Module 8 Flashcards
What are the two receptor theories that we use to describe drug receptor interactions?
Simple occupancy theory
Modified occupancy theory
The intensity of a drug’s response is proportional to the number of receptors occupied.
Simple occupancy theory
When does the maximal response occur according to the simple occupancy theory?
when all the receptors are occupied
What are the three statements of the modified occupancy theory?
1 - The intensity of a drug’s response is proportional to the number of receptors occupied
2 - two drugs occupying the same receptor can have different binding strengths (i.e. affinity)
3 - Two drugs occupying the same receptor can have different abilities to activate the receptor (i.e. intrinsic activity)
What does the modified occupancy theory also take into account, as opposed to the simple occupancy theory?
Drug’s affinity for it’s receptor and it’s intrinsic activity
Attraction a drug has for its receptor
affinity
Drugs with a _____ affinity are highly attracted to their receptor and therefore bind effectively even at _____ concentrations.
high
low
Drugs with a ____ affinity are weakly attracted to their receptor and therefore bind ineffectively to the receptor even at ______ concentrations.
low
high
The affinity of a drug is the primary determinant of a drug’s _______.
Potency
Describe the relationship between affinity and potency.
Proportional
Ability of a drug to activate a receptor.
Intrinsic activity
Drugs that have a ______ intrinsic activity cause intense receptor activation. Conversely, those with _____ intrinsic activity only minimally activate the receptor.
high
low
Describe the relationship between intrinsic activity and efficacy.
A drug with a high intrinsic activity has high efficacy.
A molecule that binds to a receptor and activates it. Mimic the action of endogenous ligands.
Agonist
Molecules that bind to a receptor but do not activate it.
Antagonists
Molecule that binds to the receptor but has minimal ability to activate it
Partial agonist
What are some examples of agonists?
NTs and hormones
Agonists can be thought of as having both _______ and ________ ______ since they are able to bind and activate a receptor.
Affinity, intrinsic activity
Does an agonist always increase a physiological response?
No, it may increase or decrease it, but will activate a receptor all the same
Describe the difference in dopamine effects based on dosing.
Low dose - causes renal artery vasodilation
Moderate dose - binds to B1 adrenergic receptor - increases cardiac output
high dose - binds to alpha adrenergic receptor - renal artery vasoconstriction
Antagonists can be thought of having _____ but no ______ ________.
affinity
intrinsic activity
How do antagonists generate their effect?
By preventing the binding of endogenous molecules and other agonist drugs
Explain how an antagonist can have no effect if no agonist is present.
Because in that case, it is not blocking anything, and thus cannot derive any pharmacological effect
What are some examples of antagonist drugs?
Beta blockers
Anti-histamines
Gastric acid reducers
Opioid receptor blockers
Describe the action of beta blockers
Block the binding of epinephrine to beta 1 receptors in the heart, slowing the HR
Describe the action of anti-histamines.
Block the binding of histamine to H1 histamine receptors in the nasal mucosa, preventing allergy symptoms
Describe the action of gastric acid reducers.
Block the binding of histamine H2 histamine receptors in the gut - decrease gastric acid secretion
Describe opioid receptor blockers.
Block the binding of opioids to opiate receptors, useful for treating opiate overdose
What are the different types of antagonists?
Competitive
Irreversivle
Allosteric
Binding occurs at the same site as the agonist and is reversible.
Competitive antagonist
Binding occurs at the same site as the agonist but is irreversible
irreversible antagonist
Binding occurs at different site than the agonist
Allosteric antagonist
How can the effect of the competitive antagonist be overcome?
By increasing the concentration of the agonist
How do irreversible antagonist effect the dose response curve?
Effectively remove certain receptors and thus cause a downward shift (lower maximal response) as a result
How long does the effect of irreversible antagonists last for?
Until the receptor is replaced
Because irreversible antagonists are irreversible in nature, they are very ______ used in therapeutics.
seldom
Binding of the allosteric antagonist does what to the agonist binding site?
Induces a conformational change
Describe the effect of an allosteric antagonist on the dose response curve.
Since the agonist cannot bind to the site, and cannot overcome inhibition through increased concentration, a downward shift is observed
Agonists that have only minimal or moderate intrinsic activity
partial agonist
What is another word for partial agonist? Why is it named as such?
Partial antagonist - since it essentially blocks the maximal response from occuring
When patients are continually exposed to a drug and the response to the agonist decreases.
Tolerance
What are the three types of tolerance?
Desensitization
Metabolic tolerance
Tachyphylaxis
The receptor is internalized into the cell or destroyed as a result of continuous exposure to a drug.
Desensitization
Induction of drug metabolizing enzymes due to continuous drug exposure.
Metabolic tolerance
Rapid decrease in the response to a drug
Tachyphylaxis
Describe receptor upregulation.
Continuous exposure to an antagonist causing increased cell synthesis of receptors
