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Questions and Answers
What was the mean increase in theophylline AUC due to oral administration with theophylline?
What was the mean increase in theophylline AUC due to oral administration with theophylline?
Which antibiotic is noted for its ability to decrease theophylline clearance?
Which antibiotic is noted for its ability to decrease theophylline clearance?
What is one of the serious manifestations of theophylline toxicity?
What is one of the serious manifestations of theophylline toxicity?
Which of the following quinolones has no significant interaction with theophylline disposition?
Which of the following quinolones has no significant interaction with theophylline disposition?
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What percentage of theophylline clearance reduction has been observed in several studies?
What percentage of theophylline clearance reduction has been observed in several studies?
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What condition can occur in severe cases of theophylline toxicity?
What condition can occur in severe cases of theophylline toxicity?
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What is required when adding agents that interact with theophylline therapy?
What is required when adding agents that interact with theophylline therapy?
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Which agent has not been shown to have a significant effect on theophylline disposition?
Which agent has not been shown to have a significant effect on theophylline disposition?
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What should be closely monitored during antibiotic therapy when a patient is on warfarin?
What should be closely monitored during antibiotic therapy when a patient is on warfarin?
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Which cephalosporin is noted for its potential to potentiate warfarin?
Which cephalosporin is noted for its potential to potentiate warfarin?
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What clinical condition may gradually appear due to the depletion of vitamin K stores?
What clinical condition may gradually appear due to the depletion of vitamin K stores?
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What is the proposed mechanism through which infections may amplify the effects of warfarin?
What is the proposed mechanism through which infections may amplify the effects of warfarin?
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Which antibiotic was mentioned as potentially resulting in clinically significant hypoprothrombinemia in a patient on warfarin?
Which antibiotic was mentioned as potentially resulting in clinically significant hypoprothrombinemia in a patient on warfarin?
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What is a potential impact of adding antibiotics to a medical regimen involving narrow-therapeutic-window medications?
What is a potential impact of adding antibiotics to a medical regimen involving narrow-therapeutic-window medications?
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Which medication is NOT mentioned as having interactions with antibiotics?
Which medication is NOT mentioned as having interactions with antibiotics?
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In addition to influencing anticoagulation, what other factors may lead to significant hypoprothrombinemia with cefotetan?
In addition to influencing anticoagulation, what other factors may lead to significant hypoprothrombinemia with cefotetan?
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What is the INR level that indicated hypoprothrombinemia in the reported case?
What is the INR level that indicated hypoprothrombinemia in the reported case?
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What is the significance of the cytochrome P450 system in relation to warfarin?
What is the significance of the cytochrome P450 system in relation to warfarin?
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What pharmacological effect does the N-methylthiotetrazole side chain of certain cephalosporins exert?
What pharmacological effect does the N-methylthiotetrazole side chain of certain cephalosporins exert?
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What is the role of awareness in managing drug interactions?
What is the role of awareness in managing drug interactions?
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Which statement about narrow-therapeutic-window medications is correct?
Which statement about narrow-therapeutic-window medications is correct?
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What is one of the purposes of understanding drug-drug interactions?
What is one of the purposes of understanding drug-drug interactions?
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What does the abbreviation INR stand for in relation to drug interactions?
What does the abbreviation INR stand for in relation to drug interactions?
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Which of the following medications is a calcineurin inhibitor mentioned in the content?
Which of the following medications is a calcineurin inhibitor mentioned in the content?
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What effect do azole antifungals have on tacrolimus requirements in pediatric heart/lung transplant patients?
What effect do azole antifungals have on tacrolimus requirements in pediatric heart/lung transplant patients?
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Which cephalosporin is mentioned as having effects on hemostasis in the literature?
Which cephalosporin is mentioned as having effects on hemostasis in the literature?
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How long does it take for the effects of CSA and tacrolimus to plateau after starting treatment with azoles?
How long does it take for the effects of CSA and tacrolimus to plateau after starting treatment with azoles?
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What is the proposed mechanism of interaction between azole antifungals and other medications like CBZ?
What is the proposed mechanism of interaction between azole antifungals and other medications like CBZ?
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What percentage decrease in requirements is recommended upon initiation of reversible interactions with azoles?
What percentage decrease in requirements is recommended upon initiation of reversible interactions with azoles?
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What is the approximate increase in CBZ levels observed after 10 days of fluconazole administration?
What is the approximate increase in CBZ levels observed after 10 days of fluconazole administration?
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What should be monitored when azoles are started to manage drug interactions effectively?
What should be monitored when azoles are started to manage drug interactions effectively?
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What effect does erythromycin have when used in combination with azole antifungals?
What effect does erythromycin have when used in combination with azole antifungals?
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What effect does ciprofloxacin have on warfarin metabolism?
What effect does ciprofloxacin have on warfarin metabolism?
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Which mechanism is primarily responsible for the interaction between erythromycin and theophylline?
Which mechanism is primarily responsible for the interaction between erythromycin and theophylline?
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What is the potential consequence of the interaction between metronidazole and phenytoin?
What is the potential consequence of the interaction between metronidazole and phenytoin?
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Which of the following antibiotics is known to decrease metabolism of cyclosporine?
Which of the following antibiotics is known to decrease metabolism of cyclosporine?
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How should warfarin therapy be managed when starting antibiotic treatment with clarithromycin?
How should warfarin therapy be managed when starting antibiotic treatment with clarithromycin?
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What common side effects could occur due to phenytoin toxicity influenced by sulfamethoxazole/trimethoprim?
What common side effects could occur due to phenytoin toxicity influenced by sulfamethoxazole/trimethoprim?
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What should be monitored closely during and after treatment with azole antifungals in patients on tacrolimus?
What should be monitored closely during and after treatment with azole antifungals in patients on tacrolimus?
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Which of the following antibiotics has no significant interaction with warfarin?
Which of the following antibiotics has no significant interaction with warfarin?
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If a patient on phenytoin starts treatment with azole antifungals, what might be necessary?
If a patient on phenytoin starts treatment with azole antifungals, what might be necessary?
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What type of interactions do macrolide antibiotics have with warfarin?
What type of interactions do macrolide antibiotics have with warfarin?
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Which patient management action is recommended when prescribing ciprofloxacin alongside warfarin?
Which patient management action is recommended when prescribing ciprofloxacin alongside warfarin?
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What is the potential risk when both clarithromycin and theophylline are used together?
What is the potential risk when both clarithromycin and theophylline are used together?
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What effect do azole antifungals have on the metabolism of tacrolimus?
What effect do azole antifungals have on the metabolism of tacrolimus?
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Which of the following is a consequence of the interaction between sulfamethoxazole/trimethoprim and warfarin?
Which of the following is a consequence of the interaction between sulfamethoxazole/trimethoprim and warfarin?
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Study Notes
### Introduction
- Clinically significant drug-drug interactions may occur between antibiotics and medications with narrow therapeutic windows.
- This includes medications like warfarin, phenytoin, theophylline, calcineurin inhibitors, and carbamazepine.
Warfarin
- Several antibiotics interfere with warfarin metabolism through the cytochrome P450 system.
- Warfarin is metabolized by CYP 1A2, 2C9, and 3A4.
- Warfarin potentiation can also occur due to the inhibition of vitamin K epoxide reductase by certain cephalosporins containing the N-methylthiotetrazole side chain.
- Cefotetan is the only remaining cephalosporin with this side chain in general use.
- Infections themselves can potentiate warfarin by inhibiting CYP P450 systems through interferon release.
Phenytoin
- Phenytoin metabolism can be inhibited by metronidazole and sulfamethoxazole/trimethoprim through their effects on CYP 2C8/9.
- Azole antifungals can also inhibit phenytoin metabolism through their interaction with CYP 2C8/9 and 2C19.
Theophylline
- Erythromycin and clarithromycin decrease theophylline clearance by inhibiting CYP 1A2 leading to theophylline toxicity.
- Ciprofloxacin can also interact with theophylline but the mechanism is unclear.
Calcineurin Inhibitors
- Azole antifungals inhibit cyclosporine and tacrolimus metabolism through their interaction with CYP 3A4.
- Clarithromycin and erythromycin can also inhibit cyclosporine and tacrolimus metabolism through their effect on CYP 3A4.
- Quinupristin/dalfopristin can also inhibit cyclosporine and tacrolimus metabolism.
Important Considerations
- Drug interaction onset with warfarin may require several days to weeks.
- Phenytoin interactions may be delayed by 10 to 14 days or longer.
- Effects of azoles on calcineurin inhibitors may take 5-7 days to plateau.
- Careful monitoring of therapeutic drug levels and dosage adjustments are crucial for all interactions.
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Description
Test your knowledge about clinically significant drug-drug interactions involving antibiotics and medications with narrow therapeutic windows. This quiz covers key points about how certain antibiotics affect the metabolism of warfarin and phenytoin, along with implications for patient care.
