introduction to pharmacology Flashcards
what is pharmacology?
The study of the action of drugs on the function of living systems
what is a drug?
a chemical substance or natural product that affects the function of cells, organs, systems or the whole body (i.e. is bioactive)
where do drugs come from?
Natural products (i.e. plants, animals)
Serendipity (i.e. by accident)
Changing the structure of an existing molecule (i.e. structure-activity relationships)
Using an existing drug in a new disease (i.e. re-purposing)
Computer-aided design
Studying disease processes
what are the three types of names of drugs?
Chemical – IUPAC name that describes the chemical structure of the drug
Generic – international non-proprietary name given to a molecule
Proprietary – ‘trade’ name(s) given to an approved drug by the manufacturer
what is pharmacokinetics?
what the body does to the drug
- used as a generic term to describe the fate of a drug molecule following administration to a living organism or how a drug molecule is affected by exposure to living cells
what is pharmacodynamics?
what is drug does to the body
- used as a generic term to describe the mechanism of drug action or what happens to cells, organs, systems, etc., as a result of drug exposure
how are proteins involved with drugs?
- drug transporters
- metabolising enzymes
what cells are involved with drugs?
- epithelial cells
- endothelial cells
- hepatocytes
drug administration paths…
what are the different routes of drug penetration into cells?
Diffusion through lipid membrane
- Major route for lipophilic drugs
Diffusion through aqueous channels
- Most drugs too large!
Carrier-mediated transport
- Major route for hydrophilic drugs
Pinocytosis
- Transport of insulin into brain
what does oral absorption of drugs require?
permeation of epithelial cell membrane
what is lipinski’s rule of 5?
an oral drug must have:
- molecular mass less than 500 Daltons
- no more than 5 H-bond donors (total number of N-H and O-H bonds)
- no more than 10 H-bond acceptors (all nitrogen or oxygen atoms)
- an octanol-water partition coefficient log P not greater than 5
basics of drug metabolism…
oral dosing…
what are the drug effects at the level of the cell?
Effects on receptors, ion channels, enzymes, transporters, DNA, etc.
what are the drug effects at the level of the organ/system?
Effects on heart, kidney, cardiovascular system, central nervous system, etc.
what are the drug effects at the level of the organism?
Therapeutic effect on disease state or process; adverse effects or side effects
what are the drug effects at the level of society?
cost , misuse, drug resistance
what are the sites of drug action?
- Human body = 100 trillion cells, 200 different cell types
- Primary tissues: muscle, nerves, epithelial, bone, connective, etc.
- Tissues controlled by: innervation, extracellular fluids, blood supply, exocrine and endocrine secretions
- Many drugs mimic (or block) the action of endogenous molecules (e.g. neurotransmitters, hormones)
- Act at specific sites; receptors, ion channels, enzymes, transporters (all of which are proteins)
what are the particular constituents of cells which drug molecules must bind to to produce an effect?
drug targets
how to drugs act?
- exert a chemical influence on constituents of cells to produce a pharmacological response
- must get close enough to cellular constituents in order that they can interact chemically
- leads to an alteration in molecular / cellular function
what are the protein targets for drug binding?
- receptors
- enzymes
- ion channels
- transporters
- circulating proteins, DNA, bacterial cell wall etc.
what is the main function of receptors?
cell to cell communication
where is cell to cell communication important?
- Neurotransmission (e.g. nerve to nerve; nerve to muscle)
- Effects of chemical mediators in bloodstream (e.g. adrenaline on heart)
- Hormone and growth factor signalling (e.g. action of insulin on muscle)
what is a receptor?
A recognition molecule for a chemical mediator through which a response is transduced
- often a protein/ protein complex on cell surface
- many drugs act to mimic/block the effect of the endogenous molecules at their receptors
describe the basic lock and key concept
- Receptor is the lock, drug is the key
- Some keys fit into the lock (i.e. Drug A) but others do not (i.e. Drug B)
- Depends on chemical structure
- Most locks (i.e. receptors) have a master key (an endogenous ligand)
what are the three parts of the structure of a receptor?
- extracellular domain
- transmembrane domain
- intracellular domain
describe the extracellular domain of a receptor
Contains ligand binding sites
Comprised of hydrophilic amino acids
describe the transmembrane domain of a receptor
Anchors protein in membrane
Comprised of hydrophobic amino acids
Typically has α-helical structure
describe intracellular domain of a receptor
Interacts with effector mechanisms
Comprised of hydrophilic amino acids
describe the steps of signal transduction
- Signal: ligand arrives at receptor
- Reception: ligand binds to receptor
- Transduction: ligand-bound receptor changes conformation (i.e. shape change)
- Response: change in conformation leads to some form of intracellular response
what is an example of a very fast signal transduction?
nicotinic acetylcholine receptor
what is an example of a fast signal transduction?
muscarinic acetylcholine receptor
what is an example of a slow signal transduction?
cytokine receptor
what is an example of a very slow signal transduction?
oestrogen receptor
what is a ligand?
any chemical that binds to a receptor
what is an agonist?
a drug that binds to a specific site on a receptor, mimics the effect of the endogenous ligand for that site
- affinity and efficacy
what is an antagonist?
a drug that binds to a specific site on a receptor, blocks the effect of the endogenous ligand (same or different binding site as ligand)
- affinity NO efficacy
what is affinity?
fits in
what is efficacy?
fits and causes a response
are responses to drugs always the same?
no drug response varies
- Age
- Genetics
- Disease state
- Drug interactions
- Environment
what is the difference between general and local anaesthetics?
general sedates entire body (loss of consciousness) whereas local only sedates the localised area (consciousness remains)
how does anaesthetic work?
blocks the transmission of the impulse
what is the chemical structure of local anaesthetic?
aromatic linked by ester (shorter half-life= shorter effect) or amide bond (longer half-life=longer effect) to a basic side chain
how does conduction of a nerve action potential come about?
opening of voltage gated Na+ channel and rapid influx of Na+ which depolarises the cell
what are the three main states of the Na+ channel
resting (negative)
open
inactivated
how does local anaesthetic act on the cell?
- LA binds to taget site on INTRAcellular side of Na+ channel (blocks the channel and stabalises it in the inactivated form_
- this prevents influx of Na+, preventing depolarisation, preventing an action potential, preventing pain perception
- causes a REVERSIBLE blockage of nerve conduction
what needs to happen for local anaesthetic to be effective?
- it must diffuse from the site of administration, across the nerve cell membrane to the intracellular side
- it must bind to the local anaesthetic target site
- this being possible is linked to the chemical structures
what does the aromatic group influence on local anaesthetic?
the hydrophobicity of the drug
what does the amine group influence on local anaesthetic?
the charge on the drug
are local anaesthetics acidic or basic?
weak bases
why are local anaesthetics used along side vasoconstrictors?
- less blood loss
- prevents entry into systemic circulation
what three things would you want to know about a drug?
- what it does
- its potency (measure of dose at which it is effective, potent drug= effective at low dosage)
- its selectivity (selective= works on one receptor not on others)
