Pharmacodynamics-Konorev Flashcards
Most drugs bind to receptors via non-covalent bonds and are reversible. List the strongest to weakest types of non-covalent bonds:
Ionic –> hydrogen –> hydrophobic interactions –> van der waals
In a dose-response curve, what is on the y-axis and x-axis?
Y=response
X=drug dose
What type of curve do you get when you plot drug dose arithmetically on the x-axis vs drug effect on the y-axis?
Hyperbolic
In a dose-response curve, it is more common for a concentration-effect curve to be presented by plotting __ on the x-axis and __ on the y-axis
X-axis-Log drug dose
Y-axis-% maximum response
When plotting log drug dose (x axis) vs % maximum response (y axis), you get a __ curve
Sigmoidal
In the dose-response curve, the maximal effect that can be produced by the drug is called the __
Emax
In the dose response curve, the __ is the dose of drug that produces half of its max effect
ED50 (Effective Dose 50)
The ___ of a drug for a receptor describes how readily and tightly that drug binds to its receptor
Affinity
A drug that has high affinity has good drug-receptor interaction. Do you need more or less drug to produce a response?
Less drug needed to produce a response
A drug that has low affinity has poor drug-receptor interaction. Do you need more or less drug to produce a response?
More drug needed to produce a response
Describe the affinity of a drug for a receptor with a low Kd
The lower the Kd, the HIGHER THE AFFINITY of a drug for a receptor
Describe the affinity of a drug for a receptor with a high Kd
The higher the Kd, the lower the affinity of a drug for a receptor
__ is a property of a drug determined by its affinities at various binding sites.
Selectivity
Drug selectivity is measured by comparing affinities of a drug to different receptors or by comparing __ for different effects of a drug
ED50s
A more selective drug would affect __ targets over a specific concentration range (therapeutic range)
Fewer
___ describes the ability of a drug to change a receptor function and produce a physiological response upon binding to a receptor
Intrinsic activity
__ bind to the receptor and stabilize it in a particular conformation (usually, the active conformation), producing a physiological response.
Agonists
___ bind to the receptor but do not change its function. However, it prevents activation of the receptor in the presence of an agonist.
Antagonists
A ___ has intrinsic activity
A ___ does not have intrinsic activity
Agonist
Antagonist
___ fully activate receptors, produce a max pharmacological effect when all receptors are occupied, and have maximal intrinsic activity
Full agonists
___ do not fully activate the receptor upon binding, produce a sub-maximal pharmacological effect when all receptors are occupied and its intrinsic efficacy varies depending on drug, but is always submaximal
Partial agonists
___ decrease receptor signaling, decrease response at receptors with a significant level of constitutive receptor activity. Its intrinsic activity is present and related to the inhibition of receptor function
Inverse agonists
__ do not change the function of the receptor upon binding, does not have pharmacological effect in the absence of an agonist, and has no intrinsic efficacy
Antagonists
___ produce max pharmacological effects at full receptor occupancy
Full agonists
___ produce sub-maximal pharmacological effects at full receptor occupancy
Partial agonists
Compare Emax between full agonists and partial agonists
Emax is lower in partial agonists than in full agonists
__ produce an effect opposite to a full or partial agonist
Inverse agonists
___ antagonism-action at the same receptor as endogenous ligands or agonist drugs
Pharmacologic (receptor)
Chemical antagonism is when a chemical antagonist makes the other drug ___
Unavailable
__ antagonism occurs between endogenous pathways regulated by different receptors
Physiologic
Competitive antagonists compete with ___ for binding of the receptor. They can be displaced from the receptor by other drugs (effects are surmountable)
Endogenous chemicals or agonist drugs
In ___ antagonists, receptor inactivation is not surmountable
Non-competitive
Irreversible antagonists irreversibly bind to and occlude the agonist site on the receptor by forming ___ bonds
Covalent
__ bind to a site other than the agonist site to prevent or reduce agonist binding or activation of the receptor
Allosteric antagonists
Describe EC50 and Emax in competitive antagonism
EC50 increases, Emax does not change
Describe EC50 and Emax in noncompetitive antagonism
Emax decreases, EC50 does not change
List the nonreceptor antagonists
Chemical and physiologic antagonists
Activation of mu opioid receptors by opioid analgesics (pain killers) such as morphine, codeine, and meperidine are examples of ___
Full agonists
Beneficial
___ block the actions of endogenous ligands at receptors. An example would be the blockade of alpha1 adrenoceptors receptors by the antihypertensive drug Prazosin.
Antagonists, partial and inverse agonists
Beneficial
___ selective drugs have less side effects
Highly
__ selectivity leads to the increased incidence of side effects
Lower
__ describes the amount of drug required to produce a specific pharmacological effect
Potency
Drugs with __ affinities for a receptor (i.e., drugs with a lower Kd) tend to be more potent
Higher
__ describes the maximal pharmacological effect that a drug can produce
Efficacy
Efficacy is related to the total # of receptors available to bind a drug, also known as the ___
Bmax
Drugs with a ___ Bmax tend to have higher efficacy
Higher
___ describes the amount of a drug required to produce a specific effect
Potency
Potency is represented by the ED50. The ___ the ED50, the more potent the drug
Lower
___ determines the drug dose that will be used clinically
Potency
___ describes the max effect that a drug can produce
Efficacy
Efficacy is represented by the ___
Emax
The __ the Emax, the more efficacious the drug
Greater
__ determines clinical effectiveness
Efficacy
___ answers the question of “How much?”, the magnitude of a response varies continuously, and typically represents the mean value within a population or a single subject
Graded response
___ is all or none; yes-no; “binary” responses. It answers the questions of “does the response occur or not?” Or “how many?”. It requires a pre-defined response (e.g., death, falling asleep, 10% decrease in BP)
Quantal response
___ is used to determine the frequency of (i.e., the number of individuals showing) a response within a large population
Quantal response
___ curves relate dose to the magnitude of a drugs effect on a continuous scale (i.e., how much)
Graded dose response
___ curves relate dose of a drug to the frequncy of a response within a general population (i.e., in how many)
Quantal dose-response
__ curves represent number or % of individuals responding at a dose of a drug and only at that dose
Non-cumulative quantal dose
___ is the dose at which 50% of population shows a response to a drug
ED50: median effective dose
___ curve represents the number or % of individuals responding at a dose of a drug and at all doses lower than that dose
Cumulative quantal dose response
TD50 represents ___
ED50 represents ___
Median toxic dose
Median effective dose
Describe the Therapeutic Index (TI)
TI: TD50 / ED50
The higher the TI, the safer the drug
__ is the range of doses of a drug or of its concentration in a bodily system that provides safe and effective therapy
Therapeutic window
This type of drug-receptor interaction (bond) is irreversible; drug removal/receptor re-activation requires re-synthesis of the receptor or enzymatic removal of the drug
Covalent bond
