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Introduction and general pharmacological principles

Ján Mojžiš

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What is pharmacology

Historical background

Pharmacological terminology

Drug names

Introduction

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What is pharmacology

the word Pharmacology comes from the Greek language: pharmakon (φάρμακον) meaning drug, and lego (λέγω) to tell (about)

pharmacology is not identical with pharmacy

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What is pharmacology (cont.)

pharmacology deals with how drugs interact within biological systems to affect function

pharmacy is the profession responsible for the preparation, dispensing, and appropriate use of medication, and provides services to achieve optimal therapeutic outcomes

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History of Pharmacology

Ancient Times A series of scattered facts exists that speak of the early history of humankind's efforts to harness the healing properties of natural compounds. However, what we know for certain is that ancient peoples made extensive use of plant, animal and mineral sources for this purpose.

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History of Pharmacology The Ebers papyrus, written in Egypt in the 16th century B.C., lists the extensive pharmacopea of that civilization. Included in this are: beer, turpentine, myrrh, juniper berries, poppy,

lead, salt etc. Also included were products derived from animals, including lizard's blood, swine teeth, goose grease, donkey hooves and the excreta from various animals. The effects of many of these drugs on patients of antiquity can only be imagined.

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Ancient Greek medicine

Hippocrates (460-370 B.C.)

“Father” of western medicine (Born at Cos)Illness had a natural causeFirst to use observation of symptoms for clinical diagnosis; “observe patients”No dissection Used diet to counteract disease

Four Humours - Illness was caused by natural factors inside the patient. Yellow bile, black bile, blood, and phlegm.

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Ancient Roman medicine„Disease is a contraction or relaxation of pores which allowed fine atoms to pass sensation to parts of the body“

Galen (c. AD 129 - 201)

Doctor to gladiators, later doctor of Marcus AureliusDissected animals, not humansLaid groundwork for physiological connections to anatomical designDiaphragm in respirationClinical observation was key to diagnosis

His texts were the basis of western medicine for 1500 yearsyears

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History of Pharmacology From ancient From ancient ChinaChina comes evidence of that comes evidence of that culture's extensive efforts to heal through the use of culture's extensive efforts to heal through the use of natural products. The natural products. The Pen TsaoPen Tsao, or Great Herbal, , or Great Herbal, comprised forty volumes describing several comprised forty volumes describing several thousands of prescriptions.thousands of prescriptions.

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History of Pharmacology

Interestingly, the eastern herb Artemisia annua L. (wormwood), used in China since antiquity to treat fevers, is the source of the modern drug artemisinin, which shows great promise as a modern anti-malarial compound.

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Medicine in the Middle AgesIbn Sina (Avicenna, 980-1037 AD)

The cannon of medicine

Medical standard text until the mid-1600’sSignificant advances in pharmacology

Compilation of Greek, Roman, & Persian medical knowledge;

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History of Pharmacology

Antiquity to the modern eraThe ancients considered disease a consequence of demonic possession, or the wrath of god. Thus, in ancient times, the treatment of illness with natural products was invariably accompanied by religious rituals deemed essential to the healing process.

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History of Pharmacology

With time, the thoughts returned to the With time, the thoughts returned to the appreciation that the natural products themselves appreciation that the natural products themselves held the power to cure. held the power to cure. Although, traditional remedies still generally consisted of complex mixtures of distinct herbs and minerals, perhaps only one of which possessed any activity. Many poisonous mixtures were made.

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History of Pharmacology

For example, the purple foxglove, Digitalis purpurea, was one of twenty herbs used in a folk remedy to treat dropsy in 18th century England. From the leaves of this plant was isolated the cardiac glycoside digitalis, a drug still used today to treat heart failure.

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History of Pharmacology

Over time, as a more Over time, as a more sophisticated view of sophisticated view of illness evolved, an illness evolved, an increasingly scientific increasingly scientific approach to the isolation approach to the isolation of drugs from natural of drugs from natural products was taken. In the products was taken. In the early 19early 19thth century, century,

morphine was isolated from the opium poppy (Papaver somniferum) and the anti-malarial compound quinine from the bark of the cinchona tree (Cinchona officinalis).

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History of Pharmacology

In 1897, Felix Hoffman, a research chemist employed by the In 1897, Felix Hoffman, a research chemist employed by the "Farbenfabrikin vorm. Freidr. Bayer and Co." synthesized "Farbenfabrikin vorm. Freidr. Bayer and Co." synthesized acetylsalicylic acid. On February 1, 1899, Aspirin® was acetylsalicylic acid. On February 1, 1899, Aspirin® was registered as a trademark. On March 6registered as a trademark. On March 6thth of the same year, this of the same year, this drug was registered with the Imperial Patent Office in Berlin. drug was registered with the Imperial Patent Office in Berlin. Aspirin quickly become popular Aspirin quickly become popular worldwide, and remains an important drug today. (Interestingly, it was not until 1971 that Sir John Vane discovered the mechanism of action of aspirin, a feat that earned him the 1981 Nobel Prize for Medicine.)

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History of Pharmacology

Paul Ehrlich described drug-receptor binding:

“Corpora non agunt nisi fixate”.P. Ehrlich (1908)

 (“Agents do not act unless they are bound”)

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History of Pharmacology

The modern eraAdvances in the fields of chemistry and physiology, lead to the birth of modern pharmacology in the latter half of the 19th century.

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Morphine: Sertirner in 1805 isolated morfin (the first pure drug)Salicylic acid: synthesized in 1860 by Kolbe and LautemannAcetylsalicylic acid: synthesized in 1897 by F. Hoffman 1899 introduced into medicine : „aspirin’ Barbiturates: introduced into medicine in 1904 Salvarsan: Ehrlich in 1908 introduced into treatment of syphilis. Proposed the term chemotherapyPenicillin: discovered by Fleming in 1928Chlorpromazine: in 1952 used in the treatment of schizophrenia Propranolol, Cimetidine developed by Black in 1960Cyclooxygenase (COX): Vane in 1971NO: Ignaro 1992

History of Pharmacology

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Pharmacological terminology

DrugDrug PharmacokineticsPharmacokinetics PharmacodynamicsPharmacodynamics PharmacotherapyPharmacotherapy SelectivitySelectivity ToxicityToxicity

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Pharmacological terminology (cont.) Therapeutic effectTherapeutic effect

IndicationIndication ContraindicationContraindication

Undesired effectsUndesired effects Side effectsSide effects Toxic effectsToxic effects Idiosyncratic effectsIdiosyncratic effects AllergyAllergy

AnaphylaxisAnaphylaxis

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What is drug ?

Medicine - in the past was plant or animal substances a drug or a mixture of drugs combined with other substances to make it stable, palatable and useful for therapy

Agent - a collective noun antihypertensive, anticancer agents.

Compound - is a chemical used for pharmacological purpose, but not as a therapeutic agent

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Drug names

A single drug have a variety of names.

1. Chemical name

2. Generic name

3. 3. Commercial or trade name

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Chemical name Generic name

Trade name

1,4-Dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester

nifedipineADALAT, CITILAT, NIFELAT

3,5-Diamino-N-(aminoiminomethyl)-6-chloropyrazinecarboxamide hydrochloride

amilorideGUANAMPRAZINE, AMIPRAMIDIN, AMIPRAMIZIDE

7-chloro-3-methyl-2H-1,2,4-benzothiadiazine-1,1-dioxide

diazoxide HYPERSTAT, HYPERTONALUM, MUTABASE, PROGLYCEM, SRG 95213

7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol

morphine MORPHIN 1%, MST CONTINUS, SEVREDOL, ORAMORPH, CYCLIMORPH

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Drug names (contin.)

G e n e r i c n a m e sG e n e r i c n a m e s

It is the name which appears in official national Pharmacopeias (pure drugs). Often the only international differences betwen generic names is a difference in spelling.

Generic name can vary : Norepinephrine is noradrenaline in Europe.

Acetaminophene in USA is paracetamol in Europe.

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Sources of drugs

Plants and animals (most of drugs in ancient civilization came from plants or animal parts or fluids).

From plants: alkaloids, glycosides and others. Extraction of hormones from animal endocrine glands

Determination of chemical structure of active substance led synthetic chemists to produce many structural analogs

During the last four decades introduction of new synthetized drugs (de novo).

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Sources of drugs (cont.)Genetic engineering

Insulin – E. coli

Artemisinin is the most effective treatment for malaria

it is made from plant found in China and Vietnam

supplies of the plant are limited and it takes a lot of plant material to get enough of the drug to treat one patient

researchers placed genes from the wormwood plant into a yeast organism and got it to produce large amounts of artemisinic acid - this would end the need for a lot of plants 

 

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Drug sources

PlantsPlants

ElementsElements

Living Living oorganismsrganisms

Chemical Chemical ssynthesisynthesis

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Drug Living organism

Pharmacokinetics Pharmacodynamics 1. Absorption drug action 2. Distribution how drugs act 3. Metabolism (mechanism of drug action) 3. Excretion

metabolism + excretion = elimination

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Pharmacokinetics

Is what the body does to the drug.

The magnitud of the pharmacological effect of a drug depends on its concentration at the site of action.

Absorption

Distribution

Metabolism

Elimination

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Pharmacodynamics

Is what the drug does to the body. Is what the drug does to the body. Interaction of drugs with cellular proteins, such Interaction of drugs with cellular proteins, such as receptors or enzymes, to control changes in as receptors or enzymes, to control changes in physiological function of particular organs.physiological function of particular organs.

Drug-Receptor InteractionsDrug-Receptor Interactions BindingBinding

Dose-ResponseDose-Response EffectEffect

Signal TransductionSignal Transduction Mechanism of action, PathwaysMechanism of action, Pathways

Actions of aspirin

1. Analgetic2. Antipyretic

3. Antiinfammatory 4. Antiagregatory,

5. Anticancerogenic

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COX-2 Hypothesis (1990s)

CytokinesGrowth factors

Normal Tissue

Inflammation Site

Physiolgical ProstaglandinProduction

PathologicalProstaglandinProduction

COX-1Constitutive

COX-2Inducible

Arachidonic Acid

Normal Functions Inflammation, pain, fever

NSAIDsCOX-2

Inhibitors

+

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Recomended sources

Lectures

Practical excersises

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lizard