Introduction to pharmacology

1. Assoc. Prof. I. Lambev
Medical University of Sofia
E-mail: itlambev@mail.bg
INTRODUCTION
TO
PHARMACOLOGY

2. 1. OBJECT OF
PHARMACOLOGY.
RELATIONSHIPS
WITH OTHER
SCIENCES.

3. The word pharmacology is derived
from the Greek words pharmacon
(drug or poison) and logos (science).
Pharmacology deals with the fate
and actions of drugs at various
levels (molecular, cellular,
organ, and whole body)
in any animal species.

4. 1. Pharmacodynamics - how
the drugs act on the body?
2. Pharmacokinetics - how
the body act on the drugs?
3. Drug Indications and Application
4. Drug Interactions
5. Unwanted (adverse) effects
Object of Pharmacology

5. Pharmacology is the base
of Pharmacotherapeutics
(the treatment of diseases
with drugs).
It overlaps extensively with
pharmacy - the science of
drug production.

6. 2. SCOPE AND
SUBDIVISIONS OF
PHARMACOLOGY
How Pharmacology
is divided?

7. 1. Basic (fundamental) pharmacology
2. Special (organ pharmacology)
3. Experimental (animal) pharmacology
4. Clinical pharmacology
5. Biochemical pharmacology
6. Immunopharmacology
7. Perinatal pharmacology
8. Geriatric pharmacology
9. Pharmacogenetics, etc.
Main branches

8. •Chronopharmacology

9. BABYLONIA
The ancient man
learned from instinct,
from observation
of birds and beasts.
ANCIENT
CHINA
3. HISTORICAL REVIEW

10. Hippocrates
Egypt: Imhotep

11. Avicenna Paracelsus
Galenus

12. UK
France
Nativelle
(1869)
•Digitoxin
Digitalis purpurea (Foxglove)
W. Withering (1785)

13. F. SERTÜRNER
(1783 – 1841)
Morphine
Papaver somniferum L. (Poppy)
•Opium
- morphine (1806)
- codeine
- papaverine
Afghanistan
Pakistan
Thailand

14. Cinchona
succirubra L.
(S. America)
Quinine
Quinidine

15. A. FLEMING
(1881–1955)
•Penicillin G
A. FLEMING
(1881–1955)
•Penicillin G
- P. notatum

16. William Osler (1849 – 1919)
,,Good humour ...
helps enormously
both in the study
and practice of
medicine.”

17. Rauwolfia serpentina
•Ajmaline
•Reserpine (1948)
In 1920’s - discovery of Insulin
and vitamins
In 1930’s - modern anaesthetics
In 1940’s - penicillins
In 1950’s - antihypertensive drugs
In 1960’s - neuroleptics
In 1970’s - H2-blockers,
antiasthmatics
In 1980’s - immunosuppressive
and antiviral drugs

18. Atropa
belladonna L.
(Deadly night shade)
Radix
Belladonnae:
(cura bulgara)
– atropine
Belladonna alkaloids have been empirically used for
treatment of PD in 1920s in Bulgaria by Ivan Raev.

19. The
founders
of the Dept.
of Pharmaco-
logy (1945),
Faculty of
Medicine -
Sofia
Prof. P. Nikolov
(1894-1990)
• D. lanata
• A. belladonna
Prof. D. Paskov
(1914-1986)
• Galantamine
• Aminopyridine
Morbus
Alzheimeri

20. Samuel Hahnemann
(1755 – 1843)

21. 4. DRUGS
“One of the features which is thought
to distinguish man from other animals
is his desire to take medicine“.
Sir William Osler (1849 – 1919)

22. The drugs are chemical substances which
are applied to or introduced into a living
organism to treat, prevent or diagnose of
diseases, and as well as to change some
physiological functions (e.g. reproduction).

23. - 50% of Drugs have
synthetic or SS origin.
- 25% are received from plants
and they include:
• alkaloids,
• glycosides,
• vitamins,
• bioflavonoids, etc.

24. Drug nomenclature
• Chemical name
• INN (“generic name”) or
official, resp. approved names,
(in USA: Adopted Name – USAN)
(in UK: BAN – British Approved Name)
• Proprietary name
(manufacturer’s trade name™
or registered name®)

25. Pharmacopoeian names:
•European Pharmacopoeia
(Ph. Eur. )
•Pharmacopoeia
Internationalis (PhI)

27. ATC classification (WHO, EMA)

28. INN (DCI) + 
ATC Code
Paracetamol (INN)
Acetaminophen (USAN)
ATC code: N02BE01
(= Internet address)
INDEX NOMINUM
Swiss Pharmaceutical Society

29. Pethidine (INN):
(Meperidine - USAN)
•Demerol®
•Lydol®
1-methyl-4-phenyl-
4-carbethoxypiperidine
ATC code:
N02AB02

30. Stages in
development
and regulation
of new drugs

31. Preclinical stage
Drug isolation, semisynthesis or synthesis
Pharmaceutical development
Animal
Pharmacology
Animal
Toxicity
(1)
(2)
(3) (4)

32. May apple (Podophyllum
peltatum - India, USA)
Epipodophyllotoxin
Etoposide
Podophyllin

33. Animal
Pharmacology
Preclinical testing determines:
•screening
•the specificity of effect and the
mechanism of action of a new drug
•the pharmacokinetics of a new drug

34. Animal
toxicity
• subacute toxicity (lasts 14 or 28 days)
• chronical toxicity (lasts 3 or 6 months)
• mutagenicity, carcinogenicity
• reproductive studies (teratogenicity)
• acute toxicity (after a single dose within
a 24-hour period which determines
median lethal dose – LD50)

35. • 84% were rats and mice
• 11% fish, birds and reptiles
• 3% rabbits and ferrets
• 1% sheep, cows and pigs
• 0.5% dogs and cats
• 0.14% monkeys (not for over 12 years!)

36. •49% for development of new drugs
•20% for fundamental biological
and medical research
These animals are used:

37. SHR & SHRSP

38. Clinical stage
(4 phases)
Children and
pregnant women
cannot participate.

39. Human pharmacology
(Phase I)
This is the first administration
of a drug to humans and it
usually follows the completion
of pharmacological and toxi-
cological studies in animals.

40. The investigational drug is
given to 12-15 healthy
volunteers first in single,
increasing doses, and then by
multiple administration to
cover the range of therapeutic
use. These studies are conducted
to obtain data of safety (the range
of dose) and kinetics only.

41. It is forbidden!

42. •A common rule is to begin with
one-fifth or one-tenth of the
maximum tolerated dose
(mg/kg) in the most sensitive
animal species.

43. Initial clinical trials
(Phase II)
This is the first administration
of a drug to patients.
The investigational drug is
given to 150 – 500 patients.

44. Elimination of drug should be
assessed, because patients may
metabolize it differently than
healthy subjects do.
In this phase the efficacy of the
investigational drug can be compared
with placebo (dosage form without
active substance but with the same
flavour, mode, appearance).

45. The placebo effect is a psychogenic
effect. Drugs for treatment of asthma,
duodenal ulcer, arterial hypertension
have a high placebo effect.
Clinical trials with placebo
are forbidden if the potential
drug has antimicrobial, antidia-
betic, or antineoplastic activity.

46. Comparative clinical trials
(Phase III)
The investigational drug is
given to 1000 or more patients
to provide data permitting
statistical evaluations of the
drug’s efficacy and safety.

47. The studies include double-blind,
randomized controlled clinical
trials. The efficacy of a new agent
must be compared with famous
drugs. If there are advantages,
the manufacturer can file a
Drug Submission with the
Regulatory Agency for permission
to market the new drug.

48. •USA: Food and Drug Administration (FDA)
•UK: Medicines Control Agency (MCA)
•Bulgaria: Bulgarian Drug Agency (BDA)
www.bda.bg; hot line: (02) 944 16 36
Regulatory
Drug Agency

49. Post marketing control
(Phase IV)
•Standard of Productions (purity,
efficacy, safety)
•Packing, labeling, advertising
•Scheduling of drugs, to indicate
how to use and prescribe.

50. Post marketing control
also includes control for:
•Unwanted effects
•Drug interactions
•New therapeutic
effects (example
with Aspirin®)

51. Arachidonic acid
Cyclooxygenase (Cox)
Endoperoxides
PGs TxA2
(-)
Aspirin
Thromboxane A2 synthase
(-) 100 mg/24 h
>1 g/24 h

52. Many severe side effects
•Infertility (> PGF2α)
•Thrombosis (< PGI2; > TxA2)
Bextra® (Valdecoxib): Pfizer (penalty!)

53. Creating of new drugs –
social and financial aspects

54. GLP, GMP, GCP

55. Drugs for rare diseases –
the so-called orphan drugs can be
difficult to research, develop,
and market. It is very expensive.
Since 1983, the FDA has
approved for marketing 268
orphan drugs to treat more
than 82 rare diseases.

56. THE MAIN APPROACHES
OF DRUG DISCOVERY
AND DEVELOPMENT ARE:
1. Irrational Approach. It involves emperical
observations of the pharmacological effects
from screening of many chemical compounds,
mainly those from natural products.

57. 2. Rational Approach. It requires three-
dimensional knowledge of the target structure
involved in the disease. Drugs are designed
to interact with this target’s structures to
create a beneficial response.
3. Antisense Therapy requires the modifications
to oligonucleotides that can bind to RNA and
DNA. The antisense drugs stop transcriptional
(from DNA) or translocational (from RNA)
pathways which participate in the pathogenesis of
disease (e.g. antimetabolic drugs and cancer).

58. 4.Biologics. These are protein-based drugs in
the form of antibodies, vaccines and cytokines.
5.Gene Therapy. Its aim is to replace or insert
a diseased gene. The diseased gene is taken
out from the patient, fixed outside the body (ex
vivo) and then reinserted back into the body. In
the case of a missing gene, a copy of a new gene is
inserted into the patients. This is a hot new topic
that raises many ethical considerations to resolve.
6.Stem Cell Therapy: the aim is to grow body parts
to replace defective human organs and nerves.

59. Regenerative
Medicine

62. www.bda.bg
John Atanasoff
(1903 – 2003)
Handbooks

63. The Swiss Anti-PowerPoint Party has been founded
to ban to use of PP. According to the APPP, the use of
presentation software costs the Swiss economy US
$2.5 billion annually, while across the whole of Europe,
presentation software causes an economic loss of US
$160 billion. APPP bases its calculations on unverified
assumptions about the number of employees attending
presentations each week, and supposes that 85% of
those employees see no purpose in the presentations.
Anti-PowerPoint Party

65. www.medpharm-sofia.eu

75. Integrative medicine is the combination of the
practices and methods of alternative medicine
with conventional medicine. The term is
relatively recent, and is mainly promoted by
proponents of alternative therapies in the west.
Some universities and hospitals have
departments of integrative medicine.
Integrative medicine