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Categories of Medicines and
their actions.
Natalie Craythorne
27th September 2013
Aims for today
• To know what a drug is and how they are
classified
• To understand where drugs come from
• Be able to explain the “lock and key” and
induced fit hypotheses
• To define pharmacodynamics and
pharmacokinetics
What is a drug?
In simple terms a drug is;
A substance that has a physiological effect
when administered into the body.
However, some drugs are actually found
occurring naturally within the body. Inside the
body they are known as endogenous
substances and when introduced to the body
they are known as drugs. Example?
Where do they come from?
• Drugs are either naturally derived and come
from
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Animals
Fungi
Bacteria
Plants
• Or they are synthetically made in the
laboratory
Animals
• Insulins and Incretin hormones from pigs, cows
and reptiles or in fact humans
• Anti-venom – derived from the venom of snakes
and scorpion
• Heparin – an anti-coagulant derived from pig
intestines
• Premarin – derived from mare urine to treat
menopause
• Snake and Scorpion venom – use to treat
cancerous tumours
Plants
Can you identify the drug from the plant?
• Sallix spp - Aspirin
• Coca – Cocaine
• Atropa Belladona - Atropine
• Digitalis purpurea - Digitoxin
• Cinchona succiruba – Quinine
• Papaver somniferum - Heroin and morphine
• Hevea brasiliensis - Latex
Fungi, Bacteria and viruses
• Some of the most famous drugs are derived
from Fungi, bacteria and viruses including
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Penicillins - used as antibiotics
Statins – used to treat high cholesterol
MMR vaccine
Live attenuated influenza vaccine
Some hormones are made from transgenic bacteria
Botox – derived from Clostridium botulinum
Minerals
• A mineral is a naturally occurring substance
that is solid and stable at room temperature.
• Some examples are;
• Iron (Fe) – used to treat anaemia
• Gold (Au) – used for rheumatic disease and as an antimalarial
• Bismuth (Bi) – to treat gastric ulceration
• Lithium (Li) – prophylactic treatment of mania
• Silver (Ag) – commonly used antibacterial (more of a
therapeutic agent)
Drug classification
There are many ways in which to classify drugs.
Some of the more common are by;
• Chemical name or properties
• Route of administration
• Therapeutic effects
• The biological system affected.
• For example, N-acetyl-p-aminophenol is
paracetamol of brand name calpol which is an
analgesic.
WHO ATC classification system
• The World Health Organisation’s Collaborating
Centre for Drug Statistics methodology
controls the Anatomical Therapeutic Chemical
(ATC) Classification System
• It divides drugs into different groups according
to the organ system on which they act and/or
their therapeutic and chemical characteristics.
Code
A
B
C
D
G
H
J
L
M
N
P
R
S
V
Contents
Alimentary tract and metabolism
Blood and blood forming organs
Cardiovascular system
Dermatologicals
Genito-Urinary system including sex hormones
Systemic hormonal preparations, excluding sex hormones
and insulins
Antiinfectives for systemic use
Antineoplastic and Immunodulating
Musco-Skeletal system
Nervous system
Anti-Parasitic products, insecticides and repellants
Respiratory system
Sensory organs
Various
How the system works
• Pick a common drug, one of the penicillins for
example, Co-Amoxiclav.
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J – General Anti-infectives for systemic use
01 – Antibacterials for systemic use
C – Beta-lactam antibacterials
R – combination of penicillins
02 – Amoxicillin and enzyme inhibitor clavulanic acid.
• So, the code for co-acmoxiclav is J01CR02.
Further Classificaiton and labelling
• POM - prescription only medicine can only be
obtained with a paper prescription from a
registered prescriber eg, antidepressants
• CD – Controlled Drugs are kept in the safe and are
only dispensed with a hand written paper
prescription eg, Ritalin or Morphine
• P – Pharmacy medicines can only be purchased
with the consent of a pharmacist eg, 32
paracetamol tablets.
• OTC – Over the Counter medicines eg 16
paracetamol tablets.
How do drugs work?
• Pharmacokinetics is the study of what the
body does to medicinal substances
• Pharmacodynamics is the study of what the
medicinal substance does to the body.
• Pharmacokinetic properties of medicinal
properties include things like drug half-life,
absorption rate and elimination rate.
• Pharmacodynamic effects would be either
side effects or simply expected effects.
Antagonist or Agonist
• An antagonist is a substance that does not
illicit a response in the body when
administered.
• An agonist is a substance that illicits a
response when administered.
Opioids
• There are three opioid
receptors mu, kappa and
delta.
• When activated by an
agonist a response takes
place such as euphoria,
pain relief or constipation
eg, immodium, cocodamol or morphine.
• If occupied but no
response takes place it is
antagonistic eg, naloxone.
Induced fit model
Induced fit explained
• The induced fit hypothesis proposes that the
interaction between enzyme and substrate is
weak but the induction of conformational
change in the enzyme makes it stronger.
• It can be seen from the diagram that the
active site is not a perfect fit for the substrate
but it does change over time before releasing
the products.
Lock and Key hypothesis
Lock and Key hypothesis explained
• The lock and key hypothesis is more of a tight
fit than the induced fir model.
• The substrate fits into the active site perfectly
like a key into a lock.
• Sometimes substrates will use co-factors.
• A cofactor is an organic or inorganic substance
used to help the substrate fit.
• They are often called helper molecules.
Inhibition
EI complex and EIS
complex are nonproductive. The
possible outcomes
are EI, ES and EIS.
Inhibition explained
• Inhibitors are either reversible or non-reversible such
as cyanide.
• Competitive inhibitors - there is competition for the
active site where an increase in drug may out compete
the inhibitor eg, penicillin
• Non-competitive - there is no competition for the
active site but enzymatic function is affected. The
inhibitor binds to a site other than the active site
(allosteric site) and changes the conformation of the
enzyme eg, heavy metals
• Uncompetitive - where there is no competition for the
active site because the substrate is bound.
Routes of Administration
• The route of
administration is very
important when
considering
pharmacokinetics as it
can affect absorption
rates, elimination and
bioavailability.
• There are many routes
of delivery including;
Can you identify theses
routes of
Administration???
Oral
Intravenous
Intraperitoneal
Sublingual
Nasal
Intrathecal
Buccal
Topical
Transdermal
Epidural
Subcutaneous
Vaginal
Rectal
Intramuscular
But, why so many routes?
But where are they?
Route
Where
Example
Route
Where
Example
Oral
Mouth
Panadol
Transdermal
Through
skin
Nicotine
patch
Rectal
Rectum
Enema
Intraperitoneal
Peritoneum
Cancer
drugs
Intrathecal
Into CSF
Steroids
Sublingual
Under the
tongue
GTN spray
Buccal
Under the
upper lip
Buccastem
Vaginal
Vagina
Canesten
Intramuscular
Into a
muscle
Adrenaline
Epidural
Catheter
into spinal
columm
Anaesthetic
Subcutaneous
Under the
skin
Insulin
Topical
Onto skin
Vicks
Nasal
Through
the nose
Otrivine
Intravenous
Vein
Saline
The First Pass phenomenon
First Pass
• Some drugs have poor oral bioavailability ie,
not a lot of the drug is utilised.
• This is due to the first pass metabolism
• When ingested the drug is taken from the
gastrointestinal tract via the hepatic portal
vein to the liver where it is metabolised.
• The drug is then distributed through the
systemic circulation but at a reduced
concentration.
Routes of Administration explained
• Looking back to our slide about routes of
administration and the previous slide on first
pass metabolism it gives a clue as to why
there are so many routes.
• Some routes are not acceptable for certain
drugs
• This may be down to their properties or
structure, bioavailability or side effects.
So, what happens then?
• We must think of the following four letters
A for absorption
D for distribution
M for metabolism
E for elimination or excretion
• There are a few other words we should learn
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Dose and Dosing interval – very important!!
Bioavailability
Volume of distribution
Elimination rate and half-life
Clearance
Absorption
• Absorption is the movement of a substance or
drug into the bloodstream
• It follows all routes of administration other
than intravenous as it is being introduced to
the bloodstream
• The fastest route of absorption is by
inhalation.
• Food, other drugs, rate of gastric emptying
and pH can affect absorption.
Distribution
• Distribution is the reversible transfer of drug
from one location to another within the body.
• The distribution of a drug is dependent on
blood flow, pH partition and the ability of the
drug to bind to plasma proteins and tissue
• In highly perfused organs such as the liver
drugs are easily distributed.
• The volume of distribution of a drug is a way
of quantifying the extend of distribution.
Metabolism
• Is the biochemical modification of substances by
living organisms such as enzymes.
• It often converts lipid soluble substances to more
easily excreted water soluble products.
• Metabolism is mostly carried out by enzymes
called cytochromes.
• Metabolism is important when figuring out
dosage regimes and therapeutic index.
• The substances are modified in order to be
excreted. However some are metabolised into
more active species.
Therapeutic index
ED50 is the dose that is effective in 50% of the population and TD50 is
the toxic dose in 50% of the population. The therapeutic index is the
ratio of lethal dose/therapeutic dose.
Dosing Intervals for antibiotics
The dosing interval is the time between administration. For example three times
daily would indicate that there should be 8 hours between doses. MIC stands for
minimum inhibitory concentration, ie the minimum concentration of antibiotic that
can be used but still maintain its therapeutic inhibitory effect.
Cytochrome P450
• CYPs are the major enzymes involved in drug
metabolism and bioactivation, accounting for about 75%
of the total number of different metabolic reactions.
• Over 11,500 of the cytochrome proteins are known to
exist.
• They are numbered and lettered and responsible for the
metabolism of many drugs
CYTOCHROME
RESPONSIBLE FOR
CYP3A4
Metabolism of 50% of drugs
CYP1A2
Caffeine, paracetamol
CYP2D6
Amphetamines
Things that can effect drug metabolism
• Alcohol – Induces the action of CYP2A1 which
metabolises paracetamol.
• Tobacco – is an inducer of CYP1A2 meaning it makes
CYP1A2 more active.
• Grapefruit juice – Inhibits the CYP3A4 cytochrome.
• St John’s Wort – Inhibits and induces several CYPs
including CYP3A4 meaning that many drugs will linger
in the system or be metabolised too quickly. This
includes oral contraceptives.
• Peppermint Tea – a strong inhibitor of CYP1A2
responsible for paracetamol metabolism...who knew!!!
Differences between individuals
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Age
Sex (hormonal)
Weight
Kidney function
Liver function
Pregnancy
Dependencies ie, nicotine or alcohol.
Differences in individual metabolism
• Metabolism can be
affected by genetics
• There are liver enzymes
called cytochromes
which are used in
metabolism.
• Differences in CYP2E1
are the reason why
some races do not
process alcohol as well
as others.
• CYP2E1 metabolises
alcohol.
• In asian, korean and chinese
populations 80-100% of
people have a
polymorphism associated
with alcohol metabolism
• 50% of those people have
another gene variant on top
of this. This means they are
more effective at alcohol
metabolism than Caucasian
and African populations.
Excretion
• Drugs are excreted or cleared through the
kidneys and liver via urine. The urine may
contain the metabolites and or original
unchanged drug.
• The three main sites of excretion are urine, feaces
and breath
• Drug can also be excreted through sweat, milk,
saliva and hair.
• If excretion is incomplete drugs can accumulate
and become toxic.
What should we look out for?
• We must refer back to our letters, remove the
M and think about our bodies. ADE stands for
Adverse Drug Events
• ADEs can be anything from gastrointestinal
upset and headaches to death and blood
disorders.
• A classic example where serious adverse
effects were observed is Thalidomide. This is
now being used to treat cancer!!!
Adverse drug events
• These can be very serious, as seen with
Thalidomide.
• Even something as simple as an increase in
bruises can be very serious.
• Pharmacies carry yellow forms that we can
report these events on. They are taken very
seriously.
• However, most ADEs are picked up on during
clinical trials.
But...we don’t always need drugs!!
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Antibiotics
We need dirt!
Overuse and misuse of
antibiotics has led to
widespread antibiotic
resistance.
Bugs decide they no
longer want to respond
and so diseases like MRSA
become more prevalent.
This is why we culture
bacteria.
Headache Remedies
• If it is bearable or you
simply take for
prophylactic reasons
please do not!!
• It is a little known fact
that the more you take
the more headaches you
can get....scary?
• It is called medicationinduced headache and is
the third most common
type of headache.
To Conclude.
• Drugs undergo very thorough and lengthy testing
before coming on the market
• Without them the world would not be the same
and we would suffer for it.
• Always think about how it works and how is
doesn’t, ie lock and key/induced fit, agonist or
antagonist and inhibitors.
• Remember your lettering systems. ADME and
ADE
• Abuse of prescription medicines is just as serious
as illegal drugs and is increasingly more common.