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Questions and Answers
Which cephalosporin is available in both oral and parenteral forms?
Which cephalosporin is available in both oral and parenteral forms?
What is a notable characteristic of Cefazolin?
What is a notable characteristic of Cefazolin?
Which cephalosporin is excreted mainly through glomerular filtration?
Which cephalosporin is excreted mainly through glomerular filtration?
How can Cefuroxime be administered to improve absorption?
How can Cefuroxime be administered to improve absorption?
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What adjustment is necessary when prescribing cephalosporins in patients with renal impairment?
What adjustment is necessary when prescribing cephalosporins in patients with renal impairment?
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Which of the following oral cephalosporins is known to have the lowest bioavailability?
Which of the following oral cephalosporins is known to have the lowest bioavailability?
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What is the benefit of esterifying certain oral cephalosporins like cefuroxime axetil?
What is the benefit of esterifying certain oral cephalosporins like cefuroxime axetil?
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Which mechanism enhances the absorption of most oral cephalosporins across the intestinal epithelium?
Which mechanism enhances the absorption of most oral cephalosporins across the intestinal epithelium?
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After intestinal absorption, how are prodrugs like cefuroxime axetil activated?
After intestinal absorption, how are prodrugs like cefuroxime axetil activated?
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What effect does food intake have on the bioavailability of certain oral cephalosporins?
What effect does food intake have on the bioavailability of certain oral cephalosporins?
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What factor contributes to the better oral absorption of Cefaclor?
What factor contributes to the better oral absorption of Cefaclor?
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Which cephalosporin is primarily excreted unchanged by the kidneys?
Which cephalosporin is primarily excreted unchanged by the kidneys?
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Which cephalosporin has the longest half-life?
Which cephalosporin has the longest half-life?
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What is the oral bioavailability percentage of Cefixime regardless of food intake?
What is the oral bioavailability percentage of Cefixime regardless of food intake?
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Which cephalosporin requires dosage adjustment in renal dysfunction?
Which cephalosporin requires dosage adjustment in renal dysfunction?
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What is the primary method of excretion for most cephalosporins mentioned?
What is the primary method of excretion for most cephalosporins mentioned?
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What is the characteristic of Cefotaxime regarding its metabolism?
What is the characteristic of Cefotaxime regarding its metabolism?
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Which of the following conditions is Ceftriaxone known to treat effectively?
Which of the following conditions is Ceftriaxone known to treat effectively?
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What is a notable feature of Cefprozil?
What is a notable feature of Cefprozil?
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What is the significance of maintaining free drug concentrations above the minimal inhibitory concentration (MIC)?
What is the significance of maintaining free drug concentrations above the minimal inhibitory concentration (MIC)?
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How does hypoalbuminaemia affect the pharmacokinetics of ceftriaxone?
How does hypoalbuminaemia affect the pharmacokinetics of ceftriaxone?
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What is the potential risk associated with administering ceftriaxone to neonates with hyperbilirubinemia?
What is the potential risk associated with administering ceftriaxone to neonates with hyperbilirubinemia?
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Which of the following describes the structure of carbapenems?
Which of the following describes the structure of carbapenems?
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Which property makes carbapenems highly effective broad-spectrum antimicrobials?
Which property makes carbapenems highly effective broad-spectrum antimicrobials?
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What adverse effect should be monitored in neonates receiving ceftriaxone?
What adverse effect should be monitored in neonates receiving ceftriaxone?
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What is the consequence of ceftriaxone displacing bilirubin from albumin?
What is the consequence of ceftriaxone displacing bilirubin from albumin?
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How many FDA-approved carbapenems exist?
How many FDA-approved carbapenems exist?
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What is the role of cilastatin when administered with imipenem?
What is the role of cilastatin when administered with imipenem?
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In patients with reduced renal function, what is necessary for carbapenems?
In patients with reduced renal function, what is necessary for carbapenems?
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Which carbapenem does not require coadministration with cilastatin?
Which carbapenem does not require coadministration with cilastatin?
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What effect does the coadministration of meropenem have on valproic acid?
What effect does the coadministration of meropenem have on valproic acid?
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How is ertapenem primarily excreted from the body?
How is ertapenem primarily excreted from the body?
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Which characteristic distinguishes ertapenem from meropenem?
Which characteristic distinguishes ertapenem from meropenem?
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What is the major route of excretion for meropenem?
What is the major route of excretion for meropenem?
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Why is therapeutic drug monitoring (TDM) important when administering meropenem with valproic acid?
Why is therapeutic drug monitoring (TDM) important when administering meropenem with valproic acid?
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Study Notes
Oral Cephalosporins
- Many are acid-stable and have high bioavailability (80%-95%)
- Cefixime has a lower bioavailability (40%-50%)
- Some are esterified (eg, cefuroxime axetil) to increase lipid solubility and enhance absorption.
- These prodrugs hydrolyze to active metabolites after intestinal absorption.
- Their bioavailability is relatively low (25%-50%) and is enhanced by food intake.
1st Generation Cephalosporins
- Oral: cephalexin, cephradine, cefadroxil
- Parenteral (IV, IM): cefazolin
- Cefazolin has high plasma protein binding (85%)
- Excretion: Primarily renally excreted unchanged by glomerular filtration
- Dose adjustment needed in case of renal impairment
2nd Generation Cephalosporins
- Parenteral (IV): Cefuroxime sodium, poor oral bioavailability
- Oral: Cefuroxime axetil, prodrug with better oral absorption
- Can be combined with clavulanic acid.
- Cefaclor oral, more lipophilic (due to Cl) better oral absorption.
- Cefprozil oral, long acting.
- Cefoxitin: IV only, very short half-life
- Excreted: Unchanged by the kidney
3rd Generation Cephalosporins
- Parenteral (IV, IM): Ceftriaxone, cefotaxime, ceftazidime
- Oral: Cefixime oral suspension, tablets, and capsules
- Ceftriaxone: High potency, long acting, high protein binding, crystallization with Ca, used to treat gonorrhea and meningitis.
- Cefotaxime: Short half-life (1h), good distribution in the CNS, metabolized to a less active metabolite.
- Ceftazidime: Short half-life (1.5h), excreted unchanged renally, requires dose adjustment with renal dysfunction.
- Cefixime: Oral bioavailability (40%-50%) regardless of food, moderate half-life (3-4h), excreted unchanged renally, requires dose adjustment with renal dysfunction.
Ceftriaxone & Protein Binding
- Undergoes extensive binding to plasma proteins (albumin)
- This results in a longer half-life (i.e. the drug circulates longer)
- Antimicrobial activity and elimination are limited to the unbound drug fraction
- The free/unbound concentration should exceed the minimum inhibitory concentration (MIC) at steady state
- Hypoalbuminaemia (low albumin in blood) affects ceftriaxone PK (reduced protein binding, higher free drug, shorter half-life, higher volume of distribution).
- Dose adjustment needed based on albumin levels
Safety Criteria for Ceftriaxone Administration to Neonates
- Hyperbilirubinemia (high bilirubin blood level) is common in neonates
- Ceftriaxone should be avoided in neonates with hyperbilirubinemia due to potential risk of displacing bilirubin from albumin, increasing the risk of bilirubin encephalopathy
- Ceftriaxone competes with bilirubin for binding to human serum albumin
- Displacing bilirubin can lead to high concentrations of free bilirubin in the blood
- High bilirubin levels in the blood can deposit in brain tissue, causing irreversible damage (bilirubin encephalopathy)
Ceftriaxone & Calcium
- Ceftriaxone should not be administered through the same IV line as calcium containing solutions
- It can precipitate in the blood vessels, blocking them
General Features of Carbapenems
- Four FDA-approved carbapenems: imipenem, meropenem, ertapenem, and doripenem.
- Resemble penicillins but with a five-membered ring that is unsaturated and sulfur-free
- Highly resistant to beta-lactamases
- Administered parenterally (IV infusion) due to poor oral absorption
- Imipenem-cilastatin and ertapenem can also be administered intramuscularly
- Distributed widely in the body and primarily excreted by the kidneys
- Dose adjustment needed in patients with reduced renal function to prevent drug accumulation
Imipenem Formulations
- Imipenem undergoes rapid metabolism (deactivation) by the kidney enzyme dehydropeptidase-1 (DHP-1)
- Coadministration with cilastatin, a DHP-1 inhibitor, increases in vivo half-life, tissue penetration and prevents nephrotoxicity
- Nephrotoxicity is associated with imipenem if administered without cilastatin due to renal metabolism
- Combination of imipenem-cilastatin with relebactam extends the spectrum against carbapenemase-producing bacteria and MDR G-ve bacteria
Meropenem & Ertapenem
- Meropenem and ertapenem are more stable towards DHP-1 system and can be administered without cilastatin
- Ertapenem has a longer half-life than meropenem, allowing once daily dosing
- Meropenem: 70% of the dose is excreted unchanged in urine over 12h
- Ertapenem: 80% is recovered in urine, with nearly half intact and the other half as the ring-opened metabolite
Contraindication of Carbapenems & Valproic Acid
- Coadministration of meropenem with valproic acid significantly lowers serum valproic acid concentrations
- This can lead to subtherapeutic levels and aggravation of seizures
- To solve this, therapeutic drug monitoring (TDM) of serum valproate concentration is recommended.
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Description
This quiz covers the oral and parenteral forms of cephalosporins, focusing on their bioavailability, chemical properties, and clinical implications. You'll explore various generations of cephalosporins and their specific characteristics, including prodrugs and renal considerations. Test your knowledge of this important antibiotic class!