Related Experiment Video
Updated: May 12, 2026
10:01
High-Throughput Optical Controlling and Recording Calcium Signal in iPSC-Derived Cardiomyocytes for Toxicity Testing and Phenotypic Drug Screening
Published on: March 31, 2022
Life-threatening flecainide toxicity. A pharmacodynamic approach
Annals of Internal Medicine
|June 1, 1987
Summary
Flecainide acetate overdose can cause serious heart rhythm problems, even in healthy individuals. Prompt treatment with specific agents and sodium load can restore normal heart rhythm by lowering drug levels.
Area of Science:
- Cardiology
- Clinical Pharmacology
Background:
- Flecainide acetate is an antiarrhythmic drug with potentially serious cardiac side effects.
- Overdose of flecainide acetate can lead to severe ventricular tachyarrhythmias and bradycardia.
Observation:
- A young, healthy individual experienced polymorphous ventricular tachycardia after a significant flecainide acetate overdose (3800 mg).
- Initial flecainide serum levels were five times the upper therapeutic limit.
Findings:
- The surface electrocardiogram showed marked prolongation of PR and QRS intervals, indicating drug-induced conduction system depression.
- Sinus rhythm was successfully restored without pacing or cardioversion after administration of a beta-sympathomimetic agent, physostigmine, and a sodium load.
- Decreased electrocardiographic interval prolongation correlated with falling flecainide serum levels.
Implications:
- This case highlights the correlation between flecainide plasma levels and toxic electrocardiographic effects.
- Effective therapeutic interventions for flecainide-induced life-threatening arrhythmias include sodium loading and specific antidotes.
- Understanding flecainide toxicity is crucial for managing overdose cases and preventing adverse cardiac events.
Related Concept Videos
01:14Pharmacokinetic–Pharmacodynamic Relationship: Duration of Dose-Effect Relationship
For drugs producing a quantal response, onset occurs when plasma concentration reaches a minimum effective level (Cmin). The drug's action duration depends on how long the plasma concentration remains above Cmin.Two primary factors influence this duration: dose size and the rate of drug removal from the action site. Both depend on the drug's redistribution to poorly perfused tissues and elimination processes. A larger dose promotes rapid onset and prolongs the effect's duration.Consider a...
01:24Pharmacokinetic–Pharmacodynamic Relationship: Problems
The empirical approach to drug therapy optimization relies on correlating pharmacological response with administered dosage. Such an approach can be costly, time-consuming, and often yields poor correlation due to variables like formulation factors and drug elimination characteristics. A more precise approach correlates response with plasma drug concentration or the amount of drug in the body, rather than dosage. This is achieved through pharmacokinetic-pharmacodynamic (PK/PD) modeling, which...
01:15Pharmacodynamic Models: Linear Concentration–Effect Model
The linear concentration–effect model, underpinned by the principle that pharmacological effect (E) is directly proportional to plasma drug concentration (C), emerges as a pivotal simplification of the Emax model for conditions where C is significantly less than EC50. This model portrays a linear trajectory of the concentration–effect relationship when drug levels are markedly below the EC50 threshold.Despite its inherent assumption of continuous effect augmentation with increasing drug...
01:15Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions
PK–PD modeling has significantly influenced FDA regulatory decisions, particularly drug approval, dosage optimization, and labeling. These models integrate pharmacokinetics (PK) and pharmacodynamics (PD) to predict drug behavior and effects, aiding in optimizing dosing regimens and enhancing the probability of clinical trial success.One notable example is Nesiritide (Natrecor®), a recombinant human brain natriuretic peptide for treating acute decompensated congestive heart failure (CHF).
01:24Drug Toxicity: Dose-Dependent Reactions
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...
01:30Drug toxicity: Drug–Drug Interaction
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...