Transcript Pharmaco lecture 1 - pharmacology1lecnotes

PHARMACOLOGY
Lecture 1
Patrick Nwabueze Okechukwu
Introduction To Pharmacology
Objectives/Learning Outcome
After this class the students will be able to
understand;
 The definition of drug, medicine and
pharmacology.
 Brief history of pharmacology as a biomedical
science.
 Drug nomenclature.
 Individual drug variations and factors that affect
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 AfricanAmerican 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 nonidentical 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