Download INTRODUCTION TO PHARMACOLOGY

INTRODUCTION TO
PHARMACOLOGY
PHARMACOLOGY
(Greek “Pharmacon” – drug, “logos” teaching)
The science that studies the interaction
of the chemical substances with live
organisms, drugs administration for
treatment and prophylaxis of various
diseases and pathological processes
• Pharmaceutical explosion
• Nowadays there are over 350
thousand drugs in the world which
are used for different diseases
• In Ukraine nearly 14 thousand
drugs are registered now and
allowed for administration as
curative agents
• The volume of world
pharmaceutical market annually –
400-600 billion $
• Till 2015 – 1,1 trillion $
Ukraine: 128 preparations of
Diclofenac-sodium,
60 – Paracetamol
(Acetaminophen)
For each drug - only single
international name and different
trade names
Paracetamol (Ukraine)
•
Mono:
Мілістан, альдолор,
доломол, калпол,
медипірин, панадол,
паралгет, парацет,
піранол, спазмолекс,
тайленол, тімінол,
цефекон, ефералган
•
Combined:
Антикарал, гриппоцид,
далерон, колдакт
флю, кофан, лугаколд,
мілістан мульти,
мілістан синус,
паравіт, парафекс,
ринза, зелід плюс,
зероколд, колд-ікс,
колдрекс, колдрекс
хотрем,
блекарант фейвор, лемон
флейвор, комбігрип,
комбінекс, комбіспазм,
мексавіт, меноспаз,
неколд, новалгін, ньюкол
плюс, панадол, парацетс,
паркофен, піранол плюс,
рекофаст плюс, саридон,
солпадеїн, стоп-флю,
диетимол, терафлю, тофф
плюс, тройчатка,
фармадол, фармацитрон,
фемізол, фервекс,
ефералган, флюбен,
флюколд, флюколдекс,
циклопар, цитрамон
екстра, ефект флу,
анальгет, антифлу,
атаралгін, гевадал,
грипекс, гриппоколд,
грипостад, грипустоп,
грипфлю, доларен
Nadolol – international name
Corgard – trade name
Becotide = Beclometh – trade name
Beclomethasone dipropionate –
international name
•
Brand – original drug which is defended by
patent and may be produced during patent term
only by this pharmaceutical firm (company)
•
Generic – when term of patent is discontinued
the drug may be produced by different
pharmaceutical companies under new product
(trade) names but at the basis of original active
substance (similar quantity, route of
administration etc.)
• All generics are much more cheaper compared to
brands, that is the main reason – why they are so
popular among the patients
GENERICS
• UK, Deutschland, French, Holland,
Denmark – the part of generics
among all drugs is 50-75 % (in
Ukraine – the majority of drugs)
• Market volume of generics In Europe
is over 10 billion $ annually
Brand and generic – the same
bioavailability
bioavailability
speed and level of absorption of active
substance after administration in equal
doses under the same conditions
Bioavailability
of drugs
complex of pharmacokinetic processes
that maintenances active concentration of
drug in the area of specific receptors
(part of administered drug that reaches
the systemic circulation and effects
specific receptors)
Bioavailability – to study some pharmacokinetic parameters
concentration
Cmax
AUC
Area under curve
Tmax
time
Side effects (SE) of drugs
• Take 5th place among causes of
mortality in the whole world after cardiacvascular diseases, malignant tumors, lungs
diseases, traumas
• Among stationary patients frequency of SE
after introduction of drugs makes 2-40 %
focomelia
Talidomide
(katergan)
PHARMACOKINETICS
THE PART OF PHARMACOLOGY THAT
CONCERNED WITH THE
ABSORBTION,
DISTRIBUTION,
METABOLISM (BIOTRANSFORMATION)
AND EXCRETION OF DRUGS
WHAT THE ORGANISM DOES TO THE DRUGS
PHARMACODYNAMICS
THE PART OF PHARMACOLOGY THAT
CONCERNED WITH THE
BIOCHEMICAL AND PHYSIOLOGICAL
EFFECTS OF DRUGS AND THEIR MODE OF
ACTION
IT INCLUDES THE DOSE-EFFECT
RELATIONSHIP, FACTORS MODIFYING
DRUG EFFECTS, DOSAGE, DRUG TOXICITY
WHAT DRUGS DO TO THE ORGANISM
RECEPTOR THEORY OF DRUG ACTION
• Receptors – the places where drugs bind to
tissues: macromolecules, enzymes, channels,
transport systems, genes
• Agonists: adrenalin, isadrine, morphine etc.
• Antagonists: atropin, anaprilin, dimedrol etc.
• Agonist-antagonist:
labetolol (1, 1-adreno-blocker, but activates 2adrenoreceptors),
pentazocin (agonist delta- and kappa-opiate
receptors and mu-receptors antagonist)
Receptors – specific cell sites
GABAc receptors
Opiate receptors
steroid-receptor
Serotonine receptor
Receptors - enzymes
cholinesterase
Cox - Cyclooxygenase
MAO
ACE - angiotensin converting enzyme
Receptors – ionic channels
sodium (Na+) channels
Voltage-dependent potassium channels
calcium channels
thyroid hormone receptor - genes
PRESYSTEMIC ELIMINATION
(first pass metabolism)
presystemic elimination – extraction of the
drug from blood circulatory system during
it’s first passage through the liver– it leads to
decreasing of bioavailability (and therefore,
decreasing of biological activity) of drugs
propranolol (anaprilin), labetolol, aminazin,
acetylsalicylic acid, labetolol, hydralasin,
isadrin,
cortizone,
lidokain,
morphin,
pentazocin, organic nitrates, reserpin
PRESYSTEMIC ELIMINATION
(first pass metabolism)
• ONSET – the period between the
moment of drug introduction to the
organism and the beginning of its
action
• DURATION OF DRUG ACTION – the
period then specific effects of the drug
are maintained
• WIDENESS of therapeutic action
(therapeutic window) – the distance
between minimum therapeutic and
minimum toxic doses of drug
Drugs effecting the afferent
innervation
Substances which act in the
area of afferent nerves endings:
 Local anesthetics
 Astringent agents
 Covering agents
 Adsorptive agents
 Irritative agents
STRUCTURE OF LOCAL
ANESTHETICS
x
I
(CH2)n
II
N
III
I – lipophilic aromatic group
II – intermediate aliphatic chain
III – hydrophilic amine-group
R
R
Types of local anesthesia:
terminal
conductive
infiltrative
Erythroxylon coca
TOXICOLOGY OF COCAIN
Acute intoxication: short-time euforia, fear,
tachycardia, exophthalm, dizziness, delirium, loss
of consciousness, seizures, coma, decreasing of
arterial pressure, stop of breathing
Chronic intoxication – cocainism:
psychological and physical addiction, mental
degradation, cretinism, atrophyc disorders,
including perforation of nasal septum, gangrene,
severe cardiac arrythmias, cardiac arrest
COCAIN
Novocain (Novocainum)
– derivative of
PABA (para-aminobenzoic acid)
usage
infiltrative anesthesia – 0,125-0,25-0,5 %
solutions
truncal anesthesia - 1-2 % solutions
treatment blockades (paranephral,
vagosympathetic) – 0,25-0,5 % solutions
spinal cord anesthesia - 2-3 ml of 5 %
solution (is introduced into subarachnoid space
on the level higher than first lumbal vertebra)
At recent time novocain was used for depression of
reflexes, central nervous system, heart, in patients with
gastritis, ulcer disease, hypertonic disease, stenocardia,
neurodermitis, spasms of peripheral vessels. In this case
this drug was introduced intravenously or intramuscularly
Xycain (Lidocain)
it is 2 times stronger (activity regarding)
than novocain with the same toxicity
usage
for all kinds of local anesthesia:
infiltrative - 0,25-0,5 % solutions
conductive – 0,5-2 % solutions
peridural – 0,5 % solution
spinal cord – 5 % solution
terminal – 4-10 % solutions
Xycain (Lidocain)
Xycain (Lidocain)
Xycain eliminates cardiac arrythmias of
ventricular origin, i.e. extrasystolia, fibrillation
of ventricules in acute myocardial infarction. In
this cases xycain is administred intravenously,
dropply, slowly, in a form of
0,2 % solution.
Xycain (lidocain) can be used in individuals,
which have got allergic reaction to novocain and
other anesthetics of complexed aethers group
(dicain, anesthesin), but it also may be dangers
XYCAIN
(LIDOCAIN)
Bupivacain (marcain)
one of the most active anesthetics with
prolonged action (onset – 2-20 min, duration
of action – 7 hours)
Usage
infiltrative, truncal, epidural anesthesia
considerable cardiotoxicity !
Articain (ultracain)
usage
infiltrative and conductive
anesthesia
Anaesthetic action develops
after 1-2 min. after introduction of
the drug, lasts for 1-3,5 hours
in stomatology - combined
drug, which containes ultracain
and adrenalini hydrochloridum
(epinephrin)
- ultracain D-C
Acute poisoning with local
anesthetics
Symptoms
decreasing of arterial pressure, of heart activity,
cardiac arrest, depression of CNS and breathing,
seizures
Treatment
vasoconstriction drugs (noradrenaline,
adrenaline), cardiotonic (strophantin, corglycon),
antiseizure drugs (sibazone, tiopental-sodium)
Prophilaxis
usage of the least possible volume and the most
possible dillution of the local anesthetics
Astringent drugs
Organic, of plant origin
tannin, infusion of tea, herba Hyperici,
flores Chamomillae, cortex Quercus
Nonorganic
Bismuthi subnitras, de-nol
Oak tree (bark)
Quercus robur L.
TANNIN
usage
rinsing of mouth, pharynx, larynx – 1-2 %
solution
treatment of burned surfaces, cracks, bedsores
– 3-10 % solutions
gastric lavage in case of poisoning with salts
of heavy metals and alcaloids – 0,5 % solution
Nota bene! Tannin forms nonstable
compounds with morphine, phisostigmine,
atropin, nicotine, cocain
Saint-John’s-wort
(Hypericum perforatum L.)
Matricary
Chamomilla recutita L.
Sage
Salvia officinalis L.
Drugs, which stimulate nervous endings
IRRITATIVE DRUGS
•
•
•
•
•
Ammonium solution
Menthol
Oleum Terpenthini purified
Mustard plaster
Camphor
Leaf Mustard
Brassica juncea
Ammonium solution 10 %
(ammoniac)
Usage
• Unconsciousness (put a cotton ball
moistured with ammonium solution to a
nose) – reflex stimulation of breathing
• In case of alcohol intoxication (orally
5-10 drops of solution dilluted in half of
a glass of water)
• For washing of surgeon’s hands
(rarely) (0,5 % solution)