L8 Pharmacodynamics I Flashcards
What are the three main phases of drug action?
- Pharmaceutical phase
- Pharmacokinetic phase
- Pharmacodynamic phase
Receptor responses to drugs are graded; what does this mean?
Increasing the dose increases the response (up to some maximal point)
What is the difference between a binding site and a receptor?
Binding sites can bind a substance but are not themselves capable of initiating a subsequent response; receptors are capable of initiating a response
What is a pharmacophore?
The part of a receptor that recognizes and binds the drug (structural specificity)
What is the stereospecificity of a receptor?
The isomers of a drug may differ in their potency or maximal activity at the same receptor; they may also preferentially activate different receptors
Describe the concept of saturability as it relates to receptors.
Receptors exist in finite numbers and can be saturated by high doses of drugs
There is a quantitative relationship between the magnitude of the response and what property of the receptors?
The total number of receptors occupied
The response to a drug binding at a receptor depends on what three things?
- Amount of drug reaching its site of action
- Specific drug-receptor interaction at the site (coupling efficiency)
- Functional status of the receptor and/or target cell (desensitization or supersensitivity)
True or false - receptors are subject to regulation.
True
What are the four major chemical forces that contribute to drug binding?
- Electrostatic
- Hydrogen binding
- Van der Waal’s forces
- Hydrophobic forces
True or false - most drug binding interactions are irreversible.
False - most are reversible
True or false - drugs interact with both unoccupied and occupied receptors.
False - they only interact with free/unoccupied receptors; drug displacement generally does not occur in drug receptor interactions
The binding of drugs to receptors is dictated by the ___ equation.
Fractional occupancy
Fractional occupancy = ?
1/[1+(Kd/[D])]
What does receptor fractional occupancy depend on?
- Drug affinity (Kd)
- Drug concentration [D]
NOT receptor number (density)
Kd = ?
[D][R]/[DR] = koff/kon
What is the Kd value (affinity constant)?
A measure of the propensity of that drug of bind to a given receptor; the concentration of a drug required to occupy 50% of a receptor population
As Kd increases, drug affinity ___.
Decreases
The magnitude of the response to receptor binding = ?
f[(Fractional occupancy)(Receptor density)]
Upon what does drug selectivity depend?
The relative affinities of a drug for various receptors (various Kds)
As drug dose increases, selectivity ___.
Decreases
It takes at least ___ log units of concentration of a drug to occupy 1-91% of receptors.
3
What is the correspondence between the amount of drug and the magnitude of effect?
Dose-response relationship
Increasing the dose ___ the effect in a graded manner
Increases
What is potency?
The concentration or dose of drug needed to produce 50% of that drug’s maximal response (EC50/ED50)
Drug potency depends on what two things?
- Affinity for the receptor
2. Efficiency with which the receptor activation is coupled to the response
What is maximal efficacy?
The maximal response produced by the drug (aka intrinsic activity)
What is the intrinsic activity of a full agonist?
1
What is the intrinsic activity of a partial agonist?
<1
What is the intrinsic activity of a neutral antagonist?
0
What is the intrinsic activity of an inverse agonist (negative antagonist)?
<0
True or false - efficacy and potency are independent properties of a drug.
True
The clinical effectiveness of a drug depends on its ___, not ___.
Maximal efficacy; potency
Systems in which maximal response is achieved by doses of agonists that occupy only a small % of receptors are considered to have ___.
Spare receptors
What leads to receptor reserve?
Degree of response amplification following any given drug receptor interaction
Describe the effects of competitive antagonists on the DR curve, ED50, and Emax.
- DR curve shifts right
- ED50 increases
- Emax is unchanged
Describe the effects of non-competitive antagonists on the DR curve, ED50, and Emax.
- DR curve does not shift along the x-axis
- No change in ED50
- Emax decreases
How do partial agonists affect response?
Partial agonists reduce the effectiveness of full agonists.
What are the three non-pharmacological means of antagonizing drug effects?
- Chemical (chemical inactivation of a drug)
- Physiologic (use of opposing pathways to antagonize the effects of the drug)
- Biologic (one drug affects the metabolism of another)
