clonazepam

Clonazepam
Systematic ( IUPAC) name
6-(2-chlorophenyl)-9-nitro- 2,5-diazabicyclo[5.4.0]undeca- 5,8,10,12-tetraen-3-one
Identifiers
CAS number	1622-61-3
ATC code	N03 AE01
PubChem	2802
DrugBank	APRD00054
Chemical data
Formula	C15 H10 Cl N3 O3
Mol. mass	315.715
Pharmacokinetic data
Bioavailability	90%
Metabolism	Hepatic CYP3A4
Half life	18-50 hours
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	C ( AU ) D ( US )
Legal status	Schedule IV ( US )
Routes	Oral, I.M., I.V

Clonazepam (marketed by Roche under the trade-names Klonopin in the United States and Rivotril in Europe, South America, Canada, India, and Australia) is a drug which is a benzodiazepine derivative. It is a highly potent anticonvulsant, amnestic, and anxiolytic.

Pharmacology

Like other benzodiazepines, clonazepam is believed to act by simulating the action of GABA on the central nervous system. Because of strong anxiolytic properties and euphoric side-effects it is said to be among the class of 'highly potent' benzodiazepines. Although benzodiazepines are valuable in the treatment of anxiety disorders, they have some potential for misuse and may cause dependence or addiction. The sedative effects of clonazepam are relatively weak, when compared to its strong anxiolytic and anticonvulsant effects, as well as when compared to most other benzodiazepines. One milligram of clonazepam is approximately equivalent to twenty milligrams of diazepam. [1]

Unlike most other benzodiazepines clonazepam appears to also have a secondary effect on the neurotransmitter serotonin. [2]. It has shown itself to be useful as a short-term adjunct to SSRI treatment in Clinical Depression [3], and Obsessive Compulsive Disorder, [4] with the combination being superior to SSRI treatment alone. Similar results have been found with some other anxiety disorders, but the role of the serotonergic effects enhancing the action of the SSRI treatment remains unclear in these cases due to clonazepam's primary anxiolytic mechanism of action.

Indications

Clonazepam is commonly prescribed for:

• Epilepsy
• Hyperekplexia. Clonazepam is prescribed to dampen the effects of the disorder, reducing the startle response in sufferers. Those who fall when startled are less likely to do so once treated.
• Anxiety disorders. Due to the chronic nature of anxiety, long-term low-dose benzodiazepine treatment may be necessary for some patients; this continuation of treatment should not be considered abuse or addiction.
• Panic attacks
• Restless leg syndrome (RLS)
• Initial treatment of mania, together with firstline-drugs such as lithium, haloperidol or risperidone
• Hallucinogen persisting perception disorder (off-label use)
• Chronic fatigue syndrome
• Night terrors
• Tourette Syndrome - Clonazepam has shown to be helpful in reducing and dealing with the physical motor tics associated with TS, though is still considered an off-label usage by many.
• Schizophrenia - Clonazepam has been prescribed in order to alleviate the side effects of certain antipsychotic agents used in the treatment of Schizophrenia.

Clonazepam is rarely used as a treatment for insomnia, because its sedative effects are relatively weak compared to other benzodiazepines.

Availability

Clonazepam was approved in the United States as a generic drug in 1997 and is now manufactured and marketed by several companies.

Clonazepam is available in the U.S. as tablets (0.5, 1.0, and 2mg), orally-disintegrating tablets (wafers) (0.125, 0.25, 0.5, 1.0, and 2 mg), liquid solution (2.5mg per ml) and for injection (1mg per ml)

Side effects

Common:

• Drowsiness
• Impairment of cognition and judgment
• Impaired motor function
  • Impaired coordination
  • Impaired balance
  • Dizziness
• Anterograde amnesia (common with higher doses)

Rare:

• Paradoxical Disinhibition ^[1] (Most frequently in children, the elderly, and in persons with developmental disabilities)
  • Rage
  • Excitement
  • Irritability
  • Impulsivity
  • Some users report hangover-like symptoms of being drowsy, having a headache, being sluggish, and irritable after waking up if the medication is taken before sleep. This is likely the result of the medication's long half-life which continues to affect the user after they wake up as well as its disruption of the REM cycle.

Withdrawal-related:

• Anxiety, irritability, insomnia
• Panic attacks, tremor
• Seizures similar to delirium tremens (With long-term use of excessive doses)

Use of alcohol or other CNS depressants while taking clonazepam greatly intensifies the effects (and side effects) of the drug. Side effects of the drug itself are generally benign, but sudden withdrawal after long-term use can cause severe, even fatal symptoms.

Interactions

Similar to Diazepam.

Overdose

An individual who has consumed too much clonazepam will display one or more of the following symptoms:

• Somnolence (difficulty staying awake)
• Mental confusion
• Hypotension
• Impaired motor functions
  • Impaired reflexes
  • Impaired coordination
  • Impaired balance
  • Dizziness
• Coma

Unless combined with other drugs, deep coma or other manifestations of severe central nervous system depression are rare, and the mortality rate associated with poisoning is very low. As with other benzodiazepines, overdose symptoms of clonazepam may be reversed with flumazenil (Romazicon®).

Recreational Use

Benzodiazapines such as Clonazepam are sometimes used recreationally, when used for this function they are often referred to by the slang term "clammies", "Klonnies", or "Kpins" if in Klonopin form, most commonly as a secondary drug to increase the pleasure resulting from a primary drug, or possibly to lessen or prevent some of the primary drug's negative side effects. It should be noted that relatively few cases of addiction arise from legitimate use of benzodiazepines. [5]

Up to 30% of individuals treated on a long-term basis develop a form of dependence known as "low-dose-dependence". These patients do not develop a tolerance, and do not need increasingly large doses to experience the anxiolytic side effects of the drug.

References

• O'Brien, CP. "Benzodiazepine use, abuse, and dependence", Journal of Clinical Psychiatry. 2005;66 Suppl 2:28-33. [6]
• Wallace, Christina. "Kpin, a hit drug with teens, can be deadly, officials say." Boston Metro, Wednesday April 12, 2006. Page 2.

External links

• Rx-List - Clonazepam
• Poisons Information Monograph - Clonazepam
• FDA prescription insert

Benzodiazepines ( N05BA , N05CD )

Adinazolam • Alprazolam • Bentazepam • Bromazepam • Brotizolam • Camazepam • Chlordiazepoxide • Cinolazepam • Clobazam • Clonazepam • Clorazepate • Clotiazepam • Cloxazolam • Cyprazepam • Diazepam • Doxefazepam • Estazolam • Ethyl loflazepate • Etizolam • Fludiazepam • Flumazenil • Flunitrazepam • Flurazepam • Flutazolam • Flutoprazepam • Gidazepam • Halazepam • Haloxazolam • Ketazolam • Loprazolam • Lorazepam • Lormetazepam • Medazepam • Mexazolam • Midazolam • Nimetazepam • Nitrazepam • Nordazepam • Oxazepam • Oxazolam • Phenazepam • Pinazepam • Prazepam • Quazepam • Ro15-4513 • Temazepam • Tetrazepam • Tofisopam • Triazolam • Zolazepam

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