Peripheral neuropathy phenytoin

Common but usually transient side effects are lethargy, incoordination, blurred vision, higher cortical dysfunction, and drowsiness. At concentrations greater than 50 mcg/mL, phenytoin can exacerbate seizures. Chronic side effects include gingival hyperplasia, impaired cognition, hirsutism, vitamin D deficiency, osteomalacia, folic acid deficiency, carbohydrate intolerance, hypothyroidism, and peripheral neuropathy. 

Phenytoin (Dilantin) [Anticenvulsant/Hydantoin] Uses Sz disorders Action X Sz spread in the motor cortex Dose Load Adults Peds. 15-20 mg/kg IV, 25 mg/min max or PO in 400-mg doses at 4-h intervals Maint Adults. Initial, 200 mg PO or IV bid or 300 mg hs then follow levels Peds. 4-7 mg/kg/24h PO or IV -s- daily-bid avoid PO susp (erratic absorption) Caution [D, +] Contra Heart block, sinus bradycardia Disp Caps, susp, inj SE Nystag-mus/ataxia early signs of tox gum hyperplasia w/ long-term use. IV BP, bradycardia, arrhythmias, phlebitis peripheral neuropathy, rash, blood dyscrasias, Stevens-Johnson synd Notes Levels Trough Just before next dose Therapeutic Peak 10-20 mcg/mL Toxic >20 mcg/mL phenytoin albumin bound, levels = bound free phenytoin w/ i albumin azotemia, low levels may be therapeutic (nl free levels) Interactions T Effects W/ amiodarone, allopurinol, chloramphenicol, disulfiram, INH, omeprazole, sulfonamides, quinolones, trimethoprim t... 

Isoniazid Inhibits synthesis of mycolic acids, an essential component of mycobacterial cell walls Bactericidal activity against susceptible strains of M tuberculosis First-line agent for tuberculosis treatment of latent infection less active against other mycobacteria Oral, IV hepatic clearance (half-life 1 h) reduces levels of phenytoin Toxicity Flepatotoxic, peripheral neuropathy (give pyridoxine to prevent)... 

The use of stavudine in combination with isoniazid, vincristine, phenytoin and ethambutol may increase the risk of peripheral neuropathy and pancreatitis. It competes with zidovudine for phosphorylation and should not be used in combination. 

PHENYTOIN NUCLEOSIDE REVERSE TRANSCRIPASE INHIBITORS - DIDANOSINE, STAVUDINE, ZIDOVUDINE Possibly t adverse effects (e.g. peripheral neuropathy) with didanosine, stavudine and zidovudine Additive effect Monitor closely for peripheral neuropathy during prolonged combination... 

Adverse effects of phenytoin, many of which can be very slow to develop, include impairment of cognitive function, which has led many physicians to prefer carbamazepine and valproate. Other nervous system effects range from sedation to delirium to acute cerebellar disorder to convulsions. Peripheral neuropathy also occurs. Cutaneous reactions include rashes (dose related), coarsening of facial features and hirsutism. Gum hyperplasia (due to inhibition of collagen catabolism) may develop and is more marked in children and when there is poor gum hygiene. 

Slow acetylator Isoniazid Hydralazine, procainamide Phenelzine, sulfasalazine Increased incidence of peripheral neuropathy SLE-like syndrome and more prone to phenytoin toxicity Increased incidence of SLE-like syndrome More prone to side effects... 

Phenytoin can cause vestibulocerebellar, oculomotor, and cognitive dysfunction. It can also cause gingival hyperplasia, hirsutism, and acromegaly-hke facial features. Movement disorders, symptoms of peripheral neuropathy, and endocrine changes are uncommon. Interstitial nephritis, interstitial pneumonia, and hepatotoxicity are rare. High intravenous doses are cardiotoxic. 

Peripheral neuropathy is a known adverse effect of phenytoin, but this is the first report of an acute neuropathy within less than 1 week of treatment. 

Fetal phenytoin syndrome cerebellar syndrome (ataxia, nystagmus) chronic encephalopathy (cognitive dysfunction) extrapyramidal syndrome (chorea, dyskinesia) peripheral neuropathy Acute encephalopathy (sedation, coma) chronic encephalopathy (cognitive dysfunction)... 

Peripheral neuropathy is also common with advanced CKD and is typically indistinguishable from other types of neuropathy (e.g., diabetic neuropathy). Symptoms are often uncomfortable for the patient and prompt many clinicians to initiate pharmacologic therapy in an attempt to reduce these symptoms. Tricyclic antidepressants (e.g., amitriptyline) and anticonvulsants (e.g., phenytoin and gabapentin) may have some benefit in alleviating symptoms of neuropathy however, risks and benefits must be considered for agents... 

Transient elevations of the serum transaminases occur in 12% to 15% of patients receiving isoniazid and usually occur within the first 8 to 12 weeks of therapy. Overt hep ato toxicity, however, occurs in only 1% of cases. Risk factors for hepatotoxicity include patient age, preexisting liver disease, excessive alcohol intake, pregnancy, and the postpartum state. Isoniazid also may result in neurotoxicity, most frequently presenting as peripheral neuropathy or, in overdose, as seizures and coma. Patients with pyridox-ine deficiency, such as pregnant women, alcoholics, children, and the malnourished, are at increased risk. Isoniazid may inhibit the metabolism of phenytoin, carbamazepine, primidone, and warfarin." Patients who are being treated with these agents should be monitored closely, and appropriate dose adjustments should be made when necessary. 

Phenytoin has also been reported to cause peripheral neuropathy when used in high doses. Shorvon (S7) found that at a serum phenytoin concentration of 30 mg/liter there was a reduction in sural nerve conduction velocity in seven of nine patients and in median nerve sensory velocity in four of nine patients. It was not clear if the peripheral neuropathy was due to a toxic effect of the drug or, as seems more likely, to a folate deficiency associated wifli the anticonvulsant drug (H5). 

Long-term phenytoin therapy carries several drawbacks. It may impair cognitive functions, cause bilateral peripheral neuropathy that is characterized by decreased reflexes and sensory deficits, and produce hypokalemia and osteomalacia, resulting in accelerated vitamin D metabolism. 

Valproic acid often causes gastrointestinal distress and is potentially hepatotoxic. The use of this drug in pregnancy has been associated with teratogenicity (neural tube defects). Valproic acid inhibits the metabolism of barbiturates marked CNS depression may result if such drugs are given concomitantly. Peripheral neuropathy, in the form of diminished deep tendon reflexes in the lower extremities, is associated with chronic use of phenytoin. The answer is (C). 

The serum levels of the active metabolite of leflunomide are reduced by activated charcoal, and colestyramine. The manufacturers advise against the concurrent use of alcohol because of the potential for hepatotoxicity. Methotrexate may also increase leflunomide hepatotoxicity, so in general the combination is not recommended. A case of fatal fulminant hepatic failure has been reported in a patient taking leflunomide and itraconazole. A case of peripheral neuropathy has been reported in a patient taking leflunomide and tegafiir/uraciL The manufacturers predict interactions between leflunomide and phenytoin or tolbutamide, and advise caution with rifampicin as it may increase leflunomide metabolite levels. No clinically relevant interaction occurs with cime-tidine, corticosteroids or NSAIDs. 

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