when the agent is administered orally
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 Magnitude of first pass hepatic effect:
Extraction ratio (ER) =
CL liver
Q
where, Q is hepatic blood flow
(usually about 90 L per hour for 70 kg adult)
Drug bioavailability (F) may be determined from the extent of
absorption (f) & the extraction ratio (ER);
F = f x (1-ER)
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Parenteral Routes
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Intravenous (IV)
Absorption phase is bypassed: 100% BA
Precise, accurate & fast onset of action: valuable for emergency use
Permits titration of dosage: large quantities can be given
Fairly pain free
The most common route for drugs not absorbed orally
Greater risk of adverse effects:
High concentration attained rapidly
Can’t be reversed by emesis or charcoal
Risk of embolism
Not suitable for oily solutions or poorly soluble substances
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Intramuscular (IM)
 Advantages
Absorption reasonably uniform
Prompt from aqueous solution
Mild irritants can be given
Repository and slow release preparations
First pass avoided
Gastric factors can be avoided
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 Disadvantages
Only up to 10ml drug given
Local pain and abscess
Expensive
Infection
Nerve damage
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Subcutaneous (SC)
Slow & constant absorption, prompt from aqueous solution
Absorption is limited by blood flow, affected if circulatory
problems exist
Suitable for some poorly soluble suspensions & for instillation
of slow-release implants
Concurrent administration of vasoconstrictor will slow
absorption
Not suitable for large volumes
Possible pain or necrosis from irritating substances
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Inhalational (IH)
Aerosols (gaseous & volatile agents)-lungs
Rapid onset due to rapid access to circulation
Large surface area
Thin membranes separates alveoli from circulation
High blood flow
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Topical
 Mucosal membranes: eye drops, nasal drops, antiseptics
 Skin:
Dermal: rubbing oil or ointment (local action)
Transdermal: absorption through skin (systemic action)
Stable blood levels
No first pass metabolism
Drug must be potent or patch becomes to large
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Routes of administration & time of onset
IV: 30-60 seconds
Intraosseous: 30-60 sec
Endotracheal: 2-3 min
Inhalation: 2-3 min
Sublingual: 3-5 min
IM: 10-20 min
SC: 15-30 min
Rectal: 5-30 min
Oral: 30-90 min
Transdermal (topical)
variable (min - hrs)
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Time-release preparations
Oral: controlled-release, timed-release, sustained-release…
Designed to produce slow, uniform absorption for 8 hours or
longer
Better compliance, maintain effect over night, eliminate
extreme peaks and troughs
Depot or reservoir preparations:
Parental administration (except IV), may be prolonged by using
insoluble salts or suspensions in non-aqueous vehicles
Implantable contraceptives
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Pharmacokinetics
Deals with the fundamental processes that determine the
concentration of a drug at any moment and in any region of
the body
How and what the body does to the drug?
Drug ADME (LADME): drug disposition
Pharmacokinetic properties determine the onset, intensity, and
duration of drug action
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Absorption
The process by which a drug enters the bloodstream without
being chemically altered
Common sites of drug absorption:
Skin, mucous membrane: sublingual, nasal, rectal & vaginal
Stomach
Intestine
Lung cells
PK processes involve passage of drugs through membranes
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Passage of Drugs across Membrane Barriers
 Cell membrane
Bilayer of amphipathic lipids, with their hydrocarbon chains
oriented inward to form a continuous hydrophobic phase &
their hydrophilic heads oriented outwards
Membrane proteins embedded in the bilayer serve as structural
anchors, receptors, ion channels, or transporters to transduce
electrical or chemical signaling pathways and provide selective
targets for drug actions
50

Passage of drugs through cell membranes follow one or more
of the following major mechanisms
 Passive diffusion:
Dominates transmembrane movement of most drugs
Is along conce. gradient by virtue of drug solubility in the lipid
bilayer
Directly proportional to the magnitude of the concentration
gradient across the membrane, to the lipid: water partition
coefficient of the drug, and to the membrane surface area
exposed to the drug
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 Carrier mediated transport:
Facilitated diffusion
Active transport: primary & secondary
 Endocytosis:
Engulfing of large molecules (proteins, toxins) by the cell
membrane and release them intracellularly
Vitamin B12 is transported across the gut wall
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Passive diffusion
Aka non-ionic diffusion
>90% of drugs
Water-soluble drugs: through aqueous channels/pores
Does not require energy
Does not involve carriers
Not saturable
No structural specificity
53

Carrier mediated transport
 Facilitated diffusion
Movement down a concentration gradient
No input of energy
Structurally specific
Saturable
Levodopa & amino acids into brain
Glucose across muscle cell membrane by GLUT4
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 Active transport
Use ATP & carrier proteins
Against concentration/electrochemical gradient
Structurally specific (selective)
Saturable
Competitively inhibited by co-transported compounds
Na+/K+-ATPase
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Factors that influence absorption
Dosage form
Route of administration
Drug solubility at the site of absorption
pH (ionization)
Contact time at the absorption surface
Blood flow to the absorption site
Area of the absorbing surface
Expression of P-glycoprotein
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Bioavailability
The rate & extent to which an administered dose of a drug
reaches its site of action or a biological fluid (usually the
systemic circulation) from which the drug has access to its site
of action
Important for calculating drug doses for non-IV routes
F =
Quantity of drug reaching systemic circulation
Quantity of drug administered
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Determination of Bioavailability
By plotting [plasma] of drug vs time, AUC can be measured
Total AUC reflects the extent of absorption of the drug
BA of a drug given PO is the ratio of the AUC following oral
administration to the AUC following IV administration
(assuming IV & PO doses are equivalent)

Factors that influence bioavailability
First-pass metabolism
Extent of absorption
P-glycoprotein & gut wall metabolism:
Chemical instability: Penicillin-G, Insulin
Nature of the drug formulation
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Drug Distribution
The process by which a drug reversibly leaves the bloodstream
& enters the interstitial & cellular fluids
The reversible transfer of drug from one location to another
within the body
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Factors affecting distribution
Ability to cross cell membrane
Plasma protein binding: albumin (acidic drugs), α1-acid
glycoprotein (basic drugs), others: lipoprotein, globulin
(hormones)
Tissue binding
Physiological barriers: BBB, BPB, BTB
Rate of blood flow (perfusion)
Partitioning into fat
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Volume of Distribution (VD)
The apparent volume of body fluid in which the drug is
distributed
Polar & large molecules limited in the circulation whereas non
polar & small molecules distributed throughout the body
VD relates the amount of drug administered to the body to the
concentration of drug in blood or plasma
VD =
𝐷𝑜𝑠𝑒
𝐶o where Co= [plasma]

 High VD
High tissue protein binding
Relatively high lipid solubility
Distributed intracellularly
Low plasma protein binding
Difficult to remove by
hemodialysis
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 Low VD
 Confined to ECF (blood)
 Polar compounds, high MW
 High plasma protein binding
 Do not cross BBB or placental
barriers

Redistribution
In addition to crossing the BBB, lipid-soluble drugs redistribute
into fat tissues prior to elimination
In the case of CNS drugs, the duration of action of an initial
dose may depend more on the redistribution rate than on the
half-life
With a 2nd dose, the blood/fat ratio is less; therefore, the rate
of redistribution is less & the 2nd dose has longer duration of
action
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Elimination
The irreversible processes by which a drug is removed from
the body
Drugs have finite a duration of action in the body which is
determined by elimination
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Drug Biotransformation
 Enzyme mediated alteration of drug structure
 Drugs are chemically changed in the body
To facilitate excretion of drugs by rendering them
More polar (water soluble) or
Conjugating with highly polar molecules
68

Outcomes of Biotransformation
Drug  inactive metabolite(s): most drugs
Phenobarbital  Hydroxy phenobarbital
Pro-drug  Drug (active)
L-dopa Dopamine; Prednisone  Prednisolone
Drug  Active metabolite(s)
Terfenadine  Fexofenadine, Diazepam  nordiazepam
Drug  Toxic metabolite
Acetaminophen  NAPQI
69

Drug metabolizing systems
Are enzymatic in nature
Main site - liver, but also intestine, plasma, kidney…
 Microsomal enzymes: highly concentrated in liver ER
(microsomes) & are inducible
CYP450: major
Glucuronyl transferase
Dehydrogenase
Hydroxylase 70

 Non-microsomal enzymes
Present in the cytoplasm, mitochondria of d/t organs: lung, GI,
kidney, blood
Esterases, amidases, hydrolases, acetylases
Oxidases: monoamines
Dehydrogenases: alcohol
71

Phases of Biotransformation reactions
 Phase 1 enzymes: CYPs, FMOs, EHs
 Catalize functionalizatio/ nonsynthetic rxns
Cytochrome P450s (P450 or CYP): C & O oxidation,
dealkylation, others
Flavin-containing monooxygenases (FMOs): N, S, & P oxidation
Epoxide hydrolases (EHs): Hydrolysis of epoxides
Enzymes are located primarily in the ER
Reactions: oxidation, reduction & hydrolysis

 Phase 2 “transferases”: conjugation or synthetic rxns
Sulfotransferases (SULT): addition of sulfate
UDP-glucuronosyltransferases (UGTs): addition of glucuronic
acid
Glutathione-S-transferases (GSTs): addition of glutathione
N-Acetyltransferases (NATs): addition of acetyl group
Methyltransferases (MTs): addition of methyl group

 Other enzymes
Alcohol dehydrogenases: reduction of alcohols
Aldehyde dehydrogenases: reduction of aldehydes
NADPH-quinone oxidoreductase (NQO): reduction of quinones

Conjugation Reactions

Phase-II may precede phase-I reactions: e.g. INH
77

Factors affecting drug metabolism
Genetics
Age
Diet
Sex
Diseases
Co-administration of drugs: inducers or inhibitors
78

Excretion
The passage out of a systemically absorbed drug from the
body unchanged or in the form of metabolites
Kidneys: main organ of excretion: GF – PTR + ATS
Hepato-biliary excretion: conjugated drugs active secretory
system
Gastro intestinal excretion: left unabsorbed drug,…
Lungs: gases, alcohol, volatile substances
Sweat, saliva, tears
Mammary excretion
79

Time course of drug response
 Terms:
Loading Dose
Maintenance Dose
Onset of action
Duration of action
Therapeutic range (window)
80

The time course of drug effect
 Immediate Effects
 Delayed Effects
 Cumulative Effects
81

Clinical applications of PK
Calculation of dosage regimens
Drug switching: e.g. from IV to PO
Determination of route of administration
Calculation of doses
Prediction of drug interaction
Prediction of drug accumulation
Identification of patient factors
Bioequivalence study (PK evaluation of formulations)
82

Pharmacodynamics
Studies the MOA & biochemical, cellular & physiological effects
How & what drugs do to the body?
Deals with the r/ship between [plasma] of a drug and the body
response obtained to that drug (drug’s effect)
How drugs act?
84

Forces (bonds) in drug-target interaction
Covalent
Ionic
Hydrogen
Van der Waals

 The fundamental mechanisms of drug actions may be:
By physical action: adsorption, osmosis, radioactivity,…
By chemical interaction: antacids, chelating agents
By altering metabolic processes: sulphonamides
Through ion channels
Through transporters
Through enzymes & pumps
Through receptors: large number of drugs

Receptor
A specific protein in either the plasma membrane or interior of
a target cell with w/c a ligand/drug combines
It must be selective in choosing ligands/drugs to bind to avoid
constant activation of the receptor by promiscuous binding of
many different ligands
It must change its function upon binding so that the function
of the biologic system (cell, tissue, etc) is altered
 Orphan receptors & Spare receptors
β-adrenergic receptors of the heart
87

Types/Families of Receptors
Cell-surface receptors:
Ion-channel-coupled receptors (ionotropic receptors)
G-protein-coupled receptors (metabotropic receptors)
Enzyme-coupled receptors;
Either function as enzymes or associate directly with enzymes
that they activate
Intracellular (nuclear) receptors: regulate gene expression/
transcription

Receptors…
89

 Properties of receptors
Receives & transduces the signal to an effector mechanism
Sensitivity, (stereo) selectivity/specificity, saturable
Integral components of cell membrane
Found in the nucleus or translocated to the nucleus
Present in small number
Often many isoforms are present
Can be up- or down regulated: desensitization or super
sensitivity
92

 Classification of drugs acting on the receptors
Agonist: a chemical that binds to a receptor & activates the
receptor to produce a biological response
Full agonist
Partial agonist
Inverse agonist
Antagonist: reversible & irreversible
Competitive & non-competitive
Blocks the action of the agonist
Full agonists → partial agonists → neutral antagonists →
partial inverse agonists → full inverse agonists
93

Factors governing drug action
 Affinity:
Ability (rate/strength) of a drug to bind to a receptor
On a graded D-R curve, the nearer the curve to the y axis, the
greater the affinity
Deals with drugs acting on the same receptor
 Intrinsic activity (IA): the ability of a drug to elicit a response
after binding to the receptor 94

 Drugs effect can be evaluated by
Potency:
The amount of drug required to produce a desired effect
On a graded D-R curve, the nearer the curve to the y axis, the
greater the potency
A function of both affinity & efficacy
Efficacy: the maximal effect that a drug produces irrespective
of concentration (dose)
95

Dose Response Relationship
 Dose: amount of a drug required to produce desired response
in an individual
 Dosage: the amount, frequency & duration of therapy
 Types of dose response r/ships:
Graded (quantitative) D-R: affinity, potency (ED50), efficacy
Quantal (cumulative) D-R: ED50, LD50, TI, margin of safety
98

Drug interaction
Modulation of the activity of one drug by the prior or
concomitant administration of another drug
Enhanced or diminished
Knowledge is important for safe drug therapy
Drug interaction could be in in-vitro or in-vivo
 In-vitro interaction: pharmaceutical interaction
When drugs are added to IV drip or mixed in syringe
E.g penicillins & aminoglycosides
99

 In vivo interactions
Occurs at two stages
Pharmacokinetic level: ADME
Pharmacodynamic level: at the level of receptors & beyond
100

Types of Interactions
 Additive: 1+1=2
E.g. Aminoglycoside + furosemide = ototoxicity
 Synergism: 1+1>2, E.g.: Gentamicin + Ampicillin
 Potentiation: 1+0>1, E.g: Amoxicillin + Clavulanic acid
 Antagonism: 1+1<1
101

Antagonism
Occurs when two chemicals administered together interfere
with each other’s actions or one interferes with the action of
the other
Can be:
Functional (physiological): insulin & glucagon
Chemical: heparin + protamine
Dispositional: altering ADME of another drug
Receptor (pharmacological)
102

Pharmacokinetic drug interaction
Alteration in the delivery of drugs to their site of action
 Intestinal absorption:
Direct interaction in the gut:
TTCs with antacids containing divalent cations (Ca++, Mg++)
→↓ed absorption
Caffeine increases absorption of ergotamine
103

pH of gut contents:
Antacids raise gastric pH, so acidic drugs are more ionized &
hence more slowly absorbed
PPIs/H2-blockers Vs Ketoconazole (↓ed absorption): needs
dissociation
Alteration of gut flora: antimicrobial may potentiate oral
anticoagulant by reducing bacterial synthesis of vitamin K in
the large gut
104

 Displacement interaction: drugs with high binding affinity
Sulphonamides displace warfarin from plasma proteins
 Metabolic interaction:
Inducers: Phenobarbitone + Warfarin → ↓ed effect of warfarin
Inhibitors: Cimetidine + Warfarin → ↑ed effect of warfarin
 Excretion site: Probenecid & penicillin
105

 Drug interaction could be important
Sulphamethoxazole + Trimetoprim = Cotrimoxazole
Probenecid + Penicillin
Lopinavir + Ritonavir = Kaletra
 Some drug interactions are harmful
Diuretic + Digitalis
106

Drug-food Interaction
 Impact of food on drugs:
Decreased absorption
Calcium containing food (dairy products) + TTC antibiotics
Digoxin + higher fiber foods: wheat, oats, sunflower seeds
Increased absorption:
High calorie meal increase the absorption of saquinavir
If taken without food → absorption may be insufficient for its
antiviral activity
107

 Reduced activity
 Food rich in vitamin K (broccoli, cabbage) can reduce the
effect of warfarin
 Toxicity
 MAOIs + tyramine containing food: hypertensive crisis
 Theophylline + Caffeine: excessive CNS excitation
108

Timing of drug administration with respect to meals
Many drugs cause stomach upset, nausea and vomiting when
taken in an empty stomach (without food)
If food does not reduce their extent of absorption then
administer with meal
If food reduce their extent of absorption?
Select alternative drug that does not upset the stomach
Do not administer the drug with that type of food or
Administer a drug on an empty stomach: either 1 hour before
meal or 2 hours after
Generally drugs are better absorbed in an empty stomach!

Drug – herb interaction
St. John’s wort Vs Warfarin: ↓ed efficacy of Warfarin
Grape fruit juice Vs Phenytoin: ↑ed risk of phenytoin toxicity
110

P-Glycoprotein – Drug Interaction
Quinidine blocks P-gp in the intestinal mucosa and in the
proximal renal tubule; thus, digoxin elimination into the
intestine and urine is inhibited: ↑digoxin toxicity
Loperamide, which is an opiate antidiarrheal normally kept out
of the brain by the P-gp pump; however, inhibition of P-gp
allows accumulation of loperamide in the brain, leading to
respiratory depression
111

Spectrum of drug effects
112

 ADRs: any noxious, unintended response to a drug at doses
used in man for prophylaxis, diagnosis or therapy

Other forms of ADRs
 Drug intolerance
 Iatrogenic diseases (physician-induced)
 Photosensitivity: sensitize the skin to sunlight (UV rays)
 Drug dependence: a state of compulsive use of drugs in spite
of the knowledge of the risks associated with their use
Psychological & physical dependence
 Teratogenicity: now use based on NPLLR
 Carcinogenicity & mutagenicity
 Organ toxicities: hepatotoxicity, nephrotoxicity,…

 Type-A:
Predictable, dose-related and quantitative adverse effects
E.g. hypotension following α-blockers, insulin-induced
hypoglycaemia, bleeding following anticoagulants
Mostly reversible by dose reduction or stopping the drug
Secondary effects: indirect consequences of a primary drug
action
E.g. super-infection on treatment of a primary infection by
broad spectrum antibiotics

 Type B (bizarre) reactions
Unrelated to the primary pharmacological effects of the drug,
therefore, not predictable
Are less common, not tolerated and are an abnormal reactions
to a drug
 Type C (continuous or chronic use) reactions
Occur on prolonged use of drugs and both dose and duration
of drug use influence these ADRs
E.g. chloroquine retinopathy

 Type D (delayed effects)
Occur long after stopping treatment, sometimes after years
E.g. leukaemia following treatment of Hodgkin’s lymphoma;
teratogenic effects
 Type E (end of use)
Due to sudden discontinuation of a drug after prolonged use
E.g. acute adrenal insufficiency after sudden cessation of
glucocorticoids

1-General Pharmacology.pptx

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