drug abuse is the hot topic

1. Drug abuse
DR.SULTHAN AL RASHID
JUNIOR RESIDENT-1
DEPARTMENT OF PHARMACOLOGY
JNMC MEDICAL COLLEGE, AMU,ALIGAR

2. Important terminologies

3. Misuse
• Indiscriminate use of any drugs other than a CNS stimulant or
depressant called misuse.
• example: misuse of laxatives, purgatives or antibiotics.

4. Abuse
• While misuse of any CNS stimulant or a depressant drug is
called abuse.

5. Drug seeking behaviour
• Almost all drugs or abused substances produce an effect on
brain that is perceived as desirable and will initiate drug
seeking behaviour.

6. Reinforcing properties
• Properties of drug that are responsible for drug seeking
behaviour often referred to reinforcing property.
• These drugs produce effects that are so desirable that the
user is compelled to get more of the drug.

7. Positive affective state
• Primary reinforcing property of drug is positive affective state
called euphoria that it produces.
• this term indicates anything from pleasantness or a sense of
well being to an excitement resembling orgastic pleasure.
• Euphoria considered to be positive reinforcing property of
drug that individual would desire or would like to seek.

8. Negative reinforcer
• In addition the drug can also function as negative reinforcer in
that as it offers relief from negative affective state e.g.
dysphoria.

9. Drug addiction
• Chronic exposure to reinforcing drugs can lead to drug
addiction.
• Characterised by an increase in drug seeking behaviour called
“CRAVING”

10. Qualitative assessment of abuse
potential of drug.
• To check the abuse potential which may be strong, moderate
and mild.
• It is assessed on a rodent model by implanting a cannula in
the reward area(mesolimbic area) of brain.
• In an animal cage, a bar is placed in such a way that pressing
the bar automatically delivers a fixed dose of trial drug to
animals.

11. • Results: if animal eventually and repeatedly presses the bar
or tries to overcome the intentionally placed obstacles to
press the bar,
• It can be concluded that the drug has a positive reinforcing
behaviour/abuse potential.

12. habituation
• Term can be used
1. If detrimental effects of abused drug are restricted to the
person himself and not to the society.
2. There is no intense craving for seeking the drug.
3. There is no development of tolerance.
4. There are no distressful withdrawl effects.
5. Example: taking tea or coffee

13. addiction
• Recurrent abuse of drug where the individual becomes so
obsessed to procure and use the drug that it becomes his
primary aim.
• Which inturn disrupts his ability to adjust in family, the
society or at his place of work.

14. Features of addictions
1. detrimental effects not only harm the individual but society as
well.
2. Always an intensive craving to procure the drug by any means
3. There is development of tolerance and hence need to
increase the dose to get the same rewarding experience.
4.There are life threatening or alarming withdrawl effects after
cessation of drug and there is a physical need to continue
with the use of drug for fear of abstinence syndrome.

15. • In 1974-1975, WHO deleted all such terms like
habituation and addiction and introduced new
term
• “DRUG DEPENDENCE”

16. Drug dependence
• A state arising from repeated, periodic or continuous use of
drug.
• A state which includes all types of detrimental effects
whether to himself, to the family, to the society or to the
career.
• A state that includes all grades of craving to procure the drug.
• A state which includes all types of psychological or physical
needs to continue with use of drug for fear of getting
distressful withdrawl effects.

17. • WHO provided wider canvas for presenting
the picture by using the terms
1. All grades of craving
2. All types of psychological or physical needs.
3. All sorts of detrimental effects.

18. Substance dependence
• Diagnostic and statistical manual of mental disorders(DSM)
suggest the use of single term “substance dependence”
• In place of so many confusing terms like habituation,
addiction and drug dependence.

19. Criterias for substance dependence
1. Development of tolerance
2. Distressful abstinence syndrome after cessation of drug.
3. Persistent desire to use the drug(craving)
4. Substance used in larger amounts than intended.
5. Withdrawl from social, occupational or recreational
activities.

20. 6. Considerable time spent for obtaining drug which becomes
his life style. E.g. visting doctors, quacks or his contacts in
illicit drug trade.
7. Continued use despite health, social, economic, family and
legal problems resulting from substance use.

21. Substance abuse
• DSM IV TR criteria for substance abuse requires atleast one of
the following symptoms
1.Recurrent substance use resulting in failure to fulfill his/her
major obligations at work, school or home i.e. repeated
absence or poor performance at work and expulsion from
school.
2.Recurrent substance use even in situations where it should not
be used. E.g. during driving, operating upon a patient,
operating a machine.
3.Recurrent substance use despite punitive action e.g.
punishment for disorderly conduct

22. • 4. recurrent substance use despite having interpersonal and
family problems e.g. arguments or physical fight with spouse
about the consequence of abuse.
• The substance abuse discards all other terms like misuse,
abuse or habituation.
• Substance abuse doesn’t apply on taking tea, coffee or
smoking 10 cigarettes a day without inhalation.

23. tolerance
• Tolerance develops if after repeated administration, a given
dose of a drug produces a decreased effect than expected.
• Or conversely when larger doses are needed to obtain the
effects obtained with previous dose.
• Classification: it may be classified as pharmacokinetics(as
with barbiturates) or pharmacodynamics(as with opioids) or
as reverse tolerance(sensitisation as with cocaine).

24. Cross tolerance
• Where once tolerance to primary drug develops, the
Individual also exhibits cross tolerance to related class of
drugs.
• Example: individuals tolerant to morphine are also tolerant to
other opioids.
• Chronic alcoholics are tolerant to benzodiazepines or even
general anaesthetics.

25. dependence
• It is a physiological state of neuroadaptation resulting from
repeated administration of drug necessitating its continued
use,
• to prevent the appearance of distressing withdrawl
(abstinence) syndrome which is manifested as opposite to
the pharmacological effects of drug.

26. Cross dependence
• It means the ability of a drug to suppress the manifestation
of withdrawl(or physical dependence) produced by another
drug.

27. Withdrawl or abstinence syndrome
• It is a term used for the adverse (sometimes life threatening)
psychologic and physiologic reactions to an abrupt
discontinuation of a dependence producing drug.

28. Types of substance dependence.
• There are two types:
1. psychological(psychic) dependence which is characterised
by
a. Moderate compulsive drug seeking behaviour(craving) for
personal satisfaction e.g. cigarette smoking.
b. Tolerance may or may not be present and if present it is
usually either of pharmacokinetic type or tachyphylaxis but
rarely of pharmacodynamic type(cellular adaptive).
c. Withdrawl effects are less frequent and mild which can be
tolerated as these are never life threatening.

29. 2. Physical dependence:
a. Characterised by intensive craving for the drug. E.g. alcohol
and opioid use.
b. Tolerance is invariably present(mainly pharmacodynamic
type)
c. Withdrawl effects are severe and distressing manifested by
symptoms that are frequently opposite to those sought by
abuser.

30. • Psychological dependence appears prior to physical
dependence but inevitably doesn’t lead to it.
• Agents having physical dependence do possess psychic
dependence as well but reverse may not be true.
• Physical dependence is closely associated with the
phenomenon of tolerance but the reverse may not be true.

31. rebound
• Rebound means exaggregated manifestation of original
disease symptoms experienced immediately after
discontinuation of the drug providing clinical benefits.
• E.g.Rebound hypertension occuring after sudden
discontinuation of clonidine and B-blockers.
• Rebound phenomenon should not be confused with
withdrawl syndrome as there is no craving or dysphoria after
the cessation of the drug.

32. relapse
• It refers to re-occurrence of the same disease symptoms from
which the patient suffered after discontinuation of the
treating drug.
• E.g. if a diabetic person suddenly stops taking insulin there
would be relapse of diabetes not rebound or withdrawl
syndrome.

33. detoxification
• It means slow tapering of drug that has caused dependence
and would cause withdrawl if stopped suddenly.
• It can be accomplished either by slowly withdrawing the
dependence producing drug or by substituting the cross
dependent drug.
• So that the neuroadpative mechanism can slowly become
normal without causing withdrawl symptoms
• Tapering of the doses of B blockers or clonidine to prevent
rebound hypertension is not called detoxification but tapered
dose discontinuation.

34. Why people go for drugs?

35. • It is due to drives that induce a person to resort to the drugs
a. To get relief from tension and anxiety
b. To satisfy their curiosity about the “Kicks and pleasure “ the
drugs provide
c. to show their identity by exhibiting hostility towards the
society.
d. A notion of being accepted by the Hi-fi modern society
e. A notion that drugs provide new ideas of creativity

36. Drive state
• The drives cited above bring a normal person to drive state
and to cope with this situations he has two options.
1. Either to fight with the situation and circumstances with full
determination or to become an escapist or to try other
resorts to allay the anxiety.
2. To obtain chemical vacation from intolerable drives with the
help of drugs.
• If the drug provides a quick and better relief, the tendency to
reinforce increases.
• That means when a drive state arises next time ,the desire
to seek the drug will be reinforced.

37. Reinforcement power of commonly
abused drugs
• Cocaine(++++)
• Amphetamine, opioids, barbiturates(+++)
• Alcohol, inhalants, opioids partial agonist(++)
• LSD, marijuana(+)
• Diazepam(+)
• Anabolic steroids(+)

38. Drugs of abuse that engender
dependence
• Agents having only mild psychological(psychic dependence),
low withdrawl, no physical dependence.
• E.g. coffee, tea, cigarette smoking upto 10 cigarettes a day
without inhalation.

39. • Agents with moderate to severe psychological dependence,
low withdrawl, slight physical dependence:
• Marijuana, Hasish:
• Psychic dependence: mild
• Physical dependence: doubtful
• Tolerance: may develop

40. • LSD:
• Psychic dependence: mild
• Physical dependence: nil
• Tolerance + or -

41. • Amphetamines, cocaine:
• Psychic dependence: severe
• Physical dependence: mild
• Tolerance: mild

42. • Nicotine(20 cigarettes or more a day with inhalation)
• Psychological dependence: severe
• Physical dependence: mild
• Withdrawl effects: low

43. • Inhalants
• Psychic dependence: moderate
• Physical dependence: nil
• Withdrawl effects: low
• Tolerance: + or -

44. • Agents having moderate to severe psychological dependence with
mild physical dependence
• Benzodiazepines:
• Psychic dependence – moderate
• Physical dependence – mild on moderate and prolonged use.
• Withdrawl effects – mild
• Tolerance - occurs

45. • Alcohol(moderate use)
• Psychic dependence – severe
• Physical dependence – mild
• Withdrawl effects – mild
• Tolerance - develops

46. • Agents having severe psychological and physical
dependence.
• Opioids:
• Psychic as well as physical dependence – severe
• Pharmacodynamic tolerance – marked
• Withdrawl effects – severe and precipitated by naloxone

47. • Barbiturates:
• Psychic as well as physical dependence – severe
• Withdrawl effects – severe
• Tolerance – pharmacokinetic type

48. • Alcohol (heavy use)
• Psychic dependence – severe
• Physical dependence – moderate on prolonged use
• Tolerance – occurs
• Withdrawl effects - severe

49. Neuropharmacology of the reward and
reinforcement.
• Almost all dependence-producing drugs activate the reward
reinforcement pathway called the mesolimbic dopaminergic
pathway.
• Some even consider this to be “pleasure centre” of the brain
• And dopamine as “ pleasure neurotransmitter”

50. • Eventhough the primary sites of action of dependence
producing drugs are different and generally elsewhere in the
brain,
• All these drugs increase the release of dopamine in the
nucleus accumbens.
• Opioids( u, k and Delta receptors), cannabinoids(CB1
receptor), amphetamines, cocaine(dopamine transporters),
barbiturates( cl- channel of GABA receptor), nicotine( Na+
channel linked to nicotinic receptor) and ethanol( ca2+
channel linked to NMDA receptor)

51. • They elicit their acute behavioural effects by different
mechanisms.
• The ultimate drug actions at these targets lead to an elevation
of extracellular DA levels in nucleus accumbens.
• D2 receptor antagonists injected into the mesolimbic area of
the brain reduce the self-administration of the drug in
rodents.
• Similarly removal of D2 receptors in a transgenic mouse strain
eliminated the reward and reinforcement properties of
morphine administration

53. Mechanism for the development of tolerance,
dependence and withdrawl effects.
• In the major areas of brain usually there is a balance between
an excitatory (E) and inhibitory (I) neurotransmitter (state 1)
• Our body tries to counteract the stimulant or depressant
effects of abused drug, if it is subjected to prolonged use by
increasing the inhibitory or excitatory activity respectively.
• Example: abused drug shown is inhibitory(ID), which mimics
the inhibitory neurotransmitter(I).
• As a result of its primary action, the balance would be altered
to a state of inhibition ( I + ID) or depression ( state 2)

54. • After its prolonged use, the body would try to increase the
excitatory activity (as counteradaptation, E+E).
• The balance E + E = I + ID would then be restored and the
increasing doses of the drug would now be required to obtain
the same inhibitory effect of drug ( i.e. , tolerance develops,
state 3).
• If this drug ID is suddenly withdrawn , a disbalance would
occur which must obviously produce effects and symptoms
opposite to those of drug ( withdrawl effects, state 4)

55. • The latent hyperexcitability in such a situation is unmasked(E
+ E) because physiological restoration of normal balance
would take its own time.
• The biological restoration to normal levels could be achieved
by proper treatment ( state 5).
• However the state of inhibition I + ID to which the addict was
used to could be obtained by providing him the same drug ID.

56. • The very fact that the discontinuance of an abused drug may
precipitate withdrawl symptoms provides an incentive to
continue its use.
• If a physically dependent addict oscillates between feeling of
euphoria and thereafter dysphoria related to withdrawl, he
would exhibit drug seeking behaviour to negate the
unpleasant feelings.
• Dependence is more commonly associated with abuse of
short to intermediate acting drugs such as secobarbital,
pentobarbital, lorazepam, alprazolam, pethidine, morphine
and heroin etc.

57. • Dependence on longer acting agents like phenobarbital,
cholrdiazepoxide, flurazepam and methadone is less common
because drugs with longer half-lives produce a less severe
withdrawl syndrome, that too of longer duration.
• Dependence is rarely assocaiated with intravenously
administered ultra-short acting drugs like pentothal,
methohexital, midazolam and fentanyl derivatives because
these agents cannot be taken frequently enough to maintain
adequate plasma concentrations need to avoid withdrawl
effects.

58. Neuropharmacological adaptations
during dependence
• 1.Chronic exposure to ethanol: leads to compensatory
increase in the density of NMDA receptors and L type voltage
gated Ca 2+ channels in the brain.
• This leads to neuronal hyperactivity observed during alcohol
withdrawl.
• NMDA and L type channel antagonists therefore decrease
withdrawl effects of alcohol in rodents.
• Chronic exposure to ethanol also down-regulates the GABA A
receptor activity. This also contributes to alcohol withdrawl.

59. • Benzodiazepines therefore due to their GABA ergic properties
are useful in reducing alcohol withdrawl symptoms.
• Ethanol also upregulates cAMP mediated signaling in other
brain areas including midbrain ventral tegmental area and
nucleus accumbens.

61. • 2.Opioids: on brief exposure activate U receptors leading to
Gi –mediated inhibition of adenylyl cyclase AC and
consequently of cAMP, protein kinase A and voltage gated N
type calcium channels.
• But an activation of K+ channel all leading to decrease in
cellular excitability.
• Chronic exposure of opioids on the otherhand induces a
compensatory rise in AC, cAMP, PKA and cAMP response
element binding protein(CREB).

62. • Simultaneously the increased cAMP signaling in locus ceruleus
enhances functioning of Na + channels by promoting NE
release.
• Hyperactivity of this adrenergic nulcelus(locus ceruleus) has
been implicated in opioid withdrawl.
• The upregulation of CREB also mediates cAMP dependent
gene expression.
• All these changes increase the intrinsic firing rate of neurons
in locus ceruleus partly through activation of an inward Na +
current.

63. • Thus the upregualtion of cAMP signaling cascade not only
opposes the acute inhibitory actions of opioid but also
contributes to opioid tolerance as well as hyperexcitability
during opioid withdrawl.
• It has been reported that animals lacking CREB show reduced
withdrawl symptoms of opioid drugs.

64. • 3. chronic response to cocaine and amphetamines: also leads
to compensatory up-regulation of cAMP signaling in nucleus
accumbens which contributes to psychostimulant tolerance.
• because pharmacological activation of PKA or overexpression
of CREB in nucleus accumbens decrease the rewarding
properties of cocaine.
• The receptor neuroimaging studies have demonstrated that
chronic abuse of cocaine downregulates D2 receptors and
upregulates dopamine transporters.

65. • Normally on brief exposure cocaine binds to dopamine
transporters and inhibits dopamine reuptake.
• While amphetamines causes intracellular release of dopamine
from its vesicles.
• And then reverse transports this dopamine through dopamine
transporters.

66. • 4. at cellular level nicotine: acts on nicotinic acetyl choline
receptors NN to produce neuronal excitation
• Its reinforcing properties are also associated with increased
activity in the mesolimbic dopaminergic pathway.
• Effects of nicotine are mediated by enhancing the
permeability of Na+ through nicotinic cholinergic receptor
gated Na+ channels.
• Chronic exposure of nicotine desensitises these receptors but
simultaneously also leads to substantial increase in number of
receptors

67. • It may represent an adaptive response to prolonged receptor
desensitisation.
• The overall effect of nicotine may reflect balance between the
activation of neuronal nicotinic receptors causing excitation
and desensitisation causing synaptic block.
• However as the cellular effects of nicotine get diminished
after chronic exposure, it is also possible that additional
binding sites represent the desensitised rather than functional
receptors.

68. • 5. cannabinoids and opioids: share common signaling
pathways in the brain for reward and reinforcement
• But there is hardly any physical dependence or withdrawl
syndrome developing with the use of cannabinoid,
• And the associated neuroadaptive mechanisms of
cannabinoids have little relevance.

69. Designer drugs
• Designer drugs are synthetic substances, prepared in
clandestine laboratories.
• These drugs are inexpensive to produce and difficult to
detect.
• Such molecular manipulations of the widely abused drugs are
done by some chemists to avoid drugs and narcotic act
regulations and to make huge profits
• Examples: MDMA/ecstasy which is amphetamine analogue
3,4-methylenedioxymethamphetamine on the streets

70. • China white which is a synthetic anologue of fentanyl with
1000-1500 times of potency.
• Consequences of designer drug abuse are however
unpredictable and in some instances lethal.
• For example efforts to make pethidine substitute resulted in
an end product MPTP(methyl phenyl tetrahydropyridine)
which unfortunately causes nigrostriatal lesions and produces
parkinsonism.
• It is now used as pharmacological tool to produce
parkinsonism

71. Treatment of drug dependence

72. • The ultimate goal of the treatment program is to achieve a
“drug free status”as early as possible and to prevent the
relapse of drug abuse.
• The drug free status is achieved with the help of
pharmacotherapy.
• While relapse prevention strategies involve rehabilitation and
psychosocial interventions.

73. Pharmacological approaches to treat drug
dependence and withdrawl
1. Short term or long term substitution of the abused drug by a
similar drug having longer plasma half life.
2. An aversive therapy by using a drug which produces
unpleasant response after an intake of abused drug.
3. Use of proper antagonist to prevent relapse once the drug
free status is achieved.
4. Use of drugs which reduce craving for the abused drug
5. Rehabilitation and psychosocial interventions

74. Treatment of opioid dependence
• Substitution therapy: the most commonly used strategy is to
switch the patient from short acting opioid such as heroin to a
long acting agonist like methadone.
• With such a substitution the addict is spared from the
undesirable side effects of withdrawl because the opioid
receptors remain occupied for a longer duration.
• Thereafter methadone can be withdrawn in tapering doses
over a period of weeks.
• Pharmacological basis of using methadone depends on its oral
effectiveness(once daily dosing), longer duration of action and
development of cross tolerance between it and other opioids.

75. • An even longer acting analogue LAAM levo alfa acetyl
methadol with alternate day oral dosing and reduced abuse
potential can also be used.
• But with caution as it prolongs QT interval and may lead to life
threatening arrythmias
• Another option is buprenorphine a partial opioid agonist that
can be given orally once daily.

76. Use of an opioid antagonist:
• A long acting orally active opioid antagonist naltrexone
provides another treatment option in that addicts who are
completely withdrawn from opioid after methadone therapy.
• Can be maintained in such a state further to block pleasurable
effects leading to relapse.
• It can be given three times a week in doses of 50mg OD or in
the form of depot injection on monthly basis.
• However the therapy is successful only if the patient is already
detoxified and is opioid free for the past 10 days otherwise
opioid withdrawl reactions will be precipitated.

77. • To detoxify the patient and to prevent relapse clonidine, a
centrally acting sympatholytic agent can also be used.
• By reducing the central NE outflow from locus ceruleus,
clonidine reduces the severity of distressful withdrawl effects
of opioids such as hypertension, anxiety, headache, tremors,
intestinal cramps and diarrhea.
• Lofexidine causes lesser hypotension compared to clonidine.
• Both have no narcotic action and are not addictive.

78. Rehabilitation and other aspects:
• The pharmacotherapy is more rewarding if combined with
rehabilitation program which includes proper education and
counselling.
• Besides treating withdrawl and dependence, all possible
efforts should be made to prevent AIDS, hepatitis, bacterial
endocarditis and other consequences of contaminated needle
exchange between IV opioid dependent addicts.

79. Treatment of alcoholism
• A. management of acute alcohol toxicity:
• Intoxication due to acute intake of ethanol is managed by
maintenance of vital signs and prevention of aspiration of
vomitus.
• Treatment of hypoglycemia and ketosis can be made by giving
IV glucose.
• Thiamine IV or IM and correction of electrolytes may also be
required.

80. • B. management of withdrawl syndrome:
• It is usually managed by administration of long acting sedative
hypnotic(e.g. chlordiazepoxide or diazepam)
• The intensity of withdrawl syndrome may be reduced by
clonidine and propranolol.
• Clonidine an alpha 2 adrenoceptor agonist acts by inhibiting
the exaggregated transmitter release that occurs during
withdrawl.
• While propranolol being B blocker antagonises the effects of
excessive sympathetic effects.

81. • Once the withdrawl phase is over, the benzodiazepines may
be withdrawn with gradual dose tapering.
• Complete detoxificationis not achieved with just a few days of
alcohol abstinence.
• Several months may be needed for restoration of normal
sleep and decrease of tremors and anxiety.

82. • C. management of alcohol dependence:
• Alcohol dependence/ alcoholism is seen in 4-5% of the
population and is difficult to treat because of high relapse
rate.
• The main pharmacological approaches are:
• The first approach is to render ethanol consumption
unpleasant by aversion therapy.
• This is accomplished by giving disulfiram.
• Dose: 1g on first day, reduce by 250mg daily and keep 250mg
for maintenance once daily.

83. • Another approach is to use a drug which reduces the craving
for alcohol.
• This is achieved by naltrexone, an opioid receptor antagonist
in a dose of 50mg once a day is used to treat alcoholic
dependence.
• it has been demonstrated that opioid antagonists inhibit
craving for alcohol. While opioids increase craving for alcohol.
• Recently it has been shown that the anticonvulsant drug
topiramate is also effective in reducing craving in chronic
alcoholics.

84. • Topiramate potentiates the inhibitory effects of GABA like
benzodiazepines but acts at a site different from
benzodiazepines or barbiturates.
• The selective serotonin reuptake inhibitors SSRIs such as
fluoxetine which can increase serotoninergic activity in CNS
may also be helpful in this regard.
• Ondansetron 5HT3 antagonist has also been successfully
used.
• To reduce craving for alcohol, acamprosate is being used
recently.

85. • Acamprosate reduces the effects of excitatory aminoacids
such as glutamate on NMDA receptor and at the same time
facilitates GABA neurotransmission.
• It also possesses some opioid antagonistic activity and
increase serotonin level in synapses.
• Acamprosate may cause GIT upset and skin eruptions as side
effects.

86. Treatment of barbiturates and
benzodiazepine dependence.
• If short acting barbiturates such as pentobarbital or
secobarbital have been abused, a long acting barbiturate such
as phenobarbital may be substituted as a pharmacologically
equivalent drug and gradually withdrawn with tapering doses
• If long acting barbiturate is abused, the same drug is allowed
to continue but is gradually withdrawn at a rate of 10% of
daily requirement.
• Complete detoxification may be achieved in 2-3 weeks
duration.

87. • For detoxification of barbiturates, an osmotic diuretic with
sodium bicarbonate can also be used to alkalinise the urine
and to hasten the elimination of drug.
• During this period the abused barbiturate may also be
substituted with a antihistamine(diphenhydramine) for
symptomatic treatment of withdrawl effects.
• The latter may be withdrawn after successful detoxification.
• Seizures represents a medical emergency during withdrawl
and can be treated by parenteral administration of diazepam
or carbamazepine.

88. • With benzodiazepines the physical dependence is rare but
may occur following long treatment with doses of 40mg/ day
or more of diazepam.
• However if an intermediate to short acting BZD has been
abused, a long acting BZD such as chlordiazepoxide can be
substituted as the pharmacologically equivalent drug which
can be subsequently withdrawn in tapering doses.
• The BZD receptor antagonist flumazenil can be used to
specifically block the toxicity of BZDs overdose or to prevent
relapse after detoxification.

89. Withdrawl from anabolic steroids
• Patients abusing anabolic steroids e.g. stanozolol for body
building are seldom covered by deaddiction programs.
• Yet they may come to deaddiction centres if they suffer from
excessive aggression, sexual dysfunction or mood
fluctuations.
• Mere counselling may suffice, with gradual withdrawl of
anabolic steroids.
• Such patients are advised to avoid going to gyms as these are
the favourable sites for acquisition of steroids.

90. Treatment of withdrawl from inhalants
• There is little evidence that the signs of abstinence occurs in
the individuals when inhalants are withdrawn suggesting that
physical dependence is not the part of the experience of
these abusers.
• Since abusers are still taking these agents repeatedly there
seems to be some psychic dependence on them.
• No specific treatment is available because the toxic effects of
inhaled solvents and aerosols may be caused by more than
one substance and also because solvents typically contain
more than one volatile compound.

91. • These may be tainted with also with heavy metals such as
lead, mercury, nickel and cadmium.
• Rehabilitation and education of such patient is more
rewarding.

92. Treatment of amphetamines toxicity
• Treatment of amphetamine toxicity can be done by using
diazepam slow IV or haloperidol to treat agitation and
psychotic symptoms
• Gastric lavage and acidification of urine can be done to
facilitate its excretion.
• To control hypertension nifedipine/labetolol can be used
• While cardiac arrythmias can be controlled with esmolol.

93. Treatment of cocaine toxicity
• It includes the use of diazepam slow IV with propranolol IV or
calcium channel blockers to control hypertension, cardiac
arrythmias and convulsion.
• Psychotic manifestations may require treatment with
haloperidol
• DA agonist like amantadine can be used to cure withdrawl
effects of cocaine.

94. Treatment of LSD toxicity
• Diazepam for sedation
• Haloperidol for psychotic symptoms

95. Treatment of nicotine toxicity
• Clonidine is a very effective drug for reducing withdrawl
effects of nicotine and is considered superior to the buffered
nicotine chewing gum which is not suitable for nicotine
dependent person having cardiac ailments.
• Clonidine reduces craving for smoking and also antagonises
insomnia.
• Nicotine transdermal patches available as an aid to smoking
cessation but with limited success as they donot suppress
craving forsmoking.

96. • Bupropion 150-300mg BD orally is another atypical
antidepressant that is used clinically for smoking cessation
• Varenicilline is another effective, recently approved synthetic
drug for cessation of smoking.
• it has a partial agonist-antagonistic action on presynaptic NN
receptors located on dopaminergic neurons in ventral
tegmental area covering nucleus accumbens, prefrontal
cortex, amygdala and hippocampus.
• It has longer half life, it decreases the release of DA leading to
lack in craving for smoking.

97. • Dose of varenicilline: initially 0.5mg BD once daily, then 1mg
BD from day 8 for 6 months
• Side effects: nausea, headache, insomnia and
depression(suicidal tendencies) which may limit its use in
future.