Seizure risk assessment

One of the more worrisome adverse effects of bupropion is seizures. At dosages of 450 mg/day or less, the rate of seizures is 0.4% for individuals without risk factors (Davidson, 1989). Because of this risk, a single dose of bupropion should not exceed 150 mg and a second dose should be separated in time by a minimum of 8 hours. Also, patients who are metabolically unstable (i.e., have bulimia) should be carefully assessed for the risk of seizures before initiating medication. Finally, bupropion is not associated with sexual side effects. 

Easter A, Bell ME, Damewood JR Jr, Redfem WS, Valentin JP, Winter MJ, Fonck C, Bialecki RA (2009). Approaches to seizure risk assessment in prechnical drug discovery. Drug Discov Today 14(17-18) 876-884. 

The impacts of TSCA, such as those on two specific exemplary industries, surface coating polymers and metal-cutting fluids, by S.Oslosky and H.Fribush, respectively, are implied but actually not explicit within TSCA. Consider the required assessment of risks, the need for test-data describing effects on health and the environment, aside from plant inspections, subpoenas, prohibited acts, penalties for prohibited acts, enforcement and seizure, judicial review, citizens civil actions and petitions, and employee protection provisions in the Act. Thus, it s inevitable that the alert manufacturer will adjust his product research, development and selection processes to identify and use substances with reduced risk to health and the environment wherever possible. As structure-(biological)-activity relationships become more reliable, the alert... 

Oliver AP, Luchins DJ, Wyatt RJ Neuroleptic-induced seizures an in vitro technique for assessing relative risk. Arch Gen Psychiatry 39 206-209, 1982... 

An in vitro technique, claimed to assess the relative risks of neuroleptic drug-induced seizures, was reported to produce striking differences between neuroleptic drugs in spike activity in hippocampal slices. Tentatively, molindone, pimozide, and butaclamol were the safest compounds, based on these in vitro experiments (172). 

All narcotics are expected to have this problem. The most common side effects demonstrated with narcotics include decreased gastrointestinal motility and risk of hypotension. Lorazepam is the preferred sedative agent in the absence of pain owing to its fast onset of action, its lack of hemodynamic toxicities, and its low risk of metabolite accumulation in comparison with diazepam. Midazolam continuous infusion is a reasonable altemative, although more costly and requiring additional fluid, which may be detrimental in a patient predisposed to PDA. Muscle paralysis has been used to reduce ventilator fighting and the consequent comphcations. However, its role in RDS has diminished owing to adverse effects (e.g., edema and hypoventilation). If paralysis is induced, assessment of sedation and seizures is confounded. Consequently, concurrent phenobarbital serum concentrations of 40 mg/L are recommended. Independent of... 

After assessing the risks and benefits to both patient and society from a recurrent seizure, the discontinuance of antiepileptic drugs may be considered by the physician and informed patient or parent/guardian if the patient meets the following profile ... 

A careful haseline physical examination, ECG, and laboratory work-up are essential. Underlying ECG changes (U waves, prolonged QT interval, or flattened T waves) secondary to hypokalemia or bradycardia and atrioventricular block from starvation may be present. AU antidepressants can cause seizures thus a careful risk-benefit assessment is warranted if the patient has predisposing factors such as a personal or family history of seizures, cerebrovascular disease, or alcohol or sedative-hypnotic withdrawal. 

Spinet O, Hedenmalm K, Dahl M-L, Wiholm B-E, D qvistR. Seizures and myoclonus associated with antidepressant treatment assessment of potential risk fectors, includii CYP2D6 and CYP2C19 polymorphisms, and treatment with CYP2D6 inhibitors. Acta Psy-chiatrScand( 997) 96,379-84. 

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