EPILEPTIC PATIENTS

DIAZEPAM-THE DRUG OF CHOICE
first marketed as Valium ( /ˈvæliəm/) by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms (such as in cases of tetanus), restless legs syndrome, alcohol withdrawal, benzodiazepine withdrawal and Ménière’s disease. It may also be used before certain medical procedures (such as endoscopies) to reduce tension and anxiety, and in some surgical procedures to induce amnesia.[1][2] It possesses anxiolytic, anticonvulsant, hypnotic, sedative, skeletal muscle relaxant, and amnestic properties.[3] The pharmacological action of diazepam enhances the effect of the neurotransmitter GABA by binding to the benzodiazepine site on the GABAA receptor leading to central nervous system depression.[4]

Adverse effects of diazepam include anterograde amnesia (especially at higher doses) and sedation as well as paradoxical effects such as excitement, rage or worsening of seizures in epileptics. Benzodiazepines also can cause or worsen depression. Long-term effects of benzodiazepines such as diazepam include tolerance, benzodiazepine dependence as well as a benzodiazepine withdrawal syndrome upon dose reduction; additionally after cessation of benzodiazepines cognitive deficits may persist for at least 6 months and may not fully return to normal, however it was suggested that longer than 6 months may be needed for recovery from some deficits.[4] Diazepam also has abuse potential and can cause serious problems of addiction. Urgent action by National Governments to improve prescribing practices has been recommended.[5][6]

Advantages of diazepam are a rapid onset of action and high efficacy rates which is important for managing acute seizures; benzodiazepines also have a relatively low toxicity in overdose.[4] Diazepam is a core medicine in the World Health Organization’s “Essential Drugs List”, which is a list of minimum medical needs for a basic health care system.[7] Diazepam is used to treat a wide range of conditions and has been one of the most frequently prescribed medications in the world for the past forty years. It was first synthesized by Leo Sternbach.[8]
Diazepam is mainly used to treat anxiety, insomnia, and symptoms of acute alcohol withdrawal. It is also used as a premedication for inducing sedation, anxiolysis or amnesia before certain medical procedures (e.g., endoscopy).[9][10]

Intravenous diazepam or lorazepam are first line treatments for status epilepticus;[4][11] However, lorazepam has advantages over diazepam including a higher rate of terminating seizures and a more prolonged anticonvulsant effect.[12] Diazepam is rarely used for the long-term treatment of epilepsy because tolerance to the anticonvulsant effects of diazepam usually develops within 6 to 12 months of treatment, effectively rendering it useless for that purpose.[13][14] Diazepam is used for the emergency treatment of eclampsia, when IV magnesium sulfate and blood pressure control measures have failed.[15][16] Benzodiazepines do not have any pain relieving properties of themselves and are generally recommended to be avoided in individuals with pain.[17] However, benzodiazepines such as diazepam can be used for their muscle relaxant properties to alleviate pain which is caused by muscle spasms, caused by various dystonias, including blepharospasm[18][19] Tolerance often develops to the muscle relaxant effects of benzodiazepines such as diazepam.[20] Baclofen[21] or tizanidine is sometimes used as an alternative to diazepam. Tizanidine has been found to be equally effective as other antispasmodic drugs and have superior tolerability than baclofen and diazepam.[22]

The anticonvulsant effects of diazepam, can help in the treatment of seizures, due to a drug overdose or chemical toxicity as a result of exposure to sarin, VX, soman (or other organophosphate poisons; See #CANA), lindane, chloroquine, physostigmine, or pyrethroids[13][23] Diazepam is sometimes used intermittently for the prophylaxis of febrile seizures which occur as a result of a high fever in children and neonates under 5 years of age.[4][24] Long-term use of diazepam for the management of epilepsy is not recommended; however, a subgroup individuals with treatment resistant epilepsy benefit from long-term benzodiazepines and for such individuals clorazepate has been recommended due to its slower onset of tolerance to the anticonvulsant effects.[4]

Diazepam has a broad spectrum of indications (most of which are off-label), including:
Treatment of anxiety, panic attacks, and states of agitation[9]
Treatment of neurovegetative symptoms associated with vertigo[25]
Treatment of the symptoms of alcohol, opiate and benzodiazepine withdrawal[9][26]
Short-term treatment of insomnia[9]
Treatment of tetanus, together with other measures of intensive-treatment[27]
Adjunctive treatment of spastic muscular paresis (para-/tetraplegia) caused by cerebral or spinal cord conditions such as stroke, multiple sclerosis, spinal cord injury (long-term treatment is coupled with other rehabilitative measures)[28]
Palliative treatment of stiff person syndrome[29]
Pre-/postoperative sedation, anxiolysis and/or amnesia (e.g., before endoscopic or surgical procedures)[28]
Treatment of complications with a hallucinogen crisis and stimulant overdoses and psychosis, such as LSD, cocaine, or methamphetamine.[13]
Prophylactic treatment of oxygen toxicity during hyperbaric oxygen therapy[30]

Dosages should be determined on an individual basis, depending upon the condition to be treated, the severity of symptoms, the body weight of the patient, and any comorbid conditions the patient may have.[13