Prodigy - Pharmacodynamics Flashcards
Where in the cell are most drug receptors located?
Most are proteins bound in the cell membrane. A few, however, are located in the cytoplasm or nucleoplasm.
Do all (or almost all) of the receptors for a drug have to be bound to a drug for the drug to exert its maximum effect?
No, there are typically far more receptors than needed for a drug to exert its maximum effect. It is quite possible for a drug to exhibit its maximum effect at very low drug concentrations with numerous receptors still available.
*What is the difference between an agonist, an antagonist, a partial agonist, and an inverse agonist?
A drug that has an affinity for a receptor but lacks efficacy (meaning that it is unable to produce the conformational change in the receptor necessary to elicit the response in the tissues for which the receptor is designed) is an antagonist.
An agonist has both affinity and efficacy.
A partial agonist can bind with the receptor and has some efficacy, but it cannot elicit the maximal tissue response.
An inverse agonist can bind with the receptor, but results in the opposite reaction of an agonist.
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*Does the ionized or non-ionized form of a drug confer its clinical effect?
In solution, the non-ionized form of a drug is considered to confer pharmacologic activity, because it is in the non-ionized form that the drug is able to pass through lipid soluble biologic membranes to reach its point of action.
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How does the overabundance of receptors for a drug affect the dosing of an agonist for that receptor compared to an antagonist for that receptor?
Because a drug can exert its maximum effect and still leave a large number of receptors available, an agonist can exert its effects at low concentrations. An antagonist, however, must bind to a much larger number of receptors and requires higher concentrations to do so.
For example, acetylcholine (agonist) only needs to bind to about 25% of the available nicotinic cholinergic receptors in the neuromuscular junction to produce a muscle contraction. A nondepolarizing muscle relaxant (antagonist), however, must block 75% of the receptors to exert a significant reduction in muscle fiber contractility.
*What is the occupancy theory?
The Occupancy Theory states that the magnitude of a drug’s effect is proportional to the number of receptors it occupies.
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*How will the chronic administration of an antagonist affect the number and sensitivity of the receptors it antagonizes?
When chronically exposed to an antagonist, the receptors upregulate, which means that both the number of receptors and their sensitivity both increase.
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Is the binding of acetylcholine to a cholinergic receptor an example of a G-protein mediated mechanism or an ionophore?
It is an ionophore because an ion channel is affected by the binding of acetylcholine to the cholinergic receptor. When acetylcholine binds to the receptor, a sodium channel is opened which allows the influx of Na+.
What is meant by steady-state with regards to drug concentration?
Steady-state is the point at which the plasma concentration of a drug is in equilibrium with all other tissues is the body.
*What is the function of the GABA-a receptor and how is it similar/dissimilar to the acetylcholine receptor?
The GABA-a receptor allows the inward flow of chloride through the central pore of the protein channel. Chloride (and therefore GABA-a) transmits an inhibitory signal.
The acetylcholine receptor functions in a manner similar to the GABA receptor, but utilizes sodium to accomplish the transduction of an excitatory signal.
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What is a partial agonist?
A partial agonist is not able to produce the maximum effect of agonism of a particular receptor.
*In the context of receptors, what does the term ‘affinity’ mean?
Affinity is the ability of a drug to bind with a receptor to form a stable complex.
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What is the difference between potency and efficacy?
Efficacy refers to the maximum effect a drug can produce when binding to a receptor.
Potency refers to the relative dose of a drug that is required to produce the effect and is closely associated with the affinity of the drug for the receptor.
*What does ‘half-life’ mean?
the time it takes for one-half of the drug to be eliminated from the body.
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What is volume of distribution?
a number that describes the amount of drug in the body compared to how much is actually in the bloodstream.
It is calculated as Vd = Amount of drug in body/Plasma concentation of the drug.
It actually describes an apparent volume. If a large amount of a drug has been administered and only a small amount of the drug appears in the plasma, the drug is said to have a large volume of distribution.
- What refers to the amount of the drug that is able to reach its target receptor after it is introduced into the circulatory system.
Bioavailability
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*How is receptor affinity for a drug related to the potency of a drug?
The lower the affinity of a receptor for a certain drug, the greater the concentration of the drug must be present to form a significant number of drug-receptor complexes.
In other words, the lower the affinity, the more of the drug you have to administer to achieve a certain effect. Potency relates the amount of a drug that must be administered to achieve its clinical effect.
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*In what circumstance can the volume of distribution for a drug be greater than the total volume of the body?
Drugs that leave the plasma and accumulate in fat or other tissues can actually exhibit a calculated volume of distribution that is greater than the volume of the body.
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*What percentage of the body weight does plasma constitute?
- 5%
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*How does protein binding affect the ability of a drug to exert its pharmacologic effects?
The more protein bound a drug is, the less of the drug is available to exert its effects and vice versa.
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*What is the most prevalent protein in the bloodstream?
Albumin
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*How do albumin, alpha-1 acid glycoprotein, and beta-globulin differ in their ability to bind with drugs?
Although albumin is able to bind to drugs that are acidic, neutral, or basic, it binds more readily to acidic compounds. Alpha-1 acid glycoprotein and beta-globulin bind more readily to basic compounds.
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*How does hypoalbuminemia affect the action of a highly protein-bound drug like warfarin?
About 98% of warfarin is protein-bound. As the plasma protein level decreases, there is less of the protein available for the drug to bind with, and more of the free form of the drug is available to exert its pharmacologic action. In summary, hypoalbuminemia intensifies the action of highly protein-bound drugs.
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- What refers to the degree a drug reaches the blood stream from the site of administration. For example, only about 70% of a dose of digoxin reaches the bloodstream when it is administered orally.
Extent of absorption
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- What factors affect the extent of absorption of a drug?
Factors that affect the ability of the drug to cross from the GI tract to the bloodstream affect the extent of absorption (e.g. the drug is too hydrophilic or too lipophilic, transport mechanisms may tend to pump the drug back into the gastrointestinal system, etc).
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*What refers to the ability for a chemical to have more than one possible structural arrangement. It is based on the presence of a structural component called a chiral carbon. The chiral carbon acts as a point in which a portion of the chemical can be rotated into another position. The two chemicals are isomers of each other and often have substantial differences in their pharmacologic effect.
Stereochemistry
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*How does the term metabolism differ from the term biotransformation and what do they mean?
Metabolism and biotransformation are synonyms that refer to enzyme-catalyzed changes in the structure of a drug. The change in the chemical structure also changes the pharmacologic effect of the drug.
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