other benzodiazepines, barbiturates, antiepileptic drugs, alcohol, antihistamines, opioids, neuroleptics, sleep aids are likely to magnify the effects of clorazepate on the central nervous system. Drugs that may interact with clorazepate include, digoxin, disulfiram, fluoxetine, isoniazid, ketoconazole, levodopa, metoprolol, hormonal contraceptives, probenecid, propranolol, rifampin, theophylline, valproic acid. Selective serotonin reuptake inhibitors, cimetidine, macrolide antibiotics and antimycotics inhibit the metabolism of benzodiazepines and may result in increased plasma levels with resultant enhancement of adverse effects. Phenytoin, phenobarbital, and carbamazepine have the opposite effect, with coadministration leading to increased metabolism and decreased therapeutic effects of clorazepate. Contraindications and special caution
Benzodiazepines require special precaution if used in the elderly, children, alcohol- or drug-dependent individuals and individuals with comorbid psychiatric disorders.Clorazepate if used late in pregnancy, the third trimester, causes a definite risk of severe benzodiazepine withdrawal syndrome in the neonate with symptoms including hypotonia, and reluctance to suck, to apnoeic spells, cyanosis, and impaired metabolic responses to cold stress. Floppy infant syndrome and sedation in the newborn may also occur. Symptoms of floppy infant syndrome and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth.Special precaution is required when using clorazepate in the elderly because the elderly metabolise clorazepate more slowly, which may result in excessive drug accumulation. Additionally the elderly are more sensitive to the adverse effects of benzodiazepines compared to younger individuals even when blood plasma levels are the same.
A lipid storage disorder (or lipidosis) is any one of a group of inherited metabolic disorders in which harmful amounts of fats or lipids accumulate in some body cells and tissues. People with these disorders either do not produce enough of one of the enzymes needed to metabolize and break down lipids or, they produce enzymes that do not work properly. Over time, the buildup of fats may cause permanent cellular and tissue damage, particularly in the brain, peripheral nervous system, liver, spleen, and bone marrow. Inside cells under normal conditions, lysosomes convert, or metabolize, lipids and proteins into smaller components to provide energy for the body. Classification
Disorders that store this intracellular material are part of the lysosomal storage diseases family of disorders. Sphingolipidoses
Many lipid storage disorders can be classified into the subgroup of sphingolipidoses, as they relate to sphingolipid metabolism. Members of this group include Niemann-Pick disease, Fabry disease, Krabbe disease, Gaucher disease, Tay–Sachs disease, metachromatic leukodystrophy, multiple sulfatase deficiency, and Farber disease. They are generally inherited in an autosomal recessive fashion, but Fabry disease is X-linked. Taken together, sphingolipidoses have an incidence of approximately 1 in 10,000. Enzyme replacement therapy is available mainly to treat Fabry disease and Gaucher disease and people with these types of sphingolipidoses may live well into adulthood. Generally, the other types are fatal by age 1 to 5 years for infantile forms, but progression may be mild for juvenile-onset or adult-onset forms.Alternatively, some of the sphingolipidoses may be classified into either GM1 gangliosidoses or GM2 gangliosidoses.