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INTRODUCTION TO INTRODUCTION TO PHARMACOLOGYPHARMACOLOGY
PHARMACOLOGYPHARMACOLOGY(Greek “Pharmacon” – drug, “logos” -
teaching)
The science that studies the interaction The science that studies the interaction of the chemical substances with live of the chemical substances with live organisms, drugs administration for organisms, drugs administration for treatment and prophylaxis of various treatment and prophylaxis of various diseases and pathological processesdiseases and pathological processes
• Pharmaceutical Pharmaceutical explosionexplosion
• Nowadays there are overNowadays there are over 350 350 thousandthousand drugs in the world drugs in the world which are used for different which are used for different diseasesdiseases
• In Ukraine nearlyIn Ukraine nearly 16 thousand 16 thousand drugsdrugs are registered now and are registered now and allowed for administration as allowed for administration as curative agentscurative agents
UkraineUkraine:: 14147 7 preparations of preparations of Diclofenac-sodium, Diclofenac-sodium, 60 – 60 –
ParacetamolParacetamol
(Acetaminophen)(Acetaminophen)
For each drug - only single For each drug - only single international name and different trade international name and different trade
namesnames
ParacetamolParacetamol ((UkraineUkraine))
• MonoMono:: Мілістан, альдолор,
доломол, калпол, медипірин, панадол, паралгет, парацет, піранол, спазмолекс, тайленол, тімінол, цефекон, ефералган
• CombinedCombined:: 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)
• BrandBrand – original drug which is defended by – original drug which is defended by patent and may be produced during patent term patent and may be produced during patent term only by this pharmaceutical firm only by this pharmaceutical firm
• GenericGeneric – when term of patent is discontinued – when term of patent is discontinued the drug may be produced by different the drug may be produced by different pharmaceutical companies under new product pharmaceutical companies under new product (trade) names but at the basis of original active (trade) names but at the basis of original active substance (similar quantity, route of substance (similar quantity, route of administration etc.)administration etc.)
• All generics are much moreAll generics are much more cheapercheaper compared compared to brands, that is the main reason – why they are to brands, that is the main reason – why they are so popular among the patientsso popular among the patients
GENERICSGENERICS
• UKUK,, Deutschland, French, Holland, Deutschland, French, Holland, Denmark Denmark – – the part of generics the part of generics among all drugs isamong all drugs is 50-75 % ( 50-75 % (in in UkraineUkraine – – the majority of drugsthe majority of drugs))
• Market volume of generics In Europe Market volume of generics In Europe is overis over 10 10 billion $ annuallybillion $ annually
SE (side effects) and complications of drugsSE (side effects) and
complications of drugs
• 200 000 people in U.S.A. die from 200 000 people in U.S.A. die from side effects of drugs annuallyside effects of drugs annually
• 76,6 76,6 billion $ are spared in U.S.A. billion $ are spared in U.S.A. annually to treat complications annually to treat complications attached to drugs usageattached to drugs usage
Side effects (SE) of drugs
• Take 5th place5th 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 clinicsMedical mistakes in clinics
• DoctorsDoctors: : - overdosing - administration of drugs to patients with
allergy - mixing up names of the drugs• Medical nursesMedical nurses:: - introduction of other drug by a mistake - violation of drug introduction regime - mistake in medical form - mixing up names of the drugs
focomeliafocomelia
Talidomide Talidomide (katergan)(katergan)
PHARMACOKINETICSPHARMACOKINETICS
THE PART OF PHARMACOLOGY THAT THE PART OF PHARMACOLOGY THAT CONCERNED WITH THE CONCERNED WITH THE
ABSORBTION, ABSORBTION,
DISTRIBUTION, DISTRIBUTION,
METABOLISM (BIOTRANSFORMATION) METABOLISM (BIOTRANSFORMATION)
AND EXCRETIONAND EXCRETION OF DRUGSOF DRUGS
WHAT THE ORGANISM DOES TO THE DRUGSWHAT THE ORGANISM DOES TO THE DRUGS
PHARMACODYNAMICSPHARMACODYNAMICS THE PART OF PHARMACOLOGY THAT
CONCERNED WITH THE
BIOCEMICAL AND PHYSIOLOGICAL EFFECTS EFFECTS OF DRUGS AND THEIR MODE OF ACTIONMODE OF ACTION
IT INCLUDES THE DOSE-EFFECT RELATIONSHIP, FACTORS MODIFYING
DRUG EFFECTS, DOSAGE, DRUG TOXICITY
WHAT DRUGS DO TO THE ORGANISMWHAT DRUGS DO TO THE ORGANISM
PHARMACODYNAMICSPHARMACODYNAMICSPharmacological effectPharmacological effect – clinical manifestation of drug influence on the organism
Its basis is primary pharmacological reactionpharmacological reaction – the result of drug influence on special structures of the organism • Pharmacological effects may be identical but caused by different pharmacological reactions: atropinatropin and adrenalinadrenalin dilates the pupils, 1st inhibits M-cholinoreceptos, 2nd – activates adrenoreceptors
• In contrary, different pharmacological effects may appear due to the same pharmacological reaction: anaprilinumanaprilinum causes β-adrenoreceptors blockade that resulted in hypotension, antiarrhythmic action and antianginal effect
PHARMACOLOGICAL EFFECTSPHARMACOLOGICAL EFFECTS• Local actionLocal action: local anesthesia, astringent, covering,
irritating, necrotizing, adsorbing• Reflex actionReflex action: as a result of local irritation (Sol.
Ammonii caustici, Validolum, Charta Sinapis, expectorants of plant origin)
• ResorbtiveResorbtive (systemic) actionsystemic) 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
• SelectiveSelective action (salbutamol, celecoxyb, doxazosin) • NonspecificNonspecific action – on all cells of the organism:
drugs for general anesthesia, salts of heavy metals • BasicBasic (beneficialbeneficial) action and adverse reaction adverse reaction • ReversibleReversible and irreversibleirreversible
RECEPTOR THEORY OF DRUG ACTIONRECEPTOR THEORY OF DRUG ACTION
• ReceptorsReceptors – the places where drugs bind to tissues: macromolecules, enzymes, channels, transport systems, genes
• Agonists:Agonists: adrenalin, isadrine, morphine etc. • AntagonistsAntagonists:: atropin, anaprilin, dimedrol etc. • Agonist-antagonist:Agonist-antagonist: labetolol (1, 1-adreno-blocker, but activates 2-
adrenoreceptors),
pentazocin (agonist delta- and kappa-opiate receptors and mu-receptors antagonist)
NONSPECIFIC ACTION OF DRUGSNONSPECIFIC ACTION OF DRUGSDue to their physical and chemical properties
• Mannit increases osmotic pressure in kidneys canalicules and causes diuretic effect
• Direct chemical interactionDirect chemical interaction: Antacides (MgO, NaHCO3) neutralize HCl, Trilon B (EDTA) binds salts of heavy metals, Na citrate binds Ca-ions
• Physical-chemical interactionPhysical-chemical interaction: Protamine sulfate binds Heparin
• Due to the same structuresame 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)
BioavailabilityBioavailability of drugs
complex of pharmacokinetic processes complex of pharmacokinetic processes that maintenance active concentration of that maintenance active concentration of drug in the area of specific receptors drug in the area of specific receptors (part of administered drug that reaches (part of administered drug that reaches the systemic circulation and effects the systemic circulation and effects specific receptors)specific receptors)
PRESYSTEMIC ELIMINATIONPRESYSTEMIC ELIMINATION (first pass metabolism) (first pass metabolism)
presystemic elimination – extraction of the presystemic elimination – extraction of the drug form blood circulatory system during drug form blood circulatory system during it’s first passage through the liver– it leads to it’s first passage through the liver– it leads to decreasing of bioavailability (and therefore, decreasing of bioavailability (and therefore, decreasing of biological activity) of drugsdecreasing of biological activity) of drugs
propranolol (anaprilin), labetolol, aminazin, propranolol (anaprilin), labetolol, aminazin, acetylsalicylic acid, labetololacetylsalicylic acid, labetolol, , hydralasin, hydralasin, isadrin, cortizone, lidokain, morphin, isadrin, cortizone, lidokain, morphin, pentazocin, organic nitrates, reserpinpentazocin, organic nitrates, reserpin
• ONSETONSET – the period between the moment of drug introduction to the organism and the beginning of its action
• DURATION OF DRUG ACTIONDURATION OF DRUG ACTION – the period then specific effects of the drug are maintained
• WIDENESSWIDENESS of therapeutic action (therapeutic windowtherapeutic window) – the distance between minimum therapeutic and minimum toxic doses of drug
Drugs Drugs effecting theeffecting the afferent afferent innervationinnervation
Substances which act in the Substances which act in the area of afferent nerves endings:area of afferent nerves endings:
local anestheticslocal anestheticsastringentastringentcoveringcoveringadsorbtiveadsorbtiveirritative irritative
Local anesthetics Local anesthetics
Local anestheticsLocal anesthetics
1.1.Natural compoundNatural compound – aether of aether of benzoilekgonin - cocainbenzoilekgonin - cocain
2.2.Synthetic neutrogen compoundsSynthetic neutrogen compoundsAether compounds (derivatives from PABAAether compounds (derivatives from PABA)a) easily dilluted in watera) easily dilluted in water : novocain (procain), novocain (procain),
dicain (tetrakain)dicain (tetrakain)bb)) badly dilluted in waterbadly dilluted in water: anaesthesin anaesthesin
(benzokain), orthokain(benzokain), orthokain Amide compoundsAmide compounds: lidocain (xycain), lidocain (xycain),
trimecain, etydocain (duranest), prilocain trimecain, etydocain (duranest), prilocain (citanest), articain (ultracain), piromecain (citanest), articain (ultracain), piromecain (bumekain), marcain (bupivacain)(bumekain), marcain (bupivacain)
STRUCTURE OF LOCAL STRUCTURE OF LOCAL ANESTHETICSANESTHETICS
x (CH2)n NRR
I II III
I – lipophilic aromatic group
II – intermediate aliphatic chain
III – hydrophilic amine-group
Kinds of local anesthesia:Kinds of local anesthesia:
terminalterminal
conductive conductive
infiltrativeinfiltrative
TTerminal (superficial)erminal (superficial) anesthesia anesthesia - - local anesthetic is spread over mucous local anesthetic is spread over mucous membranes, wounds, ulcers, fresh membranes, wounds, ulcers, fresh granulations granulations
For terminal anesthesia we often For terminal anesthesia we often useuse anaesthesin, dicain, xycain, anaesthesin, dicain, xycain, trimecaintrimecain,, very rarely – novocain, very rarely – novocain, because it badly penetrates thbecause it badly penetrates thrrough ough mucous membranesmucous membranes
Conductive (regional)Conductive (regional) anesthesiaanesthesia - is an introduction of anesthetic into area of nervous truncs, ganglia, sensitive roots of spinal cord.
Kinds of regiKinds of regioonal anesthesianal anesthesia:: truncal (conductive), plexal (anesthesia of nervous
plexuses), paravertebral (anesthesia of nerovus ganglia), spinal-cord, peridural
For performing of this anesthesia novocain, novocain, xycain, trimecain, ultracain xycain, trimecain, ultracain are used
Infiltrative anesthesia – is a mixed – is a mixed kind of local anesthesia, in which kind of local anesthesia, in which nervous endings and fibres get turned nervous endings and fibres get turned off because of layer by layer infiltration off because of layer by layer infiltration of tissues with a solution of local of tissues with a solution of local anesthetic.anesthetic.
For infiltrative anesthesia novocain, xycain, trimecain, ultracain are used
Cocain Cocain ((CocainumCocainum)) –– alcaloid, which is alcaloid, which is extracted from leaves of South-American extracted from leaves of South-American
plant plant Erythroxylon cocaErythroxylon coca. Its local anesthetic . Its local anesthetic action overwhelms local anesthetic activity action overwhelms local anesthetic activity
of novocain in 3 times and toxicity is 3-5 of novocain in 3 times and toxicity is 3-5 times greatertimes greater
It is usedIt is used very rarelyvery rarely
onlyonly for superficial anesthesia for superficial anesthesiain stomatology, otholaryngology, urology in stomatology, otholaryngology, urology
in a form of 2-5 % solutions in a form of 2-5 % solutions
ErythroxylErythroxylonon coca coca
TOXICOLOGY OF COCAINTOXICOLOGY OF COCAIN
Acute intoxicationAcute intoxication: short-time eshort-time euuforia, fear, foria, fear, tachicardia, exophtalm, dizziness, delirium, loss tachicardia, exophtalm, dizziness, delirium, loss of consciousness, seizures, comatous condition, of consciousness, seizures, comatous condition, decreasing of arterial pressure, stop of breathingdecreasing of arterial pressure, stop of breathing
Chronic intoxicationChronic intoxication – cocainism– cocainism:psychological and physical addiction, psychological and physical addiction, mentmental al degradation, cretinism, degradation, cretinism, aatrophtrophyyc disorders, c disorders,
including perforation of nasal septum, gangrene, including perforation of nasal septum, gangrene, heavy cardiaheavy cardiacc ar arrrythmias, ythmias, cardiac arrestcardiac arrest
Novocain (Novocainum) – derivative of derivative of PABA (para-aminobenzoic acid) PABA (para-aminobenzoic acid)
usageusageinfiltrative anesthesia - 0,25-0,5 % solutionsanesthesia - 0,25-0,5 % solutions
truncal anesthesia - 1-2 % solutionsanesthesia - 1-2 % solutions treatment blockades (paranephral, (paranephral,
vagosympathetic) – 0,25-0,5 % solutionsvagosympathetic) – 0,25-0,5 % solutions spinal cord anesthesia - 2-3 ml of 5 % anesthesia - 2-3 ml of 5 %
solution (is introduced into subarachnoid space solution (is introduced into subarachnoid space on the level higher than first lumbal vertebra) on the level higher than first lumbal vertebra)
At recent timeAt recent time novocain was used for depression of novocain was used for depression of reflexes, central nervous system, heart, in patients with reflexes, central nervous system, heart, in patients with gastritis, ulcer disease, hypertonic disease, stenocardia, gastritis, ulcer disease, hypertonic disease, stenocardia, neurodermitis, spasms of peripheral vessels. In this neurodermitis, spasms of peripheral vessels. In this case this drug was introduced intravenously or case this drug was introduced intravenously or intramuscularlyintramuscularly
XycainXycain (Lidocain)(Lidocain)
it is 2 times stronger (activity regarding) it is 2 times stronger (activity regarding) than novocain with the same toxicitythan novocain with the same toxicity
usage usage for all kinds of local anesthesia: for all kinds of local anesthesia:
infiltrativeinfiltrative - 0,25-0,5 % solutions - 0,25-0,5 % solutionsconductive conductive – 0,5-2 % solutions– 0,5-2 % solutionsperidural peridural – 0,5 % solution – 0,5 % solution spinal cordspinal cord – 5 % solution– 5 % solutionterminalterminal – 4-10 % solutions – 4-10 % solutions
XycainXycain (Lidocain)(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 %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 XYCAIN (LIDOCAIN)(LIDOCAIN)
Trimecain anesthetic avtivity and action duration are
2 times greater, comparatively to novocain, toxicity is a bit higher
Usage Usage infiltrative - 0,125 %, 0,25 % and 0,5 %
solutionstruncal - 1 % and 2 % solutions peridural
- 1 %, 2 % solutionsspinal 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 Analgetic action develops after 1-2 min. after introduction of after 1-2 min. after introduction of
the drug, lasts for 1-3,5 hoursthe drug, lasts for 1-3,5 hours
in stomatology - combined in stomatology - combined drug, which consists of ultracain drug, which consists of ultracain and adrenalini hydrochloridum and adrenalini hydrochloridum
(epinephrin)(epinephrin)
- ultracain D-C
Acute poisoning with local Acute poisoning with local anestheticsanesthetics SymptomsSymptoms
decreasing of arterial pressure, of heart activity, decreasing of arterial pressure, of heart activity, cardiac arrest, cardiac arrest, depression of CNS and breathing, depression of CNS and breathing,
seizuresseizures
TreatmentTreatment vasoconstriction drugs (noradrenaline, vasoconstriction drugs (noradrenaline,
adrenaline), cardiotonic (strophantin, corglycon), adrenaline), cardiotonic (strophantin, corglycon), antiseizure drugs (sibazone, tiopental-sodium) antiseizure drugs (sibazone, tiopental-sodium)
ProphilaxisProphilaxisusage of least possible volume and most possible usage of least possible volume and most possible
dillutiondillution of the local anesthetics of the local anesthetics
Astringent drugsAstringent drugs
Organic, of plant originOrganic, of plant origin
tannin, infusion of tea, tannin, infusion of tea, hherba Hyperici,erba Hyperici, fflores Chamomillae, lores Chamomillae, ccortex Quercusortex Quercus
Nonorganic Nonorganic
Bismuthi subnitras, de-nol Bismuthi subnitras, de-nol
Oak tree (bark) Oak tree (bark) Quercus robur Quercus robur L.L.
T A N N I N
usageusagerinsing of mouth, pharynx, larynx – 1-2 %
solutiontreatment of burned surfaces, cracks, bedsores
– 3-10 % solutionsgastric lavage in case of poisoning with salts of heavy metals and alcaloids – 0,5 % solution
Nota beneNota bene!! Tannin forms nonstable compounds with morphine, phisostigmine,
atropin, nicotine, cocain
Saint-JohnSaint-John’’s-worts-wort(Hypericum perforatum L.)(Hypericum perforatum L.)
MatricaryMatricaryChamomilla recutita L.Chamomilla recutita L.
SageSageSalvia officinalis L.Salvia officinalis L.
Drugs, which stimulate nervous endingsDrugs, which stimulate nervous endings
IRRITATIVE DRUGSIRRITATIVE DRUGS
• Ammonium solution Ammonium solution
• Menthol Menthol
• Oleum Oleum TTerpenthini purifiederpenthini purified
• Mustard plasterMustard plaster
• CamphorCamphor
Leaf MustardLeaf MustardBrassicaBrassica junceajuncea
Ammonium solution 10 % Ammonium solution 10 % (ammoniac)(ammoniac)
Usage• Unconsciousness (put a cotton ball Unconsciousness (put a cotton ball
moistured with ammonium solution to a moistured with ammonium solution to a nose)nose)
• In case of alcohol intoxication (orally In case of alcohol intoxication (orally 5-10 drops of solution dilluted in half 5-10 drops of solution dilluted in half of of a glass of water)a glass of water)
• For washing of surgeon’s hands For washing of surgeon’s hands (rarely) (rarely) (0,5 % solution)(0,5 % solution)
Thanks for your Thanks for your attention!attention!
Good-bye !Good-bye !