Drug Receptors and Pharmacodynamics Flashcards
Simple explanation of Pharmacodynamics
What the drug does to the body
Drugs must interact with a _____ to exert an effect
molecular target
_____: the component of a cell or organism that interacts with a drug and initiates the chain of events leading to the drug’s observed effects
Receptors
Drug interaction with molecular targets is the initiating event in a multistep process that ultimately alters ______ function
Tissue
Receptors (regulatory proteins) that are targets for drugs can also be the targets
for ______, such as neurotransmitters and hormones
endogenous substances
______ - measure of how tightly or strongly a drug (ligand) binds to a receptor
Affinity
Receptors mediate the actions of pharmacologic _____ and _____
agonists and antagonists
______- drugs that bind to receptors and produce some effect or signal from the tissue. It is similar to the response produced by endogenous agents. They posses intrinsic activity
Agonists
______- drugs that bind to receptors but do not produce an effect or signal. They possess no intrinsic activity. They block responses from the tissue
Antagonists
______- the ability of a drug to evoke a response or effect in a target by altering some activity in the target
Intrinsic activity
______- the strength of a single drug-receptor interaction that evokes a response
Efficacy
_____- the concentration or dose of a drug required to produce 50% of the drug’s max effect
Potency
Types of receptors (4)
- Regulatory proteins- best-characterized receptors
- Enzymes- generally inhibited by drug binding
- Transport proteins- can be useful drug targets
- Structural proteins
Two types of dose response curves:
1) Graded dose-response curve
-drug concentration v. percentage of maximal effect
- log of drug concentration v. percentage of max. effect
2) Quantal dose-response curve
Maximal response that can be produced by a drug on a graded dose-response curve
Emax
The concentration of drug that produces 50% of maximal effect on a graded dose response curve
EC50
What does the logarithmic graded dose response curve accomplish?
Expands the scale at lower concentration and compresses the scale at higher concentrations (sigmoid curve)
T/F If Kd is low, binding affinity is high
T
Which of these drugs is the most potent?
B
Therapeutic index - the ratio of the ____ to ____
TD50 to ED50
______: the range between the minimum toxic dose and the minimum therapeutic dose
Therapeutic window
What do ED50, TD50 and LD50 illustrate?
- ED50- dose at which 50% of individuals exhibit the specified quantal event (median effective dose)
- TD50- median toxic dose
- LD50- median lethal dose
T/F all receptors have to be occupied to exhibit a full response
F - you cannot directly correlate physiological responses to binding
An antagonist that binds to the receptor in a reversible mass-action manner is referred to as a ____ ____
competitive antagonist
What is happening in the graph on the left?
- Reversible binding to the receptor
- Can be overcome by increasing the agonist concentration
- The maximal response of the agonist is not decreased
- The agonist dose-response curve in the presence of a competitive antagonist is displaced to the right
the degree of inhibition produced by a competitive antagonist depends on the ____ of the antagonist
Concentration
the clinical response to a competitive antagonist depends on the concentration of the competing _____
Agonist
_____ Bind irreversibly to receptors
Non-competitive antagonists
What does an allosteric antagonist do?
- Bind at a site on the receptor
different than the agonist binding site - or - effect
Chemical vs. Physiologic antagonists
Chemical- does not utilize receptors
- Example: heparin (Neg charge) can be counteracted by protamine (Pos charge). It makes the other drug unavailable for interactions with blood clotting proteins.
* Physiologic- between endogenous regulatory pathways. less specific, harder to control than receptor specific antagonist
- Example: glucocorticoid hormones v. insulin
What do partial agonists do?
Produce a lower response, at full receptor occupancy, than full agonists
* Competitively inhibit the responses produced by full agonist
How do lipid soluble agents work?
Move directly through the plasma membrane into the cell
- intracellular receptors
- Steroids, thyroid hormone (receptors stimulate transcription of genes)
- lag time to onset of effects
- effects persist longer
How do ligand-regulated transmembrane proteins work?
Regulates intracellular enzyme activity
- Example: insulin, epidermal growth
factor
How do cytokine receptors work?
Have extracellular and intracellular domains and form dimers
Examples: growth hormone, erythropoietin, types of interferon
What is this an example of?
Cytokine receptor
What is this an example of?
Ligand-regulated transmembrane
How do ion channels work?
Many of the most useful drugs act on ion channels
* Drugs can mimic or block the actions of natural agonists
Examples: acetylcholine,
serotonin, GABA, glutamate
What is this channel called?
Ion channels
How do G proteins and 2nd messangers work?
Extracellular ligands that increase the intracellular concentration of 2nd messengers
3 components of transmembrane signaling
-agonist binding
-activation of G protein
-G protein changes activity of
effector enzyme/ion channel
______: caused by genetic differences in metabolism or by immunologic mechanisms, including allergic reactions
Idiosyncratic drug response
_____: responsiveness diminishes rapidly
Tachyphylaxis
What does clinical selectivity mean with regards to drugs?
No drug causes only a single, specific effect
* Unlikely that a drug binds only to a single type of receptor
* Biochemical processes are coupled to many other biochemical functions
Clinically, selectivity is considered by separating effects into
1) beneficial or therapeutic
2) toxic or adverse
