Fluconazole (FZL) is a widely used antifungal medication that may cause serious adverse effects, particularly acute liver injury, convulsions, and QT prolongation, which can lead to ventricular arrhythmias like Torsades de Pointes (TdP). FZL is contraindicated in pregnancy due to risks of abortion and birth defects. To mitigate the risk of TdP associated with FZL, it is advisable to avoid combining it with other QT-prolonging medications. The calcium-channel blocker verapamil has been identified as a potential therapeutic agent for managing TdP, while also influencing the pharmacokinetics and pharmacodynamics of FZL. Not only does verapamil demonstrate antifungal activity against certain species, but it also enhances the antifungal efficacy of FZL and significantly reduces the occurrence of TdP. Clinical case studies suggest that verapamil can effectively suppress TdP developments in patients at risk, thereby indicating that the combination of verapamil and FZL may offer dual benefits of increased antifungal efficacy and reduced adverse cardiac effects.

Acetaminophen is a non-narcotic analgesic used as an analgesic and antipyretic. Acetaminophen is used for mild to moderate pain; its efficacy is low as analgesic as compared to non-steroidal anti-inflammatory drugs (NSAIDs) as it has no any anti-inflammatory effect. Despite of its well-known use and safely, however; the precise mechanism of acetaminophen still enigmatic. Findings from preclinical studies suggest that the main mechanism of acetaminophen is related to the inhibition of cyclooxygenase 3 (COX-3) which is variant of COX-1 expressed in the brain. However, the profound analgesic antinociceptive effects of acetaminophen cannot depend merely on this pathway. Further findings from preclinical and clinical studies confirmed that acetaminophen and its metabolites can modulate different signaling pain pathways other than COX pathway. Thus, this review revises the potential mechanistic pathways of acetaminophen in relation to its clinical applications.