Transcript úvod do farmakológie - TOP Recommended Websites

Introduction and general
pharmacological principles
Ján Mojžiš
1
Introduction
What is pharmacology
Historical background
Pharmacological terminology
Drug names
2
What is pharmacology

the word Pharmacology comes from the
Greek language: pharmakon (φάρμακον)
meaning drug, and lego (λέγω) to tell
(about)

pharmacology is not identical with
pharmacy
3
What is pharmacology (cont.)

pharmacology deals with how drugs
interact within biological systems to affect
function

pharmacy is the profession responsible for
the preparation, dispensing, and
appropriate use of medication, and
provides services to achieve optimal
therapeutic outcomes
4
History of Pharmacology
Ancient Times
A series of scattered facts exists that
speak of the early history of humankind's
efforts to harness the healing properties of
natural compounds. However, what we
know for certain is that ancient peoples
made extensive use of plant, animal and
mineral sources for this purpose.
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History of Pharmacology
The Ebers papyrus, written in Egypt in the 16th
century B.C., lists the extensive pharmacopea of
that civilization. Included in this are: beer,
turpentine, myrrh, juniper berries, poppy,
lead, salt etc. Also included were
products derived from animals,
including lizard's blood, swine
teeth, goose grease, donkey
hooves and the excreta from
various animals. The effects of
many of these drugs on patients
of antiquity can only be imagined.
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Ancient Greek medicine
Hippocrates (460-370 B.C.)
“Father” of western medicine (Born at Cos)
Illness had a natural cause
First to use observation of symptoms for
clinical diagnosis; “observe patients”
No dissection
Used diet to counteract disease
Four Humours - Illness was caused by
natural factors inside the patient. Yellow bile,
black bile, blood, and phlegm.
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Ancient Roman medicine
„Disease is a contraction or
relaxation of pores which
allowed fine atoms to pass
sensation to parts of the body“
Galen (c. AD 129 - 201)
Doctor to gladiators, later
doctor of Marcus Aurelius
Dissected animals, not
humans
Laid groundwork for
physiological connections to
anatomical design
Diaphragm in respiration
Clinical observation was key to
diagnosis
His texts were the basis of western medicine for 1500 years
9
History of Pharmacology
From ancient China comes evidence of that
culture's extensive efforts to heal through the use of
natural products. The Pen Tsao, or Great Herbal,
comprised forty volumes describing several
thousands of prescriptions.
10
History of Pharmacology
Interestingly, the eastern
herb Artemisia annua L.
(wormwood), used in
China since antiquity to
treat fevers, is the source
of the modern drug
artemisinin, which shows
great promise as a
modern anti-malarial
compound.
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Medicine in the Middle Ages
Ibn Sina (Avicenna, 980-1037 AD)
The cannon of medicine
Medical standard text until
the mid-1600’s
Significant advances in
pharmacology
Compilation of Greek, Roman,
& Persian medical knowledge;
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History of Pharmacology
Antiquity to the modern era
The ancients considered
disease a consequence of
demonic possession, or the
wrath of god. Thus, in ancient
times, the treatment of illness
with natural products was
invariably accompanied by
religious rituals deemed
essential to the healing
process.
13
History of Pharmacology
With time, the thoughts returned to the
appreciation that the natural products themselves
held the power to cure.
Although, traditional
remedies still generally
consisted of complex
mixtures of distinct
herbs and minerals,
perhaps only one of
which possessed any
activity. Many
poisonous mixtures
were made.
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History of Pharmacology
For example, the purple
foxglove, Digitalis purpurea,
was one of twenty herbs
used in a folk remedy to
treat dropsy in 18th century
England. From the leaves
of this plant was isolated
the cardiac glycoside
digitalis, a drug still used
today to treat heart failure.
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History of Pharmacology
Over time, as a more
sophisticated view of
illness evolved, an
increasingly scientific
approach to the isolation
of drugs from natural
products was taken. In the
early 19th century,
morphine was isolated from the opium poppy
(Papaver somniferum) and the anti-malarial
compound quinine from the bark of the cinchona tree
(Cinchona officinalis).
16
History of Pharmacology
In 1897, Felix Hoffman, a research chemist employed by the
"Farbenfabrikin vorm. Freidr. Bayer and Co." synthesized
acetylsalicylic acid. On February 1, 1899, Aspirin® was
registered as a trademark. On March 6th of the same year, this
drug was registered with the Imperial Patent Office in Berlin.
Aspirin quickly become popular worldwide, and remains
an important drug today. (Interestingly, it was
not until 1971 that Sir John Vane discovered
the mechanism of action of aspirin, a feat
that earned him the 1981 Nobel Prize for
Medicine.)
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History of Pharmacology
Paul Ehrlich described drug-receptor binding:
“Corpora non agunt nisi fixate”.
P. Ehrlich (1908)
(“Agents do not act unless they are bound”)
18
History of Pharmacology
The modern era
Advances in the fields of chemistry and
physiology, lead to the birth of modern
pharmacology in the latter half of the 19th
century.
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History of Pharmacology
Morphine: Sertirner in 1805 isolated morfin (the first pure drug)
Salicylic acid: synthesized in 1860 by Kolbe and Lautemann
Acetylsalicylic acid: synthesized in 1897 by F. Hoffman
1899 introduced into medicine : „aspirin’
Barbiturates: introduced into medicine in 1904
Salvarsan: Ehrlich in 1908 introduced into treatment of syphilis.
Proposed the term chemotherapy
Penicillin: discovered by Fleming in 1928
Chlorpromazine: in 1952 used in the treatment of schizophrenia
Propranolol, Cimetidine developed by Black in 1960
Cyclooxygenase (COX): Vane in 1971
NO: Ignaro 1992
20
Pharmacological terminology






Drug
Pharmacokinetics
Pharmacodynamics
Pharmacotherapy
Selectivity
Toxicity
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Pharmacological terminology (cont.)


Therapeutic effect
 Indication
 Contraindication
Undesired effects
 Side effects
 Toxic effects
 Idiosyncratic effects
 Allergy
 Anaphylaxis
22
What is drug ?
Medicine - in the past was plant or animal
substances a drug or a mixture of drugs
combined with other substances to make
it stable, palatable and useful for therapy
Agent - a collective noun
antihypertensive, anticancer agents.
Compound - is a chemical used for
pharmacological purpose, but not as a
therapeutic agent
23
Drug names
A single drug have a variety of names.
1. Chemical name
2. Generic name
3. Commercial or trade name
24
Chemical name
Generic
name
Trade name
1,4-Dihydro-2,6-dimethyl-4-(2nitrophenyl)-3,5pyridinedicarboxylic acid
dimethyl ester
nifedipine
3,5-Diamino-N(aminoiminomethyl)-6chloropyrazinecarboxamide
hydrochloride
amiloride
GUANAMPRAZINE, AMIPRAMIDIN,
AMIPRAMIZIDE
7-chloro-3-methyl-2H-1,2,4benzothiadiazine-1,1-dioxide
diazoxide
HYPERSTAT, HYPERTONALUM,
MUTABASE, PROGLYCEM, SRG 95213
7,8-didehydro-4,5-epoxy-17methylmorphinan-3,6-diol
morphine
MORPHIN 1%, MST CONTINUS,
SEVREDOL, ORAMORPH, CYCLIMORPH
ADALAT, CITILAT, NIFELAT
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Drug names (contin.)
Generic names
It is the name which appears in official national
Pharmacopeias (pure drugs). Often the only
international differences betwen generic names
is a difference in spelling.
Generic name can vary : Norepinephrine
is noradrenaline in Europe.
Acetaminophene in USA is paracetamol in Europe.
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Sources of drugs
Plants and animals (most of drugs in ancient
civilization came from plants or animal parts or
fluids).
From plants: alkaloids, glycosides and others.
Extraction of hormones from animal endocrine
glands
Determination of chemical structure of active
substance led synthetic chemists to produce
many structural analogs
During the last four decades introduction of new
synthetized drugs (de novo).
27
Sources of drugs (cont.)
Genetic engineering
Insulin – E. coli
Artemisinin is the most effective treatment for malaria
it is made from plant found in China and Vietnam
supplies of the plant are limited and it takes a lot of plant
material to get enough of the drug to treat one patient
researchers placed genes from the wormwood plant into
a yeast organism and got it to produce large amounts of
artemisinic acid - this would end the need for a lot of
plants
28
Drug sources


Plants

Living organisms

Chemical synthesis
Elements
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Drug

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
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
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Pharmacokinetics
1. Absorption
2. Distribution
3. Metabolism
3. Excretion
Living organism
Pharmacodynamics
drug action
how drugs act
(mechanism of drug action)
metabolism + excretion = elimination
30
Pharmacokinetics
Is what the body does to the drug.
The magnitud of the pharmacological effect of
a drug depends on its concentration at the
site of action.
Absorption
Distribution
Metabolism
Elimination
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Pharmacodynamics
Is what the drug does to the body.
Interaction of drugs with cellular proteins, such
as receptors or enzymes, to control changes in
physiological function of particular organs.
 Drug-Receptor Interactions
 Binding
 Dose-Response
 Effect
 Signal Transduction
 Mechanism of action, Pathways
32
Actions of aspirin
1. Analgetic
2. Antipyretic
3. Antiinfammatory
4. Antiagregatory,
5. Anticancerogenic
COX-2 Hypothesis (1990s)
Normal
Tissue
Inflammation Site
Arachidonic Acid
+
COX-1
Constitutive
Cytokines
Growth factors
COX-2
Inducible
COX-2
Inhibitors
NSAIDs
Physiolgical
Prostaglandin
Production
Normal Functions
Pathological
Prostaglandin
Production
Inflammation, pain, fever
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Recomended sources
Lectures
Practical excersises
36
lizard
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