Pharmacodynamics Flashcards
Do all (or almost all) of the receptors for a drug have to be bound to a drug for the drug to exert its maximum effect?
No, there are typically far more receptors than needed for a drug to exert its maximum effect. It is quite possible for a drug to exhibit its maximum effect at very low drug concentrations with numerous receptors still available.
Where in the cell are most drug receptors located?
Most are proteins bound in the cell membrane. A few, however, are located in the cytoplasm or nucleoplasm.
Does the ionized or non-ionized form of a drug confer its clinical effect?
In solution, the non-ionized form of a drug is considered to confer pharmacologic activity, because it is in the non-ionized form that the drug is able to pass through lipid soluble biologic membranes to reach its point of action.
How will the chronic administration of an antagonist affect the number and sensitivity of the receptors it antagonizes?
When chronically exposed to an antagonist, the receptors upregulate, which means that both the number of receptors and their sensitivity both increase.
What is the occupancy theory?
The Occupancy Theory states that the magnitude of a drug’s effect is proportional to the number of receptors it occupies.
How does the overabundance of receptors for a drug affect the dosing of an agonist for that receptor compared to an antagonist for that receptor?
Because a drug can exert its maximum effect and still leave a large number of receptors available, an agonist can exert its effects at low concentrations. An antagonist, however, must bind to a much larger number of receptors and requires higher concentrations to do so. For example, acetylcholine (agonist) only needs to bind to about 25% of the available nicotinic cholinergic receptors in the neuromuscular junction to produce a muscle contraction. A nondepolarizing muscle relaxant (antagonist), however, must block 75% of the receptors to exert a significant reduction in muscle fiber contractility.
What are the two major scenarios by which drug receptors bind to a drug and exert their effect. What are they?
The two major ways in which a drug can bind to a receptor and cause a change in cellular function are ionophores (ion channels) and G-proteins.
What is the difference between an agonist, an antagonist, a partial agonist, and an inverse agonist?
A drug that has an affinity for a receptor but lacks efficacy (meaning that it is unable to produce the conformational change in the receptor necessary to elicit the response in the tissues for which the receptor is designed) is an antagonist. An agonist has both affinity and efficacy. A partial agonist can bind with the receptor and has some efficacy, but it cannot elicit the maximal tissue response. An inverse agonist can bind with the receptor, but results in the opposite reaction of an agonist.
What does the term LD50 mean?
The LD50 is the dose that is lethal in half of the population.
What does the term C50 mean?
The C50 represents the site concentration at which a drug exhibits half of its maximal effect.
Is the binding of acetylcholine to a cholinergic receptor an example of a G-protein mediated mechanism or an ionophore?
It is an ionophore because an ion channel is affected by the binding of acetylcholine to the cholinergic receptor. When acetylcholine binds to the receptor, a sodium channel is opened which allows the influx of Na+.
Is the gamma-aminobutyric acid (GABA) receptor an example of an ionophore or a G-protein mediated receptor?
The GABA receptor is an ionophore. The binding of drugs or neurotransmitters to a GABA receptor opens a chloride channel, allowing the influx of chloride into the cell.
What is meant by steady-state with regards to drug concentration?
Steady-state is the point at which the plasma concentration of a drug is in equilibrium with all other tissues is the body.
With regards to drug-receptor complexes, what is desensitization?
When receptors are exposed to an agonist more than normal, they become desensitized. This means that the binding of the agonist to the receptor exerts a lower-intensity response than normal.
What is a pharmacodynamic interaction and what are some common examples that would apply to anesthesia?
A pharmacodynamic interaction is the effect one drug has on the performance of another drug. It can be antagonistic or synergistic. For example, cholinesterase inhibitors increase the amount of acetylcholine, which antagonizes the effect of nondepolarizing muscle relaxants. Hypnotics and narcotics act on separate receptors, but have a synergistic effect which increases the clinical effect of both drugs.
