Transcript Different categories of medicines and their actions

Different categories of
medicines and their actions
Iain G. Jack
4th February 2011
Content of today’s lecture
• How can we categorise drugs?
• How do drugs cause their effects?
• Specific receptors: lock & key
• Non-specific effects
• Pharmacokinetics
Introduction
• What is a drug?
• Any biologically active
chemical that does not occur
naturally in the human body
that can affect living
processes
A little light history
16th century Egypt
•Ebers papyrus
•Poppy
•juniper berries
•beer
•lead
•swine teeth
•goose grease
•lizard's blood
•donkey hooves
•crushed precious stones
•excreta from various animals
Where do drugs come from
now?
• Plants:
• Digoxin (foxglove)
• Belladonna (deadly nightshade)
• Diamorphine (opium poppy)
• Animal tissue:
Insulin, growth hormone
• Synthetic manufacture:
Most modern medicines
Names of drugs
• Chemical name: describes the chemical
structure:
acetyl-p-amino-phenol
• Generic name: a name that can be used
by anyone:
paracetamol
• Trade name: owned by the
manufacturer:
Calpol
Other ways to categorise drugs
• What kind of molecule is it?
• What organ system (or what
disease) is it for? e.g., cardiac,
psychotropic
• What parts of cells are affected?
What is the drug used for?
• To cure e.g., infections, cancer
• To suppress diseases or symptoms
without attaining a cure e.g.,
hypertension, diabetes, pain control
• To prevent disease (prophylactic)
e.g., immunisation
How does the drug act?
• Replace a deficiency, e.g., vitamins,
minerals, hormones
• Interfere with cell function, e.g.,
block enzyme action
• Kill / prevent growth of viruses,
bacteria, fungi, protozoa, cancer
Categories of drug
•
•
•
•
•
•
•
Anti-inflammatory
Analgesic
Antipyretic
Vaccine
Antihypertensive
Vitamin supplement
Antitussive
• Antiviral
• Antifungal
• Antibiotic
• Anaesthetic
• Surfactant
• Laxative
Content of today’s lecture
• How can we categorise drugs?
• How do drugs cause their effects?
• Specific receptors: lock & key
• Non-specific effects
• Pharmacokinetics
How do drugs work?
• Pharmacodynamics: study of how
chemicals exert their effects
• The practical importance of this is
enabling the design of new and better
drugs
Receptors
• Receptors are proteins on the cell surface or inside
the cell.
• They bind the body’s own chemical messenger
chemicals
• Convert the binding event to a signal that the cell
can recognize and respond to
signal
receptor
“Lock & Key”
• Interaction between a receptor and its
•
signal molecule (ligand) is like “lock &
key”.
Perfect fit depends on exact 3D shape
and size of both molecules.
Receptors
• Drugs also bring information to cells
by fitting into the same receptor
molecules.
• The drug picks the lock and triggers
a response by the cell.
drug
receptor
Cannabinoid receptor
• Where?
• Surface of brain cells
and cells of digestive
system and immune
system
• What for?
• Normal brain function
and healthy appetite
• So what?
• THC picks the lock.
Agonists and Antagonists
• Agonist: a drug that fits into a
receptor and activates a response
e.g., morphine, nicotine
• Antagonist: a drug that fits into a
receptor but blocks the receptor
and does not activate a response.
• ??? new anti-obesity drug:
antagonist to cannabinoid receptor
Content of today’s lecture
• How can we categorise drugs?
• How do drugs cause their effects?
• Specific receptors: lock & key
• Non-specific effects
• Pharmacokinetics
Non-specific effects
• Acidic or alkaline properties
• Surfactant properties (amphotericin)
• Osmotic properties (laxatives, diuretics)
• Interactions with membrane lipids
(anaesthetics)
Side-effects and other effects
• Not the “wanted” effect e.g. aspirin
causes gastric ulcer
• Diphenhydramine has a useful sideeffect
Side-effects and other effects
• Hypersensitivity / allergy:
exaggerated adverse reaction to
drug
• Toxic effects e.g., Thalidomide:
teratogenic
• Tolerance: increasing amounts are
needed to produce the same effect
Content of today’s lecture
• How can we categorise drugs?
• How do drugs cause their effects?
• Specific receptors: lock & key
• Non-specific effects
• Pharmacokinetics
Pharmacokinetics
How the body deals with the drug
We need to consider:
Dose
Route of Administration
Absorption and distribution
Metabolism and excretion
Dose:
amount of drug taken at any one time
• Aim is to give the patient a dose of
drug that achieves the desired
effect without causing harmful side
effects
• Therapeutic Index (TI) is the ratio
of the therapeutic dose to the toxic
dose
• E.g.’s of drugs with low TI include
digoxin, lithium and methotrexate
Administration
Route of administration depends on:
•How easy it is to use for patient
•The chemical make-up of the drug
•How quickly a drug needs to reach
site of action
•Where it has to work in the body
Routes of Administration
Intravenous
Inhaled
Oral
Transdermal
Subcutaneous
or intramuscular
injection
Topical
Rectal
Oral Route
• Medications taken by mouth
• Formulated in either a solid or
liquid form
• Absorbed from the GI tract
mainly in the small intestine
which is specialised for
absorption (large surface area
due to villi and microvilli).
Disadvantages
• Onset of action is relatively slow
• Absorption may be irregular
• Some drugs destroyed by enzymes
or other secretions found in GI tract
• Because blood from GI tract passes
through liver it is subject to hepatic
metabolism before reaching
systemic circulation
Buccal Route
• Drug is formulated as a tablet or a
spray and is absorbed from the
buccal cavity
• Sublingual absorption very fast
onset of action but duration is short
• Buccal absorption quick onset of
action that is of longer duration
than sublingual route
Rectal Route
• Drugs formulated as liquids ,solid
dosages and semi solids.
• The chosen preparation is inserted
into the rectum where it is released
to give local effect or absorbed to
give a systemic effect
Rectal & Vaginal Route
Advantages
Disadvantages
• Can be used when • Absorption
oral route
irregular and
unsuitable
unpredictable
• Useful when drug
•
Less
causes GI irritation
convenient than
• Can be used for
oral
route
local action
• Low patient
acceptability
Inhalation Route
Advantages
• Drugs inhaled through the
nose or mouth to produce
local or systemic effects
• Drug dose required to
produce desired effect is
much smaller than oral
route therefore reduction
in side effects
• Used
•
predominately in
the treatment of
asthma
Drugs delivered
directly to their site
of action ie lungs
Topical Route
• Skin used as site of administration
• Lotions ,creams ,ointments,
powders
• Skin has natural barrier function but
specialised dosage forms have
been developed that when applied
they allow the drug to pass through
and produce systemic effect
Parenteral Route
(drugs that are given by injection)
• IV route -drugs injected directly into
the systemic circulation (fast onset
of action)
• Subcutaneous route -drugs injected
into the s/c layer of the skin (easiest
and least painful)
• Intramuscular route –drugs injected
into muscle layers
Examples in each category
Route
Local Action
Systemic Action
Inhaled
Vicks Vaporub
Cigarette
Oral
Gaviscon liquid
Nurofen Tabs
Transdermal
Zovirax sore
cream
Nicotene patch
Rectal
Laxative
Sippository
Paracetamol
Suppository
I.V.
Novocaine
Contraceptive
S.C / I.M
Local thrombolytic Adrenaline
therapy
ADME
• Absorption: the mechanism by
which a drug enters the body
• Distribution: the drug is transported
throughout the body
• Metabolism: the drug interacts
with, and is processed by, the body
• Elimination: the drug is removed
from the body
Absorption
• Disintegration
• Dissolution
• Direct absorption at site of
action, e.g., in the gut
Steps in distribution
• Drug must spread throughout
blood volume
• Drug must get out of the
bloodstream between or through
endothelial cells
• Drug must cross the cell
membrane into cells
Factors affecting distribution
Binding to plasma proteins: if a
drug is bound to large plasma
proteins, it will be unable to get
out as the proteins are too large.
Arggh! I
can’t fit
through!
Factors affecting distribution
Extent of blood supply.
If a tissue is well perfused with blood,
drugs will get there faster.
Adipose tissue has low blood
perfusion so drugs reach it slowly.
Factors affecting distribution
• pH. A drug will pass
•
through membranes
better if it is not ionised
Binding of drugs to other
tissue components
Metabolism: what happens to a drug
Drug Concentration
Lethal
Dose
Injected Dose
Therapeutic
Range

Oral Dose
SubTherapeutic
Time
First pass effect
• All nutrients and drugs absorbed
•
•
from the gut travel in the blood
directly to the liver. The liver breaks
down many drugs so they are
inactivated before they ever enter
the systemic circulation!
This can decrease drug delivery to
target tissues
But some drugs are activated by the
first pass effect
Elimination
• Mainly in the kidney. Also bile,
gut, lung, breast milk.
• Elimination of a drug is usually
linked to renal function.
Individual variation
• Each person is unique how they
respond to a drug
• Age and sex (hormonal differences)
• Weight: some drugs are stored in
fat so less effective and longer
lasting in obese people
• Allergy
• Kidney & liver function: how will
they affect elimination?