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https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/1812378
'Intravenous phenytoin has been known to produce cardiovascular collapse when administered too quickly; however, this is thought to be related to toxicity from its diluent propylene glycol.' 'Although phenytoin is a Vaughn-Williams Class 1B antiarrhythmic, it displays quick on-off kinetics at the sodium channel, thus making it less arrhythmogenic when compared with agents with slow on-off kinetics such as the class IC agents'
http://www.emjournal.net/htdocs/pages/art/45-phtox.html
'The acute cardiovascular toxicity seen with intravenous phenytoin infusion has frequently been ascribed to its diluent. The vehicle for the most widely used parenteral formulation of phenytoin is 40% propylene glycol and 10% ethanol, adjusted to a pH of 12 with sodium hydroxide. The glycol component has been shown to cause coma, seizures, circulatory collapse, ventricular arrhythmias, cardiac nodal depression, and hypotension in humans and animals. Propylene glycol is a strong myocardial depressant and vasodilator and increases vagal tone'
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Central Nervous System Toxicity
As toxic phenytoin levels are reached, both inhibitory cortical and excitatory cerebellar-vestibular effects begin to occur. The usual initial sign of toxicity is nystagmus, which is seen first on forced lateral gaze and then becomes spontaneous. Vertical, bidirectional, or alternating nystagmus may occur with severe intoxication.
Decreased level of consciousness is routine, with initial sedation, lethargy, ataxic gait, and dysarthria progressing to confusion, coma, and even apnea in large overdose. Chronically impaired cognitive function or acute encephalopathy may occur without other common signs of ataxia and nystagmus. This is usually seen at toxic levels but again may occur in the therapeutic range. Nystagmus will commonly disappear at levels sufficient to cause coma (above 35 to 55 mg/mL), and complete ophthalmoplegia and loss of corneal reflexes may occur. Therefore, absence of nystagmus does not exclude severe phenytoin toxicity. Nystagmus then returns as serum drug levels decrease and coma lightens.
Phenytoin-induced seizures are usually brief, and are usually generalized. They are quite rare and almost always preceded by other signs of toxicity, especially in acute overdose.
Cerebellar stimulation and alteration in dopaminergic and seroto-nergic activity may be responsible for acute dystonias and movement disorders seen in overdose, including opisthotonos and choreoathetosis. Either depressed or hyperactive deep tendon reflexes, clonus, and extensor toe responses may also be elicited. Some signs of neurologic toxicity may outlast the presence of drug by months, especially mild peripheral neuropathy or acute reversible cerebellar degeneration with ataxia.
Psychosis, toxic delirium, visual and auditory hallucinations, euphoria, irritability, agitation, and combativeness have all been reported with toxicity.
Cardiovascular Toxicity
Significant cardiac toxicity after oral phenytoin overdose in an otherwise healthy patient has never been reported and, if observed, should mandate a rapid assessment for other causes (e.g., hypoxia, other drugs). Cardiovascular complications have been almost entirely limited to cases of intravenous administration. These include hypotension with decreased peripheral vascular resistance, bradycardia, conduction delays progressing to complete AV nodal block, ventricular tachycardia, primary ventricular fibrillation, and asystole. Electrocardiographic changes include increased PR interval, widened QRS interval, and altered S-T and T-wave segments. Bradycardia, hypotension, and syncope in healthy volunteers have been reported even after small intravenous doses. Slowly administered (<25 mg/min) intravenous phenytoin has also been reported to cause precipitous, refractory hypotension and cardiac arrest in critically ill patients receiving dopamine infusions to support blood pressure. Most of these complications can be attributed to rapid intravenous administration of the propylene glycol diluent fraction and are avoidable with cautious administration (Table 3'
When googling for 'phenytoin cardiovascular collapse' You have to be
very, very careful about trusting doctors ...
