HOW DO DRUGS WORK? Flashcards
What is a drug?
A drug is a chemical that produces a biological effect when given to a living organism. It’s structure must be known.
What needs to happen for a drug to exert a pharmacological effect?
They have to be bound to macromolecular components of a cell. The binding is highly specific,
What are the main regulatory proteins that are targets for drugs?
Enzymes
Carrier (transporter) proteins
Ion channels
Recceptors
Where are the targets for drugs found?
Outside cells - in extracellular space
Anchored in the cell membrane
Inside cells - inside the cytoplasm, in intracellular membranes or in the nucleus
What causes unwanted drug action or side effects?
If the drug binds to regulatory proteins that are non specific targets or interacts with more than one target protein.
What is a receptor?
A cellular sensor for chemical messengers within the body. They allow coordinated function of different cells/tissues.
What is an agonist?
An agonist activates the receptor and has a direct effect
What is an antagonist?
An antagonist binds but does not activate the receptor. It blocks the action of endogenous ligands.
What is an allosteric modulator?
It alters the action of an agonist by binding to the accessory site on a receptor. There is no effect in the absence of an agonist.
What is a ligand?
Any drug that binds with specificity to a molecular (protein) target.
What is affinity?
Describes the ability of a drug to bind to its target. Determines receptor occupancy. Agonists and antagonists/ blockers/ inhibitors all have affinity
What is efficacy?
Describes ability of a drug to activate a receptor once bound i.e. the ability to elicit an effect. Only agonists have efficacy.
What is potency?
Usually an indication of dose of drug needed to achieve desired effect. For an agonist potency is a combination of affinity and efficacy. For an antagonist, potency may depend solely on affinity.
What is bioavaliabilty?
The fraction of an orally administered dose reaching the systematic circulation (plasma)
What factors govern the concentration of drug that reaches its desired target when administered to the body?
Absorption
Distribution
Metabolism
Elimination
What is absorption?
Defined as the passage of a drug from site of administration to the
plasma (blood).
Absorption is intimately related to route of drug administration
What is enteral administration?
Drug placed directly into gastrointestinal (GI) tract:
- oral
- sublingual
- rectal
What is parenteral administration?
Delivery through route other than GI tract
- epithelial surfaces (topical)
- inhalation
- injection
What factors affect the absorption of a drug after oral administration?
- Ionisation and lipid solubility-strongly ionised drugs are poorly absorbed
- Metabolism in the gut wall and liver – “first-pass metabolism”
- Gastrointestinal motility – both stasis and increased motility can affect
absorption - Splanchnic blood flow – absorption can be increased by increased blood
flow after a meal - Particle size and formulation of drug can affect absorption - slow and fast release formulations
- Physicochemical factors e.g. calcium binding can prevent absorption
How are drugs carried to compartments?
By circulation
What does distribution depend on?
- Barrier permeability e.g. Blood-Brain Barrier
- Binding in compartments
- pH partition
- Water-fat partition
What is the blood brain barrier?
A continuous layer of epithelial cells joined by tight junctions forming a
barrier to drug entry.
What needs to happen to lipid soluble drugs before they can be eliminated?
They must be made water soluble
What is phase 1 metabolism?
alterations to molecule by oxidation, reduction,
hydrolysis
What is phase 2 metabolism?
conjugation usually in the liver with glucuronide or
sulphate prior to elimination
What are possible routes of elimination?
kidneys
liver / bile
lungs - respiratory
(anaesthetics)
What quantifies the lifetime of a drug in the body?
Its half-life – the time taken to reduce the concentration of drug to half its original
concentration
What are the advantages of oral administration?
- convenient, self administration
- no pain
- absorption area large
- cheap
What are the disadvantages of oral administration?
- often only partial absorption
- mucosa irritation
- gastric acid/enzymic
breakdown - slow onset
- taste unpleasant
- cannot be used when
unconscious - first pass metabolism
What are the advantages of intravenous administration?
- allows accurate control of amount of drug delivered to target - pharmacological effects produced very quickly - bypasses major sites of drug metabolism – GI tract and liver
What are the disadvantages of intravenous administration?
- difficult to reverse if too much drug delivered
- can lead to harmful effects
caused by blood clotting or the introduction of air or microbes into the vessel.
