INTRODUCTION TO PHARMACOLOGY

1. INTRODUCTION TO PHARMACOLOGY Lector prof. Posokhova K.A.

2. 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

3. Pharmaceutical explosion • Nowadays there are over350 thousanddrugs in the world which are used for different diseases • In Ukraine nearly16 thousand drugsare registered now and allowed for administration as curative agents

4. Ukraine:147 preparations of Diclofenac-sodium, 60 – Paracetamol (Acetaminophen) For each drug - only single international name and different trade names

5. 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 Paracetamol(Ukraine)

6. Nadolol(β1, β 2- adrenoblocker)

7. Becotide = Beclometh(beclomethasone dipropionate)

8. 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 morecheapercompared to brands, that is the main reason – why they are so popular among the patients

9. 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

10. 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

11. 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 %

12. 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

13. focomelia Talidomide (katergan)

14. PHARMACOKINETICS THE PART OF PHARMACOLOGY THAT CONCERNED WITH THE ABSORBTION, DISTRIBUTION, METABOLISM (BIOTRANSFORMATION) AND EXCRETIONOF DRUGS WHAT THE ORGANISM DOES TO THE DRUGS

15. 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

16. 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 M-cholinoreceptos, 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

17. 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 andadverse reaction • Reversibleandirreversible

18. 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2-adrenoreceptors), pentazocin (agonist delta- and kappa-opiate receptors and mu-receptors antagonist)

19. 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)

20. 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)

21. 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

22. 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

23. Drugs effecting the afferent innervation

24. Substances which act in the area of afferent nerves endings: • local anesthetics • astringent • covering • adsorbtive • irritative

25. Local anesthetics

26. Local anesthetics • Natural compound –aether of benzoilekgonin - cocain • 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)

27. STRUCTURE OF LOCAL ANESTHETICS R x (CH2)n N R I II III I – lipophilic aromatic group II – intermediate aliphatic chain III – hydrophilic amine-group

28. Kinds of local anesthesia: terminal conductive infiltrative

29. Terminal (superficial)anesthesia - local anesthetic is spread over mucous membranes, wounds, ulcers, fresh granulations For terminal anesthesia we often useanaesthesin, dicain, xycain, trimecain,very rarely – novocain, because it badly penetrates through mucous membranes

30. 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 anesthesianovocain, xycain, trimecain, ultracainare used

31. 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, ultracainare used

32. 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 usedvery rarely only for superficial anesthesia in stomatology, otholaryngology, urology in a form of 2-5 % solutions

33. Erythroxylon coca

34. TOXICOLOGY OF COCAINAcute intoxication: short-time euforia, fear, tachicardia, exophtalm, dizziness, delirium, loss of consciousness, seizures, comatous condition, decreasing of arterial pressure, stop of breathingChronic intoxication– cocainism:psychological and physical addiction, mental degradation, cretinism, atrophyc disorders, including perforation of nasal septum, gangrene, heavy cardiac arrythmias, cardiac arrest

35. Novocain (Novocainum) –derivative of PABA (para-aminobenzoic acid) usage infiltrativeanesthesia - 0,25-0,5 % solutions truncal anesthesia - 1-2 % solutions treatment blockades(paranephral, vagosympathetic) – 0,25-0,5 % solutions spinal cordanesthesia - 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

36. 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

37. Xycain(Lidocain) Xycaineliminates cardiac arrythmias of ventricular origin, i.e. extrasystolia, fibrillation of ventricules in acute miocardial infarction. In this casesxycain is administredintravenously, 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)

38. Xycain(Lidocain)

39. XYCAIN (LIDOCAIN)

40. 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

41. 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 !

42. Articain(ultracain) usage infiltrativeand conductiveanesthesia 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

43. 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

44. Astringent drugs Organic, of plant origin tannin, infusion of tea, herba Hyperici, flores Chamomillae, cortex Quercus Nonorganic Bismuthi subnitras, de-nol

45. Oak tree (bark) Quercus robur L.

46. T A N N I Nusagerinsing of mouth, pharynx, larynx –1-2 %solutiontreatment of burned surfaces, cracks, bedsores–3-10 %solutionsgastric lavage in case of poisoning with saltsof heavy metals and alcaloids –0,5 %solutionNota bene!Tannin forms nonstable compounds with morphine, phisostigmine, atropin, nicotine, cocain

47. Saint-John’s-wort(Hypericum perforatum L.)

48. MatricaryChamomilla recutita L.

49. SageSalvia officinalis L.

50. Drugs, which stimulate nervous endingsIRRITATIVE DRUGS • Ammonium solution • Menthol • Oleum Terpenthini purified • Mustard plaster • Camphor