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GENERAL PHARMACOLOGY
1) HISTORY OF MEDICINE 2) INTRODUCTION TO PHARMACOLOGY 3) PHARMACOKINETIC ABSORPTON DISTRIBUTION BIOTRANSFORMATION ELIMINATION CLINICAL PHARMACOKINETIC 4) PHARMACODYNAMIC 5) DRUG INTERACTIONS 6) FACTORS THAT MODIFY DRUG ACTIONS 7) CLINICAL PHARMACOLOGY 8) DRUG TOXICOLOGY 9) PHARMACOGENETIC 10)

HISTORY OF MEDICINE
As old as the history of human being As old as the age of pain an sufferings So, PAIN and sufferings were the first sensed alarm reactions that drew the attention of human being. Thus, surge was focused on how to combat with these leading symptoms By experience, the analgesic power of certain plants was explored accidentally first HISTORICAL DEVELOPMENT a) PRE-EXPERIMENTAL PERIOD (might be up to 1789) b) EXPERIMENTAL PERIOD PRE-XPERIMENTAL PERIOD: Depends on experience rather than experimentation Mostly uses trial and error method Under strict influence of religious and traditional beliefs No experimentation at all No questioning by what, why and how Curative potential of plants was discovered accidentally

The reason of illnesses was widely believed to be due to bad spirits which were dismissed from body by magicians SO, magicians were the first medical men who were also the religious leader who were conducting ritual ceremonies Belief in the curative powers of plants and certain substances was exclusively depending upon traditional knowledge which was empirical rather than subject to critical examination The effects of Opium, Belladonnae, Rauwolfia, Digitalis, Curare etc. were discovered by experience accidentally and were used empirically EXPERIMENTAL PERIOD: Questioning with what, how and why Not under religious and traditional false beliefs Depending on experimental results Reached by revolution in the brain cortex CHRONOLOGICAL BACKGROUND First informations on opium and other curative plants appear in the Sumerian and Egyptian manuscripts or tablets First documental knowledge on drugs are deduced from EBERS PAPYRUS written in 1550 B.C. 1sth. Century A.C.: DIOSCORIDES assembled that far known drugs in a book which is considered the first PHARMACOPEA 2nd. Century A.C.: CLAUDIUS GALEN (129-200 A.C.) He says: All is found, is in part be experience and in part theory. Neither experience nor theory alone apt to discover all He described the ways to prepare drug forms from plants, eg. powder, tincture, decoction, extract etc. which are called GALENIC PREPARATIONS. MIDDLE AGE: Orientation to polypharmacy. A pharmaceutical form possessing more than 100 active principle in it is called THERIACA or TRIACA Development in chemistry and synthesis of new substances increased therapeutic facilities. Thus, new substances were introduced into the therapy. - John Rudolph Glauber (1604-1688): Na sulphate -Aureolus Theophrastus Bombastus (PARACELSUS) from Hochenheim (1493-1541): Iron and Arsenic - He rejected irrational medicaments of medieval medicine

- He prescribed chemically defined substances with success only The influence of magic and religion (i.e. church) were crushed down. Experimental results and rationalism became the leading approach for the treatment. Johan Jacob Wepfer (1620-1695) was the first to verify th pharmacologic and toxic actions of drugs by animal experimentation Serturner isolated morphine from opium milk Emil Fisher synthesized barbital, a hypnotic Paul Ehrlich by trying more than 500 bacteria dyes and 606 newly synthesized chemicals on animals, discovered the first useful chemotherapeutics Oswald Schmiedeberg (1838-1921) -Insisted on -structure activity relationship -drug receptors -selective toxicology -With his students: T. Frazer from Scothland Langley from England P, Ehrlich from Germany J. Clark from England Was the first a) to propose receptor theories b) to apply law of mass action to drug-receptor interaction -Published the first journal of pharmacology John Abel, a student of O. Schmiedeberg, was the first to publish J Pharmacol Exp Ther in USA Pharmacology developed within physiology as pharmacodynamic by experimentation of drugs on animals The first pharmacologists were in fact physiologists -Rudolph Bucheim (1846) in Dorpat Medical Faculty was appointed as pharmacology lecturer for the fist time. He investigated certain effects of atropine and ergot alkaloids. -Claud Bernard investigated the effects of curare and morphine O. Schmiedeberg was appointed as the director of pharmacology department in Strasburg for the first time. -Otto Loewi and Guddum improved biological essay methods and developed comparative pharmacology -Most recently gene cloning technology was developed

By this way, pharmacology became an independent discipline in medicine. COCLUSION: Cordial respect to those who did their best for human being.

INTRODUCTION TO PHARMACOLOGY
PARMACOLOGY = Pharmacon + Logos Drug Scence

SUBDIVISION OF PHARMACOLOGY:

= = The science that deals with the interaction of living systems with chemicals (endogenous or exogenous)

Drug Science

1) MEDICAL PHARMACOLOGY: Deals with materials used to prevent, diagnose and treat diseases. 2) PHARMACOTHERAPY: Employment of drugs for the prevention and treatment of diseases. Its scope: -Indications -Contraindications -Drug interactions -Rational therapy design (art of therapy planning) -Good prescribing THERAPY: i) Radical (full healing) ii) Symptomatic(treatment of symptoms only) iii)Prophylactic (eg. contraception, vaccine) 3) CLINICAL PHARMACOLOGY: Deals with: -the discovery and development of new drug molecules -evaluation of these on healthy and diseased human being after enough experimentation on animals -should not be mixed with pharmacotherapy and art of prescription writings 4) CHEMOTHEREAPY: Deals with the treatment of infectious and neoplastic disorders 5) PHARMACOKINETIC: Deals with how the body handles a drug. Its scope: - Absorption - Distribution - Biotransformation (metabolism) - Elimination

6) PHARMACODYNAMIC: -Deals with how drug handles the body -Deals with the biochemical and physiological effects (beneficial or toxic) of drugs and their mechanism of action in human being. 7) PHARMACOGENETIC: Deals with:- the influence of genetic on the mode of drug actions (eg. metabolism) - and biological variations of drug responses 8) BIOPHARMACEUTIC: Deals with: - the production of drug forms - and the relationship between the pharmacokinetic of these forms and their effects 9) PHARMACOGNOSIA: Deals with plants possessing active principles Eg. Digitalis purpurea Atropa belladonnae Papaver somniferum 10) IMMUNOPHARMACOLOGY Deals with drugs that can bring about an effect by acting on immune System: - Immunosuppressive agents used in organ transplantation and in autoimmune disorders - Immunomodulators like immunostimulants used in immune deficiencies 11) TOXCOLOGY: Deals with undesirable or adverse effects of chemicals in biological systems. Drug Effects Desirable (therapeutic) Undesirable Non-deleterious (side effects) Deleterious (toxic effects) -Pharmacologic -Pathologic -Genotoxic (nitrogen mustard)

Liver: Acetaminophene Lung: Paraquat (herbesite) Phototoxicity: Sulfonamides, tetracyclines

There is no strict limit between drugs, nutrients and poisons DRUG

NUTRIENT

POISON Eg. - Water - Vitamines - d-Tubocurarine

DRUG

The main concern of pharmacology. Definitions: 1) Drugs are active chemical principles used in medicine 2) WHO: Drug is a compound used to change the physiological functions or pathophysiological condiditions for the benefit of human being. 3) MORE GENERAL: Any substance that bring about changes in biological functions through its chemical action. 4) OR: Drug is any small molecule that alter body functions by interaction at the molecular level. Drug actions are mediated by 3 ways: 1) By acting on somatic or psychic processes or functions. 2) By correction of deficiencies 3) By toxic action on pathogenic microorganism Drug effects: - Should be -selective -temporary -dose-related (controllable) - And show close relationship with bioavailability HOW ARE DRUGS RESPONSES PRODUCED? By interaction with active binding sites called RECEPTORS - Inert binding sites (plasma & tissue proteins) do not bring about a biological response - Drug may be agonist or antagonist for the receptors - Interaction wit receptors may be covalent, electrostatic.. - For best fitting, drug size, shape, electrical charges and atomic composition are important - Majority of drug size fall in 100 to 1000 -Small molecules are more selective in its action -Large molecules move more slowly (mw 1000)

Influence of physical nature of drugs Physical state: -solid (aspirin) -liquid(nicotine, ethanol) -Determine -Gas route of -Vaporizable liquid forms administration Chemical structure: Protein, lipid, carbohydrate To be weak acid or weak base Primary amine : R-NH2 Secondary amine: R2-NH Tertiary amine : R3-N Quaternary : R4-N+ Isomeric forms: (+)d, (-)l, dl Drug-body interactions: -PHARMACOKINETIC -PHARMACOYNAMIC SOURCES OF DRUGS: 1) NATURAL - Plants - Animals - Bacteria, fungi - Inorganic compounds 2) SEMISYNTHETIC 3) Synthetic 4) DNA recombinant technology DRUGS FROM PANTS: - Active principles are found in roots, leaves and seeds in 2 forms: 1) Glycoside 2) Alkaloid TO BE ALKALOD TO BE GLYCOSIDE -Must be of plant origin -Must be of plant origin -Has a nitrogen atom in a -aglycone-O-carbohydrate heterocyclic ring system linkage -Has bitter taste -Genin (aglycone) is the avtive -Base form is not soluble in component water but in alcohol -eg. Digital glycosides -Salt form is soluble in water -eg. Morphine, curare, atropine Pharmaceutical forms obtained from plans: (GALENIC PREPARATIONS) 1) POWDERS 2) EXTRACTS: -Obtained by incubation in solvents - May be soft, semisolid or dry

3) INFUSIONS: -Obtained by incubation in hot water -eg. Tea - Must be prepared freshly 4) DECOCTIONS: -Obtained by boiling in water -eg. Lindon blossom 5) TINCTURES: -Obtained by treatment with alcohol -eg. Digital tincture DRUGS FROM ANIMALS -Hormones like heparin, insulin -Plasma or serum from blood -Gonadotrophines from urine of pregnant women DRUGS FROM MICROORGANISMS: -Antibiotics -Streptokinase, streptodorinase INORGANIC METALS: -Iodine -Lithium -Radioactive elements: 131I, 198Au, 60Co SEMISYNTHETIC DRUGS -Semisynthetic penicillins from 6-aminopenicillnic acid -Semisynthetic cephalosporins from 7-amino cephalosporinic acid -LSD from natural lysergic acid DRUGS BY DNA RECOMBINANT TECHNOLOGY Cells from animals or human that produce active principle Isolation of DNA Release of DNA fragments By endonuclease Transfer to E-coli by plasmids (Gene cloning) A new E-coli form that synthesize the the new substance

CRITERIA FOR DRUG CLASSIFICATION 1) Chemical structure: - Cholinester - Organophosphates - Catecholamines 2) Locus of action: - Heart glycosides - Autonomic drugs 3) Purpose of medication: - Antihypertensive - Diuretic - Antiemetic - Analgesic 4) Name of plant: - Opium alkaloids - Digital glycosides Papaver somniferum - Belladonnae alkaloids DRUG NAMES: 1) General or generic name given by WHO 3) Trade name given by the DRUG FIRMS 4) Chemical name which is LONG, COMPLEX AND NOT USED CURRENTLY

Papaver somniferum

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