1. INTRODUCTION TO PHARMACOLOGY

2. (Greek “Pharmacon” – drug, “logos” - teaching)
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 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

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

5. 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

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 more cheaper compared 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 % (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
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

13. Talidomide (katergan)
focomelia
Talidomide (katergan)

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

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. of drugs Bioavailability
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. local anesthetics astringent covering adsorbtive irritative
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 ANESTHETICSx
(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 use anaesthesin, 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 anesthesia novocain, xycain, trimecain, ultracain are 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, ultracain are used

32. only for superficial anesthesia
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

33. Erythroxylon coca

34. 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

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

36. for all kinds of local anesthesia:
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)
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)

38. Xycain (Lidocain)

39. XYCAIN (LIDOCAIN)

40. Trimecain
anesthetic avtivity and action duration are times greater, comparatively to novocain, toxicity is a bit higher
Usage infiltrative ,125 %, 0,25 % and 0,5 % solutions
truncal - 1 % and 2 % solutions peridural - 1 %, 2 % solutions
spinal cord - 5 % solution
terminal % 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. considerable cardiotoxicity !
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. infiltrative and conductive anesthesia
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

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. Organic, of plant origin
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 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

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

48. Matricary Chamomilla recutita L.

49. Sage Salvia officinalis L.

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

51. Leaf Mustard Brassica juncea

52. Ammonium solution 10 % (ammoniac)
Usage
Unconsciousness (put a cotton ball moistured with ammonium solution to a nose)
In case of alcohol intoxication (orally drops of solution dilluted in half of a glass of water)
For washing of surgeon’s hands (rarely) (0,5 % solution)

53. Thanks for your attention!
Good-bye !