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Questions and Answers
In the context of combination chemotherapy, how does it mitigate the development of drug resistance?
In the context of combination chemotherapy, how does it mitigate the development of drug resistance?
- By using drugs with similar mechanisms of action to overwhelm the resistant bacteria.
- By using drugs that directly inhibit resistance mechanisms in bacteria.
- By employing multiple drugs, each targeting different mechanisms, thereby reducing the likelihood of resistance development. (correct)
- By increasing the dosage of a single drug to ensure complete eradication of the pathogen.
Which of the following best describes the concept of positive synergism in combination therapy?
Which of the following best describes the concept of positive synergism in combination therapy?
- The combined effect of two drugs is equal to the sum of their individual effects.
- The combined effect of two drugs is greater than the sum of their individual effects, allowing for lower doses and reduced toxicity. (correct)
- The combined effect of two drugs is less than the sum of their individual effects, requiring higher doses to achieve the desired outcome.
- The interaction of two drugs cancels out their individual effects, resulting in no therapeutic benefit.
When interpreting an isobologram, what does a point below the line of additivity indicate?
When interpreting an isobologram, what does a point below the line of additivity indicate?
- Antagonism between the two drugs.
- An additive effect where the combined effect is the sum of the individual effects.
- Synergism, where the combined effect is greater than the sum of the individual effects. (correct)
- Negative synergism, requiring higher doses of both drugs.
Which of the following exemplifies a scenario where combination therapy is used to achieve a desired effect while minimizing toxicity?
Which of the following exemplifies a scenario where combination therapy is used to achieve a desired effect while minimizing toxicity?
How do trimethoprim and sulfamethoxazole (TMP-SMX) demonstrate synergism in antibacterial therapy?
How do trimethoprim and sulfamethoxazole (TMP-SMX) demonstrate synergism in antibacterial therapy?
In the context of combination therapy, what characterizes 'negative synergism'?
In the context of combination therapy, what characterizes 'negative synergism'?
Why might tetracyclines interfere with the efficacy of penicillins when used in combination?
Why might tetracyclines interfere with the efficacy of penicillins when used in combination?
What is the primary mechanism behind pharmacodynamic antagonism?
What is the primary mechanism behind pharmacodynamic antagonism?
Which of the following defines pharmacokinetic antagonism?
Which of the following defines pharmacokinetic antagonism?
How does naloxone reverse the effects of opioids?
How does naloxone reverse the effects of opioids?
Flashcards
Chemotherapy Definition
Chemotherapy Definition
Eradicating or slowing the growth of rapidly growing cells.
Major benefits of combination chemotherapy
Major benefits of combination chemotherapy
Reduced drug toxicity and reduced development of drug resistance.
Synergism Definition
Synergism Definition
When two drugs work together to produce a combined effect greater than the sum of their individual effects.
Positive Synergism
Positive Synergism
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Negative Synergism
Negative Synergism
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Drug Antagonism
Drug Antagonism
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Isobologram
Isobologram
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Beta-Lactams
Beta-Lactams
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Trimethoprim + Sulfamethoxazole
Trimethoprim + Sulfamethoxazole
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Study Notes
- Combination therapy involves using multiple drugs to treat conditions like tuberculosis, cancer, resistant bacteria, and HIV.
- A key benefit is the reduction in the development of drug resistance via multiple agents acting together.
- Combination therapy can also reduce drug toxicity by using lower doses of individual drugs.
- Drugs with different mechanisms of action can produce additive or synergistic effects.
Additive vs. Synergistic Effects
- Additive effect refers to a combined drug response equals the sum of individual drug effects (1+1=2).
- Synergistic effect refers to a combined drug response exceeds the sum of individual drug effects (1+1=3).
- Positive synergism (super-additivity) occurs when the combined effect is greater than expected; lower drug concentrations achieve the desired effect.
- Negative synergism occurs when the efficacy of the drug combination is less than would be expected; higher doses are needed to achieve the expected response.
- Negative synergism and antagonism may be used interchangeably.
- Antagonism involves drugs with opposite effects, which interferes with treatment goals.
Understanding Isobolograms
- An isobologram is a graph that visualizes drug interactions, determining if combinations are additive, synergistic, or antagonistic.
- The line of additivity on an isobologram represents a 50% effect achieved with a combination of two drugs.
- The concentrations of Drug A and Drug B needed for a 50% response are represented by points on the axes.
- If the combination effect falls below the line of additivity, it indicates positive synergism (super-additivity).
Practical Examples of Synergistic Drug Combinations
- Combining antibacterial agents with different sites can lead to synergistic effects.
- Drugs inhibiting key production or metabolic products at different steps, such as trimethoprim-sulfamethoxazole (affecting folic acid synthesis), can result in synergy.
- The combination of a cell wall synthesis inhibitor (e.g., penicillins) and a drug that acts intracellularly (e.g., aminoglycosides) is a classic example.
Aminoglycosides and Beta-Lactams
- Aminoglycosides can cause odo- and nephrotoxicity, so synergism allows lower doses to achieve desired effects.
- Positive synergism or super additive effects allow lower concentrations of both drugs A and B to get the desired effect.
- In some patients with HIV, an optimal combination includes two nucleoside reverse transcriptase inhibitors (NRTIs) and one integrase strand transfer inhibitor (INSTI), but this may change.
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