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Drug Toxicity: Dose-Dependent Reactions01:24

Drug Toxicity: Dose-Dependent Reactions

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Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...
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Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations01:15

Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations

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Gentamicin, an aminoglycoside antibiotic, is commonly administered via intermittent intravenous infusion to treat severe infections. An intermittent one-hour infusion of gentamicin, administered at eight-hour intervals, allows for precise control of plasma drug concentrations, minimizing toxicity while ensuring therapeutic efficacy. Pharmacokinetic principles govern the dynamics of plasma concentrations and can be mathematically described using specific equations.The plasma drug concentration...
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Pharmacokinetics in Pediatric Patients: Drug Excretion01:26

Pharmacokinetics in Pediatric Patients: Drug Excretion

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In pediatric medicine, understanding the renal function and drug elimination nuances is crucial for administering safe and effective treatments. Newborns, in particular, display markedly slower renal functions than adults, profoundly affecting how drugs are cleared from their bodies. This slower drug clearance requires clinicians to extend the dosing intervals for many medications to prevent drug accumulation and toxicity while ensuring therapeutic efficacy.One key area where these adjustments...
284
Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment01:08

Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment

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Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
282
Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant01:25

Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant

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In patients with renal disease, dosage adjustments are necessary to maintain therapeutic plasma drug concentrations and prevent toxicity or subtherapeutic exposure. Renal impairment alters drug pharmacokinetics, especially in conditions like uremia, where changes such as prolonged elimination half-life and altered apparent volume of distribution can significantly affect drug disposition. These changes require careful modification of the dosing regimen to achieve the desired clinical...
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Renal Failure: Dose Adjustments01:11

Renal Failure: Dose Adjustments

502
In patients with renal impairment, drugs undergo significant changes in their pharmacokinetics, which require dosage adjustments to ensure safe and effective therapy.
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
502

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Updated: Feb 17, 2026

Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291
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Cefepime neurotoxicity despite renal adjusted dosing.

Venu Gopala Reddy Gangireddy1, Lauren C Mitchell, Teresa Coleman

  • 1Department of Internal Medicine, Georgia Health Sciences University, Augusta, Georgia, USA. venureddy82@gmail.com

Scandinavian Journal of Infectious Diseases
|May 25, 2011
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Summary

Cefepime neurotoxicity, a rare side effect, can occur even with adjusted dosages in kidney disease patients. Promptly recognizing and stopping cefepime can reverse neurological complications like seizures.

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Area of Science:

  • Neurology
  • Pharmacology
  • Infectious Disease

Background:

  • Neurotoxicity is a rare but serious adverse effect associated with cefepime use.
  • Previous reports suggest a link between cefepime neurotoxicity and inadequate dosage adjustment in patients with renal impairment.

Observation:

  • A 70-year-old woman with febrile neutropenia developed altered mental status and orofacial myokymia on day 4 of renally-dosed cefepime therapy.
  • Electroencephalogram revealed non-convulsive status epilepticus, unresponsive to anticonvulsants.
  • Cerebrospinal fluid analysis and neuroimaging were unremarkable for acute intracranial processes.

Findings:

  • Cefepime was identified as the probable cause of neurotoxicity due to the temporal relationship between drug administration and symptom onset.
  • Discontinuation of cefepime led to significant improvement in mental status within 24 hours, with full recovery in 3 days.
  • This case highlights that cefepime neurotoxicity can occur despite appropriate renal dose adjustments.

Implications:

  • Clinicians should maintain a high index of suspicion for cefepime-induced neurotoxicity, even in renally adjusted doses.
  • Identifying additional risk factors, such as a history of stroke or seizures, is crucial for patient management.
  • Early recognition and cefepime discontinuation are vital for preventing severe neurological morbidity and mortality, as the condition is reversible.