Benzodiazepine drugs (xanax, alprazolam etc…)

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Benzodiazepine drugs are widely used in medicine to treat anxiety and insomnia. These are synthetic substances normally seen as pharmaceutically-manufactured tablets, capsules and occasionally as injectables. They act as depressants of the central nervous system (CNS). Chlordiazepoxide (Librium) was the first to be synthesised in 1957 and introduced into medicine in 1961. Benzodiazepines are under international control.

Chemistry

The fully systematic (IUPAC) name for the nucleus of the benzodiazepine group (CAS 12794-10-4) is 2,3-diazabicyclo[5.4.0]undeca-3,5,7,9,11pentaene. The different drugs have varying substituents on this basic skeleton.

Pharmacology

Benzodiazepine drugs are a group of CNS depressants which induce feelings of calm (anxiolysis), drowsiness and sleep.  They act by facilitating the binding of the inhibitory neurotransmitter GABA at various GABA receptors throughout the CNS. Because they have a lower tendency to cause a potentially fatal CNS depression compared to earlier drugs such as barbiturates, benzodiazepine drugs are widely used in medicine for the treatment of anxiety (anxiolytics) and insomnia (sedative/hypnotics), as well as other psychological conditions such as panic attacks and panic disorders. There is no clear division between anxiolytics and hypnotics, since most anxiolytics will induce sleep if taken at night and most hypnotics will sedate when taken during the day.

Different benzodiazepines vary in the rate in which they are metabolised to pharmacologically active forms and particularly in their half-lives (see Table 1): short-acting drugs have a half-life of less than 24 hours e.g. midazolam; intermediate-acting compounds such as nitrazepam have half-lives greater than 24 hours, whereas long-acting compounds such as diazepam have half-lives greater than 48 hours. Such half-lives vary between individuals, and the elderly tend to eliminate these drugs much more slowly. They are thus more at risk from the side-effects which include drowsiness, ataxia (staggering gait), mental confusion, impaired judgement and anterograde amnesia. There is a significantly increased risk of adverse events in the elderly such as falls, diminished cognitive function and driving impairment, although the latter is not confined to the elderly. The European prevalence studies show that, excluding alcohol, benzodiazepines are along with cannabis the psychoactive substances most prevalent in the driving population. Experimental studies show that these drugs impair driving ability and when alcohol is also used, the risk of being involved in or responsible for a road accident is significantly increased.

Benzodiazepine intoxication can be associated with behavioural disinhibition, potentially resulting in hostile or aggressive behaviour. The effect is perhaps most common when benzodiazepines are taken in combination with alcohol. The combined use of alcohol and benzodiazepines also increases the risk of a fatal overdose because both act as CNS depressants. A similar fatal interaction can occur when opiates are taken with benzodiazepines as part of a pattern of polydrug use. A significant number of problem drug users swallow, ‘snort’ or inject high doses of benzodiazepines to enhance the euphoriant  effects of opiates or to minimise unpleasant effects of psychostimulants. The EMCDDA’s Annual report on the state of the drugs problem in Europe highlights the fact that concomitant use of benzodiazepines and opiates is a major risk factor in drug-related deaths. Apart from the increased risk of fatal overdoses, the usual injection-specific diseases such as tissue damage, gangrene and transmission of HIV and Hepatitis C also occur if the drugs are injected.

There is also the risk of cross-dependence developing to benzodiazepines. Medically, benzodiazepines should only be used for the short-term relief of anxiety or insomnia which is severe and disabling. This is because tolerance and dependence can occur just weeks after use has commenced. Withdrawal signs and symptoms can be classified as major or minor, like those of the alcohol syndrome. According to that classification, minor symptoms include anxiety, insomnia and nightmares. Major symptoms include perceptual disturbances, psychosis, hyperpyrexia and life-threatening convulsions.

When and how should benzodiazepines be used?

Benzodiazepines should only be used to treat severe anxiety or severe insomnia that is having a significant impact on your day-to-day life.

There are some situations when their use may not be appropriate. After a bereavement, for example, tranquillisers may numb your emotions and prevent you from grieving properly. But if you are unable to sleep because of grief and anxiety, a sleeping pill may help you to relax and start to recover.

Benzodiazepines are likely to be most effective if you take them as a one-off dose for one occasion, and not as continuous treatment.

The usual advice is that they should not be taken for longer than four weeks, and should not be taken every day. However, depending on individual circumstances, some doctors may prescribe them at low doses for long periods and this does not always cause a problem – this could be the best treatment for some people.

Mode of use

Benzodiazepines are usually swallowed as tablets but can be injected for both medical and non-medical purposes and there are some reports of intranasal (snorting) misuse.

Can I take benzodiazepines with other medication?

If you are taking any other medicines (on prescription, over-the-counter, or from an alternative health practitioner), tell your doctor or the pharmacist. Combining other medication with benzodiazepines can change the effects of the drugs or cause additional side effects.

Benzodiazepines are often used in combination with other psychiatric drugs:

Benzodiazepines and antidepressants – if you are prescribed antidepressants, some doctors may suggest that you also take a benzodiazepine at first. This is because benzodiazepines work quickly, while antidepressants may take a few weeks to have an effect. Once the antidepressants start to have an effect, you can stop the benzodiazepine and continue with the antidepressant.

Benzodiazepines and antipsychotics – sometimes used together to treat schizophrenia or similar conditions. You may be given them short-term to calm you down quickly if you are very agitated or over-excited, or having a severe mental health crisis (especially if you are in hospital).

For specific drug interactions, see the Sleeping Pills and Minor Tranquillisers A-Z.

Note: drinking alcohol increases the sedative effect of benzodiazepines. Ask your doctor or pharmacist whether it’s safe to drink alcohol while you’re taking these drugs.

Benzodiazepine Abuse Causes

Although some people may have a genetic tendency to become addicted to drugs, there is little doubt that environmental factors also play a significant role. Some of the more common environmental influences are low socioeconomic status, unemployment, and peer pressure.

 Benzodiazepine Abuse Symptoms

At normal or regular doses, benzodiazepines relieve anxiety and insomnia. They are usually well tolerated. Sometimes, people taking benzodiazepines may feel drowsy or dizzy. This side effect can be more pronounced with increased doses.

Benzodiazepine Abuse Treatment

– Benzodiazepine Abuse Treatment Self-Care at Home

Drug abusers often deny their problem by playing down the extent of their drug use or blaming job or family stress. The most important thing that can be done at home is to recognize that there may be a problem and to seek help.

– Awareness of the signs and symptoms of abuse help with recognition.

– The next step is to try to obtain help for the person. This can be done either through your doctor or by contacting many of the drug abuse help lines in your community.

– Medical Treatment

Acute toxicity: The treatment required usually depends on what drugs were taken and how much. Often, you need only a period of evaluation in a hospital emergency department:

– If the drugs were taken within the previous 1-2 hours, the doctor may consider gastric lavage. With this procedure, a large tube is placed directly into your stomach through the mouth or nose. Large volumes of water can then be pushed into the stomach in an attempt to wash out the pill fragments. This is not used often and only if you are known to have swallowed other potentially more lethal medications.

– A single dose of activated charcoal is recommended for people who come to the emergency department within 4 hours of taking drugs. This acts to prevent absorption of the medication. It is a black powder that is mixed with water and given to you to drink. Side effects can include nausea, vomiting, and abdominal cramps.

– There is an antidote to counteract the toxic effects of benzodiazepines called flumazenil (or Romazicon). This reverses the sedative effect of benzodiazepines. It is, however, usually reserved for severe poisoning, because it can cause withdrawal and seizures in people who are chronic benzodiazepine abusers, and also may require repeated administrations, with careful monitoring, due to its fairly short duration of action.

Chronic abuse:

The treatment of chronic abuse can usually be done at home with the help of your doctor or in specific drug rehabilitation centers. The first step consists of gradual reduction of benzodiazepines to prevent withdrawal and seizures. This is often much easier than the prolonged recovery phase in which the person attempts to stay drug-free. In addition to the medical care, someone abusing these drugs often requires social support and help in finding housing and employment. The involvement of family and friends can be very helpful in this difficult stage.

Expert advice: Dr Girard

I have worked with manufacturers of psychotropic drugs, and in particular on “paradoxical reactions”; the beneficial consequence of this state of affairs is that I was able to devote a lot of time to these problems, with almost unlimited access to the available documentation, including numerous non-public access documents (internal pharmacovigilance data, for example).

A few words of definition, first: is “paradoxical” a reaction which, as its name suggests, goes in the opposite direction to the effect we were looking for when prescribing the drug. Very many parents have the experience of children who transform themselves into an electric battery once they have been prescribed a syrup “to sleep” … Relative to psychotropic drugs which aim, according to molecules and indications, to tame a delirium, to calm an agitation or an anxiety, or to soften a depression, one will call “paradoxical” any reaction which goes in opposite direction: in practice, the most spectacular and those which hold the most attention of the media, these are acts of criminal violence, suicidal behavior, sleepwalking. It is also classic to classify as “paradoxical” the reactions of sexual disinhibition, chemical submission or amnesia, even if I am not sure that they correspond exactly to the definition which has just been given.

To tell the truth, there is nothing very mysterious in the very existence of such reactions: the human brain is a complicated organ, the determinism of psychological reactions is extraordinarily complex, and when one begins to want to play pharmacologically with everything that is a bit like the image of the elephant in a porcelain store. But it’s not just drugs, and any centrally acting substance can cause similar ones; thus, everyone has had the opportunity to observe such reactions to alcohol, which are declined according to two main models: “fundamental intolerance”, which is expressed in these people who start to unlock as soon as ‘they drink even a very small dose (“the slightest drop of alcohol made him crazy”, writes Zola in The Human Beast), and “bad alcohol”, namely this tendency that some people have to become naughty or aggressive when they have been drinking a lot, instead of foolishly laughing or going to sleep.

From this single example, we immediately understand that the problem is not only a question of dose, and we see at the same time the question of “terrain” – or, more specifically in this case, of personality. One does not need to have read all of Freud to know that, in some people, the control of the ego over the impulses is extremely precarious and that sometimes it takes very little to break down barriers: is not everyone who, under the influence of a psychotropic, will exterminate his partner with a screwdriver … The medical press has also published the case1 of this excessively pious young woman who intended for a very ascetic religious life and who , under the influence of a treatment with a benzodiazepine, found herself a stripper in a night club – apparently very excited by this (re) conversion (“enthusiastically” said the English text) … at least until that she stop taking her medication2 (less spectacularly, some honest fathers of families confide not without satisfaction that their wives are much more sexually available as soon as they take their sleeping pills…). Sometimes, however, a preexisting psychological fragility has been more or less concealed and ignored, hence the impression – which tends to attract the attention of the media – of a “thunderclap in a serene sky”. I thus knew the case of a young woman who, presenting herself as absolutely “normal”, had developed a delirium at her dentist, after the administration of a banal analgesic of central action: by insisting a little, i ended up learning that she had a heavy history of drug addiction

These considerations introduce the difficult problem of causation. In the hundreds of cases I have studied, I do not remember seeing many without “associated factors”: psychiatric history often in proportion to the reported paradoxical reaction, concomitant use of other toxic drugs (alcohol, drugs ), association with other psychotropic drugs. It must be understood, on the other hand, that most subjects with mental pathology receive psychotropic drugs, and that it is sometimes very difficult to distinguish between the effect of the treatment or the condition which led to such a treatment: it is a classic of lawyers specialized in medical damage to receive people wishing to file a complaint against the manufacturer or the prescriber of such or such drug because of the psychic effects supposedly induced in them, and which it appears that it s are psychotics who, more often than not in a press article, have started to take the flu from one or other of the many drugs they have received for decades. Another great forensic classic, when you have committed a crime, to incriminate the drugs that you were supposed to be taking at the time of the offense – even if it is not always certain that had taken them.

Implicitly, I answered the question about the frequency of such paradoxical reactions: we just don’t know it, because of all these difficulties in establishing causation on a case-by-case basis. It goes without saying, too, that organizing clinical trials against placebo to assess said frequency would pose great difficulties. There are certainly retrospective epidemiological studies which claim to identify risk factors, but do not allow a precise frequency to be measured.

As for the question of age, I am not informed of specific risks in childhood – knowing that, personally, the idea of ​​prescribing psychotropic drugs to subjects whose neurological constitution is not completed seems to me fairly criminal , except in special cases (surgical intervention, extreme stress, serious neuro-psychiatric pathology, etc.). At the other end of life, on the other hand, old age is clearly a cause of exaggerated sensitivity to the toxic effects of all these agents and psychotropic overprescription in the elderly is an odious scandal: it is certain, for example, that Alzheimer’s figures are swollen by all these old people who are artificially mad because of these drugs which they have no real need for.

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I now come to the question of whether certain drugs are more involved than others. In fact, all drugs (not only psychotropic) that may have an action, even secondary, on the central nervous system can trigger such reactions: I mentioned earlier some painkillers, we could also talk certain cough syrups (which have the same chemical structure as the “sleeping syrups” which I have already mentioned, which is more or less that of a neuroleptic : it’s good to know…). We are also talking, at the moment, about certain smoking cessation drugs. Carefully handled by whoever has an interest in it, the relentlessness that is already old on the benzodiazepine class is not neutral: these are products that are very old, as such not badly studied, remarkably effective and extremely well tolerated all other things being equal moreover, but which, because of their age, no longer yield enough, in comparison with newer drugs, not necessarily well known, of more problematic efficacy and tolerance, but much more profitable for their manufacturers – and the same more costly blow for “national solidarity”. Some of your readers may have witnessed a recent altercation on television, during a program in which another speaker took the liberty of taking me back when I said that we must stop demonizing old ladies who could not switch from their quarter of Lexomil in the evening, at bedtime: if the problem of geriatric overprescription was limited to the small sub-population of elderly people who take a quarter of Lexomil in the evening, there would be no problem at all – and it should be, among others, a shame for our health authorities to have devoted so much energy (besides in vain) to this poor question in view of the real problems which threaten public health. On this subject, I would also like to once again take issue with the preconceived idea that the French are “the biggest consumers of psychotropic drugs” in the world: they are perhaps the biggest buyers thanks to insurance- illness that encouraged them to be irresponsible (I’m not talking about that of prescribers …), but I don’t know of any study that measures the actual consumption of drugs – and I invite anyone who wants to go and see those that remain unused in the neighbor’s medicine cabinet.

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Benzodiazepine drugs (xanax, alprazolam etc…)

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