Download INTRODUCTION TO PHARMACOLOGY

INTRODUCTION TO
PHARMACOLOGY
Lector prof. Posokhova K.A.
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 16 thousand
drugs are registered now and
allowed for administration as
curative agents
Ukraine: 147 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
( β1, β 2 - adrenoblocker )
Becotide = Beclometh
(beclomethasone dipropionate)
•
Brand – original drug which is defended by
patent and may be produced during patent term
only by this pharmaceutical firm
•
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
SE (side effects) and
complications of drugs
• 200 000 people in U.S.A. die from
side effects of drugs annually
• 76,6 billion $ are spared in U.S.A.
annually to treat complications
attached to drugs usage
Side effects (SE) of drugs
• Take 5th place among causes of
mortality on the Earth after cardiac-vascular
diseases, malignant tumors, lungs
diseases, traumas
• Among stationary patients frequency of SE
after introduction of drugs makes 2-40 %
Medical mistakes in clinics
• Doctors:
- overdosing
- administration of drugs to patients with
allergy
- mixing up names of the drugs
• Medical nurses:
- introduction of other drug by a mistake
- violation of drug introduction regime
- mistake in medical form
- mixing up names of the drugs
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
BIOCEMICAL 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
PHARMACODYNAMICS
Pharmacological effect – clinical manifestation of
drug influence on the organism
Its basis is primary pharmacological reaction – the
result of drug influence on special structures of the
organism
• Pharmacological effects may be identical but caused
by different pharmacological reactions:
atropin and adrenalin dilates the pupils, 1st inhibits Mcholinoreceptos, 2nd – activates adrenoreceptors
• In contrary, different pharmacological effects may
appear due to the same pharmacological reaction:
anaprilinum causes β-adrenoreceptors blockade that
resulted in hypotension, antiarrhythmic action and
antianginal effect
PHARMACOLOGICAL EFFECTS
• Local action: local anesthesia, astringent, covering,
irritating, necrotizing, adsorbing
• Reflex action: as a result of local irritation (Sol.
Ammonii caustici, Validolum, Charta Sinapis, expectorants of
plant origin)
• Resorbtive (systemic) action – after drug
absorption or its introduction to blood stream):
1) direct (primary) and 2) indirect (secondary):
cardiac glycosides: 1 – on heart, 2 – diuretic effect
• Selective action (salbutamol, celecoxyb, doxazosin)
• Nonspecific action – on all cells of the organism:
drugs for general anesthesia, salts of heavy metals
• Basic (beneficial) action and adverse reaction
• Reversible and irreversible
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)
NONSPECIFIC ACTION OF DRUGS
Due to their physical and chemical properties
• Mannit increases osmotic pressure in kidneys
canalicules and causes diuretic effect
• Direct chemical interaction: Antacides (MgO,
NaHCO3) neutralize HCl, Trilon B (EDTA)
binds salts of heavy metals, Na citrate binds
Ca-ions
• Physical-chemical interaction: Protamine
sulfate binds Heparin
• Due to the same structure with metabolites of
the organism drugs interferences with
corresponding metabolic processes :
Sulfonamides (have the same structure to
PABA), Mercaptopurin (to folic acid and purin)
Bioavailability
of drugs
complex of pharmacokinetic processes
that maintenance active concentration of
drug in the area of specific receptors
(part of administered drug that reaches
the systemic circulation and effects
specific receptors)
PRESYSTEMIC ELIMINATION
(first pass metabolism)
presystemic elimination – extraction of the
drug form 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
• 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
 covering
 adsorbtive
 irritative
Local anesthetics
Local anesthetics
1. Natural compound – aether of
benzoilekgonin cocain
2. Synthetic neutrogen compounds
Aether compounds (derivatives from PABA)
a) easily dilluted in water : novocain (procain),
dicain (tetrakain)
b) badly dilluted in water: anaesthesin
(benzokain), orthokain
Amide compounds: lidocain (xycain),
trimecain, etydocain (duranest), prilocain
(citanest), articain (ultracain), piromecain
(bumekain), marcain (bupivacain)
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
Kinds of local anesthesia:
terminal
conductive
infiltrative
Terminal (superficial) anesthesia local anesthetic is spread over mucous
membranes, wounds, ulcers, fresh
granulations
For terminal anesthesia we often
use anaesthesin, dicain, xycain,
trimecain, very rarely – novocain,
because it badly penetrates through
mucous membranes
Conductive (regional) anesthesia - is an
introduction of anesthetic into area of nervous
truncs, ganglia, sensitive roots of spinal cord.
Kinds of regional anesthesia: truncal
(conductive), plexal (anesthesia of nervous
plexuses), paravertebral (anesthesia of nerovus
ganglia), spinal-cord, peridural
For performing of this anesthesia novocain,
xycain, trimecain, ultracain are used
Infiltrative anesthesia – is a mixed
kind of local anesthesia, in which
nervous endings and fibres get turned
off because of layer by layer infiltration
of tissues with a solution of local
anesthetic.
For
infiltrative
anesthesia
novocain, xycain, trimecain,
ultracain
are used
Cocain (Cocainum) – alcaloid, which is
extracted from leaves of South-American
plant Erythroxylon coca. Its local anesthetic
action overwhelms local anesthetic activity
of novocain in 3 times and toxicity is 3-5
times greater
It is used very rarely
only for superficial anesthesia
in stomatology, otholaryngology, urology
in a form of 2-5 % solutions
Erythroxylon coca
TOXICOLOGY OF COCAIN
Acute intoxication: short-time euforia, fear,
tachicardia, exophtalm, dizziness, delirium, loss
of consciousness, seizures, comatous condition,
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,
heavy cardiac arrythmias, cardiac arrest
Novocain (Novocainum)
– derivative of
PABA (para-aminobenzoic acid)
usage
infiltrative anesthesia - 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 eliminates cardiac arrythmias of
ventricular origin, i.e. extrasystolia, fibrillation
of ventricules in acute miocardial 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
are sensybilized towards novocain and other
anesthetics of complexed aehters group (dicain,
anesthesin)
Xycain (Lidocain)
XYCAIN
(LIDOCAIN)
Trimecain
anesthetic avtivity and action duration are
2 times greater, comparatively to novocain,
toxicity is a bit higher
Usage
infiltrative - 0,125 %, 0,25 % and 0,5 %
solutions
truncal - 1 % and 2 % solutions
peridural - 1 %, 2 % solutions
spinal cord - 5 % solution
terminal - 2-5 % solutions
as an antiarythmic drug in cardial arythmias
of ventricular origin - intravenously, at the
begging in a form of 2 % solution very slowly
after - dropply 0,2 % soluiton
Bupivacain (marcain)
one of the most active anesthetics of
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
Analgetic action develops
after 1-2 min. after introduction of
the drug, lasts for 1-3,5 hours
in stomatology - combined
drug, which consists of 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 least possible volume and 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)
• 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)
Thanks for your attention!
Good-bye !