Clonazepam, epilepsy

Clonazepam Epilepsy Ataxia, dizziness, slurred speech... 

Table 32.1 describes 30 persons who have been observed to use one of four available therapeutic compounds for the treatment of one of three possible disorders. The four compounds in this measurement table are the benzodiazepine tranquillizers Clonazepam (C), Diazepam (D), Lorazepam (L) and Triazolam (T). The three disorders are anxiety (A), epilepsy (E) and sleep disturbance (S). In this example, both measurements (compounds and disorders) are defined on nominal scales. Measurements can also be defined on ordinal scales, or on interval and ratio scales in which case they need to be subdivided in discrete and non-overlapping categories. 

In Table 32.7 we observe a contrast (in the sense of difference) along the first row-singular vector u, between Clonazepam (0.750) and Lorazepam (-0.619). Similarly we observe a contrast along the first column-singular vector v, between epilepsy (0.762) and anxiety (-0.644). If we combine these two observations then we find that the first singular vector (expressed by both u, and v,) is dominated by the positive correspondence between Clonazepam and epilepsy and between Lorazepam and anxiety. Equivalently, the observations lead to a negative correspondence between Clonazepam and anxiety, and between Lorazepam and epilepsy. In a similar way we can interpret the second singular vector (expressed by both U2 and V2) in terms of positive correspondences between Triazolam and sleep and between Diazepam and anxiety. 

The two plots can be superimposed into a biplot as shown in Fig. 32.7. Such a biplot reveals the correspondences between the rows and columns of the contingency table. The compound Triazolam is specific for the treatment of sleep disturbances. Anxiety is treated preferentially by both Lorazepam and Diazepam. The latter is also used for treating epilepsy. Clonazepam is specifically used with epilepsy. Note that distances between compounds and disorders are not to be considered. This would be a serious error of interpretation. A positive correspondence between a compound and a disorder is evidenced by relatively large distances from the origin and a common orientation (e.g. sleep disturbance and Triazolam). A negative correspondence is manifest in the case of relatively large distances from the origin and opposite orientations (e.g. sleep disturbance and Diazepam). 

Myoclonic Not mentioned Lamotrigine Valproate Valproate Topiramate (children with severe myoclonic epilepsy of infancy) Second-line Clobazam6 Clonazepam Lamotrigine Levetiracetam Piracetam6 Topiramate... 

Clonazepam Klonopin Oral Long 0.5-4 Anxiety disorders, epilepsy, mania... 

The third drug of the benzodiazepine family used for epilepsy is called clonazepam. 

Clonazepam is used in somnambulic epilepsy, various forms of muscular tonus, insomnia (especially in patients with structural brain lesions), and psychomotor agitation. Synonyms of this drag are clonopin and rivotril. 

Nearly all central nervous system depressants have some capacity to suppress seizures by virtue of their depressant activity on the brain and spinal cord. Clonazepam and diazepam are two benzodiazepines that depress epileptiform activity and are used in the treatment of epilepsy and seizure disorders (see Chapter 32). 

It is a benzodiazepine useful in the treatment of petitmal epilepsy, myoclonic seizures and infantile spasms. It is used in the treatment of petitmal epilepsy not responding to ethosuximide and sodium valproate. Clonazepam and diazepam act by increasing the effectiveness of the inhibitory neurotransmitter GABA, within the central nervous system. 

It is 1,5 benzodiazepine with a chemical structure slightly different from that of diazepam and clonazepam. This change in structure results in less sedative and psychomotor retardation. Though introduced as an anxiolytic it has been found to be useful in treatment of patients with refractory epilepsy. 

Six benzodiazepines play prominent roles in the therapy of epilepsy (see also Chapter 22). Although many benzodiazepines are similar chemically, subtle structural alterations result in differences in activity. They have two mechanisms of antiseizure action, which are shown to different degrees by the six compounds. This is evident from the fact that diazepam is relatively more potent against electroshock and clonazepam against pentylenetetrazol (the latter effect correlating with an action at the GABA-benzodiazepine allosteric receptor sites). Possible mechanisms of action are discussed in Chapter 22. 

Specific myoclonic syndromes are usually treated with valproate an intravenous formulation can be used acutely if needed. It is nonsedating and can be dramatically effective. Other patients respond to clonazepam, nitrazepam, or other benzodiazepines, although high doses may be necessary, with accompanying drowsiness. Zonisamide and levetiracetam may be useful. Another specific myoclonic syndrome, juvenile myoclonic epilepsy, can be aggravated by phenytoin or carbamazepine valproate is the drug of choice followed by lamotrigine and topiramate. 

A patient with uncontrolled posttraumatic epilepsy and acute intermittent porphyria was given phenytoin, carbamazepine, and clonazepam on successive occasions (123). Phenytoin and carbamazepine caused significant increases in porphobilinogen excretion and acute attacks of porphyria. In contrast, clonazepam caused no increase in porphobilinogen excretion. 

Larson AW, Wasserstrom WR, Felsher BF, Chih JC. Posttraumatic epilepsy and acute intermittent porphyria effects of phenytoin, carbamazepine, and clonazepam. Neurology 1978 28(8) 824-8. 

Several members of the benzodiazepine group are effective in treating epilepsy, but most are limited because of problems with sedation and tolerance. Some agents such as diazepam (Valium) and lorazepam (Ativan) are used in the acute treatment of status epilepti-cus (see Treatment of Status Epilepticus ), but only a few are used in the long-term treatment of epilepsy. Clonazepam (Klonopin) is recommended in specific forms of absence seizures (e.g., the Lennox-Gastaut variant) and may also be useful in minor generalized seizures such as akinetic spells and myoclonic jerks. Clorazepate (Tranxene) is another benzodiazepine that is occasionally used as an adjunct in certain partial seizures. 

Another serious concern is that young drug users may not be able to distinguish Rohypnol from other potentially harmful drugs. The DEA has received reports of benzodiazepines other than Rohypnol being passed off by drug dealers as Rohypnol pills. One such substitute Rivotril, a benzodiazepine sold in Mexico for the treatment of epilepsy. In the United States, this drug is known as Klonopin (clonazepam). 

Benzodiazepines used to treat epilepsy include diazepam, clonazepam, clobazam and lorazepam. Of these, diazepam and lorazepam have been most widely used to control status epilepticus, while use of clonazepam is usually restricted to the chronic treatment of severe mixed types of seizures (e.g. Lennox-Gastaut syndrome and infantile spasm). The major problem with most of the benzodiazepines, with the possible exception of clobazam, is sedation. 

Clonazepam is the most potent of the benzodiazepine anticonvulsants and is particularly indicated in the treatment of the more difficult cases of epilepsy, especially those of the multiple seizure type. More recently, clobazam, which at therapeutic doses has the advantage of causing little... 

Seizures Clonazepam [kloe NA ze pam] is useful in the chronic treatment of epilepsy, whereas diazepam is the drug of choice in terminating grand mal epileptic seizures and status epilepticus (see p. 149). Chlordiazepoxide [klor di az e POX ide], clorazepate [klor AZ e pate], diazepam, and oxazepam [ox A ze pam] are useful in the acute treatment of alcohol withdrawal. 

This fivefold clinical activity is possessed, to a greater or lesser extent, by all benzodiazepines in current clinical use. The properties of benzodiazepines make them ideally useful for managing anxiety (e.g. diazepam, chlordiazepoxide, lorazepam) insomnia (e.g. diazepam, temazepam, nitrazepam, loprazolam, flurazepam, lormetazepam) epilepsy (e.g. clobazam, diazepam, lorazepam) sports injuries where muscle relaxation is required (e.g. diazepam) and as premedications prior to surgery (e.g. midazolam, lorazepam). The benzodiazepines have a number of other uses, including management of alcohol withdrawal syndrome (chlordiazepoxide, diazepam) and restless legs (clonazepam). Short... 

Clonazepam is a benzodiazepine that is used predominantly in epilepsy, panic disorder, and mania, and also appears to be effective in relieving antipsychotic drug-induced akathisia (1). The use of clonazepam in psychiatric disorders is complicated by significant drowsiness in a majority of patients, and additional behavioral problems in children (SEDA-19, 34). 

A 2-year old girl with epilepsy and dyskinetic cerebral palsy due to kemicterus, who was taking carbamaze-pine and valproate, was also given clonazepam 0.05 mg/day and 3 days later developed urinary retention, which did not improve with antibiotic treatment (10). A urine sample obtained by catheterization was sterile. Urinary retention persisted for 10 days, requiring repeated catheterization, but resolved after clonazepam was withdrawn. She was symptom free for the next 6 months. 

The mutual interaction of clonazepam and carbamazepine has been investigated in 183 children and adults with epilepsy during routine clinical care (13). Carbamazepine increased the clearance of clonazepam by 22% and clonazepam reduced the clearance of carbamazepine by 21%. 

The effects of concomitant carbamazepine, phenytoin, sodium valproate, and zonisamide on the steady-state serum concentrations of clonazepam have been investigated in 51 epileptic in-patients under 20 years of age (14). Serum concentrations of clonazepam correlated positively with the dose of clonazepam and negatively with the doses of carbamazepine and valproic acid, but not with phenytoin or zonisamide. These results confirm that as the oral doses of carbamazepine and sodium valproate increase, the serum concentration of clonazepam falls, but there is no interaction with either phenytoin or zonisamide. In the case of carbamazepine the mechanism of action is thought to be enzyme induction, increasing the metabolism of clonazepam. It is not known what the mechanism is with sodium valproate. In patients with epilepsy, the co-administration of either sodium valproate or carbamazepine will reduce the serum concentration of clonazepam and increase the risk of a seizure. When... 

Uses. Benzodiazepines are used for insomnia, anxiety, alcohol withdrawal states, muscle spasm due to a variety of causes, including tetanus and cerebral spasticity, epilepsy (clonazepam, see p. 421), anaesthesia and sedation for endoscopies and cardioversion. 

Clonazepam (Rivotiil) (tV 25 h) is a benzodiazepine used as a second line drug for treatment of primary generalised epilepsy and for status epilepticus (see Table 20.1). 

Melon G, Nasta L, Pinto RM, Spalice A, Raucci U, lannetti P. Clonazepam prophylaxis and busulfan-related myoclonic epilepsy in autografted acute leukemia patients. Haematologica 1995 80(6) 532-4. 

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