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
Where do drugs come from
- natural products
- serendipity (accident)
- changing the structure of an existing molecule
- using an existing drug
What are the three types of names for drugs
- chemical (named after the structure)
- generic (non proprietary name given to a molecule)
- proprietary (trade name)
What is pharmacokinetics
What the body does to the drug
What is pharmacodynamics
What the drug does to the body
Describe the process of drugs entering the body and then getting excreted
Absorption, distribution, metabolism and then excretion
What ways are drugs absorbed
Absorbed through the gastrointestinal transport, gastrointestinal metabolism and hepatic first pass effect
Describe drug distribution
Distributed in the intravascular space, extravascular space and through protein binding
Where are drugs metabolised
In the liver
What are the routes of drug penetration into cells
- diffusion through the lipid membrane
- diffusion through aqueous channels
- carrier mediated transport
- pinocytosis
What is the major route for lipophilic drugs
Diffusion through the lipid membrane
What is the major route for hydrophilic drugs
Carrier mediated transport
What is pinocytosis
Transport of insulin into the brain
What is lipinskis rule of 5
- a molecular mass less than 500 daltons
- no more than 5 H- bond donors
- no more than 10 H- bond acceptors
- an octanol water partition coefficient log P no greater than 5
Describe phase 1 of drug metabolism
Phase 1
Reaction - oxidation, reduction, hydrolysis
Effect - functionalisation (adding new functions), addition or unmasking of reactive group
What is the consequence of phase 1 metabolism of a drug
Small decrease in lipophilicity
Slight increase in excretion
Change in pharmacological effect
Describe phase 2 metabolism of a drug
Reaction
Effect - conjugation, addition of large and often charged group
Consequences - large decrease in lipophilicity, large increase in excretion, usually a decrease in pharmacological effect
At Cmax rate of … equals rate of …
At cmax rate of absorption equals rate of elimination
What are the drug effects at a cellular level
Drugs can have an effect on receptors, ion channels, enzymes, transporters and DNA ect
What are the sites that drugs usually act upon
Many drugs mimic or block the action of endogenous molecules (eg. Hormones and neurotransmitters) they act at specific sites : receptors, ion channels, enzymes and transporters (all of which are proteins)
How do drugs act
Drugs are typically small chemical molecules, they exert a chemical influence on constituents of cells to produce a pharmacological response, they get close enough to cellular constituents in order that they can interact chemically
What are the protein targets for drug binding called
Receptors
What is the direct effect of an agonist binding to a receptor
Ion channel opening or closing
What are the transduction mechanisms when an agonist binds to a receptor
- enzyme activation/inhibition
- ion channel modulation
- DNA transcription
What is the effect of an antagonist binding
No effect
Why are receptors important
They are used for cell to cell communication
What is the basic receptor structure
1) extracelllar domain (contains ligand binding sites comprised of hydrophilic amino acids)
2) transmembrane domain (anchors proteins in membrane , comprised of hydrophobic amino acids)
3) intercellular domain (interacts with effectors mechanisms compromised of hydrophilic amino acids)
What kind of signal transduction would a ligand gated ion channel be used for
Very fast signal transduction (milliseconds)
What signal a G protein coupled receptor transduce
A fast signal transduction (seconds)
What signal would a kinase linked receptor be used to transduce
A slow signal transduction (hours)
What signal would a nuclear receptor be used to transduce
Very slow signal transduction (hours to days)
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
What is an antagonist
A drug that binds to a specific sit on a receptor, blocks the effect of the endogenous ligand (same or different binding site as ligand)
Agonists posses both …. and ….
Agonists posses both affinity and efficacy
What is efficacy
Can cause a response
Antagonists have …. but not …..
Antagonists posses affinity but not efficacy
What is affinity
A measure of the strength of association between ligand and receptor
What is pharmacological variability
Drug response is not always the same, different people react to drugs differently due to age, sex ect
What is general anaesthetic
- sedates entire body
- loss of consciousness
Block presynaptic calcium entry therefore no neurotransmitter release.
Increases post synaptic hyperpolarisation (Cl- influx or K+ efflux)
What is local anaesthetic
- sedates localised area
- no loss of consciousness
Block conduction axonal Na+ entry
Block sodium channels
Why are esters used rather than amides for short term use anaesthetic
Esters are metabolised quickly which means they have a shorter effect than amides, amides have a longer half life because they are metabolised in the liver therefore have a longer effect
What are do anaesthetic drugs generally consist of
Typically weak bases
What are the three states that sodium channels can exist in
Resting, open and inactivated
Describe the mechanism of action of local anaesthetics
- LAs bind to a target site on the intercellular side of the Na+ channel
- LAs prevents sodium influx > prevents depolarisation > prevents action potential propagation > prevents perception of pain
- LAs prevents Na+ influx in 2 ways, both blocks channel and stabilises it in its inactivated conformation
Causes reversible block of nerve conduction
To be effective LAs need to:
1) Diffuse from site of administration, across the nerve cell membrane to the intercellular side
2) Bind to LA target site
Their ability to do this is related to their chemical structure
Describe ester linked anaesthetics
Rapidly metabolised by tissue and plasma cholinesterase
Lasts <3mins
Describe amide linked anaesthetics
Primarily metabolised slowly in the liver last about 1-3 hours
What is the use of topical anaesthetics
They affect mucous membranes only, not effective on the skin
What is potency of a drug
A measure of the dose (or concentration) of a drug at which it is most effective
A potent drug is one that is effective in low doses
What does it mean if a drug is selective
A drug is selective if it works on one receptor but not on other
