GENERAL PHARMACOLOGICAL PRINCIPLES
Pharmacology
Pharmacology is the science of drugs (Greek:
Pharmacon-drug; logos-discourse in). In
a broad sense, it deals with interaction of
exogenously administered chemical molecules
with living systems, and any single chemi
cal substance which can produce a biological
response is a 'drug'. Pharmacology encompasses
all aspects of knowledge about drugs, butlrQ
importantly those that are relevart_ to ef(ecti\l_e
and safe use of drugs for medicinal purposes.
For thousands of years most drugs were crude
natural products of unknown composition and
limited efficacy. Only the overt effects of these
substances on the body were rather imprecisely
known, but how the same ere produced was
entirely unknown. Animal experiments, primarily
aimed at understanding pn siological processes,
were started in the 18th century. These were
pioneered by F. Magendie and Claude Bernard,
who also adapted them to study effects of
certain drugs. Pharmacology as an experimental
science was ushered by Rudolf Buchheim who
f
ounded the first institute of pharmacology
in 1847 in Germany. In the later part of the
19th century, Oswald Schmiedeberg, regarded
as the 'father of pharmacology', together with
his many disciples like J Langley, T Frazer, P
Ehrlich, AJ Clark, JJ Abel propounded some
of the fundamental concepts in pharmacology.
Since then drugs have been purified, chemically
characterized and a vast variety of highly potent
and selective new drugs have been developed.
The mechanism of action including molecular
target of many drugs has been elucidated. This
has been possible due to prolific growth of
pharmaco ogy which forms the backbone of
ational therapeutics.
The two main divisions of pharmacology
are pharmacodynamics and pharmacokinetics.
Pharmacodynamics
(Greek: dynamis-power) -What the drug does to the body.
This includes physiological and biochemical
effects of drugs and their mechanism of action
at organ system/subcellular/macromolecular
levels, e.g.-Adrenaline ➔ interaction with
adrenoceptors ➔ G-protein mediated stimu
lation of cell membrane bound adenylyl cyclase
➔ increased intracellular cyclic 3 ',5' AMP ➔
cardiac stimulation, hepatic glycogenolysis and
hyperglycaemia, etc.
Pharmacokinetics (Greek: Kinesis-move
ment)-What the body does to the drug.
This refers to movement of the drug in and
alteration of the drug by the body; includes
absorption, distribution, binding/localization/stor
age, biotransformation and excretion of the drug,
e.g. paracetamol is rapidly and almost completely
absorbed orally attaining peak blood levels at
30-60 min; 25% bound to plasma proteins, widely and almost uniformly distri buted in the
body (volume of distribution ~ 1L/kg); exten
sively metabolized in the liver, prima rily by
glucuronide and sulfate conju gation into inac
tive metabolites which are excreted in urine;
has a plasma half life (t½) of 2–3 hours and
a clearance value of 5 ml/kg/min.
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Drug (French: Drogue—a dry herb) It is
the single active chemical entity present in a
medicine that is used for diagnosis, prevention,
treatment/cure of a disease.
This disease oriented definition of drug does
not include contraceptives or use of drugs for
improvement of health. The WHO (1966) has
given a more comprehensive definition—“Drug
is any substance or product that is used or
is intended to be used to modify or explore
physiological systems or pathological states for
the benefit of the recipient.”
The term ‘drugs’ is being also used to mean
addictive/abused/illicit substances. However,
this res tric ted and dero gatory sense usage is
unfor tunate degradation of a time honoured
term, and ‘drug’ should refer to a substance
that has some health promoting/therapeutic/
diagnostic application. Nevertheless, to avoid
any misinterpretation, the term ‘medicine’ is
being employed to designate such a substance
in place of the term ‘drug’.
Some other important aspects of pharmacol
ogy are:
Pharmacotherapeutics It is the application
of phar ma cological information together with
know ledge of the disease for its prevention,
mitigation or cure. Selection of the most appro
priate drug, dosage and duration of treatment
taking into account the stage of disease and
the specific features of a patient are a part of
pharmacotherapeutics.
Clinical pharmacology
It is the scientific
study of drugs (both old and new) in man. It
includes pharma codynamic and pharmacokinetic
investigation in healthy volun teers as well as
in patients. Evaluation of efficacy and safety
of drugs and comparative trials with other
forms of treatment; surveillance of patterns of
drug use, adverse effects, etc. are also part of
clinical pharmacology.
The aim of clinical pharmacology is to gen
erate data for optimum use of drugs and the
practice of ‘evidence based medicine’.
Chemotherapy It is the treatment of sys
temic infection/malignancy with specific drugs
that have selective toxicity for the infecting
orga nism/malignant cell with no/minimal effects
on the host cells.
Drugs in general, can thus be divided into:
Pharmacodynamic agents These are designed
to have pharmacodynamic effects in the reci pient.
Chemotherapeutic agents These are designed
to inhibit/kill invading parasites/malignant cell,
but have no/minimal pharmacodynamic effects
in the recipient.
Pharmacy It is the art and science of
compoun ding and dispensing drugs or prepar
ing suitable dosage forms for administration of
drugs to man or animals. It includes collection,
identification, purification, isolation, synthesis,
standardization and quality control of medicinal
substances. The large scale manufacture of drugs
is called Pharmaceutics, which is primarily a
technological science.
Toxicology It is the study of poisonous
effect of drugs and other chemicals (household,
environ mental pollutant, industrial, agricultural,
homi cidal) with emphasis on detection, pre
vention and treatment of poisonings. It also
includes the study of adverse effects of drugs,
since the same substance can be a drug or a
poison, depending on the dose
nature of drugs
All drugs are chemical entities with simple or
complex molecules. While majority are organic
compounds, some are purely inorganic, like
lithium carbonate, ferrous sulfate, magnesium
hydroxide, etc. Organic drugs may be weakly
acidic (aspirin, penicillin) or weakly basic (mor
phine, chloroquine) or nonelectrolytes (alcohol,
diethyl-ether). Most drugs are normally solids,
e.g. paracetamol, propranolol, furosemide, ampi
cillin, etc., but some such as ethanol, glyceryl
trinitrate, propofol, castor oil are liquids, and
few like nitrous oxide are gaseous.
The molecular weight of majority of drugs
falls in the range of 100-1000 D, because
molecules smaller than 100 D do not generally
have sufficiently specific features in terms of
shape, size, configuration, chirality, distribution
of charges, etc. to selectively bind to only one/
few closely related target biomolecules, to the
exclusion of others. On the other hand, larger
molecules than 1000 D do not readily pass
through membranes/barriers in the body to reach
the target sites in various tissues/cells. However,
few drugs are as small as lithium ion (7D), and
some like heparin (10-20 KD), gonadotropins
(>30 KD), enzymes, proteins, antibodies (>50
KD) are much bigger. Bulky molecule drugs
have to be administered parenterally.
Drugs are generally perceived to be chemical
substances foreign to the body (Xenobiotics).
However, many endogenous chemicals like
hormones, autacoids, metabolites and nutrients
are also used as drugs. Chemical congeners of
these metabolites/signal molecules are an im
portant class of drugs which act by modifying
the synthesis, storage, degradation or action of
these metabolites/signal molecules.
sources of drugs
Drugs are obtained from a variety of sources:
1. Plants Many plants contain biologically
active substances and are the oldest source
of drugs. Clues about medicinal plants were
obtained from traditional systems of medicine
prevalent in various parts of the world; e.g.
use of opium, belladonna, ephedra, cinchona,
curare, foxglove, sarpagandha, qinghaosu
has been learnt from Egyptian, Greek, Aztec,
Ayurvedic, Chinese and other systems of
medicine. Chemically the active ingredients
of plants fall in several categories:
a. Alkaloids: These are alkaline nitrogenous
bases having potent activity, and are the
most important category of vegetable
origin drugs. Prominent examples are:
morphine, atropine, ephedrine, nicotine,
ergotamine, reserpine, quinine, vincristine,
etc. They are mostly used as their water
soluble hydrochloride/ sulfate salts
b. Glycosides: These compounds consist of
a heterocyclic nonsugar moiety (aglycone)
linked to a sugar moiety through ether
linkage. Cardiac glycosides (digoxin,
ouabain) are the best known glycosidic
drugs. The active principle of senna and
similar plant purgatives are anthraquinone
glycosides. Aminoglycosides (gentamicin,
etc.) are antibiotics obtained from
microorganisms, and have an aminosugar
in place of a sugar moiety.
c. Oils: These are viscous, inflammable liquids,
insoluble in water. Fixed (nonvolatile)
oils are calorie yielding triglycerides of
higher fatty acids; mostly used for food
and as emollients, e.g. groundnut oil,
coconut oil, sesame oil, etc. Castor oil is
a stimulant purgative. Essential (volatile)
oils, mostly obtained from flowers or
leaves by steam distillation are aromatic
(fragrant) terpene hydrocarbons that have
no food value.
They are used as flavouring
agents, carminatives, counterirritants and
astringents; examples are eucalyptus oil,
pepermint oil, nilgiri oil, etc. Clove oil is
used to allay dental pain. Menthol, thymol,
camphor are volatile oils that are solids at
room temperature.
Mineral oils are not plant products, but
obtained from petroleum; liquid paraffin is
a lubricant laxative, soft and hard paraffin
are used as emollient and as ointment
bases.
Other plant products like tanins are astringent;
gums are demulcents and act as suspending agents
in liquid dosage forms. Glycerine is a viscous,
sweet liquid used as vehicle for gum/throat paint.
Resins and balsams are used as antiseptic and in cough mixtures. The antimalarial drug artemisinin
is a sesquiterpene endoperoxide obtained from a
Chinese plant.
2. Animals Though animal parts have been used
as cures since early times, it was exploration
of activity of organ extracts in the late 19th and
early 20th century that led to introduction of
animal products into medicine, e.g. adrenaline,
thyroxine, insulin, liver extract (vit. B12
). Antisera
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and few vaccines are also produced from animals.
3. Microbes Most antibiotics are obtained
from fungi, actinomycetes and bacteria,
e.g. penicillin, gentamicin, tetracycline,
erythromycin, polymyxin B, actinomycin D
(anticancer). Some enzymes, e.g. diastase from
a fungus and streptokinase from streptococci
have a microbial source. Vaccines are produced
by the use of microbes.
4. Minerals Few minerals, e.g. iron salts,
calcium salts, lithium carbonate, magnesium/
aluminium hydroxide, iodine are used as
medicinal substances.
5. Synthetic chemistry Synthetic chemistry
made its debut in the 19th century, and
is now the largest source of medicines.
Synthetic drugs have the advantage of purity
and uniformity of the product. They can be
manufactured in any quantity as per need,
in contrast to drugs from natural sources
whose availability may be limited. Not only
diverse congeners of naturally obtained
drugs (atropine substitutes, adrenergic b2
agonists, synthetic glucocorticoids/progestins/
cephalosporins, etc.) have been introduced
to achieve greater selectivity of action
or even novel type of activity, but many
entirely synthetic families of drugs, e.g.
benzodiazepines, thiazides, benzimidazoles,
f
luoroquinolones, etc. have been produced.
Many drugs are being synthesized to target
specific biomolecules, e.g. ACE inhibitors,
glycoprotein IIb/IIIa receptor antagonists,
HIV-reverse transcriptase inhibitors, etc.
Synthetic drugs that are chiral can also be
produced as single active enantiomer products,
which may be therapeutically superior.
6. Biotechnology Several drugs, especially
peptides and proteins are now produced by
recombinant DNA technology, e.g. human
growth hormone, human insulin, altaplase,
interferon, etc. Monoclonal antibodies,
regulator peptides, erythropoietin and
other growth factors are the newer drugs of
biotechnological origin. Protein therapeutics
is rapidly expanding, because specifically
designed and customized proteins can now be
produced.
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