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Drug toxicity: Drug–Drug Interaction01:30

Drug toxicity: Drug–Drug Interaction

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Drug–drug interactions can precipitate toxicity through multiple mechanisms. Absorption interactions alter how drugs enter the body, exemplified when ranitidine increases the absorption of basic drugs, while cholestyramine decreases the levels of propranolol. Protein binding interactions occur when drugs share the same binding sites on plasma proteins. Drugs like aspirin and warfarin, when bound in excess, can lead to increased free drug concentrations, enhancing the potential for...
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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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Drug Toxicity: Risk factors01:24

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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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Drug Toxicity: Overview01:00

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Drug toxicity quantifies the harm a compound causes to an organism, varying by dose and potentially impacting whole systems or specific organs like the liver. Toxic reactions may arise from venomous insect or spider bites, with effects ranging from mild symptoms to severe outcomes such as brain damage or death. Common forms of acute poisoning include ethanol intoxication and overdose of pain or fever medications, with substances like GHB and heroin being particularly lethal at doses close to...
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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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Drug Toxicity: Allergic Reactions01:30

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Drug-related allergies are immune-mediated responses triggered by the administration of pharmacological agents. These hypersensitivity reactions are classified based on the immune mechanisms involved. The four primary types—Type I, II, III, and IV—are mediated by different immunological pathways and exhibit distinct clinical manifestations.Type I Hypersensitivity/ IgE-Mediated Reactions: Immunoglobulin E (IgE) immediately mediates Type I hypersensitivity reactions. Upon initial...
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Diagonal Method to Measure Synergy Among Any Number of Drugs
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Multidrug toxicity involving sumatriptan.

Jessica L Knittel1, Shawn P Vorce2, Barry Levine2

  • 1Division of Forensic Toxicology, Armed Forces Medical Examiner System, Dover AFB, Dover, DE 19902, USA jessica.l.knittel.ctr@mail.mil.

Journal of Analytical Toxicology
|October 18, 2014
PubMed
Summary
This summary is machine-generated.

A fatal overdose case highlights the dangers of sumatriptan (a migraine medication) when combined with other prescription drugs. High concentrations of sumatriptan and multiple other substances were found in the deceased, indicating acute mixed drug toxicity.

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Area of Science:

  • Forensic Toxicology
  • Pharmacology
  • Clinical Medicine

Background:

  • Sumatriptan, a 5-HT(1B/1D) receptor agonist, is a common treatment for migraines.
  • Multidrug fatalities require thorough toxicological investigation to determine the contributing substances and their concentrations.

Observation:

  • A 21-year-old female was found deceased with numerous prescription medications at the scene.
  • Postmortem toxicological analysis revealed significantly elevated sumatriptan levels (1.03 mg/L) compared to therapeutic guidelines (≤0.095 mg/L).
  • Other drugs detected in blood included carisoprodol, meprobamate, fluoxetine, doxylamine, orphenadrine, dextromethorphan, and hydroxyzine.

Findings:

  • Tissue distribution studies showed varying concentrations of sumatriptan across different organs and bodily fluids.
  • The highest sumatriptan concentration was found in stomach contents (78.54 mg/45 mL), suggesting recent ingestion.
  • The combination of sumatriptan with other central nervous system depressants likely contributed to the fatal outcome.

Implications:

  • This case underscores the potential for sumatriptan toxicity, especially in polydrug use scenarios.
  • Accurate toxicological analysis is crucial for determining the cause and manner of death in suspected drug fatalities.
  • Healthcare providers should counsel patients on the risks associated with combining sumatriptan with other medications.