Pharmacodynamics Flashcards
Drug-receptor interactions and Dose-response Relationships
The vast majority of drugs have MW values between
100 and 1,000
Drug-receptor binding initiates a chain of events leading to the drug’s
observed effect or
Response
Drugs can show a differential capacity for initiating a pharmacologic response upon binding to a
Receptor
What are the three models linking drug binding to a pharmacologic response?
- ) Agonism
- ) Partial Agonism
- ) Antagonism
Drugs that mimic actions of endogenous compounds (e.g., neurotransmitters or hormones) are called
Agonists
Some bind to a given receptor and produce a maximal response, while others bind to the same receptor and produce only a partial response
Agonists
An agonist that produces a partial response when the receptor is fully saturated is considered a
Partial Agonist
Interferes with the action of an agonist by binding to receptors
Antagonist
Although antagonists bind to receptors, they do not produce
Pharmacological responses
Determine the quantitative relationship between drug dose and pharmacologic response
Receptors
Determines the maximal effect a drug may produce
Total number of receptors
A measure of how much drug is required to elicit a response, and is reflected in the EC50 value
Potency
Highly potent drugs have
Low EC50 values
High concentrations of a drug with low potency are required to achieve
Emax
The value of Emax determines the drugs
Efficacy
In a clinical setting, drug selection is typically based on
Efficacy and potential side effects
Once a drug is chosen, the amount of drug to be administered is determined by the drugs
Potency
Drugs that work by blocking the actions of endogenous agonists
Antagonists
By definition, antagonists have no
Activity
Typically, one would plot the dose-response curve of an agonist and determine how the curve is affected by differing concentrations of
Antagonists
An antagonist whose effects can be overcome by adding more agonist
Competitive antagonist
Competitive antagonism is typically observed with antagonists that bind receptors
Reversibly
Binds B-adrenoreceptors and competitively inhibits the actions of the endogenous B-agonists norepinephrine and epinephrine
-example of competitive antagonism
Propanolol
The degree of inhibition produced by a competitive antagonist depends on the concentration of the
Antagonist
The clinical response to a competitive antagonist depends on the concentration of endogenous agonist competing for binding to
Receptors
Episodic increases in endogenous agonist levels may reduce the therapeutic response of the administered
Antagonist
Prevents an agonist from producing a maximal effect
Noncompetitive antagonist
No amount of agonist can overcome the addition of a
Noncompetitive antagonist
In such a case, antagonist-bound receptors are essentially removed from the pool of agonist targets
Noncompetitive antagonist
Binds covalently to and irreversibly inactivates the proton pump in the stomach lining, preventing acidification
Omeprazole
Omeprazole is an example of a
Noncompetitive antagonist
What is the therapeutic advantage of a non-competitive irreversible antagonist?
Antagonist will maintain blockade even when concentration of endogenous agonist episodically increases
What is the therapeutic disadvantage to non-competitive irreversible antagonist?
If overdose occurs, antagonist-induced blockade is difficult to overcome
One drug may antagonize the actions of a second drug by binding to and inactivating the second drug
Chemical antagonism
Antagonizes the anticoagulant actions of heparin by binding to heparin in an electrostatically driven manner
Protamine
Protamine is an example of a
Chemical antagonist
The actions of glucocorticoids lead to increased blood sugar, an effect that can be countered through use of insulin is an example of
Physiologic antagonism
Some drugs induce the metabolism of other drugs, thereby antagonizing the actions of the metabolized drugs. This is called
Pharmacokinetic antagonism
Induces the metabolic clearance of the anticoagulant warfarin
Phenobarbital
Phenobarbital is an example of a
Pharmacokinetic antagonist
Drug specificity for a given receptor depends on factors like
Molecular size, shape, and electrical charge
Tissue selectivity can also arise from over-expression of a given receptor. In such a scenario, the tissue is said to have
Spare receptors
Means that an agonist can induce a maximal response in a tissue without binding to all of the available receptors
Presence of spare receptors
Spare receptors increase the likelihood of a drug being bound when present at low concentrations, and thereby increase tissue
Sensitivity
Spare receptors are demonstrated by using
Noncompetitive irreversible antagonists
They are difficult to construct when the pharmacological response is an “eitheror” (i.e., a quantal) event
Dose-response curves
A quantitative dose-response relationship in a single individual may have limited applicability to other individuals, due to inter-individual
Variability
Such limitations may be circumvented by determining the dose of drug required to produce a specified response in a large number of
Individuals
Provide a convenient way for comparing the potencies or effective doses (i.e., ED50 values) of drugs in a clinical setting
Quantal dose-response curves
Analogous to ED50, the dose required to produce a particular toxic response in 50% of the individuals is termed the
Median toxic dose
The margin of safety of a drug is typically given by its
Therapeutic index
