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Drug Toxicity: Dose-Dependent Reactions01:24

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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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Drug toxicity: Idiosyncratic Reactions01:16

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Idiosyncratic drug reactions represent abnormal chemical responses that vary significantly among individuals, ranging from extreme sensitivity to low doses to insensitivity to high doses. These reactions often occur due to the drug's covalent binding with serum proteins, forming a foreign hapten that triggers an immunotoxicological response. The variability in drug reactions has a strong pharmacogenetic foundation, with genetic differences crucial in how individuals metabolize drugs. For...
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Pharmaceutical Poisoning: Potential Scenarios01:26

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Pharmaceutical poisoning can occur through various channels, impacting an estimated 2 million hospitalized patients in the U.S. annually with serious adverse drug responses. These scenarios encompass both therapeutic uses, such as drug toxicity, where even standard dosages can lead to severe central nervous system depression, and non-therapeutic exposures, including accidental ingestion by children, and environmental and occupational exposures.Unintentional poisonings often involve exploratory...
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A drug interaction occurs when the concurrent use of another drug, food, or an external substance alters the pharmacological activity of a drug. This interaction can modify the action of the original drug, affecting its effectiveness and safety.Drug–food interactions are significant as they impact drug absorption, metabolism, and excretion. For example, grapefruit juice is a well-known disruptor of drug metabolism. It inhibits the cytochrome P450 3A4 enzyme, crucial for the metabolism of...
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Drug distribution in the pediatric population exhibits unique challenges and considerations due to the physiological differences between children, particularly neonates and infants, and adults. A crucial aspect of pediatric pharmacology is understanding how these differences impact the pharmacokinetics of various drugs, necessitating age-specific dosing strategies to ensure efficacy and safety.Neonates and infants have a higher total body water content, ~75%–90% of their body weight,...
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Adverse Drug Reactions (ADRs) are potential complications that arise during pharmacotherapy, influenced by multiple risk factors. Age plays a significant role; both neonates and the elderly are at heightened risk due to their respective immature and diminished metabolic and elimination processes. Gender also impacts ADRs, with females experiencing a 1.5 to 1.7-fold greater risk than males, which may be linked to pharmacokinetic, pharmacodynamic, and hormonal differences. Notably, neonates, the...
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Free phenytoin toxicity.

Syed Haider Imam1, Kristen Landry1, Viren Kaul1

  • 1Department of Internal Medicine, SUNY Upstate, Syracuse, NY, USA.

The American Journal of Emergency Medicine
|April 29, 2014
PubMed
Summary
This summary is machine-generated.

Phenytoin toxicity can be missed in elderly patients due to falsely low total serum phenytoin levels. Calculating free phenytoin levels using the Sheiner-Tozer equation is crucial for accurate toxicity assessment.

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Area of Science:

  • Pharmacology
  • Clinical Toxicology

Background:

  • Phenytoin is an anticonvulsant medication with a narrow therapeutic index.
  • Accurate monitoring of phenytoin levels is essential for effective treatment and toxicity prevention.

Observation:

  • An elderly male patient presented with symptoms suggestive of phenytoin toxicity, including drowsiness, gait disturbances, and elevated liver enzymes.
  • Initial total serum phenytoin level was within the normal range (18 ng/dL).

Findings:

  • Low albumin levels in elderly or critically ill patients can lead to falsely low total serum phenytoin measurements.
  • The Sheiner-Tozer equation accurately estimated the free phenytoin level to be 27 ng/dL, indicating toxicity.
  • Discontinuation of phenytoin resulted in symptom resolution and normalization of liver function tests.

Implications:

  • Clinicians should consider calculating free phenytoin levels in elderly or hypoalbuminemic patients presenting with potential toxicity symptoms.
  • The Sheiner-Tozer equation is a valuable tool for managing phenytoin therapy in specific patient populations.
  • Accurate assessment of free phenytoin levels is critical for preventing adverse drug events and optimizing patient outcomes.