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 explosionPharmaceutical explosion Nowadays there are over 350 thousand drugs in the world which are used for different diseasesNowadays 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 agentsIn Ukraine nearly 14 thousand drugs are registered now and allowed for administration as curative agents The volume of world pharmaceutical market annually – billion $The volume of world pharmaceutical market annually – billion $ Till 2015 – 1,1 trillion $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:Mono: Мілістан, альдолор, доломол, калпол, медипірин, панадол, паралгет, парацет, піранол, спазмолекс, тайленол, тімінол, цефекон, ефералган Combined: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 Corgard Nadolol – international name Corgard – trade name

Becotide = Beclometh Beclomethasone dipropionate 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) 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.) 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 patientsAll 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 % (in Ukraine – the majority of drugs)UK, Deutschland, French, Holland, Denmark – the part of generics among all drugs is % (in Ukraine – the majority of drugs) Market volume of generics In Europe is over 10 billion $ annuallyMarket 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)

time concentration T max C max AUC Area under curve Bioavailability – to study some pharmacokinetic parameters

Side effects (SE) of drugs 5th placeTake 5th place among causes of mortality in the whole world after cardiac- vascular 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 EXCRETIONOF DRUGS 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 Receptors – the places where drugs bind to tissues: macromolecules, enzymes, channels, transport systems, genes Agonists:Agonists: adrenalin, isadrine, morphine etc. Antagonists:Antagonists: 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)

Receptors – specific cell sites Opiate receptors GABAc receptors steroid-receptorSerotonine receptor

Receptors - enzymes cholinesterase MAO Cox - CyclooxygenaseACE - angiotensin converting enzyme

Receptors – ionic channels sodium (Na+) channels calcium channelsVoltage-dependent potassium 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)

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 WIDENESS therapeutic windowWIDENESS 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 Local anesthetics Astringent agents Astringent agents Covering agents Covering agents Adsorptive agents Adsorptive agents Irritative agents Irritative agents

STRUCTURE OF LOCAL ANESTHETICS x (CH 2 ) n N R R IIIIII I – lipophilic aromatic group II – intermediate aliphatic chain III – hydrophilic amine-group

Types of local anesthesia: terminalconductiveinfiltrative

Erythroxylon coca

TOXICOLOGY OF COCAIN Acute intoxicationshort-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 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

derivative of PABA (para-aminobenzoic acid) Novocain (Novocainum) – derivative of PABA (para-aminobenzoic acid) usage usage anesthesia – 0,125-0,25-0,5 % solutions infiltrative anesthesia – 0,125-0,25-0,5 % solutions anesthesia % solutions truncal anesthesia % solutions (paranephral, vagosympathetic) – 0,25-0,5 % solutions treatment blockades (paranephral, vagosympathetic) – 0,25-0,5 % solutions anesthesia ml of 5 % solution (is introduced into subarachnoid space on the level higher than first lumbal vertebra) spinal cord anesthesia 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 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 myocardial 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 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) 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 tannin, infusion of tea, herba Hyperici, flores Chamomillae, cortex QuercusNonorganic Bismuthi subnitras, de-nol Bismuthi subnitras, de-nol

Oak tree (bark) Quercus robur L.

T A N N I N 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 T A N N I N 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 Menthol Oleum Terpenthini purified Oleum Terpenthini purified Mustard plaster Mustard plaster Camphor 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) 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) For washing of surgeon’s hands (rarely) (0,5 % solution)