PHARMACOLOGY

Patrick Nwabueze Okechukwu

Lecture 1

Introduction To Introduction To PharmacologyPharmacology

Objectives/Learning OutcomeObjectives/Learning Outcome After this class the students will be able to After this class the students will be able to understand;understand; The definition of drug, medicine and The definition of drug, medicine and

pharmacology.pharmacology. Brief history of pharmacology as a biomedical Brief history of pharmacology as a biomedical

science.science. Drug nomenclature.Drug nomenclature. Individual drug variations and factors that affect Individual drug variations and factors that affect

variations in human.variations in human.

Drugs; are defined as a chemical substance of known structure, other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect.

Drugs are chemicals that affects physiological function in a specific way.

However drugs are different from medicine. A medicine is a chemical preparation, which usually but not necessarily contains one or more drugs, administered with the intention of producing a therapeutic effect.

Medicines usually contain other substances (excipents, stabilizers, solvents etc) besides the active drug, to make them more convenient to use.

Drugs may be synthetic chemicals, chemicals obtained from plants or animals or products of genetic engineering.

To be count as a drug, the substance must be administered as such, rather than released by physiological mechanism.

Many substances, such as insulin or thyroxine, are endogenous hormones but are also drugs when they are administered intentionally.

Pharmacology can be defined as the study of the effects of drugs (chemical substances) on the function of living systems

As a science, it was born in the mid-19th century, one of a host of new biomedical sciences based on principles of experimentation rather than dogma that came into being in the remarkable period.

Long before that –indeed from the dawn of civilization -herbal remedies were widely used, pharmacopoeias were written, and the apothecaries’ trade flourished, nothing resembling scientific principles was applied to

therapeutics.

The impetus for pharmacology came from the need to improve the outcome of therapeutic intervention by doctors, who were at that time skilled at clinical observation and diagnosis but broadly ineffectual when it came to treatment.

Until the late 19th century, knowledge of the normal and abnormal functioning of the body was too rudimentary to provide even rough basis for understanding drug effect; at the same time, disease and death were regarded as semisacred subjects, appropriately dealt with by authoritarian, rather than scientific, doctrines.

The motivation for understanding what drugs can do and cannot do came from clinical practice, but the science could be built only on the basis of secured foundations in physiology, pathology and chemistry.

It was not until 1858 that Virchow proposed the cell theory. The first use of a structural formula to describe a chemical compound was in 1868. Bacteria as a cause of disease was discovered by Pasteur in 1878.

Previously, pharmacology hardly had the legs to stand on , and we may wonder at the bold vision of Rudolf Buchheim, who created the first pharmacology institute (in his own house) in Estonia in 1874.

In its beginnings, before the advert of synthetic organic chemistry, pharmacology concerned itself exclusively with understanding the effects of natural substances, mainly plant extracts and few chemicals.

Beginning in the 20th century, fresh wind of synthetic chemistry began to revolutionize the pharmaceutical industry, and with it the science of pharmacology.

New synthetic drugs, such as barbiturates and local anesthetics, began to appear, and the era of antimicrobial chemotherapy, sulfonamide. The discovery of hormones, neurotransmitters and inflammatory mediators.

The emergence of biotechnology as a major source of new therapeutic agents in the form of antibodies, enzyme and various regulatory proteins, including hormones, growth factors and cytokines

Although such products (known biopharmaceuticals) are generally produced by genetic engineering rather than by synthetic chemistry, the pharmacological principles are essentially the same as for conventional drugs.

Pharmacodynamics and Pharmacokinetics.

Pharmacology is divided into two major branches known as Pharmacodynamics and Pharmacokinetics.

Pharmacodynamics deals with the detailed study of how drugs act, it describes what the drug does to the recipients.

Pharmacokinetics is the study of how the body absorbs, distributes, metabolizes and excretes drugs

It describes what the recipient does to the drug, i.e. drug disposition, measurement of concentration of drugs at various times; Intensity of drug effect per concentration

Other terms are Pharmaceutics: The science of dispensing medicine (pharmacy store).

Pharmacotherapeutics : The use of drugs to treat disease, such as :- i) to alter symptoms or signs of pains, fever etc. ii) to replace substances that are not present, or insufficient quantity e.g. insulin in patients with type one DM. iii) to kill parasites. etc.

Drug Nomenclature.A drug may be named in a number of ways such as :

1) A chemical name – identifies chemical structure and the type of chemicals or type of compounds contained in the drug e.g. Alkaloids,Tanins, Saponins etc.

2) Generic (official) name – This is the name that is assigned by the government authorities such as the U.S Adopted Name Council. It is always used by pharmacologist.Examples are; Acetylsalicylic acid (Aspirin), Acetaminophen (Paracetamol). Cetirizine, Ephedrine, etc.

3) Trade (proprietary) name- This is a name that is assigned by the company that developed the drug. It is usually short and catchy. A drug can only be recognised by its trade name, examples are; Panadol, Zyrtec-D, Salmax etc.

Individual variation to drug use

Variability is a serious problem when drugs are used clinically. If variability is not taken into account it can result in : a) lack of efficiency/efficacy, b) unexpected effected side effect

Types of variability may be classified as :

-Pharmacokinetic

-Pharmacodynamics

-idiosyncratic.

The main causes of variability are;

1) Effects of Ethnicity ; Ethnic means ‘pertaining to race’. Citizens of several modern societies are asked to define their race or ethnicity from a list of options e.g. ‘white’, ‘black’, ‘mixed’, ‘Chinese’, ‘Asian’, or ‘others’. Members of self – defined groups arrived at in such ways share some characteristics on the basis of shared genetic and cultural heritage, but there is obviously also enormous diversity within each group.

Tropical example is the evidence that African- American with heart failure gain a mortality benefit from treatment with combination of hydralazine plus a nitrate, whereas white Americans do not.

2) Effects of Age: Drug elimination is less efficient in newborn and in old people, so that drugs commonly produce greater and more prolonged effects at the extremes of life.

Other age – related factors, such as variations in pharmacodynamics sensitivity, are also important with some drugs. Physiological factors (e.g. altered cardiovascular reflexes and pathological factors ( e.g. hypothermia), which are common in elderly people also influence drug effects.

Body composition changes with age, fat contributing a greater proportion of the body mass in the elderly, with consequent changes in distribution volume of drugs. Elderly people consume more drugs than do younger adults, so the potential for drug interactions is also increased.

3) Effects of Pregnancy: Pregnancy causes physiological changes that can influence drug disposition in mother and fetus. Maternal plasma albumin concentration is reduced, influencing drug protein binding.

Cardiac output is increased, leading to increased renal flow and GFR, and increased renal elimination of drugs.

Lipophlic molecules rapidly traverse the placental barrier, whereas transfer of hydrophobic drugs is slow, limiting fetal drug exposure following a single maternal dose.

The placental barrier excludes some drugs ( e.g. low- molecular-weight heparins) so effectively that they can be administered chronically to the mother without causing effects in the fetus.

4 Genetic Factor: Studies on identical and non-identical twins have shown that much individuals variability is genetically determined. Thus half-life values for antipyrene, a probe of hepatic drug oxidation and for warfarin, an oral anticoagulant, are 6-22 times less variable in identical than in fraternal twins. Genes influences the pharmacokinetics, pharmacodynamics and the susceptibility to idiosyncratic reactions.

5) Idiosyncratic Reactions: An idiosyncratic reaction is a qualitatively abnormal, and usually harmful, drug effects that occurs in a small proportion of individuals. For example, chloramphenicol causes aplastic anemia in approximately 1 in 50 000 patients. In many cases, genetic anomalies, although the mechanism are often poorly understand.

Glucose 6-phosphate dehydrogenase (G6PD) deficiency is the basis for the most common known form of genetically determined adverse reaction to drugs, a discovery that stemmed from investigation of the antimalarial drug primaquine which, while well tolerated in most individuals, causes haemolysis leading to severe anemia in 5-10% of African Caribbean men.

This reaction in sensitive individuals, also occurs with other drugs, including dapsone, doxorubicin and some sulfonamide drugs, and after eating the bean Vicia fava or inhaling its pollen. This underlines the condition known as favism.

G6PD is needed to maintain the content of the reduced glutathione (GSH) in red cells. GSH being necessary to prevent haemolysis. Primaquine and related substances reduce red cell GSH harmlessly in normal cells but enough to cause haemolysis in G6PD-deficient cells.

6) Effect of diseases: Disease can cause pharmacokinetic and pharmacodynamic variations. Common disorders such as impaired renal or hepatic functions predispose to toxicity.

7) Drug interaction: Administration of drug A can alter the action of drug B. Drug interaction can be either pharmacokinetic or pharmacodynamics.

END OF LECTURE 1

Thank You