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PloS One 2023Phosphodiesterase 5 inhibitors (PDE5i) are the first line treatment for erectile dysfunction; however, several articles and case reports have shown central nervous...
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.
Topics: Animals; Male; Rats; Anticonvulsants; Diazepam; Pentylenetetrazole; Phenobarbital; Phosphodiesterase 5 Inhibitors; Rats, Wistar; Seizures; Sildenafil Citrate; Tadalafil
PubMed: 38033148
DOI: 10.1371/journal.pone.0294754 -
Cureus Nov 2023Epilepsy is not a common cause of morbidity in pregnancy. It has widespread effects on maternal and fetal health necessitating adequate control of seizures. Many...
Epilepsy is not a common cause of morbidity in pregnancy. It has widespread effects on maternal and fetal health necessitating adequate control of seizures. Many anti-seizure medications (ASM) have teratogenic effects on the fetus. We report a case of severe fetal hydantoin syndrome resulting in life-threatening major congenital anomalies. The mother was on phenytoin for the last three years and the pregnancy was not registered. We discuss various features of fetal hydantoin syndrome and the ideal management of epilepsy in pregnancy in brief.
PubMed: 38161950
DOI: 10.7759/cureus.49663 -
Journal of Ayub Medical College,... 2023Status Epilepticus (SE) is a life-threatening neurological emergency requiring appropriate therapy to terminate seizure activity. SE is managed with supportive measures... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Status Epilepticus (SE) is a life-threatening neurological emergency requiring appropriate therapy to terminate seizure activity. SE is managed with supportive measures and ultra-short-acting benzodiazepines. However, limited data is available in the paediatric population regarding the next best option when this fails. This study aimed at finding new data to recommend levetiracetam or phenytoin as the second-line option.
METHODS
One hundred and thirty-seven patients with status epilepticus were randomized into two groups; group-I was given IV Levetiracetam (LEV) at 20 mg/kg/dose over 5 minutes followed by a maintenance dose of 20mg/kg/dose BID, whereas Group II received phenytoin at 20mg/kg IV loading dose followed by a maintenance dose of 5-8 mg/kg/day divided BID. The primary outcome was seizure cessation, defined as the termination of the apparent convulsion 30 min after the administration of phenytoin or levetiracetam. Secondary outcomes were the use of different anti-convulsants for continued management, admittance to critical treatment, and severe adverse events (including mortality, Stevens-Johnson syndrome, rash, airway problems, cardiovascular instability, extravasation, and severe agitation). Data was recorded via a clinical proforma and was analyzed by SPSS software version 25. All numerical data were expressed in mean±SD forms, and frequency was determined for qualitative baseline data. Secondary outcomes were tested through the χ2 test, A p-value of ≤0.05 was considered statistical significance.
RESULTS
Levetiracetam terminated seizures in 94% of children compared to 77% in those treated with phenytoin. The mean time to seizure termination was 19.94±3.76 minutes for the LEV Group as compared to 23.791±9.1 min for the PHT group. (p=0.046). Regarding safety, a profile study shows LEV has fewer and less severe side effects compared to Phenytoin.
CONCLUSIONS
Levetiracetam is a safe, well-tolerated, and effective treatment as a second-line antiepileptic drug in the management of status epilepticus.
Topics: Child; Humans; Anticonvulsants; Phenytoin; Levetiracetam; Benzodiazepines; Piracetam; Status Epilepticus; Seizures
PubMed: 38404082
DOI: 10.55519/JAMC-03-11897 -
Journal of Emergencies, Trauma, and... 2024Phenytoin is one of the commonly used anti.seizure medications in nontraumatic seizures. However, its utility and safety in young patients with traumatic brain injury...
INTRODUCTION
Phenytoin is one of the commonly used anti.seizure medications in nontraumatic seizures. However, its utility and safety in young patients with traumatic brain injury (TBI) for the prevention of early-onset seizures (EOS) are debatable. We sought to explore the use of phenytoin as a seizure prophylaxis following TBI. We hypothesized that administering phenytoin is not effective in preventing EOS after TBI.
METHODS
This was a retrospective observational study conducted on adult TBI patients. EOS was defined as a witnessed seizure within a week postinjury. Data were compared as phenytoin versus no-phenytoin use, EOS versus no-EOS, and among TBI severity groups.
RESULTS
During 1 year, 639 TBI patients were included with a mean age of 32 years; of them, 183 received phenytoin as seizure prophylaxis, and 453 received no prophylaxis medication. EOS was documented in 13 (2.0%) patients who received phenytoin, and none had EOS among the nonphenytoin group. The phenytoin group was more likely to have a higher Marshall Score ( = 0.001), lower Glasgow Coma Scale (GCS) ( = 0.001), EOS ( = 0.001), and higher mortality ( = 0.001). Phenytoin was administrated for 15.2%, 43.2%, and 64.5% of mild, moderate, and severe TBI patients, respectively. EOS and no-EOS groups were comparable for age, gender, mechanism of injury, GCS, Marshall Score, serum phenytoin levels, liver function levels, hospital stay, and mortality. Multivariable logistic regression analysis showed that low serum albumin (odds ratio [OR] 0.81; 95% confidence interval [CI] 0.676.0.962) and toxic phenytoin level (OR 43; 95% CI 2.420.780.7) were independent predictors of EOS.
CONCLUSIONS
In this study, the prophylactic use of phenytoin in TBI was ineffective in preventing EOS. Large-scale matched studies and well-defined hospital protocols are needed for the proper utility of phenytoin post-TBI.
PubMed: 38681877
DOI: 10.4103/jets.jets_93_23 -
The American Journal of Emergency... Jul 2023Tacrolimus is commonly used for immunosuppression in patients following solid organ transplantation. For transplant patients with COVID-19 infection, early treatment is...
Tacrolimus is commonly used for immunosuppression in patients following solid organ transplantation. For transplant patients with COVID-19 infection, early treatment is indicated due to the risk of progression to severe disease. However, the first line agent, nirmatrelvir/ritonavir, has multiple drug-drug interactions. We report a case of tacrolimus toxicity in a patient with a history of renal transplant due to enzyme inhibition related to nirmatrelvir/ritonavir. An 85-year-old woman with a history of multiple comorbidities presented to the emergency department (ED) with weakness, increasing confusion, poor oral intake, and inability to walk. She had been recently diagnosed with COVID-19 infection and was prescribed nirmatrelvir/ritonavir due to her underlying comorbidities and immune suppression. In the ED, she was dehydrated and had an acute kidney injury (creatinine 2.1 mg/dL, up from a baseline of 0.8 mg/dL). The tacrolimus concentration on initial labs was 143 ng/mL (5-20 ng/mL) and it continued to rise despite being held, to a peak of 189 ng/mL on hospital day 3. The patient was treated with phenytoin for enzyme induction and the tacrolimus concentration began to fall. She was discharged to a rehabilitation facility after a 17 day hospitalization. ED physicians must be cognizant of drug-drug interactions when prescribing nirmatrelvir/ritonavir and evaluating patients recently treated with the drug to identify toxicity due to these interactions.
Topics: Humans; Female; Aged, 80 and over; Ritonavir; COVID-19; COVID-19 Drug Treatment; Tacrolimus; Antiviral Agents
PubMed: 37173153
DOI: 10.1016/j.ajem.2023.04.045 -
Pharmaceutics Jan 2024Hot melt extrusion (HME) offers a high-throughput process to manufacture amorphous solid dispersions. A variety of experimental and model-based approaches exist to...
Hot melt extrusion (HME) offers a high-throughput process to manufacture amorphous solid dispersions. A variety of experimental and model-based approaches exist to predict API solubility in polymer melts, but these methods are typically aimed at determining the thermodynamic solubility and do not take into account kinetics of dissolution or the associated degradation of the API during thermal processing, both of which are critical considerations in generating a successful amorphous solid dispersion by HME. This work aims to develop a material-sparing approach for screening manufacturability of a given pharmaceutical API by HME using physically relevant time, temperature, and shear. Piroxicam, ritonavir, and phenytoin were used as model APIs with PVP VA64 as the dispersion polymer. We present a screening flowchart, aided by a simple custom device, that allows rapid formulation screening to predict both achievable API loadings and expected degradation from an HME process. This method has good correlation to processing with a micro compounder, a common HME screening industry standard, but only requires 200 mg of API or less.
PubMed: 38258087
DOI: 10.3390/pharmaceutics16010076 -
Skin Research and Technology : Official... Jun 2024Severe acne breakouts often lead to atrophic acne scars, which affect millions of people worldwide and can significantly affect a person's self-confidence and... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Evaluation and comparison of the efficacy and safety of the combination of topical phenytoin and microneedling with microneedling alone in the treatment of atrophic acne scars: A controlled blinded randomized clinical trial.
INTRODUCTION
Severe acne breakouts often lead to atrophic acne scars, which affect millions of people worldwide and can significantly affect a person's self-confidence and self-image. Given the difficulty in treating atrophic acne scars, this study aims to investigate the efficacy of topical phenytoin in the treatment of atrophic acne scars.
METHOD
This split face clinical trial on 25 patients between the ages of 18 and 40 involved the application of microneedling on one side of the face, with three sessions taking place over the course of a month. On the other side, a 1% phenytoin cream was administered three times daily for 1 week following the microneedling procedure. Baseline information was collected for all patients, and follow-up assessments were conducted during the treatment sessions and 2 months after the last session. The assessments included evaluating the number and area of pores and spots, determining scar severity, assessing patient satisfaction, and recording any potential complications.
RESULTS
Among patients, 20 individuals (80%) were females, and the average age of the participants was 35.96 ± 9.23. In terms of the fine pore area, despite the fine pore count, both groups showed improvement over time (p: 0.03 vs. 0.06). Also, regarding large pore count and area, and the count and area of spots, both groups showed improvement over time (p: 0.001). However, there were no significant differences between the two groups (p > 0.05). On the other hand, when it comes to acne scar grade and patients' satisfaction, the phenytoin group outperformed the control group in all follow-up sessions and this difference was found to be significant (p: 0.001). It is worth noting that no complications were observed among any of the patients.
CONCLUSION
It appears that combining phenytoin cream with microneedling has a more effective therapeutic outcome in enhancing atrophic acne scars, when compared to microneedling alone, and this method can be regarded as a viable alternative in treating these types of scars.
Topics: Humans; Female; Phenytoin; Adult; Acne Vulgaris; Male; Cicatrix; Young Adult; Needles; Adolescent; Treatment Outcome; Patient Satisfaction; Administration, Cutaneous; Combined Modality Therapy; Atrophy; Administration, Topical; Percutaneous Collagen Induction
PubMed: 38807440
DOI: 10.1111/srt.13766 -
The Lancet Regional Health. Europe Mar 2024The short- and long-term consequences of restricted fetal growth cause considerable concern, and how prenatal exposure to different antiseizure medications (ASMs)...
BACKGROUND
The short- and long-term consequences of restricted fetal growth cause considerable concern, and how prenatal exposure to different antiseizure medications (ASMs) affects fetal growth remains uncertain.
METHODS
This was a population-based cohort study of liveborn singleton children born in Denmark, Finland, Iceland, Norway, and Sweden from 1996 to 2017. Prenatal exposure was defined as maternal filling of prescriptions for ASM during pregnancy registered in national prescription registries and primary outcomes were adjusted odds ratios (aORs) of microcephaly or being born small for gestational age.
FINDINGS
We identified 4,494,918 children (males: 51.3%, 2,306,991/4,494,918), including 38,714 (0.9%) children of mothers with epilepsy. In the overall population, prenatal monotherapy exposure with carbamazepine (aOR: 1.25 (95% CI: 1.12-1.40)), pregabalin (aOR: 1.16 (95% CI: 1.02-1.31)), oxcarbazepine (aOR: 1.48 (95% CI: 1.28-1.71)), clonazepam (aOR: 1.27 (95% CI: 1.10-1.48)), and topiramate (aOR: 1.48 (95% CI: 1.18-1.85)) was associated with risk of being born small for gestational age, and carbamazepine was associated with microcephaly (aOR: 1.43 (95% CI: 1.17-1.75)). In children of mothers with epilepsy, prenatal exposure to carbamazepine (aOR: 1.27 (95% CI: 1.11-1.47)), oxcarbazepine (aOR: 1.42 (95% CI: 1.18-1.70)), clonazepam (aOR: 1.40 (95% CI: 1.03-1.89)), and topiramate (aOR: 1.86 (95% CI: 1.36-2.54)) was associated with being born small for gestational age; carbamazepine, with microcephaly (aOR: 1.51 (95% CI: 1.17-1.95)). No associations with small for gestational age and microcephaly were identified after prenatal exposure to lamotrigine, valproate, gabapentin, levetiracetam, phenobarbital, acetazolamide, phenytoin, clobazam, primidone, zonisamide, vigabatrin, ethosuximide and lacosamide, but except for lamotrigine, valproate, gabapentin, and levetiracetam, numbers of exposed children were small.
INTERPRETATION
Prenatal exposure to carbamazepine, oxcarbazepine, clonazepam, and topiramate was associated with increased risk of being born small for gestational age in both the overall population and in children of women with epilepsy suggesting that prenatal exposure to these drugs is associated with fetal growth restriction.
FUNDING
The NordForsk Nordic Program on Health and Welfare (83539), the Independent Research Fund Denmark (1133-00026B), the Danish Epilepsy Association, the Central Denmark Region, the Novo Nordisk Foundation (NNF16OC0019126 and NNF22OC0075033), and the Lundbeck Foundation (R400-2022-1205).
PubMed: 38476755
DOI: 10.1016/j.lanepe.2024.100849 -
Wounds : a Compendium of Clinical... Feb 2024Although phenytoin's potential benefits in wound healing, pain relief, and infection control across various wound types have been previously reported, its use in wound...
BACKGROUND
Although phenytoin's potential benefits in wound healing, pain relief, and infection control across various wound types have been previously reported, its use in wound care remains limited.
OBJECTIVE
To conduct a comprehensive review to assess the efficacy of topical phenytoin compared with standard and alternative treatments for different wound types.
MATERIALS AND METHODS
The authors last searched Cochrane Library, PubMed, PubMed Central, and MEDLINE in June 2023. All English-language human RCTs and NRCTs from any time were included. The RoB 2 was used to assess quality of randomized trials, and the ROBINS-I was used to assess the quality of nonrandomized trials. Studies with a low risk of bias or some concerns in no more than 1 domain were included. Data collected and analyzed included wound type, interventions, sample size, outcome measures, and adverse effects.
RESULTS
The search yielded 101 studies, of which 17 RCTs and 8 NRCTs were eligible for inclusion. Of the included studies, 56% had a low risk of bias in all domains. The sample sizes varied between 20 and 130 (median, 60), with a total sample size of 1653 patients. Phenytoin improved wound healing in 17 of the 24 studies that evaluated it (71%), increased granulation tissue in 9 of the 10 studies that evaluated it (90%), provided analgesic effects in 7 of the 13 studies that evaluated it (54%), and inhibited bacterial contaminants in 6 of the 8 studies that evaluated it (75%). Adverse effects were rare (29%), minimal, and transient.
CONCLUSION
Phenytoin enhances wound healing and offers analgesic and antibacterial properties with minimal adverse effects. Further research is needed on optimal dosage of phenytoin, as well as frequency, delivery vehicles, and effects on other postoperative wounds.
BACKGROUND
Although phenytoin's potential benefits in wound healing, pain relief, and infection control across various wound types have been previously reported, its use in wound care remains limited.
OBJECTIVE
To conduct a comprehensive review to assess the efficacy of topical phenytoin compared with standard and alternative treatments for different wound types.
MATERIALS AND METHODS
The authors last searched Cochrane Library, PubMed, PubMed Central, and MEDLINE in June 2023. All English-language human RCTs and NRCTs from any time were included. The RoB 2 was used to assess quality of randomized trials, and the ROBINS-I was used to assess the quality of nonrandomized trials. Studies with a low risk of bias or some concerns in no more than 1 domain were included. Data collected and analyzed included wound type, interventions, sample size, outcome measures, and adverse effects.
RESULTS
The search yielded 101 studies, of which 17 RCTs and 8 NRCTs were eligible for inclusion. Of the included studies, 56% had a low risk of bias in all domains. The sample sizes varied between 20 and 130 (median, 60), with a total sample size of 1653 patients. Phenytoin improved wound healing in 17 of the 24 studies that evaluated it (71%), increased granulation tissue in 9 of the 10 studies that evaluated it (90%), provided analgesic effects in 7 of the 13 studies that evaluated it (54%), and inhibited bacterial contaminants in 6 of the 8 studies that evaluated it (75%). Adverse effects were rare (29%), minimal, and transient.
CONCLUSION
Phenytoin enhances wound healing and offers analgesic and antibacterial properties with minimal adverse effects. Further research is needed on optimal dosage of phenytoin, as well as frequency, delivery vehicles, and effects on other postoperative wounds.
Topics: Humans; Phenytoin; Anti-Bacterial Agents; Wound Healing; Analgesics; Pain
PubMed: 38479432
DOI: No ID Found -
Epilepsia Open Sep 2023Response to antiseizure medications (ASMs) can be influenced by several gene polymorphisms, causing either lower efficacy or higher occurrence of adverse drug reactions...
Response to antiseizure medications (ASMs) can be influenced by several gene polymorphisms, causing either lower efficacy or higher occurrence of adverse drug reactions (ADRs). We investigated the clinical utility of salivary pharmacogenomic testing on epilepsy patients. A commercialized pharmacogenomic salivary test was performed in a cohort of epileptic patients. Genetic variants on five genes (i.e., CYP1A2, CYP2C9, CYP2C19, EPHX1, and ABCB1) involved in common ASMs metabolism were selected. Twenty-one individuals (median age [Q -Q ]: 15 [6.5-28] years) were enrolled. Six patients harboring the homozygous *1F allele in CYP1A2 could have reduced chance of response to stiripentol due to fast metabolism. CYP2C9 had reduced activity in 10 patients (alleles *2 and *3), potentially affecting phenytoin (PHT), phenobarbital (PB), primidone, lacosamide (LCM), and valproic acid metabolism. Seven patients, carrying the *2 allele of CYP2C19, had an increased risk of ADRs with clobazam (CLB), PB, PHT, LCM, brivaracetam; while one individual with the *17 allele in heterozygosity reported a CLB fast metabolism. Six patients showed a CC polymorphism of EPHX1 associated with the impaired efficacy of carbamazepine. ABCB1 polymorphisms related to drug-resistance (3435 CC) or drug-sensitive phenotype (CT or TT) were found in 6 out of 7 patients. Pharmacogenomic testing on saliva proved easy and safe in clinical practice to convey information for the management of epileptic patients, especially those resistant to treatment or sensitive to severe ADRs.
Topics: Humans; Anticonvulsants; Pharmacogenetics; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2C19; Pilot Projects; Cytochrome P-450 CYP2C9; Saliva; Epilepsy; Phenytoin; Clobazam; Phenobarbital
PubMed: 36840436
DOI: 10.1002/epi4.12717