This presentation well describes the general pharmacology in detail.

1. Introduction to Pharmacology
Jony Mallik
Executive, Quality Control,
Popular Pharmaceuticals Limited.

2. Introduction & Definition
■ Pharmacology
❑ Pharmacon - Drug
❑ Logos - Study
■ It is defined as the study of the substances which interact with
living system by activating or inhibiting normal body processes.
❑ (In simple terms, it is study of all the aspects of drug.)

3. INTRODUCTION TO PHARMACOLOGY
■ Pharmacology: It is the science of drugs derived from two
Greek words: Pharmakon (Greek word for drugs) and logos (the
Greek word for science). It is the study of the actions of drugs on
living system.
■ It includes physical and chemical properties, biochemical and
physiological effects, mechanism of action, therapeutic uses and
adverse effects of drugs.

4. PHARMACOLOGY, Link to other biomedical principles

5. Subdivisions of Pharmacology:
■ These are followings
■ Pharmacy: It deals with study of collection, compounding, and
dispensing of drugs so as to make them fit for administration to
patient.
■ Immuno pharmacology: It deals with the immunological
actions of drugs in immune system and development of
antibodies in response to a drug.
■ Pharmacoeconomics: It is the branch which deals with
economics of drug, which aims to quantify drug in economic
terms, the cost and benefit of drugs used therapeutically.
■ Pharmacokinetics: It deals with Absorption, Distribution,
Metabolism and Excretion (ADME) of drugs.

6. Subdivisions of Pharmacology
■ Pharmacodynamics: It deals with study of biochemical and
physiological effects of drugs and their mechanism of actions.
■ Pharmacotherapeutics: it deals with the use of drugs in
prevention and treatment of diseases.
■ Clinical Pharmacology: It deals with the study of drugs in
human/animals when given in diseased condition.
■ Pharmacognosy: It deals with the sources of drugs.
■ Pharmacogenetics: It deals with the study of genetically
determined variations in response to drugs.
■ Pharmacometrics: It deals with the study of qualitative and
quantitative evaluation of drugs activity.

7. Subdivisions of Pharmacology
■ Experimental Pharmacology: It deals with the study of drugs
action in animals under laboratory conditions.
■ Pharmacoepidemiology: It deals with the study of both
beneficial and adverse effects of drug on human/animal
population.
■ Chemotherapy: It deals with study of drugs that inhibits specific
agents of diseases such as bacteria, virus and fungi
■ Toxicology: It deals with the study of adverse effects of drugs or
chemicals on living system.
■ Materia Medica: It is a book containing information about
pharmacy, pharmacognosy, posology and uses of drugs. Now a
days it is replaced by modern science of pharmacology

8. INTRODUCTION TO PHARMACEUTICS
■ Pharmaceutics: It deals with the process of turning a new
chemical entity into a medication to be used safely and effectively
by patients. It is also called the science of dosage form design.
There are many chemicals with pharmacological properties, but
need special measures to help them achieve therapeutically
relevant amounts at their sites of action. Branches of
pharmaceutics include:
■ Pharmaceutical formulations
■ Pharmaceutical manufacturing
■ Dispensing Pharmacy
■ Pharmaceutical Technology
■ Physical Pharmacy
■ Pharmaceutical Jurisprudence

9. HISTORY OF PHARMACOLOGY
■ Knowledge of drugs and their uses in diseases are as old as history
of mankind.
■ Primitive men gather the knowledge of healing and medicines by
observing the nature, noticing the animals while ill and personal
experience after consuming plants and herbs as remedies.
■ Ancient civilizations discovered that extracts from plants, animals,
and minerals had medicinal effects on body tissue. These
discoveries became the foundation of pharmacology.
■ Pharmacology in the present form is relatively recent branch
about hundred years old.

10. Historical developments in Pharmacology
■ PEN PSAO (2700 BC) It was the great herbal materia medica
written in china.
■ Kahun Papyrus (2000 BC) is an oldest Egyptian document
containing information about veterinary medicines and uterine
diseases of women.
■ Ebers papyrus (1550 BC) also an Egyptian document containing
information about number of diseases and 829 prescription
where castor oil, opium like drug are being used.
■ Hippocrates (460-375 BC) A greek physician consider “father of
Medicine”. He was the first person who recognize disease as
abnormal reaction of body. He introduce use of metallic salts for
the treatment of disease.

11. Historical developments in Pharmacology
■ Theophrastus (380-287 BC) a great philosopher called father of
Pharmacognosy. He classified medicinal plants on the base of
medicinal characteristics.
■ Dioscorides (AD 57) a greek, produced one of the first materia
medica of approximately 500 plants and remedies.
■ Claudius Galen (AD 129–200) first attempted to consider the
theoretical background of pharmacology.
■ Paracelsus (1493–1541) a Swiss scholar and alchemist, often
considered the “grandfather of pharmacology”. He introduces
the use of chemicals for treatment of disease.
■ Valerius Cordus (1514-1544) He compiled the first pharmacopeia
where he described techniques for the preparation of drugs.

12. MODERN PHARMACOLOGY
■ Conversion of old medicines into the modern pharmacology start
taking shape following the introduction of animal experimentation
and isolation of active ingredients from plants.
■ Francois Megendie (1783-1855) a first pharmacologist established
the foundation of modern pharmacology. He developed
experiment to elucidate the physiological processes and action of
drugs on the body.
■ Frederich Sertürner, German pharmacist’s assistant, isolated
morphine—the first pure drug—in 1805
■ Claude Bernard (1813-1878) considered Father of experimental
Medicine. He identifies the site of action of curare (arrow
Poisoning).

13. MODERN PHARMACOLOGY
■ Rudolph Buchheim (1820–1879) German pharmacologist a key
figure in the development of pharmacology, a who at the
University of Dorpat, created the first pharmacological institute.
■ Oswald Schmiedeberg (1838–1921) “Father of Pharmacology”
established pharmacology as an independent discipline. He start
teaching Pharmacology in University of Strasbourg (France).
■ John Jacob Abel (1857-1938) founded first department of
pharmacology in USA in the University of Michigan in 1893. In
1897 he established pharmacology department at Johns Hopkins
University. Abel also co-founded the Journal of Pharmacology and
Experimental Therapeutics in 1909.

14. MODERN PHARMACOLOGY
■ L. mayer Jones (1912-2002) regarded as father of modern
veterinary pharmacology. He authored first book of veterinary
pharmacology therapeutics in 1954.
SCOPE OF PHARMACOLOGY
■ It provides the rational basis for the therapeutic use of the drug.
Before the establishment of this discipline, even though many
remedies were used, but doctors were reluctant to apply scientific
principles to therapeutics.
■ In 1920s, many synthetic chemicals were first introduced and the
modern pharmaceutical companies began to develop.

15. SCOPE OF PHARMACOLOGY
■ Scientific understanding of drugs enables us to predict the
pharmacological effect of a new chemical that will produce a
specified therapeutic effect.
■ The scope of pharmacology has expanded greatly over the last
decade to incorporate many new approaches such as computer-
assisted drug design, genetic screens, protein engineering and use
of novel drug delivery vehicles including viruses and artificial cells.
■ Our society needs pharmacologists who understand the basis of
modern therapeutics for careers within academic, pharmaceutical
and governmental laboratories to study and develop tomorrow’s
drugs.

16. Pharmacodynamics Pharmacokinetics

17. Routes of drug administration (R.O.A.)
IV:Intravenous, IM:Intramuscular, SC:Subcutaneous, SL:Sublingual,
TD:Transdermal

18. Routes of drug administration (R.O.A.) Continued..
■ Local Routes:
❑ Very low or no systemic absorption
■ Systemic Routes:
❑ Oral: Safer and Economical, some drugs are ineffective because of High
first Pass Metabolism (eg. nitrates, lignocaine, propranolol, ),
Degradation (Insulin, penicillin G)
❑ Sublingual: Avoids First Pass Metabolism , Used in Emergencies, Only
lipid soluble and non irritating drugs
(eg. of drugs administered by this route Nitroglycerine,
isosorbidedinitrate etc.)
❑ Transdermal: Only for drugs Highly lipid soluble

19. Routes of drug administration (R.O.A.) Continued.
✓ Nasal: eg. Nafarelin (GnRH agonist), calcitonin and desmopressin
✓ Inhalational: Rate of drug delivery can be controlled like I.V. Infusion,
antiasthmatic and inhalational anaesthetic agents
✓ Rectal: Avoids first pass metabolism upto 50% (Diazepam in febrile
seizures)
✓ Intravenous: Bolus(Dose injected at once) or Infusion(Continuous
delivery over a period of time)
✓ Intradermal: Through Bleb, Vaccines

20. PHARMACOKINETICS
■ ADME study: Absorption, Distribution, Metabolism, Excretion
■ ABSORPTION:

21. 1. Absorption
contd…
■ So, for absorption of drug from biological membrane it should be present
in unionised lipid soluble form
■ Ionisation depends on pH of surrounding medium and pKa of drug
■ Lets make it simple, ABSORPTION WILL OCCUR WHEN MEDIUM IS SAME,
Means acidic drugs will remain unionised in acidic environment and get
absorbed while basic drugs will remain unionised in basic environment and
get absorbed
■ Ionisation of a drug is neither 100% nor 0% (Weak acids or bases),
therefore a drug should never be 100% lipid or water soluble

22. Absorption (contd…)
■ pH-pka relationship
pka is the pH at which drug is 50% ionised and 50% unionised
■ Acidic drug will remain unionised in acidic medium but will ionise in basic medium and basic drug
will remain unionised in basic medium and ionise in acidic medium
■ Suppose an acidic drug having pKa of 4 was placed in pH 4, it will be 50 % ionised and 50%
unionised, NOW same drug is kept in medium of pH 3 (acidic), it remains lipid soluble. But, if it is
kept in pH 2 what will happen, obviously it becomes more lipid soluble because more of the drug
is un-ionised, But Numerically HOW MUCH???
■ Concepts:
■ If the pH of the medium is less than pKa (Medium becomes acidic)
❑ For Acidic drugs, unionised form increases and ionised form decreases
❑ For Basic drugs, ionised form increases and unionised form decreases
■ If the pH of the medium is more than pKa (Medium becomes basic), opposite happens

23. Bioavailability
■ Fraction of administered drug that reaches into the systemic
circulation in the unchanged form
■ By IV route it is 100%
Pre-systemic or first pass metabolism

24. Bioavail. (contd…)
Fig. Plot between plasma conc. and
time to calculate bioavailability
• It can be calculated by
comparing AUC (Area under
the curve) for I.V. route and
for the desired route or can
also be calculated by
comparing excretion in urine
• AUC tells about extent of
absorption
• Tmax tells about rate of
absorption
• Cmax is max conc. obtained
in plasma
• Bioequivalence = ±20%
bioavailability
MEC: Min. effective
conc., MTC: Max
therapeutic conc.

25. 2. Distribution
■ After drug reaches to the blood it is distributed to many tissues, which is
determined by a hypothetical parameter Volume of Distribution (Vd)
■ It is the volume that would be required to contain the administered dose if that
dose was evenly distributed at the at the conc. measured in plasma
■ Higher Vd means more amount of drug was entering in tissue
■ Depends on lipid solubility and protein binding
❑ Lipid soluble drug crosses blood vessel easily and thus have high Vd
❑ If a drug is highly bound to plasma protein it behaves like a large molecule and unable to cross the
blood vessel, thus goes less into the circulation and have low Vd
■ Only free form (not bound to plasma protein) of drug is responsible for action as
well as metabolism of a drug. Thus, Plasma protein binding makes drug long acting
by reducing its metabolism

26. Distribution (contd…)
■

28. 3. Metabolism (Biotransformation)
■ Chemical alteration of the drug in the body
■ Needed to render the nonpolar (lipid soluble) compounds into polar
(lipid-insoluble) to excrete them outside the body
■ Primary site is liver, others are kidney, intestine lungs and plasma
■ Biotransformation of drug may lead to following three events:
❑ 1. Inactivation
Most drugs render inactive or less active metabolites
❑ 2. Active metabolite from an active drug
Many drugs are partially converted to one or more active metabolites;

29. Active Drug Active Metabolite
Chloral hydrate Trichloroethanol
Morphine Morphine-6-Glucoronide
Cefotaxime Desacetyl cefotaxime
Allopurinol Alloxanthine
Procainamide N-acetyl procainamide
Primidone Phenobarbitone
Diazepam Oxazepam
Digitoxin Digoxin
Imipramine Desipramine
Amitriptyline Nortriptyline
Codeine Morphine
Spironolactone Canrenone

30. Metabolism (Contd…)
■ Biotransformation reactions are of two types:
❑ 1. Nonsynthetic/Phase I/Functionalisation reactions:
Functional group is generated or exposed
Metabolite may be active or inactive
Major reactions involved are:
■ Oxidation (Major), Reduction, Hydrolysis, Cyclisation, De-cyclisation
❑ 2. Synthetic reaction/Phase II
Conjugation by endogenous substrate to form a highly polar water soluble
compound which is easily excreted
Major reactions involved are:
■ Glucuronide conjugation (Major), Acetylation, Methylation, sulphate, glycine, or
glutathione conjugation

31. Metabolism (Contd…)
Metabolism may occur with the help of:
❑ Microsomal enzyme: present in smooth endoplasmic reticulum
■ Ex; monooxygenases, cytochrome P450, and glucoronyl transferases
May be induced or inhibited by other drug
❑ Non microsomal enzyme: present in cytoplasm and mitochondria
■ Ex; flavoprotein oxidases, esterases, amidases and conjugases
Not inducible by other drugs but shows genetic polymorphism

32. Metabolism (Contd…)
■ Drug metabolising by microsomal enzyme is called as substrate and
chemical increasing or decreasing that enzyme is called as inducer or
inhibitor respectively

33. Cytochrome P-450
■ 450 denotes their strong absorbance at 450 nm
■ Superfamily of microsomes
■ CYP3A4 is involved in metabolism of 50% drugs
Root word
Family Sub-family
Gene
number
CYP3A4
Nomenclature

34. 4. Excretion
■ Passage out of systemically absorbed drug
■ Major route is kidney; involves glomerular filtration, tubular reabsorption
and tubular secretion
❑ 1. Glomerular filtration: Depends on plasma protein binding and renal
blood flow. Does not depends upon lipid solubility because all
substances crosses the fenestrated glomerular membrane
❑ 2. Tubular reabsorption: Depends on lipid solubility
❑ Lipid solubility depends on ionisation, ionised drug will be excreted

35. Barbiturates,
salicylate
Sodiumbicarbonate Acidic drug in basic
medium
Morphine,
amphetamine
Ammonium
chloride

36. Excretion (contd…)
❑ 3. Tubular secretion: Does not depend on lipid solubility or plasma
protein binding.
Separate pump for acidic and basic drugs are present in nephron; drug
utilising same pump may show drug interaction; eg. Probenecid
decreases excretion of penicillin

37. Kinetics of elimination
Pharmacokinetics model may be one or two compartment
One compartment Model:
Drug having less or no distribution in tissues, elimination is continuous and the log
plasma conc. vs time curve is linear (frst order kinetics)

38. First order kinetics (linear) Zero order kinetics (Non linear)
Constant fraction of drug is eliminated per
unit time
Constant amount of drug is eliminated per
unit time
ROE proportional to Co ROE independent of Co
Clearance (Cl) remains const. Cl is more at low conc. and less at high conc.
Half life (T1/2)remains const. T1/2 less at low conc. and more at high conc.
Most drugs follow first order kinetics Very few drugs eg; Alcohol

39. Half life (t1/2)
■ Time required to reduce the plasma conc. half to its original value
■ It is a secondary P’kinetic parameter derived from two primary P’kinetic
parameter Vd and clearance (Cl)
■ Determines dosing interval and time required to reach steady state conc.
■ Does not affect dose of the drug
t1/2 = (0.693 * Vd)/Cl

40. ■ Drug : A chemical substance that is used for diagnosis,
prevention & treatment of disease.
(French: Drogue -Dry herb)
■ Contraceptives
■ General Anaesthetics
■ Vaccines
■ WHO : “Any substance or product that is used or intended to
be used to modify or explore the physiological system or
pathological state for the benefit of the recipient”

41. Classification of Drugs
■ Based on site of action
■ Based on Chemical Structure
■ Based on Mechanism of Action
■ Based on Ionization of Drugs
■ Based on Therapeutic Uses
■ Based on Anatomical Therapeutics Classification (ATC)

42. Sources of Drugs
■ A) Plant Sources
■ B) Animal Sources
■ C) Microorganism
■ D) Chemicals
■ E) Recombinant DNA Technology

43. ■ A) Plant Sources-
■ 1) Alkaloids – Atropine (Atropa belladona)
Morphine (Papaver somniferum)
■ 2) Glycosides- Digoxin (Digitalis purpura)
■ 3) Oils- Essential oil (Volatile oil)-leaves & Flower
eg- clove oil, pipermint, eucalyptus
Fixed oil- seeds
eg- ground nut, coconut, castor, olive oil
Mineral oil- liquid paraffin
■ 4) Gum - excretory products (gum acacia)
■ 5) Resins - Tolu balsam (cough mix)
■ 6) Tannins - catechu

44. ■ B) Animal Sources
■ 1) Hormones - Insulin (Pork-Procine), (Beef-Bovine )
■ 2) Vaccines - Polio, Antirabies
■ 3) Sera - ATS (Antitetanus Serum)
■ 4) Vitamins - Vit B12 from Liver extract
■ C) Microorganism- Antibiotics
■ D) Chemicals – synthetic drugs
■ E) Recombinant DNA Tech – Human Insulin,
Calcitonin, Gonadotropins, erythropoietin etc.

45. Nomenclature of Drugs
■ Chemical Non-Proprietary Proprietary
OR OR
Generic Name Brand Name
OR OR
Approved Name Trade Name
OR OR
Official Name Commercial

46. Some examples of Chemical, Generic, Brand Names
Chemical Name Generic Name/
Non- Proprietary
Name
Brand Name/
Proprietary
Name
Acetyl Salicylic
Acid
Aspirin Disprin
Acetaminophen Paracetamol Crosin, Calpol,
Metacin
Aminobenzyl
Penicillin
Ampicillin Roscillin

47. ■ Generic/Non-Proprietary Name-
❑ Given by USAN Council (United States Adopted
Name)
Advantages-
■ World-wide acceptance, name remains the
same in all countries.
■ Usually have similar suffix in a group.
■ Economical than Branded/Proprietary
Medicines.
Disadvantages-
■ Naming of Fixed Dose combinations.

48. ■ Brand Name/Proprietary Name-
Name given by Pharmaceutical company for commercial
purpose.
Advantages-
■ The consistency or Pharmacokinetics or efficacy does not change with
same brand.
■ Single brand name for a Medicine with multiple ingredients.
■ Bioavailability remains same where a patient is maintained on a
particular brand.
Disadvantages-
■ Branded Medicines are costlier.
■ Multiple brands for a same Medicine.

49. Drugs Confusing Names
■ Drugs with some similarity in names or suffix but
different in action or different in class.
DRUG NAME DIFFERENCE
Cotrimoxazole AMA
Clotrimazole Anti fungal
Omeprazole H2 blocker
Ornidazole Antiamoebic
Tenidazole Antiamoebic
Albendazole Anthelmintic
Anastrozole
Fomepizole
Aromatase inhibitor
Alcohol

50. Drug Categories
Prescription Drugs OTC
(Over The Counter)
Non-Prescription
Drugs

51. Sources of Drug Information
■ Official Compendia
■ Pharmacopoeia (IP, BP, USP)
■ Formulary (NFI)
■ Non-Official Compendia
■ Physician’s Drug References(PDR)- USA
■ Martindale Pharmacopoeia – Great Britain
■ Other Sources of Drug Information
■ Drug indices (CIMS, IDR, MIMS, Drug Index)
■ Drug advertisement
■ Internet, Medical Rep.

52. Essential Drugs
■ WHO in 1977 published a list of drug as “Model list
of Essential drugs”.
■ “List of drugs that satisfy the health care needs of
majority of the population; they should therefore, be
available at all times in adequate amount & in
appropriate dosage form.”
■ The current WHO list is revised in 2011 as 17th
edition for adults with 23 FDC & 3rd edition for
children.
■ India produced its National Essential Drug List in
1996, presently it is revised in 2011 with title “NLEM
(National List of Essential Medicines)” which
includes 348 medicines.

53. Types of Drug Action
EFFECT (Type of responses):-
1.Stimulation
2.Inhibition/Depression
3.Replacement
4.Irritation
5.Cytotoxic

54. Mechanism of Action of Drugs
■ Drug act either by receptor or by non receptor
or by targeting specific genetic changes.
Majority of drugs acts by (HOW)
Receptor mediated Non receptor mediated

55. Receptor Mediated action
■ Drug produce their effect through interacting with some
chemical compartment of living organism c/s Receptor.
■ Receptors are macromolecules
■ Most are proteins
■ Present either on the cell surface, cytoplasm or in the nucleus

56. Receptor Functions : Two essential functions
■ 1. Recognization of specific ligand molecule (Ligand binding
domain)
■ 2. Transduction of signal into response (Effector domain)
Ligand binding
domain
Transduction of signal
into response

57. Drug(D) +Receptor® Drug receptor complex Response
Drug receptor interaction:-
1. Selectivity:- Degree of complimentary co relation between drug and
receptor.
Ex:- Adrenaline Selectivity for α, ß Receptor
2. Affinity:- Ability of drug to get bound to the receptor.
3. Intrinsic activity (IA) or Efficacy:- Ability of drug to produce a
pharmacological response after making the drug receptor complex.

58. Drug classification
(on the basis of affinity & efficacy)

59. Response
No
response

60. ■ Partial agonist :These drug have full affinity to
receptor but with low intrinsic activity (IA=0 to 1).
■ These are only partly as effective as agonist
(Affinity is lesser when comparison to agonist)
Ex: Pindolol, Pentazocine

61. ■ Inverse agonist: These have full affinity towards the receptor
but intrinsic activity is zero to -1 i.e., produces effect is just opposite
to that of agonist.
Ex:- ß-Carboline is inverse agonist for Benzodiazepines receptors.

62. Receptor families
Four types of receptors families
1. Ligand-gated ion channels (inotropic receptors)
2.G-protien coupled receptor (Metabotropic receptors)
3. Enzymatic receptors (tyrosinekinase)
4.Receptor regulating gene expression (transcription
factors/ Steroid )

63. Characteristics of receptor families
Ligand
gated
G-protein
coupled
Enzymatic Nuclear
Location Membrane Membrane Membrane Intracellular
Effector Ion channel Ion Channel
or enzyme
Enzyme Gene
coupling Direct G-protein Direct Via DNA
Example Nicotinic Muscarinic Insulin Steroid ,
hormone

64. Signal transduction mechanism
■ Ion gated receptors:- Localized on cell
membrane and coupled directly to an ion
channel.
Receptor
Agoni
st
Hyper polarization or
depolarization
Receptor
Blocker
Permeation of
ion is blocked
Cellular
effect
No cellular effect
Io
n
Na+2

65. ■ Ex: Nicotinic cholinergic receptor

66. G-protein coupled receptors
■ Membrane bound, which are coupled to
effector system through GTP binding proteins
called as G-proteins
Bound to inner
face of plasma
membrane (2nd
messenger)

67. Varieties of G-protein
G-protein Receptor for Signaling pathway/
Effector
Gs ß adrenegic,
H,5HT,Glucagon
AC— cAMP
Gi1,2,3 α2 adrenergic, Ach, AC— cAMP,
Open K+
Gq Ach Phospholipase-C,
IP3’cytoplasmic Ca+2
Go Neurotransmitters in
brain
Not yet clear

68. G-protein effector systems
■ 1.Adenylase cyclase : cAMP system
■ 2.Phospholipase –C: Inositol phosphate system
■ 3. Ion channels

69. cAMP system

70. Phospholipase-C system

71. Ion channel regulation
■ G-protein coupled receptors can control the
functioning of ion channel by don't involving
any second messenger
■ Ex:- In cardiac muscle

72. ■ These receptor are directly linked tyrosine
kinase.
■ Receptor binding domain present in extra
cellular site.
■ Produce conformational changes in intra
cellular
Ex:- Insulin receptors
Enzymatic receptors

73. Enzymatic receptors
Extra cellular receptor
binding domain
Intra cellular
changes

74. Receptor regulating gene expression
(transcription factors)
Unfolds the receptor and
expose normally masked
DNA binding site
Increase RNA
polymerase activity

75. Receptor regulation theory
■ Receptors are in dynamic state.
■ The affinity of the response to drugs is not fixed.
It alters according to situation.
■ Receptor down regulation:
Prolonged use of agonist
Receptor number and sensitivity
Drug effect
Ex: Chronic use of salbutamol down regulates ß2 adrenergic receptors.

76. ■ Receptor up regulation:
Prolonged use of antagonist
Receptor number and sensitivity
Drug effect
■ Ex:- propranolol is stopped after prolong use,
produce withdrawal symptoms. Rise BP,
induce of angina.

77. Agonist: Both the high affinity as well as intrinsic
activity (IA=1)
These drug trigger the maximal biological response or
mimic effect of the endogenous substance.
Ex:- Methacholine is a cholinomimetic drug which
mimics the effect of Ach on cholinergic receptors.

78. Types of agonism
■ Summation :- Two drugs eliciting same
response, but with different mechanism and their
combined effect is equal to their summation.
(1+1=2)
Aspirin Codiene
PG Opiods receptor
Analgesic+ Analgesic+
++

79. Types of agonism
■ Additive: combined effect of two drugs acting by
same mechanism
Aspirin
PG PG
Analgesic+ Analgesic+
+ +

80. ■ Synergism (Supra additive):- (1+1=3)
The combined effect of two drug effect is higher
than either individual effect.
Ex:-
1.Sulfamethaxazole+ Trimethoprim
2. Levodopa + Carbidopa.

81. Types of antagonism
Antagonism: Effect of two drugs is less than sum
of the effects of the individual drugs.
1. Chemical antagonism
Ex: -heparin(-ve) protamine +ve, Chelating agents
1. Physiological /Functional antagonism
2. Pharmacokinetic antagonism
3. Pharmacological antagonism
I. Competitive ( Reversible)
II. Non competitive (Irreversible)

82. Pharmacokinetic antagonism
■ One drug affects the absorption, metabolism
or excretion of other drug and reduce their
effect.
Ex:-Warfarin in presence of phenobarbitone,
warfarin metabolism is increased, it effect is
reduced.

83. Pharmacological antagonism
■ Pharmacodynamic antagonism between two
drugs acting at same receptors.
■ Two important mechanism according to which
these antagonists
▪ 1.Reversible(Competitive)
▪ 2.Irreversible(Non)

84. Reversible antagonism (Competitive
antagonism)
■ These inhibition is commonly observed with
antagonists that bind reversibly to the same
receptor site as that of an agonist.
■ These type inhibition can be overcome
increasing the concentration of agonist
■ Ex:- Atropine is a competitive antagonist of
Ach.

85. Irreversible Antagonism
■ It occurs when the antagonist dissociates
very slow or not at all from the receptors
result that no change when the agonist
applied.
■ Antagonist effect cannot be overcome even
after increasing the concentration of agonist

86. Non receptor mediated action
■ All drugs action are not mediated by receptors.
Some of drugs may act through chemical action
or physical action or other modes.
▪ Chemical action
▪ Physical action (Astringents, sucralfate)
▪ False incorporation (PABA)
▪ Being protoplasmic action (antiseptics)
▪ Formation of antibody (Vaccines)
▪ Targeting specific genetic changes.

87. Dose
■ It is the required amount of drug in weight,
volumes, moles or IU to provide a desired effect.
■ In clinical it is called as Therapeutic dose
■ In experimental purpose it is called as effective
dose.
■ The therapeutic dose varies from person to
person

88. Single dose:
1.Piperazine (4-5g) is sufficient to eradicate round
worm.
2.Single IM dose of 250mg of ceftriaxone to treat
gonorrhoea.
Daily dose:
It is the quantity of a drug to be administered in
24hr, all at once or equally divided dose.
1.10mg of cetrizine (all at once) is sufficient to
relive allergic reactions.
2.Erythromycin is 1g per day to be given in 4
equally divided dose (i.e., 250mg every 6 hr)

89. ■ Total dose: It is the maximum quantity of the
drug that is needed the complete course of the
therapy.
Ex:- procaine penicillin →early syphilis is 6 million unit →
given as 0.6 million units per day for 10days.
Loading dose:- It is the large dose of drug to be
given initially to provide the effective plasma
concentration rapidly. The drugs having high Vd
of distribution.
Chloroquine in Malaria – 600 mg Stat
300mg after 8 hours
300 mg after 2 days.

90. Maintenance dose:- Loading dose normally
followed by maintenance dose.
■ Needed to maintain the steady state plasma
concentration attained after giving the loading
dose.

91. Therapeutic index:
■ Margin of safety
■ Depend upon factor of dose producing
desirable effect → dose eliciting toxic effect.
■ TI →should be more than one

92. Toxic
Therapeutic window:
Optimal therapeutic range of plasma
concentrations at which most o the patients
experience the desired effect.
Therapeutic range→ Therapeutic window
Sub
optimal
optimal

93. ■ Cyclosporine – 100-400ng/ml
■ Carbamazapine- 4-10µg/ml
■ Digoxin- 0.8-2ng/ml
■ Lithium- 0.8-1.4 mEq/L
■ Phenotoin – 10-20µg/ml
■ Qunindine- 2-6µg/ml

94. ■ Tolerance: Increased amount of drug
required to produce initial pharmacological
response.
■ Usually seen with alcohol, morphine,
barbiturates, CNS active drugs
■ Reverse tolerance:- Same amount drug
produces inc pharmacological response.
■ Cocaine, amphetamine → rats- inc. motor
activity

95. Types of tolerances
■ Innate tolerance: Genetically lack of sensitivity
to a drug.
Ex:
■ Rabbits tolerate to atropine large doses
■ Chinese→ Castor oil
■ Negros → Mydriatic action of sympathomimetics
■ Eskimos→ high fatty diets

96. ■ Acquired tolerances:
■ Occurs due to repeated use of drug
❑ Pharmacokinetic tolerances
❑ Pharmacodynamic tolerance
❑ Acute tolerance
Pharmacokinetic tolerances:- Repetitive
administration causes decrease their
absorption or inc. its own metabolism
Ex: Alcohol → dec. absorption
Barbiturates→ Inc. own metabolism

97. ● Pharmacodynamic tolerance
■ Down regulation of receptors
■ Impairment in signal transduction
■ Ex: Morphine, caffeine, nicotine.
● Acute tolerance: Tachyphylaxis Acute development
of tolerance after a rapid and repeated
administration of a drug in shorter intervals
● Ex; Ephedrine, tyramine

98. ■ Ex: Monday disease.
■ Nitroglycerine – Monday , Tuesday workers
get headache, after they get tolerances.
■ After holiday (Sunday) they get again
headache .
■ Cross tolerances: Cross tolerance among
drugs belonging to same category.
■ MORPHIN→HEROIN→ NARCOTIC

99. Factors modifying the
EFFECTS OF DRUGS

100. ■ Individuals differ both in the degree and
the character of the response that a drug
may elicit
■ Variation in response to the same dose
of a drug between different patients and
even in the same patient on different
occasions.

101. ■ One or more of the following categories
of differences among individuals are
responsible for the variations in drug
response:
❑ Individuals differ in pharmacokinetic handling
of drugs
❑ Variation in number or state of receptors,
coupling proteins or other components of
response

102. ■ These factors modify drug action either:
a) Quantitatively
■ The plasma concentration and / or the drug action is
increased or decreased
b) Qualitatively
■ The type of response is altered, eg: drug allergy and
idiosyncrasy

103. • The various factors are:
1. Body weight/size:
● It influences the concentration of drug
attained at the site of action
● The average adult dose refers to
individuals of medium built

104. • For exceptionally obese or lean individuals and for
children dose may be calculated on body weight
basis
• BSA=BW(Kg)0.425 x Height(cm)0.725 x 0.007184

105. 2. Age:
Infants and Children:
❑ The dose of drug for children often calculated
from the adult dose

106. • However, infants and children are have important
physiological differences
• Higher proportion of water
• Lower plasma protein levels
• More available drug
• Immature liver/kidneys
• Liver often metabolizes more slowly
• Kidneys may excrete more slowly

107. Elders:
• In elderly, renal function progressively declines
(intact nephron loss) and drug doses have to be
reduced
■ Chronic disease states
■ Decreased plasma protein binding
■ Slower metabolism
■ Slower excretion
■ Dietary deficiencies

108. 3. Sex:
■ Females have smaller body size, and so
require doses of drugs on the lower side
of the dose range
■ They should not be given uterine
stimulants during menstruation, quinine
during pregnancy and sedatives during
lactation

109. 4. Pregnancy:
■ Profound physiological changes which
may affect drug responses:
❑ GI motility reduced –delayed absorption of
orally administered drugs
❑ Plasma and ECF volume expands
❑ Albumin level falls
❑ Renal blood flow increases markedly

110. 5. Food:
• Delays gastric emptying, delays absorption
(ampicillin)
• Calcium in milk –interferes with absorption of
tetracyclines and iron by chelation
• Protein malnutrition
● Loss of BW
● Reduced hepatic metabolizing capacity
● Hypoproteinemia

111. 6. Species and race:
■ Rabbits resistant to atropine
■ Rat & mice are resistant to digitalis
■ In humans: blacks require higher
Mongols require lower concentrations of
atropine and ephedrine to dilate their
pupil

112. 7. Route of drug administration:
• I.V route dose smaller than oral route
• Magnesium sulfate:
● Orally –purgative
● Parenterally –sedative
● Locally –reduces inflammation

113. 8. Biorhythm: (Chronopharmacolgy)
■ Hypnotics –taken at night
■ Corticosteroid –taken at a single
morning dose
9. Psychological state:
■ Efficacy of drugs can be effected by
patients beliefs, attitudes and
expectations
■ Particularly applicable to centrally acting

114. 10. Presence of diseases/pathological states:
• Drug may aggravate underlying pathology
• Hepatic disease may slow drug metabolism
• Renal disease may slow drug elimination
• Acid/base abnormalities may change drug
absorption or elimination
• Severe shock with vasoconstriction delays
absorption of drugs from s.c. or i.m
• Drug metabolism in:
● Hyperthyroidism –enhanced
● Hypothyroidism -diminished

115. 11. Cumulation:
■ Any drug will cumulate in the body if
rate of administration is more than the
rate of elimination
❑ Eg: digitalis, heavy metals etc.

116. 12. Genetic factors:
■ Lack of specific enzymes
■ Lower metabolic rate
❑ Acetylation
❑ Plasma cholinesterase (Atypical pseudo
cholinesterase)
❑ G-6PD
❑ Glucuronide conjugation

117. 13. Tolerance:
• It means requirement of a higher dose of the
drug to produce an effect, which is ordinarily
produced by normal therapeutic dose of the
drug
• Drug tolerance may be:
● Natural
● Acquired
● Cross tolerance
● Tachyphylaxis (ephedrine, tyramine, nicotine)
● Drug resistance

118. 14. Other drugs:
• By interactions in many ways

119. Drug classification
(on the basis of affinity & efficacy)
Agonist: Both the high affinity as well as intrinsic
activity (IA=1)
These drug trigger the maximal biological response or
mimic effect of the endogenous substance.
Ex:- Methacholine is a cholinomimetic drug which
mimics the effect of Ach on cholinergic receptors.

120. ■ Antagonist:- Which have only the affinity no
intrinsic activity (IA=0). IA=0 so no
pharmacological activity.
■ Rather these drug bind to the receptor and
produce receptor blockade.
■ Atropine blocks the effects of Ach on the
cholinergic muscarinic receptors.

121. cAMP system
Some drugs, hormones or neurotransmitters
produce their effect by increasing or
decreasing the activity of adenylate cyclase
and thus raising or lower cAMP with in the cell.

122. Stimulation
■ Some of drug act by increasing the activity of
specialized cells.
Ex: Catecholamines stimulate the heart and
Heart rate, Force of contraction

123. Inhibition
■ Some drug act by decreasing the activity of
specialized cells.
Ex: Alcohol, Barbiturates, General anesthetic
these drug depress the CNS system.
Atropine inhibits Ach action.

124. Replacement
■ When there is a deficiency of endogenous
substances, they can replaced by drugs.
Ex: Insulin in Diabetes mellitus
Throxine in cretinism and myxedema

125. Irritation
■ Certain drugs on topical application cause
irritation of the skin and adjacent tissues.
■ These drugs are using for counter irritant.
Ex: Eucalyptus oil, methyl salicylates (Used in
sprains, joint pain, myalgia.

126. Cytotoxic
■ Treatment of infectious disease/cancer with
drugs that are selectively toxic for infecting
organism/cancer cells
Ex: Anticancer drugs
All Antibiotics

127. E Cam E*
G
q PLC
PIP
2
DAG
S
Ag
oni
st
Hydrolysis
Activation
IP3
PKC
A
T
P
A
D
P Product
Ca+
2
Ca
m
Water soluble
release
Response
Phospholipase-C system
Hydrolysis
PLC= Phospholipase-C PIP2 =Phosphotiydl inositol 4,5 di phosphate
IP3 =Inositol tri phosphate DAG = Diacylglycerol
E= Ezyme PKC = Phosphokinase -C

128. Extra cellular site of action
1.Antacids neutralizing gastric acidity.
2.Chelating agents forming complexes
with heavy metals.
3.MgSo4 acting as purgative by
retaining the fluid inside the lumen of
intestine.

129. Cellular Site of Action
1.Ach on Nicotinic receptors of motor end plate,
leading to contraction of skeletal muscle.
2.Effect of sympathomimetics on heart muscle
and blood vessels.

130. Intracellular site of action
-Folic acid synthesis inhibitors.
Folic acid which is intracellular component
essential for synthesis of proteins.
Trimethoprim and sulfa drug interfere with
synthesis.

131. or
FC of heart muscle
Lipolysis Glycogen Glycogen breakdown
synthesis to glucose
G
protein
+ -
Effect
or
A
C
cAMP ATP
Protein kinase
Active
Ca+2
release
Phosphorylation
Gs/Gi

132. Physical action
■ Absorption: Kaolin absorbs bacterilal toxin
and thus acts as antidiarrhoeal agent.
■ Protectives:- Various dusting powders.

133. ■ Antagonist:- Which have only the affinity no
intrinsic activity (IA=0). IA=0 so no
pharmacological activity.
■ Rather these drug bind to the receptor and
produce receptor blockade.
■ Atropine blocks the effects of Ach on the
cholinergic muscarinic receptors.

134. Physical Action
■ Osmosis:- MgSo4 acts as a purgative by
exerting osmatic effect within lumen of the
intestine.
■ Astringents:- They precipitate the surface
proteins and protect the mucosa Ex: tannic
acid in gum patients
■ Demulcent:- These drugs coat the inflamed
mucus membrane and provide soothing
effect. Ex: Menthol

135. False incorporation
■ Bacteria synthesis folic acid from PABA (Para
Amino Benzoic Acid), for growth sand
development.
■ Sulfa drugs resemble PABA, therefore falsely
enter into the synthesis process of PABA,
cause nonfunctional production and no utility
for bacterial growth.

136. Protoplasmic poison
■ Germicides and antiseptics like phenol and
formaldehyde act as non specifically as
protoplasmic poison causing the death of
bacteria

137. Through formation of antibodies
■ Vaccines produce their effect by inducing the
formation of antibodies and thus stimulate the
defense mechanism of the body
■ Ex:- Vaccines against small pox and cholera

138. Targeting specific genetic changes.
■ Anti cancer drugs that specifically target
genetic changes.
■ Inhibitors of specific tyrosine kinase that that
block the activity of oncogenic kinases.

139. Physiological antagonism
■ Two antagonists, acting at different sites,
counter balance each other by producing
opp. effect on same physiological system.
■ Histamine –Vasodilatation
■ Nor epinephrine – Vasoconstriction

140. Chemical action
1.Ion Exchanges:-Anticoagulant effect of
heparin(-ve charge) antagonized by
protamine (+ve charged) protein.
2.Neutralization:- Excessive gastric acid is
neutralized by antacids.
3. Chelation:-These are trap the heavy metals.
Ex:-EDTA, BAL.

141. References
■ Garg GR, Gupta S. Review of Pharmacology,
sixth edition, 2012, Jaypee publishers, New
Delhi
■ Tripathi KD. Essentials of medical
pharmacology, sixth edition, 2008, Jaypee
publishers, New Delhi