Benzodiazepine abuse is a growing problem and carries serious risks to health and society. Benzodiazepines are commonly used by polydrug abusers, alcoholics and sometimes as primary recreational drugs. People who abuse benzodiazepines often take very large doses orally, by injection or by snorting. Benzodiazepine use leads to dependence and a withdrawal syndrome which may include convulsions and psychosis. Further research is needed on the optimal short-term and long-term management of benzodiazepine abuse. The primary source of illicit benzodiazepines is from doctors' prescriptions.

2. Sedative-Hypnotics
• Sedative-hypnotics are drugs that depress or slow down the body's
functions.
• Often these drugs are referred to as tranquilizers and sleeping pills
or sometimes just as sedatives.
• Their effects range from calming down anxious people to promoting
sleep.
• Both tranquilizers and sleeping pills can have either effect,
depending on how much is taken.
• Barbiturates and benzodiazepines are the two major categories of
sedative-hypnotic.

3. Benzodiazepines
• A benzodiazepine (sometimes collectively benzo often
abbreviated " BZD ") is a psychoactive drug whose core
chemical structure is the fusion of a benzene ring and a
diazepine ring.
• Benzodiazepines act by enhancing presynaptic/postsynaptic
inhibition through a specific BZD receptor which is an integral
part of the GABAA receptor- Cl channel complex.
• Benzodiazepines are basically sedatives drugs that have been
prescribed around the world over several decades for a range
of indications including:
 Anxiolytic (relief of anxiety)
 Hypnotic (promotion of sleep)
 Myorelaxant (muscle relaxation)
 Anticonvulsant (control fits convulsions)
 Amnesia (sedation for surgical procedures)

4. Chemical structures of benzodiazepines

5. Pharmacokinetic Properties Of Some Benzodiazepines & Newer Hypnotic In Human
Drug peak blood Elimination Comment
level(hr) half-life(hr)
Alprazolam 1-2 12-15 rapid oral absorbtion
Chlordiazpoxide 2-4 15-40 active metabolites;erratic bioavailibility from IM injection
Clorazepate 1-2 50-100 prodrug;hydrolyzed to active from in stomach
Diazepam 1-2 20-80 active metabolites;erratic bioavailibility from IM injection
Eszopiclone 1 6 minor active metabolites
Flurazepam 1-2 40-100 active metabolites with long half-life
Lorazepam 1-6 10-20 no active metabolites
Oxazepam 2-4 10-20 no active metabolites
Temazepam 2-3 10-20 slow oral absorbtion
Triazolam 1 2-3 rapid onset;short duration of actoin
Zaleplon <1 1-2 metabolized via aldehyde dehydrogenase
Zolpidem 1-3 1.5-3.5 no active metabolites

6. BENZODIAZEPINE ABUSE

7. Key points
• Benzodiazepine abuse is a growing problem and carries
serious risks to health and society.
• Benzodiazepines are commonly used by polydrug abusers,
alcoholics and sometimes as primary recreational drugs.
• People who abuse benzodiazepines often take very large doses
orally, by injection or by snorting.
• Benzodiazepine use leads to dependence and a withdrawal
syndrome which may include convulsions and psychosis.
• Further research is needed on the optimal short-term and
long-term management of benzodiazepine abuse.
• The primary source of illicit benzodiazepines is from doctors'
prescriptions.

8. BENZODIAZEPINE ABUSE
Benzodiazepines are consumed by two main populations with
different characteristics:
(1) low-dose prescribed benzodiazepine users and
(2) high-dose, non-prescribed benzodiazepine abusers
It has been claimed that benzodiazepine abuse is 'of little or no
consequence' in the huge population of prescribed
benzodiazepine users.
However, a proportion of prescribed users do escalate dosage,
take the drugs for hedonic effects and enter into the illicit drug
scene.
It is important to remember that substance misuse can occur
across a wide spectrum of ages and not to allow prejudice to
hinder older people's diagnosis and treatment.

10. Why abuse benzodiazepines?
• The most common reason given by polydrug abusers for taking
benzodiazepines is that they enhance and often prolong the 'high'
obtained from other drugs including heroin, other opioids, cocaine
and amphetamines. Benzodiazepines are mainly taken along with the
primary drug, but sometimes used alone as an alternative or in times
of shortage.
• Second, benzodiazepines alleviate withdrawal effects, including
anxiety and insomnia, when supplies of other drugs are limited. Users
of stimulants including cocaine, amphetamines and Ecstasy also take
benzodiazepines as 'downers' to overcome the effects of their 'uppers'
and to combat hangover effects.
• In alcoholics, benzodiazepines are used partly to alleviate the anxiety
associated with chronic alcohol use, but also because the mixture of
alcohol and benzodiazepines produces a hedonic effect.
• Finally, benzodiazepines, when taken alone in high doses and
particularly when injected, can themselves provide a 'kick'.

11. Why abuse benzodiazepines?
• Although benzodiazepines in therapeutic doses have been
claimed to have little abuse potential compared with other
drugs of abuse, their abuse liability may vary along the dose-
response curve, becoming greater at doses above the
therapeutic range.
• Diazepam, alprazolam, lorazepam and triazolam have all been
shown in clinical laboratory studies to possess abuse liability.
• Alprazolam 1mg was comparable with 10mg d-amphetamine
in scores for 'elation' and 'abuse potential' in experienced but
non-dependent users.
• 'High' ratings for oxazepam and chlordiazepoxide were lower
than for other benzodiazepines.
• The non-benzodiazepine hypnotic zolpidem produced 'drug
liking' scores similar to triazolam; this drug and the similar
non-benzodiazepine hypnotic zopiclone may also have abuse
potential.

12. Which benzodiazepines are abused?
• Nearly all the available benzodiazepines have been
abused. In general, those which enter the brain rapidly
(e.g. diazepam) are preferred to those which are absorbed
more slowly (e.g. oxazepam).
• However, preferred drugs vary between countries and
over time depending on their availability and reputation
in the illicit drug world.

13. Generic name Brand name (UK)
Alprazolam Xanax
Bromazepam Lexotan
Chlordiazepoxide Librium
Diazepam Valium
Flunitrazepam Rohypnol
Flurazepam Dalmane
Ketazolam1 Anxon
Lorazepam Ativan
Medazepam1 Nobrium
Nitrazepam Mogadon
Oxazepam Serenid
Prazepam1 Centrax
Temazepam Normison, Euhypnos
Triazolam1 Halcion
(Zopiclone)2 Zimovane)
(Zolpidem)2 (Stilnoct)
Notes:
1No longer in British National Formulary.
2Non-benzodiazepine hypnotics with similar
actions to benzodiazepines; may have abuse
liability.

14. Routes of administration and dosage
• Benzodiazepines can be taken by mouth, inhaled as snuff or injected. The commonest practice
is oral ingestion but, recently, novel forms of administration have been used.
• Intranasal 'snorting' of powdered flunitrazepam.
• The main alternative to the oral route is intravenous injection.
• Diazepam and other benzodiazepines have been injected but at present temazepam is mainly
involved.
• Temazepam was the most commonly used and had been injected from preparations of
capsules, tablets and syrup.
• Other injected benzodiazepines are diazepam, lorazepam, triazolam, nitrazepam and
chlordiazepoxide.
• Attempts to discourage temazepam injections by substituting liquid with gel-filled capsules
and by introducing tablets and elixir appear to be unsuccessful since the gel can be warmed to
a liquid consistency, the tablets can be dissolved in warm water and the elixir diluted to
provide injectable solutions.

15. Sources of benzodiazepines
• Benzodiazepines are widely available on the Street and are
cheap.
• A major source is from general practitioners' prescriptions.
• Some users attend several practitioners using false names and
temporary patient status; others obtain supplies from friends or
patients (often elderly people) who exaggerate their needs to
their doctors and sell off the excess.
• Some children obtain them from prescriptions for their parents.
• Benzodiazepines are also obtained by theft from health centres
or retail chemists, and large amounts have been stolen from
pharmaceutical warehouses.

16. Health risks and social consequences
General Complications of IV use
Fatalities due to overdose (particularly
in combination with opioids)
Thrombophlebitis
Blackouts and memory loss Deep and superficial abscesses
Paranoia Deep vein thrombosis
Violence and criminal behaviour Pulmonary microembolism
Risk-taking sexual behaviour Rhabdomyolysis, tissue necrosis
Foetal and neonatal risks if taken in
pregnancy
Gangrene, requiring amputation
(usually due to inadvertent intra-
arterial injection)
Dependence Hepatitis B and C
Withdrawal seizures HIV infection

17. Health risks and social consequences
• Benzodiazepines are generally believed to be safe in overdose,
but deaths following self-poisoning do occur, even when the
drugs are taken alone, and a fatal outcome from overdose is
more likely with flurazepam and temazepam than with other
benzodiazepines.
• Benzodiazepines also add to the respiratory depression caused
by other drugs: the combination of temazepam with injected
opioids (e.g. buprenorphine) is said to cause approximately
100 deaths a year in Glasgow alone.
• Benzodiazepine use increases the risk of road traffic accidents,
especially when driving under the influence of higher doses.

18. Health risks and social consequences
• Mental disturbances caused by benzodiazepines include blackouts and memory loss,
aggression, violence and chaotic behaviour associated with paranoia.
• The loss of judgement and amnesia caused by benzodiazepines may also be
associated with high-risk sexual behaviour including casual sexual contacts and
unprotected sexual activity which appears to be a particular feature of temazepam
abusers.
• Cognitive impairment, including deficits in learning and memory and in sustained
attention, has been shown in many studies of long-term benzodiazepine users, even
at therapeutic dose levels, and may persist after benzodiazepine withdrawal.
• Risks of maternal use during pregnancy include foetal developmental abnormalities,
'floppy infant syndrome' and a neonatal benzodiazepine withdrawal syndrome.
• Regular use of benzodiazepines, especially in high doses, readily leads to physical
dependence, evidenced by withdrawal symptoms on sudden cessation.

19. Dependence and withdrawal symptoms
• Feeling faint
• Noise sensitivity
• Light sensitivity
• Peculiar taste
• Pins and needles
• Touch sensitivity
• Sore eyes
• Hallucinations
• Smell sensitivity
• Depression
• Shaking
• Feeling unreal
• Appetite loss
• Muscle twitching
• Memory loss
• Motor impairment
• Nausea
• Muscle pains
• Dizziness
• Apparent movement of still
objects

20. Management of benzodiazepine withdrawal
• Withdrawal methods for long-term prescribed therapeutic dose
benzodiazepine users are well established and consist mainly of slow
dosage tapering over weeks or months in an outpatient setting, combined
with psychological support.
• These methods are not entirely appropriate for high-dose benzodiazepine
abusers.
• First, benzodiazepine abuse is often part of polydrug abuse and attention
also has to be given to the primary drug.
• Second, a long period of outpatient dosage tapering is unlikely to be
adhered to since additional benzodiazepines may be obtained illicitly.
• On the other hand, benzodiazepine abusers commonly use high doses and
may be at particular risk of severe withdrawal symptoms including
epileptic fits if the drugs are stopped abruptly.
• Therefore, a moderately rapid, controlled schedule of detoxification in an
inpatient unit is preferable.

21. Management of benzodiazepine withdrawal
• The most common technique is substitution of a slowly
eliminated benzodiazepine (usually diazepam) for the abused
drug (commonly, a shorter acting drug such as temazepam)
followed by dosage tapering over 2 or more weeks.
• Some workers have advocated the use of carbamazepine as an
anticonvulsant in benzodiazepine withdrawal, though its ability
to prevent other withdrawal symptoms is doubtful.
• A third method of detoxification recommended in some
centres, particularly in the US, is phenobarbitone substitution.

22. Management of benzodiazepine withdrawal
• Longer term outpatient management of benzodiazepine abusers is
problematic.
• Some centres have found benzodiazepines to be helpful in reducing
overall illicit drug use and injecting, and, occasionally,
benzodiazepine use may be adaptive, allowing the opiate abusers
to manage on a smaller dose of methadone.
• However, the overwhelming advice is that it is generally
inadvisable to prescribe benzodiazepines as maintenance treatment
for drug misusers or alcoholics.
• A possible approach for opiate addicted patients who use
benzodiazepines to increase the euphoriant effects of methadone is
to alter the methadone treatment so that individuals feel less need
for benzodiazepines.

23. Management of benzodiazepine withdrawal
• Unfortunately, in the present climate the rate of relapse
after short-term benzodiazepine detoxification may be as
high as it is with opiate detoxification (i.e. over 90 per
cent after 1 year), and further experience is needed to
establish the optimal long-term management.
• Meanwhile, efforts to reduce inappropriate prescribing of
benzodiazepines both in general practice and in hospital
may help to decrease the quantity of benzodiazepines at
present spilling into the illicit drug market.

24. DIAZEPAMTaking Diazepam for longer than 4 months, even with a prescription
from a doctor, increases the likelihood of becoming addicted.

25. Understanding Diazepam Addiction
• Diazepam is an addictive benzodiazepine with longer-lasting effects than
other drugs in its class.
• An addiction to Diazepam can progress quickly if the drug is used in a
way not directed by a doctor.
• Over time, it is harder for a Diazepam abuser’s brain to function normally
without the drug. Yet, some people addicted to Diazepam may not even
realize they have a problem.
• One of the telltale symptoms of a Diazepam addiction is needing larger
doses to feel the drug’s effects. Other signs of an addiction to Diazepam
include:
• Strong cravings for the drug
• Isolation from family and friends
• Continued use despite problems caused by the drug
• Loss of interest in once enjoyable activities
• Ignoring obligations

26. Understanding Diazepam Addiction
• Once a user has a tolerance to Diazepam’s effects, they could also
have withdrawal symptoms if they stop taking it.
• Diazepam withdrawal can be dangerous and uncomfortable, which
makes it hard to for addicted people to quit on their own.
• The symptoms of withdrawal are intense, and many people addicted
to Diazepam need the drug to feel normal.

27. What Is Diazepam?
• Diazepam is most often prescribed to relieve anxiety,
muscle spasms and seizures. It is also used to ease
uncomfortable symptoms of alcohol withdrawal.
• Diazepam works by diminishing hyperactive brain
function to relieve severe stress and anxiety. It is ingested
orally in pill form and usually taken 1-4 times per day
when prescribed by a doctor.
• Diazepam is a long-acting benzodiazepine.

28. Effects of a Diazepam and
Reasons for Abuse
• While there are several reasons for Diazepam abuse, many of those
abusing the drug don’t take it to get high. They take it to feel
normal — to relieve stress and anxiety. People also abuse
Diazepam because it helps them sleep. Diazepam produces a sense
of intense calm and euphoria, especially in higher doses.
• Many people mistakenly think that because it is legal, Diazepam
must be safe and less addictive than street drugs like heroin or
cocaine. Due in part to these misconceptions, many people have
accidentally overdosed.

29. The Dangers of Diazepam
• Many people underestimate the addictive potential of Diazepam
because it’s prescribed by a doctor. Even fewer people seem to be
aware of the dangers of the drug. Diazepam can lead to
convulsions and coma in heavy users. Studies have also shown
that people on Diazepam have an increased risk of motor vehicle
accidents. And when a user stops taking the drug, Diazepam
withdrawal can be deadly.
• Diazepam is especially dangerous when mixed with other central
nervous system depressants like alcohol and opioid painkillers.
The sedative qualities of each substance taken together are
amplified. This can depress breathing or heart rates to the point
of failure.

30. Some signs of a Diazepam
overdose include:
Bluish lips
Double vision
Drowsiness
Trouble
breathing
Weakness
Uncoordinated
movement

31. Some signs that may indicate
Diazepam abuse include:
Slurred speech
Impaired
coordination
Dilated pupils
Changes in
appetite
Uncharacteristic
sadness or
irritability
Shaking (from
withdrawal)

32. Diazepam Withdrawal
• Once a physical dependence has developed, the user needs Diazepam
to function and prevent the symptoms of withdrawal. Diazepam users
often increase their doses to counter withdrawal symptoms as their
tolerance to the drug increases.
• Withdrawal from Diazepam can be dangerous, so users should never
try to quit “cold turkey.” This can lead to coma and other potentially
fatal outcomes. Quitting Diazepam requires medical management as
the body and brain recalibrate to be able to function properly without
the drug.
• According to the Diagnostic and Statistical Manual of Mental
Disorders, it takes as little as 15 mg of Diazepam each day for several
months to start experiencing withdrawal symptoms. People who have
taken more than 100 mg of Diazepam a day are more likely to
experience serious withdrawal symptoms and complications.
• he severity of withdrawal symptoms depends on the period of time the
substance was used and how much the user took on a daily basis.
Heavy Diazepam use over a long period of time leads to more difficult
withdrawal symptoms.

33. Symptoms of Withdrawal
Abdominal cramps Headache Tremors Sweating
Muscle pain Vomiting Severe anxiety Confusion
Restlessness and
insomnia
Numbness Hallucinations Seizures

34. Diazepam Detox
• Diazepam detox is the process of getting the drugs out of the user’s
body. The goal of Diazepam detox is to remove the drugs from the
body while minimizing withdrawal symptoms.
• Detoxing from Diazepam can be dangerous without medical
guidance. Most Diazepam users who want to quit follow a detox
program that gradually reduces their doses, usually on a weekly or
bi-weekly basis. This minimizes the uncomfortable withdrawal
symptoms and prevents dangerous complications such as seizures.
• The severity of the addiction is the biggest factor on how long detox
takes. Those who are more severely addicted take longer to detox
because abruptly reducing their Diazepam doses causes harmful
withdrawal symptoms.

35. Treatment for Diazepam Addiction
• Diazepam is a long-acting benzodiazepine, so it can take time
for someone’s body to readjust after they decide to quit.
Recovering from an addiction to Diazepam often takes a
combined approach of tapering down doses and attending
therapy.
• For many, withdrawal symptoms are the hardest part of a
Diazepam addiction, but medically assisted treatment can ease
these symptoms.
• The symptoms are more intense for those who took larger, more
frequent doses. The process of Diazepam detox might last
anywhere from a few weeks to several months.
• Abruptly quitting can be dangerous.

36. Treatment for Diazepam Addiction
• Those heavily addicted to Diazepam or who also suffer from an
addiction to another substance often choose to begin recovery in
rehab.
• There are many Diazepam treatment centers with a strong record
of recovery, each with their own approach to addiction treatment.

37. Treatment for Diazepam Addiction
• Diazepam addiction can be treated on an inpatient or outpatient
basis.
• A person who elects for inpatient treatment will need to check
into a diazepam rehab facility and remain there for the duration of
his or her treatment.
• A person being treated on an outpatient basis will go to the
treatment facility on a daily basis (usually excluding weekends
and holidays) to meet with an addiction specialist and obtain
medications.
• Inpatient treatment is best for people who need to remove
themselves from their environments to overcome their addictions.
• The temptation to continue using drugs may be too strong for
users to remain in their current environments.

38. Treatment for Diazepam Addiction
• Drug availability is restricted at inpatient treatment centers.
• Additionally, contact with the outside world is usually limited,
especially at the beginning of diazepam addiction treatment.
• This allows the person to focus on recovering from the addiction
and improves his or her chances of success.
• However, the person will have to leave his or her life for the
duration of the treatment, which could mean a loss of
employment.

39. Treatment for Diazepam Addiction
• Outpatient treatment allows the person remain in his or her
environment while being treated for the addiction.
• People in this situation are able to maintain employment and
benefit from the support of their social networks.
• Outpatient treatment is usually cheaper than inpatient treatment.
• Unfortunately, if the person is in an environment where diazepam
and other drugs are readily available, he or she may give into
temptation and relapse.

40. BENZODIAZEPINE: SLOW SAND
OF ADDICTION IN PAKISTAN

41. • Not only in Pakistan but around the world benzodiazepines are
among the most prescribed and consumed medication groups.
• In Pakistan, there is a dearth of properly trained and qualified
psychiatrists. The psychiatrist to population ratio is dismally low.
• Almost 67 % population resides in rural areas to which mental
health care is delivered by general physicians.
• Prevalence estimates of common mental disorders is about 30% -
ranging from 10-to-25% in urban settings to 30-to-66% in rural
settings.
• Tranquilizers have become an accepted component in the lives of a
large segment of our population.
• By a conservative estimate around seven to ten million urban
dwellers in Pakistan continue to consume these medications
regularly.
• Most of these medication are available over-the counter without
any medical prescription.

42. • In the context of Pakistan, this has stemmed from their
status as sleeping pills; in an overdose one would expect
a person to 'sleep forever'. Favorably there
pharmacological lethality index is very high. However
this in no way makes them any less dangerous than other
drugs of overdose.
• In a study done in Pakistan the proportion of
Benzodiazepine usage in deliberate self harm, it was
more than the double quoted in the western data i.e. 80%.
• However the predominant method of getting these drugs
was their availability over the counter in 44% cases, the
fact which can be safely generalized to almost all
developing nations.

43. • In the context of Pakistan Pharmaceutical companies,
driven by economic gains, marketing these tablets as
absolute recipe for peace of mind. Most Physicians act as
'agents' for sales and promotion; with their share in the
cake.
• Health care in the private sector is an industry and is
driven by the 'profit motive.' Ipso facto, hospitals are less
an instrument for providing relief from suffering than
money-making machines. The position of medical
profession, by and large, is no more, to put it in kind
words, a noble profession; self-serving motives dominate.
• Ultimately it is the patients and their families who have to
pay the cost - be it the lavish luncheons in five star hotels
or cruise trips to exotic location. This is obviously done
in the guise of science, technology and promotion of
'robust' evidence

44. Possible solutions
• In general, the three rules that apply to
benzodiazepine are that
• Prescribing should be kept to a minimum
• Reviewed regularly
• Discontinued as soon as possible

45. Possible solutions:
• Arrange Public awareness program
• Organize regular C.M.E programs involving G.P's
• Develop Good practice guidelines for drug prescription
• Better Drug regulation and dispensing mechanisms
• Need to develop and implement Legislation
• Early recognition and referral to mental health services
• Need to establish well staffed Rehabilitation centers.

46. References:
• http://www.benzo.org.uk/ashbzab.htm
• www.narconon.org/drug-abuse/effects-of-benzodiazepine.html
• http://www.addictionrecov.org/Addictions/index.aspx?AID=38
• http://www.webmd.com/mental-
health/addiction/benzodiazepine-abuse
• http://journals.plos.org/plosone/article/asset?id=info:doi/10.13
71/journal.pone.0001804.XML
• http://drugabuse.com/library/valium-abuse/
• https://www.addictioncenter.com/benzodiazepines/valium/
• http://www.projectknow.com/research/diazepam/
• Benzodiazepine: slow sand of addiction. Naqvi H1, Hussan
S, Dossa F. J Pak Med Assoc. 2009 Jun;59(6):415-7.

48. THE END