Seizures, renal impairment

The fluoroquinolones are used cautiously in patients with renal impairment or a history of seizures, in geriatric patients, and in patients on dialysis. 

Amantadine is used cautiously in patients with seizure disorders, psychiatric problems, renal impairment, and cardiac disease. Amantadine is a Pregnancy Category B drug and is used cautiously during pregnancy and lactation. Concurrent use of antihistamines, phenothiazines, tricyclic antidepressants, disopyramide, and quinidine may increase the anticholinergic effects (dry mouth, blurred vision, constipation) of amantadine... 

A loading dose of 0.2 mg/kg (repeated up to a maximum of 2 mg/kg) followed by a continuous infusion of 0.05 to 2 mg/kg per hour is recommended in RSE.29-31 The dose must be adjusted during prolonged infusions, especially in patients with renal impairment, as the active metabolite can accumulate.32 Breakthrough seizures are common with midazolam infusions and usually respond to a bolus and a 20% increase in the rate. Despite this, tachyphylaxis can occur and the patient should be switched to another agent if seizure activity continues. 

Overdose initially causes aburning feeling in the skin or throat, severe diarrhea, and abdominal pain. The patient then experiences fever, seizures, delirium, and renal impairment, marked by hematuria and oliguria. The third stage of overdose causes hair loss, leukocytosis, and stomatitis. 

Seizures may occur in those with CNS disorders (including patients with brain lesions or a history of seizures), bacterial meningitis, or severe renal impairment. 

Absence seizures PO Initially, 250 mg/day or 15 mg/kg/day in 2 divided doses. Maintenance 15-40 mg/kg/day in 2 divided doses. Use with caution in patients with renal impairment. 

Seizures and other neurologic reactions are more likely to occur in patients with renal impairment and those who have received an overdose. 

Dosage in renal impairment Expect to reduce drug dosage by 50% in patients with tonic-clonic seizures who have a creatinine clearance of less than 70 ml/min. 

Adverse effects Amantadine s side effects are mainly associated with the CNS. Minor neurologic symptoms include insomnia, dizziness, and ataxia. More serious side effects have been reported (for example, hallucinations, seizures). The drug should be employed cautiously in patients with psychiatric problems, cerebral atherosclerosis, renal impairment, or epilepsy. Rimantadine causes fewer CNS reactions since it does not efficiently cross the blood-brain barrier. Amantadine and rimantadine should be used with caution in pregnant and nursing mothers, because they have been found to be embryotoxic and teratogenic in rats. 

Oral acyclovir is a remarkably safe drug. Common side effects include nausea, vomiting, diarrhea, and abdominal pains. Additional side effects include skin rash, photosensitivity, headaches, dizziness, hallucinations, lethargy, confusion, seizures, and coma. Side effects are most frequent in patients with renal impairment. Rarer complications include anemia, leukopenia, thrombocytopenia, increases in blood urea and creatinine, acute renal failure, reversible increases in bilimbin and liver enzymes, hepatitis, and jaimdice. Cautious dosing and monitoring are recommended in elderly and immunocompromised patients and in patients with renal or liver disease. 

The safety profile of the carbapenems is comparable to that of other beta-lactam antibiotics, in particular with regard to laboratory abnormalities, the most common ones being those related to liver function (3,4). In patients with pre-existing nervous system disease or who take dosages above the recommended limits (for example in renal impairment) seizures appear to be more common with imipenem + cilastatin. 

Mefenamic acid overdosage is characterized by nervous system symptoms, such as generalized seizures, agitation, and confusion, sometimes progressing to coma, gastrointestinal problems (bloody diarrhea, abdominal pain, and vomiting), and renal impairment (SEDA-13, 83) (SEDA-14, 95) (19). 

MDMA causes a feeling of clarity or sharpness, tingling, pleasure, and a feeling of disassociation. It can result in dehydration, seizures, hyperthermia, tachycardia, and renal impairment. LSD is also a hallucinogen but does not have an amphetamine component. The drug causes visual hallucinations. Emotions can be labile and paranoia can occur. Increased body temperature, heart rate, and blood pressure can occur. Some people experience flash-backs. 

Acyclovir is the drug of choice for herpes simplex encephalitis. In patients with normal renal function, acyclovir is usually administered as 10 mg/kg intravenously every 8 hours for 2 to 3 weeks. Herpes virus resistance to acyclovir has been reported with increasing incidence, particularly from immunocompromised patients with prior or chronic exposures to acyclovir. The alternative treatment for acyclovir-resistant herpes simplex virus is foscarnet. The major toxicity of foscarnet is renal impairment, and doses must be individualized for renal function. The dose for patients with normal renal function is 40 mg/kg infused over 1 hour every 8 to 12 hours for 2 to 3 weeks. Ensuring adequate hydration is imperative. In addition, patients receiving foscarnet should be monitored for seizures related to alterations in plasma electrolyte levels. 

The incidence of phenytoin toxicity may be increased in the eideriy, or in those patients with hepatic or renal impairment, because of alterations in its pharmacokinetics. Plasma level determinations may be indicated in these cases. Although a role for P-glycoprotein transporter alleles in the development of phenytoin toxicity remains controversial, phenytoin is a robust substrate for the non-ABC efflux transporter RLIP76. Because RLIP76 has been found to be overexpressed in excised human epileptic foci, its action may account for treatment failures conversely, inhibition of transport may cause toxicity (34). There is a 2 to 3% increase in the risk of fetal epilepsy syndrome if the mother is taking phenytoin. Phenytoin is contraindicated in cardiac patients with bradyarrhythmias. Induction of CYP2C19 by ginkgo biloba may increase phenytoin clearance and precipitate serious seizures (35). 

D. FoscarneL An adult receiving 12.5 g for 3 days developed seizures and died. Adults who received 1.14-8 times (average of 4 times) the recommended doses developed seizures and renal impairment. 

Four transplant patients who were taking eiclosporin developed seizures when they were given imipenem/cilastatin 1 g daily, and a fifth patient developed myoclonia. These patients all had chronic renal impairment. In contrast, imipenem/cilastatin 2 g daily for 4 weeks, given with ciprofloxacin, was effectively and successfully used in another patient taking ciclosporin after a heart transplant. This patient was switched to imipenem/cilastatin and ciprofloxacin after developing acute renal failure while receiving amikacin. Reduced serum ciclosporin levels following the use of imipenem/cilastatin have been seen in rats ... 

Caution if hypersensitivity to other anticonvulsants risk of cross-sensitivity Caution if absence, atonic, or myoclonic seizures may increase generahzed convulsion frequency Caution if increased intraocular pressure may cause exacerbation due to cholinergic antagonism Caution if hepatic or renal impairment Caution if cardiac disease, or cardiac conduction disturbances increased risk of atrioventricular heart block Caution in SLE... 

TBW depletion (often referred to as dehydration ) is typically a more gradual, chronic problem compared to ECF depletion. Because TBW depletion represents a loss of hypotonic fluid (proportionally more water is lost than sodium) from all body compartments, a primary disturbance of osmolality is usually seen. The signs and symptoms of TBW depletion include CNS disturbances (mental status changes, seizures, and coma), excessive thirst, dry mucous membranes, decreased skin turgor, elevated serum sodium, increased plasma osmolality, concentrated urine, and acute weight loss. Common causes of TBW depletion include insufficient oral intake, excessive insensible losses, diabetes insipidus, excessive osmotic diuresis, and impaired renal concentrating mechanisms. Long-term care residents are frequently admitted to the acute care hospital with TBW depletion secondary to lack of adequate oral intake, often with concurrent excessive insensible losses. 

CNS symptoms include fine tremor, ataxia or seizures. Inhibition of the renal actions of vasopressin (p. 164) leads to polyuria and thirst. Thyroid function is impaired (p. 244), with compensatory development of (euthyroid) goiter. 

Imipenem-cilastatin IV is not recommended in pediatric patients with CNS infections because of the risk of seizures and in pediatric patients less than 30 kg with impaired renal function, as no data are available. 

Renal function impairment Do not give imipenem-cilastatin IV to patients with Ccr less than or equal to 5 mL/min/1.73 m, unless hemodialysis is instituted within 48 hours. For patients on hemodialysis, imipenem-cilastatin IV is recommended only when the benefit outweighs the potential risk of seizures. 

Statistically significant risk factors associated with seizures were low baseline absolute neutrophil count (ANC), impaired baseline renal function, and low total serum calcium. Several cases of seizures were associated with death. 

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