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Development of a Medicine
What is a drug?
Any biologically active chemical that does
not occur naturally in the human body that can affect living processes
Synthetic manufacture:
Most modern medicines
1. Drug Discovery
From traditional remedies
Aspirin Penicillin
Bacteria were not present near the fungus on the plate He concluded that the fungus was secreting an
antimicrobial agent
2. Pre-clinical Testing.
In vitro testing
Test active compound against target cell Provides evidence of beneficial / harmful effects Very simplistic, target organs/tissues made up of multiple cell types BUT lacks the homeostatic mechanisms and pathways found in animals / humans
Pre-clinical Testing
ED50 Effective Dose 50
the amount of the drug required to produce a specified effect in 50% of an animal population LD50 Lethal Dose 50 The amount of the drug required to cause death in 50% of an animal population
But only human studies can tell use how useful and safe a drug is................
Clinical Trials.
10,000 compounds
250 compounds
5 compounds
100-500 volunteers
Phase II
1 approved drug
6.5 years
7 years
1.5 yrs
Phases I trials
Use healthy volunteers How does the drug affect the human
body? Drug absorption, metabolism and excretion Preferred method of administration What dosage is safe?
Phase II trials
Use target patient group representative of
those likely to benefit from the drug. No pregnant women Does the drug have a beneficial effect on the disease? Determine therapeutic dose range. Usually placebo controlled Conducted by experts in the disease field
What is a placebo?
An inactive pill, identical in appearance to the treatment pill which is given to the control group. Used to control for the placebo effect Patient feels better due to belief in the treatment
Test pill Placebo
disease Statisticians analyse results is A better than B? Only after analysis do you tell which is A and B.
Drug Licensing
Application submitted to Medicines and
Healthcare products Regulatory Agency (MHRA)
Product Launch
When a drug has marketing authorisation,
it is not available straight away. The company first have to apply to market their product. In the UK, they will apply to the MHRA. When this is done, the product is launched, and doctors can prescribe it. The time it takes from marketing authorisation to launch in the UK is one of the fastest in the world.
Classification of a Medicine
Names of drugs
Chemical name: describes the chemical
structure: by anyone: acetyl-p-amino-phenol paracetamol
Generic name: a name that can be used Trade name: owned by the
manufacturer: Calpol
Interfere with cell function, e.g., block Kill / prevent growth of viruses, bacteria,
fungi, protozoa, cancer
Categories of drug
Anti-inflammatory Analgesic Antipyretic Vaccine Antihypertensive Vitamin supplement Antitussive
Receptors
Receptors are proteins on the cell surface or inside
the cell.
receptor
Receptors
Drugs also bring information to cells by The drug picks the lock and triggers a
response by the cell.
drug
receptor
Non-specific effects
Acidic or alkaline properties
Surfactant properties (amphotericin)
Toxic effects e.g., Thalidomide: teratogenic Tolerance: increasing amounts are needed
to produce the same effect
Pharmacokinetics
How the body deals with the drug We need to consider Dose Route of Administration Absorption and distribution Metabolism and excretion
Dose
Administration
Route of administration depends on
how easy it is to use for patient how quickly a drug needs toreach site of action where it has to work in the body
Routes of Administration
Intravenous
Inhaled
Oral Transdermal
Topical
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 GItract passes through live 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
Disadvantages Absorption irregular and unpredictable Less convenient than oral route Low patient acceptability
Inhalation Route
Advantages Drugs inhaled through
Used predominately in
the treatment of asthma Drugs delivered directly to their site of action ie lungs
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
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
local action
Vicks Vaporub
antacid
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
Injected Dose
Oral Dose
Time
Therapeutic Range
SubTherapeutic
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?
Memory work
Pharmacodynamics is Pharmacokinetics is Receptor is like Ligand or drug is like First pass occurs in Many drugs are excreted by
Memory work
Pharmacodynamics is Pharmacokinetics is Receptor is like Ligand or drug is like First pass occurs in Many drugs are excreted by