Cephalosporins Overview

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Questions and Answers

Which cephalosporin is available in both oral and parenteral forms?

Cephalexin

Cefadroxil

Cephradine (correct)

Cefazolin

What is a notable characteristic of Cefazolin?

High plasma protein binding (correct)

Poor bioavailability

Oral administration only

Low renal excretion

Which cephalosporin is excreted mainly through glomerular filtration?

Cefuroxime

Cephalexin

Cefazolin (correct)

Cefadroxil

How can Cefuroxime be administered to improve absorption?

As Cefuroxime axetil prodrug Signup and view all the answers

What adjustment is necessary when prescribing cephalosporins in patients with renal impairment?

Reduce the dosage Signup and view all the answers

Which of the following oral cephalosporins is known to have the lowest bioavailability?

Cefixime Signup and view all the answers

What is the benefit of esterifying certain oral cephalosporins like cefuroxime axetil?

To improve lipid solubility and enhance absorption Signup and view all the answers

Which mechanism enhances the absorption of most oral cephalosporins across the intestinal epithelium?

Passive diffusion due to lipophilicity Signup and view all the answers

After intestinal absorption, how are prodrugs like cefuroxime axetil activated?

By hydrolysis by esterases in the intestinal epithelium Signup and view all the answers

What effect does food intake have on the bioavailability of certain oral cephalosporins?

It enhances the bioavailability of some oral cephalosporins Signup and view all the answers

What factor contributes to the better oral absorption of Cefaclor?

Increased lipophilicity due to chlorine Signup and view all the answers

Which cephalosporin is primarily excreted unchanged by the kidneys?

Ceftazidime Signup and view all the answers

Which cephalosporin has the longest half-life?

Ceftriaxone Signup and view all the answers

What is the oral bioavailability percentage of Cefixime regardless of food intake?

40 - 50 % Signup and view all the answers

Which cephalosporin requires dosage adjustment in renal dysfunction?

Ceftazidime Signup and view all the answers

What is the primary method of excretion for most cephalosporins mentioned?

Renal excretion Signup and view all the answers

What is the characteristic of Cefotaxime regarding its metabolism?

It is converted into a less active metabolite Signup and view all the answers

Which of the following conditions is Ceftriaxone known to treat effectively?

Gonorrhea and meningitis Signup and view all the answers

What is a notable feature of Cefprozil?

It is long-acting Signup and view all the answers

What is the significance of maintaining free drug concentrations above the minimal inhibitory concentration (MIC)?

It allows for sustained antimicrobial activity over time. Signup and view all the answers

How does hypoalbuminaemia affect the pharmacokinetics of ceftriaxone?

It leads to a shorter half-life and higher volume of distribution. Signup and view all the answers

What is the potential risk associated with administering ceftriaxone to neonates with hyperbilirubinemia?

Bilirubin encephalopathy due to competitive binding. Signup and view all the answers

Which of the following describes the structure of carbapenems?

A beta-lactam ring fused to an unsaturated five-membered ring without sulfur. Signup and view all the answers

Which property makes carbapenems highly effective broad-spectrum antimicrobials?

Resistance to various beta-lactamases. Signup and view all the answers

What adverse effect should be monitored in neonates receiving ceftriaxone?

High bilirubin levels leading to jaundice. Signup and view all the answers

What is the consequence of ceftriaxone displacing bilirubin from albumin?

Potential for brain damage due to elevated free bilirubin. Signup and view all the answers

How many FDA-approved carbapenems exist?

Four Signup and view all the answers

What is the role of cilastatin when administered with imipenem?

It prevents nephrotoxicity and increases tissue penetration. Signup and view all the answers

In patients with reduced renal function, what is necessary for carbapenems?

Doses must be adjusted to prevent drug accumulation. Signup and view all the answers

Which carbapenem does not require coadministration with cilastatin?

Both B and C Signup and view all the answers

What effect does the coadministration of meropenem have on valproic acid?

It lowers valproic acid levels to subtherapeutic levels. Signup and view all the answers

How is ertapenem primarily excreted from the body?

With approximately 50% as the ring-opened metabolite. Signup and view all the answers

Which characteristic distinguishes ertapenem from meropenem?

Ertapenem allows once daily dosing due to its longer half-life. Signup and view all the answers

What is the major route of excretion for meropenem?

Unchanged in urine. Signup and view all the answers

Why is therapeutic drug monitoring (TDM) important when administering meropenem with valproic acid?

To monitor for subtherapeutic valproate levels. Signup and view all the answers

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!