Unmasking hidden risks: The surprising link between PDE5 inhibitors and seizure susceptibility.

BACKGROUND: Phosphodiesterase 5 inhibitors (PDE5i) are the first line treatment for erectile dysfunction; however, several articles and case reports have shown central nervous system effects, that can cause seizures in susceptible patients. This study aims to describe the changes caused by the use of Sildenafil and Tadalafil through the analysis of abnormalities expressed in the electrocorticogram (ECoG) of rats and evaluate the seizure threshold response and treatment of seizures with anticonvulsants. MATERIALS AND METHODS: The study used 108 rats (Wistar). Before surgery for electrode placement in dura mater, the animals were randomly separated into 3 experiments for electrocorticogram analysis. Experiment 1: ECoG response to using PD5i (Sildenafil 20mg/kg and Tadalafil 2.6mg/kg p.o.). Experiment 2: ECoG response to the use of PD5i in association with Pentylenetetrazole (PTZ-30 mg/kg i.p.), a convulsive model. Experiment 3: ECoG response to anticonvulsant treatment (Phenytoin, Phenobarbital and Diazepam) of seizures induced by association IPDE5 + PTZ. All recordings were made thirty minutes after administration of the medication and analyzed for ten minutes, only once. We considered statistical significance level of *p<0.05, **p<0.01 and ***p < 0.001. RESULTS: After administration of Sildenafil and Tadalafil, there were increases in the power of recordings in the frequency bands in oscillations in alpha (p = 0.0920) and beta (p = 0.602) when compared to the control group (p<0.001). After the use of Sildenafil and Tadalafil associated with PTZ, greater potency was observed in the recordings during seizures (p<0.001), however, the Sildenafil group showed greater potency when compared to Tadalafil (p<0.05). Phenobarbital and Diazepam showed a better response in controlling discharges triggered by the association between proconvulsant drugs. CONCLUSIONS: PDE5i altered the ECoG recordings in the rats' motor cortexes, demonstrating cerebral asynchrony and potentiating the action of PTZ. These findings demonstrate that PDE5i can lower the seizure threshold.

Electrocorticographic description of the effects of anticonvulsant drugs used to treat lidocaine-induced seizures.

INTRODUCTION: Local anesthetics are widely used in clinical practice. While toxicity is rare, these drugs can cause potentially lethal seizures. OBJECTIVE: In the present study, we investigated the electrocorticographic (ECoG) and electromyographic patterns of seizures induced by acute lidocaine (LA) toxicity and treated with anticonvulsant drugs. The study used adult male Wistar rats to describe of the seizure-related behavior of LA and investigated the treatment with anticonvulsant drugs. RESULTS: The use of LA resulted in clear changes in the ECoG pattern, which presented characteristics of Status epilepticus, with increased intensity in all brainwaves. The decomposition of the cerebral waves showed an increase in the beta and gamma waves that may be related to tonic-clonic seizure. Although the treatment with anticonvulsants drugs reduces the power of brainwaves at frequencies between 1 and 40 Hz compared to the LA group, but only diazepam (DZP) was able to decrease the intensity of oscillations. The muscle contraction power also indicated a difference in the effectiveness of the three treatments. CONCLUSION: The sum of the evidence indicates that LA causes status epilepticus and that DZP is the most effective treatment for the control of these seizures, by restoring the systemic values to levels close to those recorded in the control group.