Depressant Abuse: The Dangers of Benzodiazepines

By Dr. Mohamed Isa Abd. Majid
The Sun, August 24, 1996

DEPRESSANTS ARE A CLASS OF drugs meant for treating seizures, relaxing muscles and reducing anxietites. The primary action of these drugs is on the central nervous system where an inhibitory effect is observed, resulting in the slowing down of the nervous system.

Among the depressants that give rise to the general conditions described are chloral hydrate, abroad array of barbiturates, glutethimide, methaqualone, meprobamate and benzodiazepines, which are widely abused in many developed countries.

When taken as prescribed by a physician, depressants may be beneficial for the relief of anxiety, irritability and tension as well as insomnia. In excessive amounts, however, they may produce a state of intoxication remarkably similar to that of alcohol

As in the case of alcohol, these effects may vary not only from person to person but from time to time in the same individual. Low doses produce mild sedation. Higher doses, so far as they relieve anxiety or stress, may produce a temporary sense of well-being. However, they may also produce mood depression and apathy.

In marked contrast to the effects of narcotics as illustrated in previous issues of Poison Information, intoxicating doses invariably result in impaired judgement, slurred speech and loss of motor coordination.

In addition to the dangers of disorientation, which result in a high incidence of highway accidents, recurrent users also incur the risks of long-term involvement with depressants.

In Malaysia,there are at least 11 types of benzodiazepines in the market (see Table 2). They are mostly prescribed as minor tranquilisers or hypnotics/sedatives. They are also divided into three groups based on their duration of action (see Table 1).

DURATION OF ACTION OF DIFFERENT TYPES OF BENZODIAZEPINES
Ultra-short acting (<10 hours)
Midazolam 2 - 5 hours
Triazolam 1.7 - 3 hours
Short acting (10 - 24 hours)
Alprazolam 11 - 14 hours
Bromazepam 8 - 20 hours
Lorazepam 10 - 20 hours
Long acting (> 24 hours)
Chlordiazepoxide 5 - 30 hours
Chlorzepate 367 - 200 hours
Clobazam 11 - 77 hours
Diazepam 20 - 50 hours
Flurazepam 50 - 100 hours
Nitrazepam 21 - 25 hours
Table 1

Because of their supposedly wide safety margin, in many developed economies, benzodiazepines are considered the most common prescription drugs which people overdose with.

For example, over the last 10 years in the United Kingdom, 1,512 fatal poisonings have been attributed to benzodiazepines, with or without alcohol ingested as well. Of drugs frequently prescribed, temazepam, a type of benzodiazepine which is not available in Malaysia, has the highest number of deaths per million prescriptions (fatal toxicity index) at 11.9, above that of some tricyclic anti-depressants.

Oral ingestion of up to 1,500 mg of diazepam with only minor toxicity has been reported. The body appears to adapt rapidly to high blood levels. This tolerance tends to limit central cardiorespiratory depression.

Benzodiazepines also generally do not cause undesirable damage to the brain, heart, liver or kidneys. Respiratory depression may occur in overdose. Deep coma is rare, even following massive overdoses.

The elderly and very young children are more susceptible to the central depressant action of benzodiazepines. Among the elderly, the toxicity of benzodiazepines takes on an additional dimension. Subtle but measurable cognitive impairment may be associated with both acute and chronic therapeutic doses of benzodiazepines. Unsteadiness and an increased predisposition to falling are not uncommon. Therefore, extra caution must be exercised when benzodiazepines are prescribed.

Some side-effects of benzodiazepines in children has yet to be established. Nevertheless, two cases of psychosis had been reported in children who were given benzodiazepines. Visual and tactile hallucinations, sensitivity to bright light, impaired coordination, insomnia and feelings of fear were reported.

Tolerance to the intoxicating effects develop rapidly, leading to a progressive narrowing of the margin of safety between an intoxicating and lethal dose. The person who is unaware of the dangers of increasing dependence will often increase the daily dose up to 10 or 20 times the recommended therapeutic level.

The source of supply may be no further than the family medicine cabinet. Depressants are also frequently obtained through theft, illegal prescription or purchased from the black market.

Adherents of drug sub-cultures often resort to the use of depressants as self-medication to soothe jangled nerves brought on by the use of stimulants, to quell the anxiety of "flashbacks" resulting from prior use of hallucinogens or to ease their withdrawal symptoms from heroin abuse.

The dangers, it should be stressed, are compounded when depressants are used in combination with alcohol or other drugs. Chronic intoxication, though it affects every age group, is most common in middle age. The problem often remains unrecognised until the user exhibits recurrent confusion or an obvious inability to function. Depressants also serve as a means of suicide, a pattern particularly common among women.

The abrupt cessation or reduction of high-dose depressant intake may result in a characteristic withdrawal syndrome, which should be recognisedas a medical emergency more serious than that of any other forms of drug abuse.

An apparent improvement in the patient's condition may be the initial result of intoxication. Within 24 hours, however, minor withdrawal symptoms manifest, among them anxiety and agitation, loss of appetite, nausea and vomiting, increased heart rate, excessive sweating, tremors and abdominal cramps.

The symptoms usually peak during the second or third day of abstinence from the short-acting benzodiazepines. They may not be reached until the seventh or eighth day of abstinence from the long-acting benzodiazepines. It is duringthe peak period that the major withdrawal symptoms usually occur.

The patient may also experience convulsions indistinguishable from those occurrring in epilepsy. More thean half of those who experience convulsions will go on to develop delirium, often resulting in a psychotic state identical to the delirium tremens associated with the alcohol withdrawal syndrome.

Detoxification and treatment must thereforebe carried out under close medical supervision. While treatment techniques vary to some extent, they share a common objective: stabilisation of the drug-dependent state to ally withdrawal symptoms to prevent their recurrence.

In cases of benzodiazepine poisoning, moderate poisoning closely resembles alcoholic intoxication. The symptoms of severe poisoning are coma, cold clammy skin, a weak and rapid pulse as well as slow or rapid but shallow respiration.

Death will follow if the reduced respiration and low blood pressure are not counteracted by proper medical treatment. Usually, in such cases of poisoning, an antidote known as flumazenil has been shown to reverse the toxic effects.

There have been published scientific reports which indicate patients with pure benzodiazepine poisoning show full consciousness within minutes while those having mixed drug overdose respond only partially. These findings doprovide a specific antidote to treat suicidal or accidental cases of such poisonings.

As a conclusion, although it is generally believedto be a safe drug for treating anxiety, the therapeutic dose of benzodiazepines still holds potential hazards to a patient.

True physical dependence can emerge from a chronic therapeutic use. Thus, if possible, the introduction of non-pharmacologic treatments for anxiety such as relaxation training and cognitive restructing and problem solving techniques may be helpful.

TYPES OF BENZODIAZEPINES
Minor Transquiliser Hypnotic/Sedative
  • Alprazolam
  • Flurazepam
  • Bromazepam
  • Midazolam
  • Chlordiazepoxide
  • Nitrazepam
  • Clobazam
  • Triazolam
  • Clorazepate
 
  • Diazepam
 
  • Lorazepam
 
Table 2

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