PHA 301

What is Pharmacology?
Pharmacology can be defined as the scientific study
of the effects of drugs and chemicals on the function
of living systems (cells and tissues)

What is a drug?
A drug can be defined as a chemical substance of
known structure, which, when administered to a
living organism, produces a biological effect.
• Drugs may be synthetic chemicals, chemicals obtained from plants
or animals, or products of genetic engineering and of known
structure which when administer to a living organism, produce a
biological effect.

• A Medicine or medication is a chemical preparation administered

with the intention of producing a therapeutic effect (to prevent,
treat or cure a disease or to promote well-being).

• It usually contains other substances such as excipients, stabilizers

and solvents apart from the active drug, to make them more
convenient to use.

• To count as a drug, the substance must be administered as such,

rather than released by physiological mechanisms. Many
substances, such as insulin or thyroxine, are endogenous
hormones but are also drugs when they are administered
intentionally.
• Many drugs are not used in medicines but are
nevertheless useful research tools. In everyday
parlance, the word drug is often associated with
addictive, narcotic or mind-altering substances

• We would focus mainly on drugs used for

therapeutic purposes but also describe important
examples of drugs used as experimental tools.
SOURCES OF DRUGS

• (a) Natural sources

• (b) Semi-synthetic
• ( c) Synthetic
Natural source:
1. Microorganisms – Some antibiotics and chemotherapeutic
agents are originally obtained from micro organism e.g
Penicillium notatum is a source of Penicillin; Actinobacteria
gives Streptomycin while Aminoglycosides such as gentamicin
was obtained from Streptomyces

2. Minerals obtained naturally from the ground e.g Calcium

carbonate which is used as antacid, also, sulphur as fungicide
in sulphur ointment
3. Plants have always being sources of drugs both in African
traditional and modern medicine e.g Quinine derived from
CINCHONA trees, Digoxin from Digitalis purpurea, Eucalyptus
from leaves of Eucalyptus, Nicotine from Tobacco, Castor oil
from Castor oil seeds and Poppy belladonna somniferum
gives Morphine opiod.

Semi-synthetic source:
• When substances from natural sources are modified
chemically, they become semi-synthetic e.g base derived
from vegetable or animal sources.

Synthetic source:
• Drugs made or produced from chemicals in the laboratory.
Most of the drugs we use fall into this category e.g Aspirin
(salicylates) and Paracetamol e.t.c
Brief History

• The science of Pharmacology came into being in the mid-19th century, a

new biomedical science based on principles of experimentation rather than
dogma.

• From the dawn of civilization, herbal remedies were widely used, but
nothing resembling scientific principles was applied to therapeutics. For
examples, concoctions of worms, dung, urine, and the moss from a dead
man's skull.

• Virchow proposed the cell theory in 1858.

• The first use of a structural formula to describe a chemical compound was
in 1868.
• Bacteria as a cause of disease were discovered by Pasteur in 1878.
• Previous to these periods, pharmacology had no grounds to stand on,
despite, Rudolf Buchheim took a bold step to create the first pharmacology
institute (in his own house) in Estonia in 1847.
• 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.

• Before the advent of synthetic organic chemistry,

pharmacology exclusively understood the effects of natural
substances, mainly plant extracts-and a few toxic chemicals
such as mercury and arsenic.

• Morphine was purified from Opium in 1805 by Friedrich

Sertürner, a young German apothecary. Other substances
quickly followed, though their structures were unknown,
these compounds showed that chemicals, not magic or vital
forces, were responsible for the effects that plant extracts
produced on living organisms.
• Early pharmacologists focused most of their attention on such plant-
derived drugs as quinine, digitalis, atropine, ephedrine, strychnine and
others

• Paul Ehrlich in 1909 discovered arsenical compounds for treating syphilis.

Further breakthroughs came when the sulfonamides, the first antibacterial
drugs, were discovered by Gerhard Domagk in 1935 and with the
development of penicillin by Chain and Florey during the Second World
War, based on the earlier work of Fleming.

• The discoveries of hormones, neurotransmitters and inflammatory

mediators came about in the 20th and 21st centuries. These provided a
common ground between physiology and pharmacology, for interactions
between chemical substances and living systems.

• The concept of 'receptors' for chemical mediators, first proposed by Langley

in 1905, was quickly taken up by pharmacologists such as Clark, Gaddum,
Schild and others and is a constant theme in present day pharmacology. The
receptor concepts, and the technologies developed from it, have had a
massive impact on drug discovery and therapeutics.
These developments led to the study and effect of drugs
in human cells and tissues
Broadly subdivided into:

• Pharmacokinetics –what body does to the drug

• Pharmacodynamics – What the drug does to the body

• Pharmacokinetics – How body affect the drugs

• Absorption
• Distribution
• Metabolism
• Elimination
DRUG ABSORPTION

• Absorption is defined as the passage of a drug from its site of administration into
the plasma.

• It is therefore important for all routes of administration, except intravenous

injection.

• There are instances, such as inhalation of a bronchodilator aerosol to treat asthma,

where absorption as just defined is not required for the drug to act, but in most
cases the drug must enter plasma before reaching its site of action.

Broadly classified as:

 Enteral = G.I (Oral)

 Parenteral =I.V, I.M

 Transdermal =Skin (active ingridients are delivered across the skin for systemic
distribution – patches or ointment)

 Respiratory = Inhalation
ROUTES OF DRUG ADMINISTRATION

 Oral – drugs taken through the mouth and via GIT

 Sublingual – drug diffusion into the blood through the tissues under the
tongue
 Rectal –rectum as a route of administration (gastric irritation, nausea and
vomiting)
 Application to other epithelial surfaces (e.g. skin, cornea, vagina and nasal
mucosa)
 Inhalation
 injection
 - subcutaneous – inject into the tissue layer between the skin and the
muscle
 - intramuscular – inject deep into the muscle
 - intravenous – injection or infusion directly into the vein using I.V
catheter
 - intrathecal.- via injection into the spinal canal or subarachnoid space
ORAL ADMINISTRATION

• Most drugs are taken by mouth and swallowed. Little absorption occurs until the drug
enters the small intestine.
• Drugs given orally in liquid, tablet / capsule or powder forms.

Advantages:
• This route is most common, convinient and economical route of drug administration.

Disadvantages:
• Compliance issues when drug is bitter
• Hepatic biotransformation – First pass effects
• Instability of gastric/intestinal secretion e.g Penicillin is unstable in acidic medium
• Irritation of the stomach lining in the case of Salicylates
• Difficulty in swallowing, especially in elderly and paediatrics

Drug absorption from the intestine

The mechanism of drug absorption is the same as for other epithelial barriers, namely passive
transfer at a rate determined by the ionization and lipid solubility of the drug molecules.
Factors affecting gastrointestinal absorption

• Typically, about 75% of a drug given orally is absorbed in 1-3 hours, but numerous factors
alter this, some physiological and some to do with the formulation of the drug. The main
factors are:

• Gastrointestinal motility
• Splanchnic blood flow
• Particle size and formulation
• Physicochemical factors – presence of other chemicals / drugs e.g bile, mucus and other
drugs
• Luminal PH

• Gastrointestinal motility: Has a large effect on drug absorption. Many disorders such as
diabetic neuropathy causes gastric stasis and slow drug absorption. Drug treatment can
also affect motility, either reducing or increasing it. For example, metoclopramide, an
antiemetic used in migraine to facilitate absorption of analgesic.
• Also, excessively rapid movement of gut contents (e.g. in some forms of diarrhoea) can
impair absorption. Conversely, a drug taken after a meal is often more slowly absorbed
because its progress to the small intestine is delayed.
• Splanchnic blood flow: Several drugs (e.g. propranolol; reach a
higher plasma concentration if they are taken after a meal, probably
because food increases splanchnic blood flow. Conversely, splanchnic
blood flow is greatly reduced by heart failure, with a resultant
reduction of drug absorption.

• Particle size and Formulation: Formulation of drugs has major effects

on absorption. Small differences in the pharmaceutical formulation
can make a large difference to the extent of absorption.

• Therapeutic drugs are formulated pharmaceutically to produce

desired absorption characteristics. Capsules may be designed to
remain intact for some hours after ingestion in order to delay
absorption, or tablets may have a resistant coating to give the same
effect. In some cases, a mixture of slow- and fast-release particles is
included in a capsule to produce rapid but sustained absorption.
• BIOAVAILABILITY

• Drug administered orally is intended to be absorbed and

cause a systemic effect. For a drug to get from the lumen of
the small intestine into the systemic circulation, it must
penetrate the intestinal mucosa, also run the gauntlet of
enzymes that may inactivate it in gut wall and liver.

• The term bioavailability (F) is used to indicate the fraction of

an orally administered dose that reaches the systemic
circulation as intact drug, taking into accounts both
absorption and local metabolic degradation.

• Bioavailability is not a characteristic solely of the drug

preparation: variations in enzyme activity of gut wall or liver,
in gastric pH or intestinal motility all affect it.
SUBLINGUAL ADMINISTRATION

• Absorption directly from the oral cavity is sometimes useful (provided the drug does not
taste too horrible) when a rapid response is required, particularly when the drug is either
unstable at gastric pH or rapidly metabolised by the liver.

• Glyceryl trinitrate is an example of a drug that is often given sublingually. Drugs absorbed
from the mouth pass directly into the systemic circulation without entering the portal
system, and so escape first-pass metabolism by enzymes in the gut wall and liver.

RECTAL ADMINISTRATION
• Rectal administration is used for drugs that are required either to produce a local effect
(e.g. anti-inflammatory drugs for use in ulcerative colitis) or to produce systemic effects.

• Absorption following rectal administration is often unreliable, but this route can be useful
in patients who are vomiting or are unable to take medication by mouth (e.g.
postoperatively).

• It is used to administer diazepam to children who are in status epilepticus, in whom it is

difficult to establish intravenous access.
EPITHELIAL SURFACES

• Cutaneous administration: is used when a local effect on the skin is required (e.g. topically applied steroids).
Appreciable absorption may nonetheless occur and lead to systemic effects.

• Subcutaneous administration: This is through the subcutaneous tissue to provide sustained effect. Drugs may
be implanted into SC tissue in the form of pellet, absorption occurs over a period of several weeks or months
e.g contraceptive injection
Disadvantages are low rate of absorption, severe pain and can cause local necrosis.

Nasal sprays
• Absorption is believed to take place through mucosa overlying nasal-associated lymphoid tissue. This is similar
to mucosa overlying Peyer's patches in the small intestine, which is also unusually permeable.

Eye drops

• Many drugs are applied as eye drops, relying on absorption through the epithelium of the conjunctival sac to
produce their effects. Desirable local effects within the eye can be achieved without causing systemic side
effects

Inhalation

• Inhalation is the route used for volatile and gaseous anaesthetic, the lung serving as the route of both
administration and elimination.
• Drugs used for their effects on the lung are also given by inhalation, usually as an aerosol
ADMINISTRATION BY INJECTION
• Intravenous injection is when the drug is delivered through the veins directly into
circulation; it is the fastest and most certain route of drug administration. Bolus injection
produces a very high concentration of drug, first in the right heart and lungs and then in the
systemic circulation.
• The peak concentration reaching the tissues depends critically on the rate of injection.
Administration by steady intravenous infusion avoids the uncertainties of absorption from
other sites, while avoiding high peak plasma concentrations caused by bolus injection.

Advantages:
• Effective when immediate response is required
• Rate of drug entry into the body can be controlled
• Suitable for drugs that are poorly absorbed from the GIT or that could be destroyed by
metabolism
• Useful for formulations that are not in tablet or capsules but suspension or powder in vial

• Disadvantage:
• Once a drug is given, it cannot be retrieved
• It must be given slowly
• Embolism may occur from precipitation of drug particulate matters i.e blockage of blood
vessels
• Infections are easily transmitted through this process
Intramuscular: Injection of drugs is when given through
the muscles, usually produces a faster effect than oral
administration, but the rate of absorption depends
greatly on the site of injection and on local blood flow.

• Given when a fairly rapid response is required but

when I.V route is dangerous or unnecessary for drugs
that are poorly absorbed from the GIT

Intrathecal injection: Injection of a drug into the spinal

canal or into the subarachnoid space via a lumbar
puncture needle. Used for some specialised purposes
such as spinal anaesthesia, chemotherapy and pain
management.