History pharmacology

1. PHARMACOLOGY
Pharmacology deals with the knowledge/study of drugs.
• Pharmacology: is an experimental science dealing with the properties of
drugs and their effects on living systems.
• The word pharmacology is derived from the Greek words
“pharmakon”- Drug
“Logos” - Study/Discourse in
• In a broad sense, it deals with interaction of exogenously administered
• In a broad sense, it deals with interaction of exogenously administered
chemical molecules (drugs) with living systems.
• It encompasses all aspects of knowledge about drugs, but most importantly
those that are relevant to effective and safe use for medicinal purposes.
• The term ‘drugs’ is being also used to mean ADDICTIVE/ABUSED/ILLICIT
SUBSTANCES.
• This RESTRICTED AND DEROGATORY SENSE USAGE IS UNFORTUNATE
DEGRADATION of a time honoured term, and ‘drug’ should refer to a
substance that has some therapeutic/diagnostic application.

2. DRUG
The word drug has also a French origin-- 'drouge' (dry herb).
A drug is defined as: ( various definitions….)
• A substance recognized by an official pharmacopoeia or formulary.
• A substance intended for use in diagnosis, cure, mitigation, treatment, or prevention of disease.
• A substance (other than food) intended to affect the structure or any function of the body.
• A substance (other than food) intended to affect the structure or any function of the body.
• A substance intended for use as a component of a medicine but not a device or a component,
part or accessory of a device.
• Biological products are included within this definition and are generally covered by the same
laws and regulations, but differences exist regarding their manufacturing processes (chemical
process versus biological process.)

3. DRUG…definitions
• It is the single active chemical entity present in a medicine that is used for diagnosis,
prevention, treatment/cure of a disease..
WHO (1966) definition- Any substance or product that is used or intended to be used to
modify or to explore physiological system or pathological states for the benefit of the
recipient.
Drug is a substance which is used for :
• Diagnosis of the disease
• Prevention of the disease
• Treatment or palliation (relief of symptoms) of disease
• Treatment or palliation (relief of symptoms) of disease
• Prevention of pregnancy (i.e. contraception)
• Maintenance of optimal health
MEDICINE: -is a chemical preparation which usually but not necessarily contains one or more
drugs, administered with the intention of producing a therapeutic effect.
• Usually contain other substances (excipients, preseravtives, stabilizers, solvents etc.) in
addition to the the active drug /Active Pharmaceutical Ingredient to make them more
convenient to use.
• "All medicines are drugs, but not all drugs are medicine.”

4. Drug Dose and Dosage
DOSE:
• A dose is the quantity of medication to be administered at one
time.
DOSAGE: (RANGE OF DOSES)
It refers to determination and regulation of doses.
It refers to determination and regulation of doses.
• Loading dose: It is one or series of doses that may be given at
the onset of therapy with the aim of achieving the target
concentration rapidly.
• Maintenance dose: It is a series of relatively small doses that
follow the loading dose in order to maintain an effective
concentration in the bio-phase.

5. Sources of Drugs
1. Minerals: -Organic and Inorganic
Liquid paraffin, magnesium sulfate, magnesium trisilicate, kaolin, Iron,Copper etc.
2. Animals: -Tissues
Insulin, thyroid extract, heparin and antitoxin sera, etc.
3. Plants: -Alkaloids,glycosides
Morphine, digoxin, atropine, castor oil, etc.
4. Synthetic source:- Majority of the drugs currently used in therapeutics
4. Synthetic source:- Majority of the drugs currently used in therapeutics
Aspirin, sulphonamides, paracetamol, zidovudine, etc.
• Semi synthetic-Ampicillin
5. Micro organisms: -Bacteria/Fungi
Penicillin, streptomycin and many other antibiotics.
6. Genetic engineering/Recombinant/Biosynthetic :
Human insulin, human growth hormone etc.

6. DRUG NOMENCLATURE/ DRUG NAMES
• CHEMICAL NAME: This name is given according to the chemical structure/constitution of a
drug.
• NON-PROPRIETARY /GENERIC NAME/(INN- INTERNATIONAL NON PROPRIETARY
NOMENCALTURE): These names are used uniformly all over the world by an international
agreement through the W.H.O.
agreement through the W.H.O.
• The non-proprietary name is often referred to as GENERIC NAME.
• PROPRIETARY /TRADE/BRAND NAME/COMMERCIAL NAME/ COMPANY APPROVED
NAME : The pharmaceutical company, which sells the non-proprietary drug selects the
proprietary name and gets it registered.

7. DRUG NOMENCLATURE/ DRUG NAMES
CHEMICAL NAME:
• It describes the substance chemically, the name is given according to the
chemical constitution of a drug.
• The nomenclature used most frequently worldwide is the one created and
developed by the International Union of Pure and Applied Chemistry (IUPAC).
• Indicates precise arrangement of atoms and atomic groups in the molecule.
• Indicates precise arrangement of atoms and atomic groups in the molecule.
• A code name, e.g. RO 15-1788 (later named flumazenil) may be assigned by the
manufacturer for convenience and simplicity before an approved name is
coined.
• However, chemical names are too complex and cumbersome to be used in
prescription.
• Eg: Acetyl salyclic acid, N Acetyl p-amino phenol

8. NON-PROPRIETARY /GENERIC NAME/(INN- Recommended International Non
Proprietary Nomencalture):
• It is the name acceptedby a competent scientific body/authority, e.g.the
United States Adopted Name (USAN) by the USAN council ;when a drug has
been found therapeutically useful
• May be abridged/ shortened version of chemical name
• Used uniformly all over world by an international agreement through W.H.O.
• Used uniformly all over world by an international agreement through W.H.O.
• However, many older drugs still have more than one non-proprietary names,
e.g. ‘meperidine’ and ‘pethidine’ or ‘lidocaine’ and ‘lignocaine’ for the same
drugs.
• Until the drug is included in a pharmacopoeia, the nonproprietary name may
also be called the approved name. After its appearance in the official
publication, it becomes the official name

9. PROPRIETARY /TRADE/BRAND NAME/COMMERCIAL NAME/ COMPANY APPROVED/REGISTERED NAME :
• The name assigned by the manufacturer(s) and is his property or trade mark
• The pharmaceutical company, which sells the non-proprietary drug selects the proprietary name and gets
it registered.
• One drug may have multiple proprietary names, e.g. ALTOL, ATCARDIL, ATECOR, ATEN, BETACARD,
LONOL, TENOLOL, TENORMIN for drug- atenolol from different manufacturers.
• The trade name then becomes the sole property of the pharmaceutical company.
• Usually smaller than the non-proprietary name, designed to be catchy, short, easy to remember and
• Usually smaller than the non-proprietary name, designed to be catchy, short, easy to remember and
often suggestive of the effect/ action it produces
e.g. LOPRESOR suggesting drug for lowering blood pressure.
• Even the same manufacturer may market the same drug under different brand names in
different countries.
• Most widely used by clinicians/doctors
Examples: Omez, Rantac, Calpol, Anacin, Crocin, Bendryl, Dettol, Savlon, Augmentin, Aten, Avil

11. STAGES IN THE DEVELOPMENT OF A DRUG
• Evolution of a New Drug
• Drug development Strategies
* Serendipity (By chance/Accidental/Luck /Intuition)
* Molecular Roulette (random clinical synthesis)
* Program Basic Research with Synthesis of Specific Chemicals.
* Program Basic Research with Synthesis of Specific Chemicals.
* Clinical Observation of Drug Action in the Practice.
• Experimental Pharmacology
• Toxicological Assessment
• Clinical Evaluation( Clinical Trials)
• Approval, Marketing and Promotion

13. Drug discovery and development
Drug development: It is a
highly complex , tedious
,competetive, costly and
commercially risk process.
Approaches to drug
discovery:
Isolate protein
involved in
disease (2-5 years)
Identify
disease
 Natural sources
 Chemical synthesis
 Rational approaches
 Molecular
modelling
 Combinational chemistry
 Biotechnology
disease (2-5 years)
PRECLINICAL
TESTING (1-3
YEARS)
Formulation
& Scale-up
Human clinicaltrials
(2-10 years)
FDA approval
(2-3 years)

14. Regulatory Agencies
• Drug regulation means to promote various activities to ensure the efficacy and safety, quality of drug.
• Every country has its own regulatory authority, which is responsible to enforce the rules and regulations
and issue guidelines for drug development, licensing, registration, manufacturing, marketing and
labelling of pharmaceutical products
• World Health Organization (WHO), Pan yankee Health Organization (PAHO), World Trade Organization
(WTO), International Conference on Harmonization (ICH), World property Organization (WIPO) -
additionally play essential role

15. History of Pharmacology ..
Intro –
•Born as a science – mid 19th century.
•Long before that – use of natural substances
eg. plants, animals, minerals.. (some of
are still used today)
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are still used today)
•But no scientific basis.
•Eg. Concoctions of worms, dung, urine &
moss from a dead man’s skull.

16. • In the late 18th & early 19th centuries :
Francois Magendie & Claude Bernard - Experimental Physiology &
Pharmacology.
• Simultaneous developments in botany, zoology, chemistry &physiology.
• New drugs  New challenges  establishment ofPharmacology.
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17. India
• Vedas – earliest records.
Rig veda (3000 BC)
• Charaka – Father of Indian medicine
- along with Sushruta & Vagbhata described
- along with Sushruta & Vagbhata described
about
300 herbal preparations (50 grps).
• Ayurveda (2500 BC) – ‘Science of life’

18. Ayurveda
• Based on 2 treatises :
Charaka Samhita – medical, > 650
drugs (animal, plants and mineral
origins) Sushruta Samhita - surgical
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• Lord Dhanvantari (Physician of the Gods)
- Father of Ayurveda
- natural remedies
- antiseptic properties of turmeric
- preservative properties ofsalt

19. MATERIA MEDICA
• Latin term for medical materials/ medicinal substances ;
materials of medicine
• The older term for the branch of medical science concerned
with the study of drugs used in the treatment of disease:
with the study of drugs used in the treatment of disease:
includes pharmacology, clinical pharmacology, and the history
and physical and chemical properties of drugs; Comprising all
organic and inorganic drugs
• The Term is Obsolote( No loner in use presently)
• More appropriate term for same at present is Pharmacopoea

20. China
SHEN NUNG PEN TSAO CHING (2700 BC)
• The earliest written compilation of drugs of Chinese herbal
formularies Pen Tsao (Chinese materia medica)
which is attributed to Emperor Shen Nung, who lived in about 2700
BC.
• Recorded over 365 medicinal substances including many vegetables
& mineral preparations and a few animal product as well, some of
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& mineral preparations and a few animal product as well, some of
which are even applicable even today.
• Pen Tsao’ - (~2500 BC)
- plant & metallic preparations, few animalproducts.
- 1st mention of the medical/euphoriant uses of
Cannabis.

21. Egypt
• KAHUN PAPYRUS(1800 BC) • Ancient Egyptian text
discussing various mathematical & medical topic
EBERS PAPYRUS (1550 BC)
• Found in a tomb of a mummy in THEBES & now
• Found in a tomb of a mummy in THEBES & now
preserved at the university of Leipzig, Germany
• Compilation of number of diseases, 700 formulas &
remedies, 829 prescriptions for medicaments
employed in Egyptian medicine •

23. Pioneers in Pharmacology

24. • ‘Father of modern medicine’
 introduced the concept of disease as a pathologic
process.- 4 humors – blood, phlegm, yellow bile
& black bile.
 Medicatrix naturae – ‘healing power of nature’
 recommended judicious use of simple & efficacious
drugs.
 Hippocratic oath- Hippocratic corpus – 70 volumes
Hippocrates (400BC)
 Hippocratic oath- Hippocratic corpus – 70 volumes
 haemorrhoid & polyp removal
THEOPHRASTUS(300 BC) –
 pupil of Aristotle, classified systematically medicinal herbs on the basis of their
individual characteristics rather than their recommended use in treatment.
 Father of Pharmacognosy

25. Dioscorides
 Greek physician, Aristotle’s student
 The first true material medica, De Materia
Medica (“Regarding medical matters”)
a compilation of therapeutic substances and
their uses, was compiled in 77 A.D., while serving
their uses, was compiled in 77 A.D., while serving
as a surgeon in Nero’s Roman Legion traveling
throughout the Mediterranean.
 This served as the basis for the later works of
Galen (131–201) that emerged as the
authoritative material medica for the next
1,400 years

26. Claudius Galen (460-355 BC)
Elevated Hippocratic humoral basis of medicine.
Drugs possessed certain fundamental
effects (warming, cooling, drying, humidifying)
Dogmatic approach  ill health & many deaths
hampered scientific growth for a 1000 years.
Pharmaceutical works - used for reference for
centuries
! In fact, some pharmaceutical preparations consisting of
primarily herbal or vegetable matter are still referred to as
galenical preparations.

27. Francois Magendie (1783-1855)
• Early 19th century
• French Physiologist.
• Pioneer of Experimental Pharmacology.
• Pioneer of Experimental Pharmacology.
• Studied action of nux vomica (Strychnine) spinal
cord – site of action.
• Introduced morphine, codeine, quinine & strychnine.
• Foramen of Magendie

28. Claud Bernard (1813 – 1878)
• Magendie’s student.
• Father of Modern Experimental Medicine
• 1842 - arrow poison Curare specifically acts at
the neuromuscular junction.
• Pancreatic juice, liver glycogen & its importance.
• Existence of Vasomotor system – Vasodilatation &
Vasoconstriction.
Vasoconstriction.
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Claude Bernard (1813 - 188) and James Blake (1814 - 1893)
established the foundations of modern pharmacology.
• They worked on dose response relationship, drug
disposition in the body, mechanism of action of drugs and
structure activity relationship (SAR).

29. PARACELSUS (1493 -1541 AD)
• Regarded as the first systematic Botanist & is also credited for
giving Zinc its name , calling it Zincum.
• pioneered the use of chemicals & minerals for treating
diseases.
• Mercury in the treatment of syphilis & distilled oils in
• Mercury in the treatment of syphilis & distilled oils in
medicine.
• Gave the great statement “All substances are poisons; there is
none which is not poison. The right dose differentiates a
poison & a remedy.”

30. • As these practices took root, official compilations of medicinal substances,
their preparation, use, and dosages, started to appear in Europe.
• These publications, termed PHARMACOPEIA ( pharamcopoea), provided a
unifying framework upon which the pharmaceutical sciences emerged.
• .The Edinburgh Pharmacopoeia published in 1689 became the most influential
• .The Edinburgh Pharmacopoeia published in 1689 became the most influential
during this period. It took until the mid-19th century before truly national
pharmacopeias took hold, with the first United States
Pharmacopeia published in 1820.

31. VALERIUS CORDUS (1514 -1544 AD)
• German physician & botanist who compiled 1st PHARMACOPOEIA &
carefully described techniques to be employed in preparation of drugs.
• The first printed pharmacopeia, titled the Dispensatorium, was published
by Valerius Cordus in 1547 in Nuremberg, Germany
• Pioneered a method for synthesizing ETHER.
• identified & described several new plant species.

32. PHARMACOPOEIA/ PHARAMACOPOEA
• It is an official code/DOCUMENT containing a selected list of the
established drugs and medicinal preparations with descriptions of their
physical properties, identification, purity, potency and the minimum
standard required and the average dose for adults.
• Each country has its own pharmacopeia.
• The first United States Pharmacopeia has been given the title USP-0
• The current edition of the United States Pharmacopeia (USP) is titled USP-
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33. FORMULARY
• It includes information on drugs, other pharmaceutical
products and formulated products in the respective countries
pharamaceutical associations.
• British National Formulary is published by the British Medical
Association
Association
• National Formulary is published by American Pharmaceutical
Association.
• National Formulary of India is published by the Government of
India.

34. Pharamcopoeas
• British Pharmacopeia BP/B.P.
• United States Pharmacopeia USP
• Indian Pharmacopeia IP / I.P.
• European Pharmacopeia EP
• Russian Pharmacopeia RP
• International Pharmacopeia Ph.I
• British Pharmaceutical Codex. BPC
• British Pharmaceutical Codex. BPC
• National formulary NF
• The British National Formulary BNF
• The British Veterinary Codex. BVC
The abbreviation of the Pharmacopoeia is written after the name of the drug
(Tr. Iodine I.P.), i.e., Tri Iodine corresponding to the standard tincture iodine
included under the Indian pharmacopoeia.

35. INDIAN PHARMACOPOEIA 2018
• The Indian Pharmacopoeia Commission (IPC) has released the Eighth Edition
of Indian Pharmacopoeia (IP-2018).
• Secretary, Ministry of Health & Family Welfare, Government of India1.
• Published by the Indian Pharmacopoeia Commission (IPC) on behalf of the
Ministry of Health & Family Welfare, Government of India, in fulfillment of
the requirements of the Drugs and Cosmetics Act, 1940 and the Rules there
under.
• help in the licensing of manufacturing, inspection and distribution of
• help in the licensing of manufacturing, inspection and distribution of
medicines.
• IP-2018 has been brought out in 4 Volumes incorporating 220 new
monographs
• (Chemical Monographs (170), Herbal Monographs (15), Blood and Blood
related products (10), Vaccines and Immunosera for Human use monographs
(02), Radiopharmaceutical monographs (03), Biotechnology Derived
Therapeutic Products (06), Veterinary monographs (14)), 366 revised
monographs and 7 omission

36. NON- OFFICIAL COMPENDIA / COMMERCIAL / DESKTOP /REFERNCE COMPENDIA
• They are secondary sources of drug information which give useful and miscellaneous information about
drugs for pharmacists and medical practitioners.
• They include both generic and trade names of the drugs. Presentations, dose, Brief pharmacology.
Periodically published
Some examples :
• 1. Modern Drug Encyclopedia: by Yorke Medical Books, New York, U.S.A.
2 Martindale Extra Pharmacopeia: by Pharmaceutical Society of Great Britain
3. Physicians' Desk Reference (PDR): by Medical Economies Publication, U.S.A.
4. Remington's Pharmaceutical Science: by Mack Publishing Company, U.S.A.
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37. Rudolf Buchheim
• World’s 1st pharmacology lab –
basement of his house
• Remembered for his pioneer work in Experimental
Pharmacology.
• He introduced the bio assay to pharmacology,
• He introduced the bio assay to pharmacology,
• Taken over by his student,- Oswald Schmiedeberg

38. Oswald Schmiedeberg (1838 – 1921)
• Father of Modern Pharmacology
• 1869 – muscarine had similar effect on the heart
as electrical stimulation of the vagus nerve.
as electrical stimulation of the vagus nerve.
• 1878 – classic text: “Outline of Pharmacology”.
• Discovered glucuronic acid.
• 1885: urethane - hypnotic

39. John Jacob Abel (1857 – 1938)
• Father of American Pharmacology.
• Gave the name ‘Pharmacology’ as a subject
(earlier – Materia Medica)
• 2nd to isolate Epinephrine from adrenal gland.
• 2nd to isolate Epinephrine from adrenal gland.
(1st - Napolean Cybulski in 1895)
• Isolated amino acids from the blood (1914)
• Isolated histamine from pituitary extracts (1919)
• Prepared pure crystalline Insulin (1926)

40. Colonel Ram Nath Chopra (1882 – 1973)
• Father of Indian Pharmacology.
• 1921 : Calcutta School of Tropical Medicine.
HOD of Pharmacology – Calcutta Medical College
• 1941 – 1957: Director – Drug Research Lab atSrinagar.
• 1941 – 1957: Director – Drug Research Lab atSrinagar.
• 1st introduced & studied RauwolfiaSerpentina
• 1st National Drug Research Institute of India,Lucknow
(Central Drug Research Institute, CDRI)
• pioneered research on herbal drugs inIndia
sarpagandha
5

41. Louis Lasagna (1923 – 2003)
• Father of Clinical Pharmacology
• 1954 - 1st clinical pharmacology dept – Johns
Hopkins University.
Conceptualized Controlled clinical trial &
• Conceptualized Controlled clinical trial &
placebo effect.
• Improvement in testing drug effectiveness &
regulation of drugs for effectiveness & safety.
• 1964 – revised the Hippocratic oath
“The incidence of patient
availability sharply
decreases when a clinical
trial begins and returns to
its original level as soon as
the trial is completed.”
- Lasagna’s Law

42. ALEXANDER WOOD (1817 - 1884)
• A Scottish physician, invented the first true hypodermic syringe 1853.
EDWARD JENNER (1749-1823)
• Discovered & established the principle of prophylactic immunization against
smallpox & was the first to describe Anaphylaxis.
• Thus Jenner set the stage for later development of preventive medicine &
immunological therapy
WILLIAM HARVEY (1578-1657 AD)
• Discovered the circulation of blood and indicated that drugs were distributed
to various parts of the body by this means.
CHRISTOPHER WREN (1632-1723 AD)
• The great English architect made the 1st intravenous injection of drugs into a
dog, but it was not until 1853 that the hypodermic needle & syringe were
devised by Alexander Wood.

43. Paul Ehrlich (1854 – 1915)
• Father of Modern Chemotherapy
• Syphilis & autoimmunity
• Coined – Chemotherapy & Receptor ‘Magic
bullet’
bullet’
• Effective preparation of diphtheria antitoxin
• 1908 – Nobel Prize in Medicine.
• 1909 - Salvarsan: most widely prescribed &
most effective drug for treating syphilis until
penicillin.

44. Humphrey Davy
• 1799 – Nitrous oxide
‘Laughing gas’ – relieved toothache
• To relieve pain of surgery.
• Euphoria Analgesia
• Euphoria Analgesia
Loss of consciousness
• Henry Hickman –
mixture of CO2 & NO in surgery.
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45. Horace Wells
• Pioneered the use of anaesthesia indentistry
• Nitrous oxide – painless toothextraction
• Experimented on himself
(“A new era of tooth-pulling!”)
(“A new era of tooth-pulling!”)
45
WILLIAM THOMAS MORTON
•American dentist
•1846 – 1st publicly demonstrated the use of inhaled
ETHER as a surgical anaesthetic .

46. James Young Simpson
• Chloroform
• Used it to relieve pain ofchildbirth.
• 1853 – Queen Victoria permitted it’s use
by John Snow.
• NO & air machines, pethidine & ‘natural’
childbirth.
11

47. FRIEDRICH WILHELM ADAM SERTURNER (1783 - 1841)
• first to isolate Specific narcotic substance MORPHINE
morphine from opium ( POPPY / Papaver
somniferum/Apheemu).
• He called the isolated alkaloid "morphium" after
the Greek god of dreams, Morpheus.

48. Local anaesthesia
(Cocaine)
• Coca leaves – South America
• Friedrich Gaedcke (1859 ) – Cocaine alkaloid
‘Erythroxyline’
• For morphine addiction & in soft drinks
• For morphine addiction & in soft drinks
(Coca cola – coca leaves & kola nuts)
• Sigmund Freud (1883) – medical use of cocaine
‘tongue-numbing’ capacity.
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49. • Carl Koller(‘Coca Koller’)
– ophthalmicuse
• William Halstead
– Fatherof AmericanSurgery
- Nerve blockanaesthesia
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50. Discovery of Prontosil
• Gerhard Domagk (1895– 1964)
• 1st clinically useful sulfonamide
• Streptococcal infections.
• Prontosil  ‘Sulphanilamide’  bacteriostatic.
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• Prontosil  ‘Sulphanilamide’  bacteriostatic.

51. Discovery of Penicillin
• Alexander Fleming (1881-1955) –
Penicillium notatum
• 1928 – culture dish contaminated by
mould spores
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mould spores
• ‘Penicillin’ –seeped out from the
mould  killed bacteria near the
mould

52. • 1935: Howard Florey & Ernst Chain –
investigated the anti-bacterial properties of Penicillin.
• Norman Heatley – isolated penicillin from themould.
• Experimented with mice inoculated withstreptococci
• Used it successfully to treat warwounds
• 1945: Fleming, Florey & Chain received Nobel prize
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53. Discovery of Streptomycin
• 1946:
Waksman – Streptomyces griseus
(chicken’s throat)
Streptomycin
(cocci, spirochaetes, tb bacilli)
53
(cocci, spirochaetes, tb bacilli)
• 1st recorded cure of tb meningitis
• 1952 – Nobel prize

54. Discovery of Insulin
• 1st description of diabetes – mid 17th
century.
• Richard Bright – Involvement of
pancreas
54
• Early 19th century: Paul Langerhans –
‘Islets of Langerhans’
• Hormone deficiency disease –
‘Insulin’
(insula = island)

55. Thalidomide Scandal
• 1950: Wilhelm Kunz – inventedThalidomide
• Sedative; butwith no obvious toxic effects
• Approved as 1st safe sleeping pill
• Reports of sideeffects
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• Reports of sideeffects

56. • 1961: Dr. William McBride – Teratogeniceffect
(babies with deformedlimbs)
• 1962 – 7400 ‘thalidomide children’ worldwide
 withdrawal of drug
• 1968 – Committee on Safety of Medicines
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57. William Withering (1741-1799)
• Dropsy – edema that often accompanies heart
& kidney failure
• Fox glove tea
• Active ingredient – Digitalis
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• Active ingredient – Digitalis
(fox glove leaves)
• 1785: An account of the fox glove
– Study of Digitalis
In Dropsy

58. Otto Loewi
• 1921 – proved the chemical transmission of nerve
impulses
• Prototype experiment - existence of chemical
transmission in a synapse
• 1st chemical neurotransmitter
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• 1st chemical neurotransmitter
identified – Ach
• 1936 – Nobel prize, along
with Henry Dale

59. Sir Henry Hallet Dale
• 1914 - distinguished muscarinic & nicotininc receptors
- 1st identified Ach as a possible neurotransmitter (shared the nobel prize
with Loewi in 1936)
• Dale’s principle (Dale’s Law) –
Each neuron releases only 1 type of neurotransmitter
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Each neuron releases only 1 type of neurotransmitter
• Dale’s Vasomotor Reversal Phenomenon

60. JAMES BLACK
• Developed propranolol – best-
selling drug
• 1975: 2nd major drug – Cimetidine
(Tagamet)
world’s 1st billion dollar drug
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world’s 1st billion dollar drug

61. ALFRED GOODMAN GILMAN
• American pharmacologist and biochemist
• 1994 – Nobel prize in Physiology or Medicine
along with Martin Rodbell for their discovery
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of G proteins & their role in signal
transduction.

62. JOHN NEWPORT LANGLEY (1852-1925)
• • British physiologist – pharmacologist, who determined in 1901
that adrenomedullary extracts clicited responses in different
tissues which were similar to those induced by sympathetic nerve
stimulation,
• also he advanced research in neurotransmitters and chemical
• also he advanced research in neurotransmitters and chemical
receptors, working with extracts from adrenal glands
• proposed in 1905 that a receptive substances (receptors) was the
site of action of chemical mediators liberated by nerve
stimulation.
• The genesis of the concept of chemical synaptic transmission has
been attributed to Langley.

63. ALFRED G. GILMAN, MARTIN RODBELL (1994)
• The Nobel Prize in Physiology or Medicine 1994, "for their
discovery of G- proteins and the role of these proteins in signal
transduction in cells
ROBERT F. FURCHGOTT, LOUIS J. IGNARRO, FERID MURAD. (1998)
ROBERT F. FURCHGOTT, LOUIS J. IGNARRO, FERID MURAD. (1998)
• The Nobel Prize in Physiology or Medicine 1998, "for their
discoveries concerning nitric oxide as a signalling molecule in the
cardiovascular system"

64. Veterinary pharmacology
• Based on the art/science of Materia Medica, veterinary therapeutics is an old
discipline, whereas the discipline of veterinary pharmacology is a new science - < 100
YEARS OLD….
• The basic principles of drug action are identical across veterinary and human
pharmacology.
pharmacology.
• Thus the principles of absorption, distribution, metabolism, and elimination covered
hare the same as in any human pharmacology text, except for a focus on crucial
species differences in anatomy, physiology, or metabolism that would alter these
processes

65. L . MEYER JONES (1913-2002 AD)
• Regarded as ‘Father of modern veterinary pharmacology’
• Professor,Department of Veterinary Physiology and Pharmacology, IOWA state
University, USA.; Instrumental in shifting emphasis in the veterinary curriculum from
materia medica to the modern science of veterinary pharmacology.
• The first edition of the textbook, Veterinary Pharmacology and Therapeutics, (1954)-A
• The first edition of the textbook, Veterinary Pharmacology and Therapeutics, (1954)-A
landmark - MAGNUM OPUS -veterinary pharmacologist’s bible, now in its TENTH
edition (2018) under the editorship of JIM RIVIERE AND MARK PAPICH .
• The American Academy of Veterinary Pharmacology and Therapeutics (AAVPT) - 1977 ;
the European Association for Veterinary Pharmacology and Toxicology (EAVPT) -1978.;
he British Association for Veterinary Clinical Pharmacology and Therapeutics
• Journal of Veterinary Pharmacology and Therapeutics (JVPT)1978- Dr. Andrew Yoxall

67. Some of the popular names under Veterinary Pharmacology in Bharat
• Late Prof. HARPAL .SINGH .SANDHU ( Ludhiana) –
2 Text books
• Dr B.K. Roy (Ranchi ) - Text book
• Late Dr K Jayakumar (Bengaluru)-Curvedrin
• Dr Anil Kumar Srivastava ( NDRI,Director) -Books
• Dr Anil Kumar Srivastava ( NDRI,Director) -Books
• Dr. Satish Kumar Garg (Mathura)-Toxicology book

68. . The most important single advance in veterinary pharmacology/therapeutics over 35 years

69. DIVISIONS/BRANCHES OF PHARMACOLOGY
Materia medica:
• It is an obsolete didactic (instructive) subject that was concerned
with pharmacy, posology, pharmacognosy and indications for
therapeutic use of drugs.
• This subject was purely descriptive in nature and has been replaced
by Pharamcopoea and in the modern veterinary medical curriculum
by Pharamcopoea and in the modern veterinary medical curriculum
by the science of comparative pharmacology.
Pharmacognosy:
It is a branch of pharmacology that deals with the sources of drugs
derived from plants and animals.and the physical and chemical
properties of such substances

71. PHARMACOKINETICS (PK)
• term derived from the Greek word 'kinesis' meaning a movement.
It deals with the time course of drug absorption, distribution,
metabolism and excretion.(ADME)
• The study of “ what the body does to the drug?” Fate of drug
DIVISIONS/BRANCHES OF PHARMACOLOGY…contd
– . Absorption - movement of drug from its site of administration into the
blood stream
– Distribution -Drug molecules from blood to tissues
– Metabolism/biotransformation - drugs are inactivated by liver enzymes
to inactive metabolites or water-soluble substance for excretion.
– Excretion-elimination of drugs or its chemical byproducts in bile, feces,
lungs, saliva, sweat, breast milk

72. PHARMACODYNAMICS (PD )
• Greek 'dynamics' means force
• The study of physiological and biochemical effects of drugs,
mechanisms of action and the relationship of the plasma
concentration of the drug with its response and the duration of
DIVISIONS/BRANCHES OF PHARMACOLOGY…contd
concentration of the drug with its response and the duration of
action.
• In other words, it means "What the drug does to the body?”
PHARMACOMETRICS:
• It deals with the study of qualitative and quantitative aspects of
drug effects in laboratory animals. It deals with measurement of
drug responses

73. • Posology:- It is the study of medicine dosage.
• Metrology: It is the study of weights and measures as applied to preparation and administration of drugs
DIVISIONS/BRANCHES OF PHARMACOLOGY…contd

74. DIVISIONS/BRANCHES OF PHARMACOLOGY…contd

75. DIVISIONS/BRANCHES OF PHARMACOLOGY…contd

76. DIVISIONS/BRANCHES OF PHARMACOLOGY…contd
• PHARMACOVIGILANCE is the science and activities relating to the detection, assessment,
understanding and prevention of adverse effects or any other drug-related problem.
• NEUROPHARMACOLOGY is the study of neurophysiological or neurobiochemical functions of the
nervous system including the brain, spinal cord, and the nerves that are modified by drug action.
• Cardiovascular pharmacology concerns the effects of drugs on the heart, the vascular system, and
those parts of the nervous and endocrine systems that participate in regulating cardiovascular
function.
• MOLECULAR PHARMACOLOGY deals with the biochemical and biophysical characteristics of
interactions between drug molecules and those of the cell. It is molecular biology applied to
interactions between drug molecules and those of the cell. It is molecular biology applied to
pharmacology and toxicology .
• BIOCHEMICAL PHARMACOLOGY is the study of action of drugs and drug metabolism, how drugs
interact with, and influences, the physiology of the organism.
• BEHAVIORAL PHARMACOLOGY studies the effects of drugs on behavior of organism. It includes
topics such as the effects of psychoactive drugs on the phenomena of learning, memory,
wakefulness, sleep and the behavioral consequences of experimental intervention in enzyme activity
and brain neurotransmitter levels and metabolism.
• ENDOCRINE PHARMACOLOGY is the study of drugs that are either hormones or hormone
derivatives, or drugs that may modify the sections of normally secreted hormones.

77. CHRONOPHARMACOLOGY
THE STUDY / investigation of drug effects as a function of biologic
timing and the investigation of drug effects upon rhythm
characteristics
SYSTEMIC PHARMACOLOGY - Study of pharamcology of
systemwise drugs acting on various body systems
• Digestive
• Cardiovascular
• Respiratory
• Genitourinary
• Reproductive
• Endocrine

78. BROAD CATEGORIES OF DRUGS
OVER THE COUNTER (OTC) DRUGS:
These are those preparations that can be sold without any restriction/prescription because they can be adequately
used for layman use. Eg: Most of the painkillers(NSAIDS-paracetamol)
PRESCRIPTION DRUGS:
Drugs that can be used only on the order/prescription of a licensed veterinarian/ physician/ dentist/ surgeon.
They are also known as LEGEND DRUGS. Eg: Antibiotics-Ampicillin
ESSENTIAL DRUGS:
Drugs that satisfy the healthcare needs of majority of the population. They should therefore be available at all
times in adequate amounts and in appropriate dosage forms. Eg: Vitamins, Antimicrobial-anthelmintics
times in adequate amounts and in appropriate dosage forms. Eg: Vitamins, Antimicrobial-anthelmintics
HARD DRUGS:
• Drugs used for non-medical purposes that are liable to disable the individual seriously as a functioning
member of the society by inducing severe psychological and/or physical dependence. Example - Heroin.
SOFT DRUGS:
Drugs used for non-medical purposes that are less dependence producing. There may be psychological
dependence but not physical dependence, except with heavy dose. Example - Amphetamine.
NOOTROPIC DRUGS:
Drugs that affect the intellect. These drugs are claimed to enhance learning, increase brain resistance to stress
including hypoxia and stimulate brain metabolism especially in senile patients. Example – Piracetam

79. WHO LIST OF ESSENTIAL DRUGS:

80. ORPHAN DRUGS:
• Drugs or biological products for diagnosis/ treatment/ prevention of a rare disease
condition for which there is no reasonable expectation that the cost of developing and
marketing it will be recovered from sales of that drug.
• Example – Acetylcysteine. These drugs may be life saving for some patients (paracetamol
poisoning), but are not readily commercially available
CONTROLLED DRUGS -“Controlled substance” is a legal term referring specifically to
substances controlled by federal or state laws. -United States Drug Enforcement
substances controlled by federal or state laws. -United States Drug Enforcement
Administration(DEA)
• The term "controlled substance" means a drug or other substance, or immediate precursor,
included in schedule I, II, III, IV, or V. -depending upon the drug’s acceptable medical use
and the drug’s abuse or dependency potential under Controlled Substances Act (CSA)

81. • Schedule I drugs have a high potential for abuse and the potential to create
severe psychological and/or physical dependence.
• As the drug schedule changes-- Schedule II, Schedule III, etc., so does the
abuse potential-- Schedule V drugs represents the least potential for abuse.
• Substances are placed in their respective schedules based on
• Whether they have a currently accepted medical use in treatment
• Their relative abuse potential
• Likelihood of causing dependence when abused.

82. Schedules under
Controlled substance act

83. PLACEBO (Latin: Placebo – I shall be pleasing or acceptable)
• Drug dosage form such as a tablet/capsule/ solution that has no pharmacologic activity
because the dosage form has no active pharmaceutical ingredients.
• It could be a dummy or inert substance , non harmful to body .
• Eg: sterile water. Glucose, saline etc
• Can be used as a control in scientific evaluation of drugs, clinical trials and to benefit or
please a patient not by pharmacological actions but by psychological means.
• Placebo reactor -an individual who report changes of physical and mental state after
taking a pharmacologically inert substance.

84. Drug related …Terms .... Clinical
• Dose and Dosage
• Route of administration and Dosage forms
• Dosing Interval(Frequency of Administration)
• Spectrum and Classification/Category
• Mechanism of action ( PD); Fate of drug (PK-ADME)
Indications , Contraindications , Precautions
• Indications , Contraindications , Precautions
• Drug label/ Labelling information
• ELU- Extra label Use of drug
• Adverse effects/Side effects
• Withdrawal period/time
• Interactions –Food, Drug,Nutrient

86. DRUG DISCOVERY
86

87. Introduction
• In the past most drugs have been discovered either by
identifying the active ingredient from traditional remedies or
by serendipitous discovery.
• But now we know diseases are controlled at molecular and
physiological level.
But now we know diseases are controlled at molecular and
physiological level.
• Also shape of an molecule at atomic level is well understood.
• Information of Human Genome

88. History of Drug Discovery :
Pre 1919
• Herbal Drugs
• Serendiptious discoveries
1970s
• Rise of Biotechnology
• Use of IT
1980s
• Commercialization of
Drug Discovery
• Combinatorial Chemistry
1920s, 30s
• Vitamins
• Vaccines
1940s
• Antibiotic Era
• R&D Boost due to WW2
1950s
• New technology,
• Discovery of DNA
1960s
• Breakthrough in Etiology
1990s
• Robotics
• Automation

89. Registration:
• The Ministry of health & Family Welfare and the Ministry of Chemicals &
Fertilizers have major role in regulation of IPM.
• NDA must be submitted to DCGI
• Phase III study reported to CDL, Kolkata
• Phase III study reported to CDL, Kolkata
• Package inserted approved by DCI
• Marketing approval from FDA

90. STAGES IN THE DEVELOPMENT OF A DRUG
• Evolution of a New Drug
• Drug development Strategies
* Serendipity (By chance/Accidental/Luck /Intuition)
* Molecular Roulette (random clinical synthesis)
* Program Basic Research with Synthesis of Specific Chemicals.
* Program Basic Research with Synthesis of Specific Chemicals.
* Clinical Observation of Drug Action in the Practice.
• Experimental Pharmacology
• Toxicological Assessment
• Clinical Evaluation( Clinical Trials)
• Approval, Marketing and Promotion

92. Drug discovery and development
Drug development: It is a
highly complex , tedious
,competetive, costly and
commercially risk process.
Approaches to drug
discovery:
Isolate protein
involved in
disease (2-5 years)
Identify
disease
 Natural sources
 Chemical synthesis
 Rational approaches
 Molecular
modelling
 Combinational chemistry
 Biotechnology
disease (2-5 years)
PRECLINICAL
TESTING (1-3
YEARS)
Formulation
& Scale-up
Human clinicaltrials
(2-10 years)
FDA approval
(2-3 years)

93. DRUG DISCOVERY
Most new drugs or drug products are discovered or developed through one or more of six approaches:
1. Identification or elucidation of a new drug target
2. Rational drug design of a new drug based on an understanding of biologic mechanisms,drug
receptor structure,and drug structure.
3. Chemical modification af a known molecule.
4. Screening for biologic activity of large numbers of natural products,banks of previously discovered
chemical entities,and large libraries of peptides,nucelic acids,and other organic molecules.
Biotechnology and cloning using genes to produce peptide and proteins.Efforts continue to focus on the
discovery of new targets and approaches,from studies with genomics,proteomics,nucleic acids and
molecular pharmacology for drug therapy.
6. Combination of known drugs to obtain additive or synergistic effects or a repositioning of a known
drug for a new therapeutic use.

94. 10,000
COMPOUNDS
250
COMPOUNDS 5 COMPOUNDS
1 FDA
APPROVED
DRUG
DISCOVERY
PRECLINICAL
CLINICAL TRIALS FDA
REVIEW
Drug Discovery & Development-
Timeline
COMPOUNDS COMPOUNDS 5 COMPOUNDS APPROVED
DRUG
~6.5 YEARS ~7 YEARS ~1.5 YEARS

98. Drug Discovery
• Drugs Discovery methods:
– Random Screening
– Molecular Manipulation
– Molecular Designing
– Drug Metabolites
– Serendipity

99. Target Selection
•Cellular and
Genetic Targets
Lead
Discovery
•Synthesis and
MEDICINAL
CHEMISTRY
•Library
Development
In Vitro
Studies
•Drug Affinity
In Vivo
Studies
• Animal models of
Clinical
Trials and
Therapeut
ics
•Genomics
•Proteomics
•Bioinformatics
•Synthesis and
Isolation
•Combinatorial
Chemistry
•Assay
development
•High-
Throughput
Screening
Development
•SAR Studies
•In Silico
Screening
•Chemical
Synthesis
•Drug Affinity
and Selectivity
•Cell Disease
Models
•MOA
•Lead Candidate
Refinement
• Animal models of
Disease States
• Behavioural
Studies
• Functional
Imaging
• Ex-Vivo Studies
ics

100. Cellular &
Genetic Targets
Genomics
Target Selection
• Target selection in drug discovery is defined as the
decision to focus on finding an agent with a particular
biological action that is anticipated to have therapeutic
utility — is influenced by a complex balance of scientific,
medical and strategic considerations.
• Target identification: to identify molecular targets that are
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Genomics
Proteomics
Bioinformatics
• Target identification: to identify molecular targets that are
involved in disease progression.
• Target validation: to prove that manipulating the
molecular target can provide therapeutic benefit for
patients.

101. Cellular &
Genetic Targets
Genomics
Target Selection
Biochemical Classes of Drug Targets
 G-protein coupled receptors - 45%
 enzymes - 28%
 hormones and factors - 11%
 ion channels - 5%
 nuclear receptors - 2%
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Genomics
Proteomics
Bioinformatics
Techniques for Target Identification

102. Cellular &
Genetic Targets
Genomics
Cellular & Genetic Targets:
Involves the identification of the function of a potential
therapeutic drug target and its role in the disease process.
For small-molecule drugs, this step in the process involves
identification of the target receptors or enzymes whereas for
some biologic approaches the focus is at the gene or
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Genomics
Proteomics
Bioinformatics
some biologic approaches the focus is at the gene or
transcription level.
Drugs usually act on either cellular or genetic chemicals in the
body, known as targets, which are believed to be associated with
disease.

103. Cellular &
Genetic Targets
Genomics
Cellular & Genetic Targets:
Scientists use a variety of techniques to identify
and isolate individual targets to learn more about
their functions and how they influence disease.
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Genomics
Proteomics
Bioinformatics
Compounds are then identified that have various
interactions with the drug targets that might be
helpful in treatment of a specific disease.

104. Cellular &
Genetic Targets
Genomics
Genomics:
The study of genes and their function. Genomics aims to
understand the structure of the genome, including the
mapping genes and sequencing the DNA.
Seeks to exploit the findings from the sequencing of the
human and other genomes to find new drug targets.
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Genomics
Proteomics
Bioinformatics
human and other genomes to find new drug targets.
Human Genome consists of a sequence of around 3 billion
nucleotides (the A C G T bases) which in turn probably
encode 35,000 – 50,000 genes.

105. Cellular &
Genetic Targets
Genomics
Genomics:
Drew’s estimates that the number of genes implicated in disease,
both those due to defects in single genes and those arising from
combinations of genes, is about 1,000
Based on 5 or 10 linked proteins per gene, he proposes that the
number of potential drug targets may lie between 5,000 and
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Genomics
Proteomics
Bioinformatics
number of potential drug targets may lie between 5,000 and
10,000.
Single Nucleotide Polymorphism (SNP) libraries: are used to
compare the genomes from both healthy and sick people and to
identify where their genomes vary.

106. Cellular &
Genetic Targets
Genomics
Proteomics:
It is the study of the proteome, the complete set of proteins
produced by a species, using the technologies of large – scale
protein separation and identification.
It is becoming increasingly evident that the complexity of biological
systems lies at the level of the proteins, and that genomics alone
will not suffice to understand these systems.
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Genomics
Proteomics
Bioinformatics
will not suffice to understand these systems.
It is also at the protein level that disease processes become
manifest, and at which most (91%) drugs act.
Therefore, the analysis of proteins (including protein-protein,
protein-nucleic acid, and protein ligand interactions) will be utmost
importance to target discovery.

107. Cellular &
Genetic Targets
Genomics
Proteomics:
Proteomics is the systematic high-throughput separation
and characterization of proteins within biological systems.
Target identification with proteomics is performed by
comparing the protein expression levels in normal and
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Genomics
Proteomics
Bioinformatics
comparing the protein expression levels in normal and
diseased tissues.
2D PAGE is used to separate the proteins, which are
subsequently identified and fully characterized with LC-
MS/MS.

108. Cellular &
Genetic Targets
Genomics
Bioinformatics:
Bioinformatics is a branch of molecular biology that involves extensive analysis of biological data using
computers, for the purpose of enhancing biological research.
It plays a key role in various stages of the drug discovery process including
 target identification
 computer screening of chemical compounds and
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Genomics
Proteomics
Bioinformatics
 pharmacogenomics

109. Cellular &
Genetic Targets
Genomics
Bioinformatics:
Bioinformatics methods are used to transform the raw sequence
into meaningful information (eg. genes and their encoded
proteins) and to compare whole genomes (disease vs. not).
Can compare the entire genome of pathogenic and non-
pathogenic strains of a microbe and identify genes/proteins
associated with pathogenism
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Genomics
Proteomics
Bioinformatics
associated with pathogenism
Using gene expression micro arrays and gene chip technologies,
a single device can be used to evaluate and compare the
expression of up to 20000 genes of healthy and diseased
individuals at once

110. Synthesis and
Isolation
Combinatorial
Chemistry
Lead Discovery:
• Identification of small molecule modulators of protein
function
• The process of transforming these into high-content lead
series.
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Chemistry
Assay Development
High Throughput
Screening

111. Synthesis and
Isolation
Combinatorial
Chemistry
Synthesis and Isolation:
• Separation of mixture
• Separation of impurities
• In vitro chemical synthesis
• Biosynthetic intermediate
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Chemistry
Assay Development
High Throughput
Screening

112. Synthesis and
Isolation
Combinatorial
Chemistry
Combinatorial Chemistry:
Rapid synthesis of or computer simulation of large
no. of different but structurally related molecules
• Search new leads
• Optimization of target affinity & selectivity.
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Chemistry
Assay Development
High Throughput
Screening
• Optimization of target affinity & selectivity.
• ADME properties
• Reduce toxicity and eliminate side effects

113. Synthesis and
Isolation
Combinatorial
Chemistry
Assay Development
• Used for measuring the activity of a drug.
• Discriminate between compounds.
• Evaluate:
• Expressed protein targets.
• Enzyme/ substrate interactions.
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Chemistry
Assay Development
High Throughput
Screening
• Enzyme/ substrate interactions.

114. Synthesis and
Isolation
Combinatorial
Chemistry
High throughput screening (HTS):
• Screening of drug target against selection of chemicals.
• Identification of highly target specific compounds.-involves testing
of large number of compounds versus a large number of targets.
• HTS involves the miniaturization and automation of in vitro tests
such that a large number of tests can be carried out in a short
period of time.
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Chemistry
Assay Development
High Throughput
Screening
period of time.
• The test should produce easily measurable effect.
• This effect may be cell growth, an enzyme catalyzed reaction which
produces a color change (may be a dye) or displacement of
radioactive labelled ligand from its receptors.

115. Library Development
SAR Studies
Medicinal Chemistry:
• It’s a discipline at the intersection of synthetic
organic chemistry and parmacology.
• Focuses on small organic molecules (and not on
biologics and inorganic compounds)
• Used in
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
SAR Studies
In Silico Screening
Chemical Synthesis
• Used in
• Drug discovery (hits)
• Lead optimization (hit to lead)
• Process chemistry and development

116. Library
Development
SAR Studies
Library Development:
• Collection of stored chemicals along with associated
database.
• Assists in High Throughput Screening
• Helps in screening of drug target (hit)
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
SAR Studies
In Silico Screening
Chemical Synthesis
• Based on organic chemistry

117. Library
Development
SAR Studies
SAR Studies:
• Helps identify pharmacophore
• The pharmacophore is the precise section of
the molecule that is responsible for biological
activity
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
SAR Studies
In Silico Screening
Chemical Synthesis
activity
• Enables to prepare more active compound
• Allow elimination of excessive functionality

118. Library
Development
SAR Studies
SAR Studies:
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
SAR Studies
In Silico Screening
Chemical Synthesis
Morphine Molecule

119. Library
Development
SAR Studies
In silico screening:
• Computer simulated screening of chemicals
• Helps in finding structures that are most likely to bind to
drug target.
• Filter enormous Chemical space
• Economic than HTS
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
SAR Studies
In Silico Screening
Chemical Synthesis
• Economic than HTS

120. Library
Development
SAR Studies
Chemical Synthesis:
• Involve production of lead compound in suitable quantity
and quality to allow large scale animal and eventual,
extensive human clinical trials
• Optimization of chemical route for bulk industrial
production.
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
SAR Studies
In Silico Screening
Chemical Synthesis
production.
• Suitable drug formulation

121. Drug Affinity
and Selectivity
Cell Disease
Models
In Vitro Studies:
• (In glass) studies using component of organism i.e. test tube experiments
• Examples-
• Cells derived from multicellular organisms
• Subcellular components (Ribosomes, mitochondria)
• Cellular/ subcellular extracts (wheat germ, reticulocyte extract)
• Purified molecules (DNA,RNA)
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Models
MOA
Lead Candidate
Refinement
• Purified molecules (DNA,RNA)

122. Drug Affinity
and Selectivity
Cell Disease
Models
In Vitro Studies:
Advantages:
• Studies can be completed in short period of time.
• Reduces risk in post clinical trials
• permits an enormous level of simplification of the system
• investigator can focus on a small number of components
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Models
MOA
Lead Candidate
Refinement

123. Drug Affinity
and Selectivity
Cell Disease
Models
Drug affinity and selectivity
• Drug affinity is the ability of drug to bind to its biological target (receptor,
enzyme, transport system, etc.)
• Selectivity- Drug should bind to specific receptor site on the cell (eg. Aspirin)
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Models
MOA
Lead Candidate
Refinement

124. Drug Affinity
and Selectivity
Cell Disease
Models
• Isogenic human disease models- are a family of cells that are selected or
engineered to accurately model the genetics of a specific patient population, in vitro
• Stem cell disease models-Adult or embryonic stem cells carrying or induced to
carry defective genes can be investigated in vitro to understand latent molecular
mechanisms and disease characteristics
Cell disease models
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Models
MOA
Lead Candidate
Refinement

125. Drug Affinity
and Selectivity
Cell Disease
Models
• Optimizing chemical hits for clinical trial is commonly referred to as lead
optimization
• The refinement in structure is necessary in order to improve
• Potency
• Oral Availability
• Selectivity
Lead Candidate refinement
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Models
MOA
Lead Candidate
Refinement
• Selectivity
• pharmacokinetic properties
• safety (ADME properties)

126. Animal models
of Disease States
Behavioural Studies
In vivo studies
• Its experimentation using a whole, living organism.
• Gives information about,
• Metabolic profile
• Toxicology
• Drug interaction
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Behavioural Studies
Functional Imaging
Ex-Vivo Studies
• Drug interaction

127. Animal models
of Disease States
Behavioural Studies
Animal models of disease states
• Test conditions involving induced disease or
injury similar to human conditions.
• Must be equivalent in mechanism of cause.
• Can predict human toxicity in 71% of the cases.
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Behavioural Studies
Functional Imaging
Ex-Vivo Studies
• Can predict human toxicity in 71% of the cases.
• Eg. SCID mice-HIV
NOD mice- Diabetes
Danio rerio- Gene function

128. Animal models
of Disease States
Behavioural Studies
Behavioural Studies
• Tools to investigate behavioural results of drugs.
• Used to observe depression and mental disorders.
• However self esteem and suicidality are hard to induce.
• Example:
• Despair based- Forced swimming/ Tail suspension
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Behavioural Studies
Functional Imaging
Ex-Vivo Studies
Despair based- Forced swimming/ ail suspension
• Reward based
• Anxiety Based

129. Animal models
of Disease States
Behavioural Studies
Functional Imaging:
• Method of detecting or measuring changes in
metabolism, blood flow, regional chemical
composition, and absorption.
• Tracers or probes used.
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Behavioural Studies
Functional Imaging
Ex-Vivo Studies
• Tracers or probes used.
• Modalities Used-
• MRI
• CT-Scan

130. Animal models
of Disease States
Behavioural Studies
Ex-Vivo Studies:
• Experimentation on tissue in an artificial
environment outside the organism with the
minimum alteration of natural conditions.
• Counters ethical issues.
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Behavioural Studies
Functional Imaging
Ex-Vivo Studies
• Counters ethical issues.
• Examples:
• Measurement of tissue properties
• Realistic models for surgery

131. Phase-I
Phase-II
Clinical trials:
• Set of procedures in medical research and drug
development to study the safety and efficacy of new drug.
• Essential to get marketing approval from regulatory
authorities.
• May require upto 7 years.
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Phase-II
Phase-III
Phase-IV
• May require upto 7 years.

132. STAGES IN DRUG DEVELOPMENT-
CLINICAL TRIALS
• Drug Discovery -Pre-Clinical Testing- Phase 0
• IND Programme
• Phase I Clinical Trials
• Phase II Clinical Trials
• Phase II Clinical Trials
• Phase III Clinical Trials
• New Drug Application (NDA) / Biologics License Application
(BLA)
• Phase IV and Beyond
132

133. IND programme- Investigational New Drug
• It is the means by which a pharmaceutical company obtains permission to ship an
experimental drug across state lines (usually to clinical investigators) before a marketing
application for the drug has been approved.
• The FDA reviews the IND application for safety and if approved, the candidate drug usually
enters a Phase 1 clinical trial.
NDA -New Drug Application
NDA -New Drug Application
• Formal proposal for the US-FDA (Food and Drug Administartaion (USA) to approve a new
drug for sale .
– Sufficient evidences to be provided to FDA to establish: Drug is safe and effective;
Benefits outweigh the risks.and Proposed labeling is appropriate.

134. Phase-I
Phase-II
Phase 0:
• Recent designation, also known as human micro-
dosing studies.
• First in human trials, conducted to study exploratory
investigational new drug.
• Designed to to speed up the development of
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Phase-II
Phase-III
Phase-IV
• Designed to to speed up the development of
promising drugs.
• Concerned with-
• Preliminary data on the drug’s pharmacodynamics
and pharmacokinetics
• Efficacy of pre-clinical studies.

135. Phase-I
Phase-II
Phase I:
• Clinical Pharmacologic Evaluation
• First stage of testing in human subjects.
• 20-50 Healthy Volunteers
• Concerned With:
– Human Toxicity.
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Phase-II
Phase-III
Phase-IV
– Human Toxicity.
– Tolerated Dosage Range
– Pharma-cology/dynamics

136. Phase-I
Phase-II
Phase I:
Types of Phase-I Trials
• SAD (Single Ascending Dose)
• MAD (Multiple Ascending Dose)
• Food effect
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Phase-II
Phase-III
Phase-IV

137. Phase-I
Phase-II
Phase II:
• Controlled Clinical Evaluation.
• 50-300 Patients
• Controlled Single Blind Technique
• Concerned With:
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Phase-II
Phase-III
Phase-IV
• Concerned With:
– Safety
– Efficacy
– Drug Toxicity
– Drug Interaction

138. Phase-I
Phase-II
Phase III:
• Extended Clinical Trials.
• Most expensive & time consuming.
• 250-1000 Patients.
• Controlled Double Blind Technique.
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Phase-II
Phase-III
Phase-IV
• Controlled Double Blind Technique.
• Concerned With:
– Safety, Efficacy
– Comparison with other Drugs
– Package Insert

139. Phase-I
Phase-II
Phase IV:
• Post Marketing Surveillance.
• Designed to detect any rare or long-term adverse effects.
• Adverse Drug Reaction Monitoring.
• Pharmacovigilance.
Target Selection Lead
Discovery
Medicinal
Chemistry
In Vitro
Studies
In Vivo
Studies
Clinical
Trials
Phase-II
Phase-III
Phase-IV

140. 140