Back pain , chills, myasthenia Uncommon 0. Myopathy, leg cramps, arthralgia, myalgia, muscular weakness, muscle twitching , muscle spasms Frequency not reported: Headache, stupor, incoordination, paresthesia, extrapyramidal syndrome, tremor, vertigo , brain edema, tinnitus , taste perversion including metallic taste , taste loss, reflexes decreased, reflexes increased, migraine , slurred speech, dysarthria, intracranial hypertension , hyperesthesia, hyporeflexia Uncommon 0.
Twitching, Babinski sign positive, circumoral paresthesia, hemiplegia, hypotonia, convulsion, meningitis , CNS depression, hypokinesia, hyperkinesia, brain edema, paralysis, aphasia, coma, myoclonus, acute brain syndrome, encephalitis , subdural hematoma, encephalopathy , akathisia Frequency not reported: At steady state, concentrations are higher in neural tissue than in the serum. Within the CNS, concentrations are higher in the brainstem and cerebellum that the cerebral cortex.
Protein Binding and Free Phenytoin Fractions Phenytoin is extensively 90 percent bound to plasma proteins, especially albumin.
The free, unbound form is the biologically active moiety responsible for the drug's clinical effect and toxicity. The free phenytoin fraction normally constitutes 10 percent of the plasma level. The unbound fraction of the drug is greater in the following groups of patients: Although patients with decreased protein binding may have higher levels of free phenytoin and a greater biological effect, they may have lower levels of total phenytoin since more of the drug is available for metabolism.
These patients may become toxic with total phenytoin levels in the therapeutic range. Patients who exhibit toxic signs in the therapeutic range and those with decreased protein binding should have their free phenytoin levels measured.
Recently, salivary levels of anticonvulsants have been found to correlate with the free fraction of drug in the plasma. Metabolism Following absorption and distribution, only 4 to 5 percent of phenytoin is excreted unchanged in the urine.
The remainder is metabolized by hepatic microsomal enzymes. The drug is primarily hydroxylated to a series of inactive compounds. The major 60 to 70 percent metabolite is the parahydroxyphenyl derivative. It is glucuronidated, secreted in the bile, reabsorbed, and subsequently excreted in the urine. Phenytoin removal from the body is not appreciably influenced by hemodialysis or hemoperfusion.
Unlike the other anticonvulsant agents, the metabolism of phenytoin is capacity-limited dose-dependent. This change in kinetics can markedly prolong the half-life of phenytoin, which is normally 6 to 24 h. An understanding of capacity-limited kinetics is essential to the proper dosing of phenytoin, the avoidance of side effects with chronic therapy, and the management of overdoses.
At higher levels in the therapeutic range, any increase in the daily dose will result in a disproportionate increase in the plasma level. After each increase in dose, the patient should be maintained on the new dose for at least 2 weeks and the plasma level should be reassessed before any further increase. Because phenytoin's half-life is 24 h or less, once-a-day regimens may result in erratic levels and become problematic for patients requiring tight control.
However, one phenytoin preparation Phenytoin Kapseals has a delayed absorption and is the only preparation approved by the Food and Drug Administration FDA for once-a-day use.
A once-a-day regimen is advisable since this facilitates compliance. Phenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase of generalized tonic-clonic seizures. A small increase in dose may lead to a large increase in drug concentration as elimination becomes saturated. The time to reach steady state is often longer than 2 weeks. In , outside scientists including H. Houston Merritt and Tracy Putnam discovered phenytoin's usefulness for controlling seizures , without the sedative effects associated with phenobarbital.
This drug is processed by your liver. This puts you at risk for toxicity and side effects. For people with diabetes: This drug may increase your blood sugar levels. For people with kidney problems: If you have severe kidney disease, your dosage may need to be adjusted or monitored more closely.
For people with thyroid disease: This drug can affect your thyroid hormone levels. Skin And Appendages Dermatological manifestations sometimes accompanied by fever have included scarlatiniform or morbilliform rashes. A morbilliform rash measles -like is the most common; other types of dermatitis are seen more rarely. There have also been reports of hypertrichosis.
Special Senses Altered taste sensation including metallic taste.
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