Pharmacodynamics Flashcards
Define what the term ‘ Pharmacodynamics ‘ means
The study of interaction of drugs on biological systems
Define what a drug is ?
A chemical substance which interacts with a receptor to produce a physiological response .
How does a drug produce a effect?
needs to be initially detected does this by Binding to target - common drug protein targets are
Receptors
Enzymes
Transporters
Ion channels
Both allow molecules to move across cell membrane
Name a drug that can bind to a transporter ( Carrier molecule )
Tricyclics antidepressant
Name a drug that can bind with the ion channels
Nimodopine
What is a receptor ?
A region of a tissue or molecule in a cell membrane which responds specifically to a particular neurotransmitter , hormone , antigen or other substance
Ultimately are proteins interacting with extra cellular physiological signals and converting them into intracellular effects .
If nothing is bound to a receptor what are they termed as ?
Functionally silent
Where can receptor proteins be found ?
Can be found on the cell membrane or within constituents of the cell such as nucleas or cytoplasm
Where can the enzyme protein be found ?
Inside or outside the cell
What is a ‘ligand “?
A ligand is a molecule which will fit into the active site of the receptor essentially turning it on
What happens when the ligand binds to the ligand binding site ?
When it binds to the binding site if the receptor proteins , the receptor will under a ‘ conformational change ‘. This change alters the proteins function
The usefulness of a drug depends on …
Its ability to act on a particular receptor.
Drug must show high degree of binding site specificity
Drugs have certain specificity . True or False
Explain why
False .
No drug has certain specificity , many drugs will produce side effects because they will interact with a number of receptors
Explain the two way process of drug specificity .
Certain classes drugs will bind to certain receptors
Certain receptors recognise certain ligands
What is an agonist ?
An agonist is a drug that is able to bind to a receptor to mimic the action of a hormone , or of a transmitter and hence induce a cullular /physiological response
Can be a full or partial response
Agonist possess two qualities , what are they ?
Affinity - they are able to bind successfully to the receptor
Efficacy - are able to generate a response as a result of the binding
Explain the concept of occupancy .
When a drug and receptor combine to form a reversible complex ( not permanent- drug will leave )
Drug + receptor = drug receptor complex = responses
What does the simple occupancy theory suggest ?
The intensity of a response of a drug is proportional to the number of receptors that the drug occupies
Max response - when all avail receptor are occupied
Name and explain a interaction that is not explained by the simple occupancy theory ?
An agonist may achieve max response when only fraction of total number of receptors are occupied
Suggest there is some receptor reserve eg. Acetylcholine
Use the whiteboard to draw a graph explaining the SOT
When high doses are reached , the receptors achieve saturation , curve flattens
Any further increase of dose will not have affect on the occupancy as all available receptors are occupied by drug
What is the term used to describe a drug and receptor coming together and breaking away ?
Association and disassociation
Equilibrium …
The rate of reaction of drug and receptor molecules coming oath there is equal to the rate of reactions where drug and receptors are breaking apart
Use the whiteboard to draw a graph showing the equilibrium association constant
We can identify the conc of drug required to occupy 50% of receptor sites at equilibrium
Ka- equilibrium association constant
How would you determine the affinity of a drug ?
Take reciprocal of Ka
1/Ka= Kd
Kd - equilibrium disassociation constant
Drug and receptor breaking apart
What does affinity mean ?
This is the strength of the binding between the drug and receptor
Drug with high affinity will disassociate at a slower rate , drugs will low affinity will break away rapidly
Characterised by the equilibrium disassociation constant
What does efficacy mean ?
Used to be referred to as intrinsic activity
Ability of drug to elicit response once bound to a receptor
The max effect the drug is capable of
What is a dose response curve ?
Graph which tracks the response to various concentrations or doses of a drug
Sate how two different type of graphs can plot the same information
Linear scale - equal jumps on x axis
Log scale - unequal jumps between doses
Name two different types of dose response curves
Graded - effects in an individual on a physiological response such as heart rates
Quantal - data in no of individuals trying to work out if drug is effective or not as dose varies
What is a partial agonist ?
An agonist that cannot elicit the max same response as a full agonist
Have reduced efficacy
Explain the two theories in why an agonist is partial ?
1) PA binds fine but is less able to change structure when binding is done - less efficient at initiating the transduction pathway
2)Receptor site is constantly changing from active and inactive
If drug binds to inactive state no response
What is potency?
Linked with affinity , number of receptors and efficacy
The dose required to produce a specific intensity of response
ED50 can be good indicator of potency
What is ED50?
Effective dose
Dose that produces an effective therapeutic response in 50% of people taking the drug
What is the TD50?
Dose which causes toxicity in 50% of people taking the drug
Animals
What is LD50?
Dose that causes death in 50% of people given the drug
Lethal dose
Animals
Plot therapeutic and toxic effects of a drug ?
Ideally should be wide margin between the two
Therapeutic index (TI) = TD50/ED50
Safe drug will have higher therapeutic index
What is an antagonist ?
Drugs that may compete with natural agonist for receptor but don’t induce a response alone - this is called a competitive antagonist
They have affinity but no efficacy
Effectively dilutes receptor concentration
What is an irreversible antagonist ?
Drugs may bind strongly and permanently to the Receptor and prevent access of natural against
Will deactivate receptor and will be out of action for a period which depends on rate of synthesis for that type of receptor
What is an non competitive antagonist ?
Binds to irreversibly to same site of agonist or bind to different site
Reduction in max effect produced
Cannot be reversed by increasing agonist concentration
