3. INTRODUCTION
DEFINITION OF DRUG:
WHO DEFINED DRUG AS “any substance OR
Product that is used OR intended to be used OR explore physiological
systems OR pathological states for the benefit of recipient.
3
4. TERMINOLOGIES
MISUSE:
Indiscriminate use of any drug other than CNS stimulant OR depressant.
eg: misuse of laxatives, purgatives, antibiotics for viral fever.
ABUSE : Usage of drugs for non -therapeutical purpose( pleasure, altered mood &
altering consciousness , for body building)
misuse of any CNS stimulant or depressant.
It produces Drug Seeking Behaviour.
This property is referred as “REINFORCING PROPERTIES”
4
5. TERMINOLOGIES
CRAVING:-
Chronic exposure to reinforcing drugs leads to drug addiction
which increase in drug seeking behaviour.
Asses “ABUSE POTENTIAL”.
EUPHORIA:-
Primary reinforcing property of drug referred as
“ POSITIVE EFFECTIVE STATE”.
Person experiences intense feeling of wellbeing,
elation , happiness and joy.
DYSPHORIA:-
RELIEF from “NEGATIVE AFFECTIVE STATE”.
profound state of uneasy ,unhappy and dissatisfaction.
Strong impulse to continue the drug.
5
6. DEFINITION
• DEPENDENCE
• DRUG DEPENDENCE:
Repeated, periodic or continuous use of a drug
All types of detrimental effects- to himself and society or career
PSYCHOLOGICAL AND PHYSICAL
Craving
Withdrawal effects
• HUFFING
• Many self-gratifying drug seekers inhale volatile substances
that affect CNS.
Eg: paint solvents, nail polish remover, whitener, deodorizers.
Active ingredient is TOLUENE AND AMYL NITRITE
SUBSTANCE ABUSE / SUBSTANCE DEPENDANCE
6
7. PHYSICAL DEPENDENCE
7
Intense craving for the drug eg:- alcohol, opioid.
Tolerance Invariably present (pharmacodynamic type).
Withdrawal effects are severe.
Mainly caused by CNS depressants(opioid, barbiturates)
LIFE THREATINIG Withdrawal effects is the actual
evidence of physical dependence.
ALCOHOL on heavy & prolonged use produces physical.
8. PSYCHOLOGICAL DEPENDENCE
8
• psychic/emotional dependence -- CNS stimulants(AMPHETAMINE).
• MILD Drug Seeking Behaviour ex: cigarette smoking.
• Tolerance may or may not present.
• Withdrawal effects are mild which can be tolerated.
• positive reinforcement
9. DEFINITIONS
• TOLERANCE:
upon repeated administration, a decreased effect is seen OR larger
doses needed to obtain the same effect of previous dose.
• CROSS TOLERANCE:
once tolerance to primary drug develops, individual also
exhibits cross tolerance to related class of drugs
EXAMPLE: Morphine and heroin & alcohol and benzodiazepines.
• CROSS DEPENDENCE: Ability Of Drug To Suppress The Withdrawal produced by another
Drug.
• eg:- methadone and heroin.
• WITHDRAWAL/ABSTINENCE SYNDROME :
Adverse(sometimes life threatening) psychologic and physiologic reactions to
abrupt withdrawal of dependence-producing drug.
9
10. 10
ACUTE TOLERANCE (TACHYPHYLAXIS):-
Tolerance of drug after rapid and repeated administration at shorter intervals.
REASONS:
1) It is due to gradual depletion of agonists from the storage vesicles.
example: sympathomimetics like amphetamine, tyramine causes depletion of
catecholamine's.
2) Change in sensitivity of target cells.
example: workers exposed to nitro-glycerine suffers from headache on Monday
and it disappears by Friday and again reappears on Monday.
“MONDAY DISEASE”
11. 11
Acquired tolerance:-divided into three major types
A) PHARMACOKINETIC
B) PHARMACODYNAMIC
C) LEARNED TOLERANCE
1. Pharmacokinetic or dispositional tolerance:-
Refers to changes in the distribution, metabolism of a
drug after repeated administrations , such that a given dose produces a lower blood
concentration than the same dose did on initial exposure. The most common
mechanism is an increase in the rate of metabolism of the drug.
FOR EXAMPLE:-
chronic administration of barbiturates induces hepatic CYPs1A2, 2C9,
2C19, and 3A4, thereby enhancing the metabolism of drugs that are substrates for
these enzymes.
12. 12
Pharmacodynamic tolerance:- (cellular adaptive)
Refers to adaptive changes that have taken
place within systems affected by the drug so that response to a given
concentration of the drug is altered (usually reduced).
Examples: include drug-induced changes in receptor density or
efficiency of receptor coupling.
Morphine, alcohol, barbiturates.
13. 13
Learned Tolerance:-
Refers to a reduction in the effects of a drug due
to compensatory mechanisms that are acquired by past experiences.
One type of learned tolerance is called behavioural tolerance.
A common example is learning to walk a straight line despite the motor
impairment produced by alcohol intoxication.
PARTIAL TOLERANCE: tolerance only to some effects of the drug.
Eg:- tolerance to euphoric& sedative effects of morphine but does not
develop to miotic & constipating effect.
14. DEPENDENCE
SUBSTANCE DEPENDENCE : requires at least ≥ 3 following symptoms for diagnosis
1.Tolerance
2.Withdrawal effects(ABSTINENCE SYNDROME)
3.Craving
4.Substance use in larger amounts than intended
5.Withdrawal from social, occupational, recreational activities
6.Considerable time is spent on obtaining drug
7.Continued use despite health , social , economic, family and legal problems 14
15. DSM - 4 CRITERIA
• SUBSTANCE ABUSE: DSM 4 criteria - ≥1 following symptoms
1. Recurrent substance use resulting in failure to fulfill obligations at work, school, home.
Eg; poor performance at work or repeated absence, expulsion from school)
2.Recurrent substance use even in situations where it should not be used
eg: driving, operating machine , during surgical procedures.
3. Recurrent substance use despite punitive action
eg: punishment for disorderly conduct.
4. Recurrent substance use despite interpersonal or family problems
eg: Argument or physical fight with spouse about consequences of drug abuse.
NOTE: Coffee, tea, Smoking 10 cigarettes a day without inhalation does not come under
substance abuse
15
16. 16
ORDER OF ADDICTION:-
cocaine> amphetamine>opioids>nicotine>alcohol>cannabinoids>LSD>phencyclidine.
GHB and ECTASY have no risk of addiction.
MANDRAX :-
METHAQUALONE + DIPHENHYDRAMINE
Highly addicted and severe physical dependence.
17. TERMINOLOGY
REBOUND:-
Recurrence of symptoms of a disease due to sudden cessation of the drug
No craving or Dysphoria after the cessation of drug.
EXAMPLE: Recurrence of REBOUND HTN after discontinuation of clonidine or
β blocker.
RELAPSE:-
The recurrence of disease which has been successfully treated earlier.
This may occur with similar symptoms of the disease after a gap
of certain period due to discontinuation of treatment.
17
19. MESOLIMBIC-DOPAMINEPATHWAY
The drug that activates this pathway is liable for
addiction.
It correlates with pleasure and reward.
Composed of ventral tegmental area(MIDBRAIN) &
ventral striatum (forebrain)
Nucleus accumbens & olfactory tubercle.
Addictive drugs dopamine levels.
19
20. THE THREE STAGES OF DEPENDENCE
1.Binge / Intoxication stage-Basal Ganglia
2.Withdrawal/Negative effect stage-Extended Amygdala
3.Preoccupation/Anticipation Stage-Prefrontal Cortex
20
24. LEGAL CLASSIFICATION
Classification:-
24
LEGAL CLASSIFICATION
Schedule I Schedule II Schedule III
1. No officially
recognized
medical use
2. Lack of safety
under medical
supervision
3. High abuse
potential
4. Cannot be legally
produced
Examples:
LSD,THC,MDMA
Schedule IV
1. Officially
recognized
medical use
2. High abuse
potential that lead
to severe
psychological or
physical
dependence
Examples:
Methamphetamine
Morphine
1. Officially
recognized
medical use
2. Abuse potential
less than schedule
I & II that can lead
to moderate or
low physical or
high psychological
dependence
Examples:
Ketamine,
Hydrocodone (<15mg)
1. Officially
recognized
medical use
2. Low abuse
potential
compared with
schedule III
Examples: Alprazolam
Diazepam
Schedule V
1. Officially
recognized
medical use
2. Low abuse
potential relative
to schedule IV
3. Consists
preparations
containing limited
amounts of
narcotics
Examples: cough
syrup with <200mg
codeine per 100ml
25. DESIGNER DRUGS
• Synthetic substances , prepared in clandestine laboratories, that are inexpensive to
produce and difficult to detect.
• Done by some chemists to avoid Drugs and Narcotic Act regulations and to make
huge profits.
• Sometimes unpredictable and sometime lethal consequences occur
Examples :
AMPHETAMINE ANALOGUES -
MDMA – 3-4 methylenedioxymethamphetamine (ECTASY).
China White – Fentanyl analogue.
MPTP- Pethidine analogue- induces parkinsonism by causing lesions in nigrostriatal
pathway.
25
26. MANAGEMENT
• The ultimate goal is to achieve a ‘drug free status’ and to prevent
relapse of drug abuse
• The former is achieved by pharmacotherapy and latter by rehabilitation
psychotherapy and psychosocial interventions.
26
27. MANAGEMENT
Treatment approach includes :
Substitution therapy- by a similar drug having longer t 1/2
Aversive therapy-by a drug that produces unpleasant response after
intake of abused drug
Antagonist drug- to prevent relapse, once drug free status achieved
Anti craving drugs
Rehabilitation and psychosocial interventions
27
30. 30
International Classification of Diseases 10th Edition (ICD-10) Classification
F10 - Mental and behavioural disorders due to use of ALCOHOL
F11 – Mental and behavioural disorders due to use of OPIOIDS
F12 – Mental and behavioural disorders due to use of CANNABINOIDS
F13. – Mental and behavioural disorders due to use of SEDATIVE HYPNOTICS
F14. – Mental and behavioural disorders due to use of COCAINE
F15. – Mental and behavioural disorders due to use of other stimulants, including CAFFEINE
F16. – Mental and behavioural disorders due to use of HALLUCINOGENS
F17. – Mental and behavioural disorders due to use of TOBBACO
F18. – Mental and behavioural disorders due to use of VOLATILE SOLVENTS
F19. – Mental and behavioural disorders due to MULTIPLE DRUG USE and use of other psychoactive
31. DRUGS OF ABUSE
31
Drug abuse is the nonmedical, self- administered use of a drug
that is harmful to the user, generally act on the CNS to modify
the user’s mental state, although some are used for enhancing
physical performance.
Common abused drugs include:
• CNS stimulants (e.g., cocaine, amphetamines, nicotine),
• hallucinogens (e.g., LSD, mescaline, phencyclidine, and marijuana)
• general CNS depressants (e.g., ethanol),
• sedative–hypnotics (e.g., alprazolam, diazepam)
• opioid analgesics (e.g., heroin)
• inhalants (e.g., toluene, nitrous oxide, amyl nitrate).
32. 32
PSYCHOMOTOR STIMULANT.
DERIVATIVES:
DEXAMPHETAMINE,METHAMPHETAMINE(CRYSTAL METH OR ICE)
MECHANISM OF ACTION:
INCREASE PRESYNAPTIC RELEASE OF CATECHOLAMINES
DOPAMINE LEVELS INHIBIT DOPAMINE METABOLISM BY BLOCKING MAO-B
INHIBIT REUPTAKE OF CATECHOLAMINES.
EFFECTS:
MOTOR ACTIVITY and PERFORMANCE
EUPHORIA
ANOREXIA
EXCITEMENT
REDUCED FATIGUE.
OTHER NAMES: SPEEED, BILLY WIZZ, POORMANS COCAINE
AMPHETAMINE
34. ADHD
34
NARCOLEPSY
CLINICAL FEATURES:
DAYTIME SLEEP
VIVID NIGHTMARES
CATAPLEXY(SUDDEN LOSS OF MUSCLE TONE)
METHYPHENIDATE IS USED
NON AMPHETAMINE USED FOR NARCOLEPSY:
MODAFINIL
HYPERKINETIC CHILD
DRUGS: DEXAMPHETAMINE
METHYLPHENIDATE
ATOMOXETINE( NE REUPTAKE INHIBIT)
C/I in patients with GLAUCOMA
35. 35
Fenfluramine, dexfenfluramine causes marked anorexia.
MECHANISM OF ACTION:-
Enhancement of 5HT Release
.
SERIOUS EFFECTS:- INSOMNIA, PULMONARY HTN.
NEW DRUG:- Sibutramine
MECHANISM OF ACTION:-
BLOCK 5HT & NE REUPTAKE AT HYPOTHALAMUS
ADVERSE EFFECTS:-
INSOMNIA,CONSTIPATION, HR,BP.
C/I in CVD patients, caution with SSRI.
Weight Reduction
36. Summary Of the Effects of Amphetamines
36
Body
Increased heartbeat
Increased blood
pressure
Decreased appetite
Increased breathing rate
Inability to sleep
Sweating
Convulsions, fever
Chest pain
Irregular heartbeat Due to
overdose
Mind
Decreased fatigue
Increased confidence
Increased feeling of
alertness
Restlessness
Increased irritability
Fearfulness
Distrust of people
Behavioral stereotypy
Hallucination
low
dose
high
dose
37. • Aamphetamine toxicity treated with DIAZEPAM(SLOW IV)
• FOR PSYCHOTIC AGITATION – HALOPERIDOL
• GASTRIC LAVAGE
Acidification of urine by administering AMMONIUM CHLORIDE & ASCORBIC ACID
This increase elimination of amphetamine in urine.
Anti-hypertensive drugs like – LABETOLOL
For ARRYTHMIAS - ESMOLOL
Treatment typically requires more than one year of Intense intervention consisting of
drug abstinence, cognitive, emotional and motivational rehabilitation.
Treatment Of Acute Poisoning
37
39. History of Cocaine
• SIGMUND FRAUD USED COCAINE FOR TREATMENT OF DEPRESSION,
• ALCOHOL & OPIOID ADDICTION
• ALBERT NEIMANN extracted cocaine
• from coca leaves and named cocaine.
• 1904
•
39
40. What is it?
• Pure cocaine was first isolated from the leaves of the coca bush in 1860.
• Contained in small amounts in the leaves of ERYTHROXYLUM (coca) bush
• Researchers soon discovered that cocaine numbs whatever tissue it touches.
• This lead to it’s use as a local anesthetic.
40
41. Where does it come from?
• Coca leaves grow on the slopes of the Andes Mountains.
• For at least 4,500 years, people in Peru & Bolivia have chewed the
coca leaves to lessen hunger & fatigue.
• Most of the world’s supply of coca is grown & refined into cocaine in
Colombia.
41
42. How is it used
SNIFFED (15 – 30 min)
42
SMOKED
(5-10 min)
INJECTED
3 min
43. Cocaine Pharmacodynamics
• Indirect Agonist for
• DA (high affinity)
• NE (high affinity)
• 5-HT (modest affinity)
43
• Mechanism:
– Blocks catecholamine reuptake
45. Short-termeffects
• Dilated pupils
• Increased body temperature, Blood pressure & heart rate
• Insomnia
• Loss of appetite
• Increased energy
• Reduced fatigue
• Talkativeness
45
46. Long-term effects
• Paranoia
• Depression
• Ulcers in the membranes of the nose
• Dulled senses of taste & smell
• Weight loss, poor health & sexual dysfunction
• Loss of social & financial supports
• Holes in bony separation between nostrils in nose
46
48. EUPHORIA
Positive Reinforcement
CRAVING
Neuroadaptations
Cycle of CocaineAddiction
Use
This addiction has biological, behavioral & psychological aspects Cocaine
Brain Reward
Cocaine
Seeking
Behavior
Negative Reinforcement
Treatment interventions are designed to reduce euphoria & craving
48
49. COCAINE+ HEROIN
Concurrent or substitute use
• Multiple drug use (nicotine, alcohol, heroin, amphetamines,
hallucinogens).
• Cocaine + heroin => “speed ball”
49
50. COCAETHYLENE
• Alcohol inhibits metabolism of cocaine
• Alcohol + cocaine chemically react to form coca ethylene
• Only known example where body forms new psychoactive compound from two
others
• Coca ethylene
– Similar effects to cocaine
– Greater cardiac toxicity than cocaine
– 3-5x the half-life of cocaine
– associated with seizures, liver damage,
compromised immune system
50
51. PHARMACOTHERAPIES
Treatment of withdrawal:
• Alpha-blockers
• Chlorpromazine: DA antagonist (also blocks alpha receptors)
• Haloperidol (antipsychotic – 50x more potent than chlorpromazine).
• Alprazolam (Xanax - benzodiazepine) for panic attacks.
• Antidepressants (fluoxetine or desipramine).
• Diazepam (Valium) for seizures - binds to benzodiazepine site of GABAa
receptor.
• Dopamine agonist for withdrawal symptoms.
51
52. New Treatment Approaches
IMMUNOLOGICAL
• Antibodies made against cocaine, to break-down the molecule and stop its
effects.
• Undergoing Phase III trials in US
• An inactive cholera toxin protein – attach inactivated cocaine
• Immune system makes antibodies against both
• When individual takes cocaine, antibodies bind to it and prevent it from reaching
brain – high does not occur, patient loses interest
53. 53
Cocaine is known to have a number of effects during pregnancy.
elevated risk of placental abruption
Due to its vasoconstrictive and hypertensive effects, they are also at
risk for haemorrhagic stroke and myocardial infarction.
Cocaine is also teratogenic it can cause birth defects and foetal
malformations.
In-utero exposure to cocaine is associated with behavioural
abnormalities, cognitive impairment, cardiovascular
malformations, intrauterine growth restriction, preterm birth, urinary
tract malformations, and cleft lip and palate.
COCAINE IN PREGNANCY
54. METHYLXANTHINES
Theophylline ( tea) : long-acting, prescribed for night-time asthma
Theo bromine: found in cocoa.
Caffeine: (short-acting) the most widely consumed
found in coffee (200 mg/cup),
carbonated soft drinks (60 mg/can),
cocoa and chocolate
55. MECHANISM OF ACTION
1) It inhibits PHOSPHODIESTERASE enz. → ↑ cAMP
2) Adenosine (A1, A2 and A3) receptors antagonist almost equally,
which explains many of its cardiac effects
A2 receptors antagonist responsible for CNS stimulation &
smooth muscles relaxation
↓calcium in Smooth muscles
55
56. Actions
56
a.CNS:
decrease in fatigue, increased alertness: 100-200 mg caffeine in 1 or 2 cups of coffees
Aanxiety & tremors- 1.5 g of caffeine: 12-15 cups of coffee
Spinal cord stimulation: 2-5 g (very high dose)
Tolerance can rapidly develop
Withdrawal symptoms: feeling of fatigue & sedation.
b. CVS: at high dose of caffeine +ve inotropic and chronotropic effects on the heart, ↑CO
c. Diuretic action: mild ↑ urinary output of Na+, Cl- and K+
d.Gastric mucosa: all methylxanthines stimulate secretion of HCl
c.Respiratory smooth muscle: bronchodilator, Rx asthma replaced by β-agonists,
corticosteroids.
57. Pharmacokinetics
57
The methylxanthines are well absorbed orally.
Caffeine distributes throughout the body, including the brain. The drugs
cross the placenta to the fetus and is secreted into the mother's milk.
All are metabolized in the liver, generally by the CYP1A2 pathway, the
metabolites are then excreted in the urine.
Adverse effects
Moderate doses: insomnia, anxiety, agitation
High doses: emesis, convulsion
Lethal dose (10 gm of caffeine): cardiac arrhythmia
Suddenly stop: lethargy, irritability, headache
58. GAMMA-HYDROXYBUTYRIC ACID (GHB)
58
1st introduced as a general anesthetic
Colourless and odourless
DATE RAPE DRUG
Max absorption is oral route
Peak effect with in 1 hour and lasts for 4 hours
Liquid ecstasy ,liquid x.
Pharmacology – GHB-receptors are present on both pre-and postsynaptic
neurons, thereby inhibiting GABA release
Binding site – GABAB receptor( agonist)
Available in salt form.
59. Side effects of GHB
• Loss of conscience
• Coma
• Seizures
• Inhibition
• Dizziness
• Loss of memory
• Loss of coordination
• Nausea
59
60. BE CAREFULAT ALL TIMES!!!
Serious side effects when mixed with alcohol
Death due to respiratory depression.
Detected in HAIR and URINE(≤ 4 HOURS)
Other date rape drug: FLUNITRAZEPAM (roofies)
Medically used in
Narcolepsy
cataplexy
60
62. NICOTINE
• Nicotine, in mild to moderate doses, is a central nervous
system stimulant.
• It enhances central cholinergic receptors (activated by acetyl
choline).
• The dependence-producing effects of nicotine appear to be
modulated by dopamine (nicotinic-cholinergic receptors lie
on dopamine neurons, nicotine increases dopamine).
62
64. NICOTINE
64
Most common route – smoking
Oral ingestionn.
ACTION
some degree of euphoria and arousal
improves attention, learning, problem solving, and reaction
time
Toxic dose - respiratory paralysis and severe hypotension
65. TOLERANCE ,DEPENDENCE, WITHDRAWAL
65
Some evidence for tolerance
Best feeling after a day of abstinence
Strong dependence
Mild withdrawal symptoms
• Irritability
Anxiety
Restlessness
Impatience
• depression
66. At higher doses
• * Seizures
• * Hypotension
• * Respiratory arrest can develop
• Long term effects:-
66
67. Hazardsof smoking
• In pregnant women, nicotine crosses the placenta freely and
is in the amniotic fluid and umbilical cord blood of neonates.
• Sustained exposure of the fetus causes:
*Slow growth in utero and lower than average birth weights.
*Increased incidences of newborns with persistent
pulmonary hypertension.
67
68. Rx of nicotine addiction
68
Nicotine substitution
- Gum
- Transdermal patch
- Nasal spray
- Electric cigarettes
All these do not achieve peak nicotine level – but suppress
the withdrawal
69. 69
ANTI SMOKING DRUGS cytisine
VARENICLINE:PARTIAL NICOTINIC AGONIST(α4β2nAchR)
S/E:SUICIDAL TENDENCY
Dose of 0.5mg OD initially then 1mg BD from day 8 to 6months
BUPROPION SR :NE DA REUPTAKE INHIBITOR
S/E: SEIZURES
DOSAGE: 150-300mg BD PO
2ND LINE DRUGS: CLONIDINE
MISCILLANEOUS:
RIMONABANT(CB1 ANTAGONIST)
71. HALLUCINOGENS
- Also called psychedelics or psychomimetics
- Classicsynthetic hallucinogens
- LSD
- Some “designer” amphetamines (i.e.
MDA, MDMA)
- Classicnatural hallucinogens
- Psilocybin (“magic mushrooms”)
- Mescaline
- Schedule I Drugs based on the FDA
classification system
- Salvia- most powerful natural hallucinogen.
Legal. Grows throughout the Americas,
including the US.In mint family.
71
72. WHAT IS LSD?
LSD is the most commonly used synthetic
Hallucinogen synthesized by HOFMANN (1938).
- LSD is a white or clear, odorless, water-soluble crystal
that can be crushed into a powder and dissolved.
- The most common form of LSD is as a liquid that has
been transferred onto a small paper square known as
“blotter”
- Experiences on LSD are known as “trips” onset of
action in 1 hour and peak effect in 2-4 hours.
72
73. LSDTRIP
- 1st hour of trip – anxiety,tingling feelings, nausea, colors appear brighter
- 3rd hour – peak - Extreme visual, open and closed eyes, hallucinations. Vivid
colors and seeing things that are not there.
- Can go from periods of giddiness, to extreme insight.
- Can become extremely paranoid, especiallywhen put in a situation with
people who are not tripping.
73
74. 74
- The most common dangers of LSD result from bad trips,
including terrifying thoughts and feelings, disorientation from
time & space, fear of losing control, and fear of death.
Can cause unpredictable long-lasting adverse neuropsychiatric
effects, relatively long-lasting psychosis, severe depression or
schizophrenia-like syndromes, especially in heavy or long-term users
or in people with an underlying mental illness
SHORT- TERM EFFECTS
LONG-TERM EFFECTS
75. Flashback(HPPD)
• Flashback – An unexpected relived experience from a hallucination.
• A flashback occurs suddenly, often without warning, and may occur
within a few days or more than a year after hallucinogen use.
• Both frequent users and one-time experimenters can find themselves
on another trip when they least expect it.
• While driving a car, swimming, playing sports.
75
77. 77
• MDMA (3,4-Methylenedioxymethamphetamine):-
• also known as Ecstasy (E, X, or XTC), molly (U.S.), Mandy ( U.K)
• A psychoactive drug with stimulant and psychedelic effects that used as a
recreational drug.
• Drugs sold under the street names ecstasy, molly, or Mandy are often advertised as
pure MDMA, but are often mixed with multiple other drugs.
• MDMA can cause feelings of euphoria (extreme happiness) and altered sensations.
• side effects include insomnia, nausea, rapid heartbeat, and addiction.
• RAVE DRUG / CLUB DRUG/ PARTY DRUG
• EFFECT TIME 3-6 HOURS
• NEUROTOXIC
78. Mescaline
• Mescaline – A hallucinogen obtained from a small spineless cactus Peyote.
• From earliest recorded time, peyote has been used by natives in northwestern
Mexico as a part traditional riots.
• Least potent psychotomimetic and does not produce sympathomimetic action
• The drug is usually taken orally, without chewing, although it can still be
smoked, or even injected.
• It’s chemical structure is close to that of an amphetamine (stimulant).
78
79. PSILOCYBIN MUSHROOMS
• How are they taken?
• Eaten raw
• Cooked in food
• Brewed in tea
• Dried and ingested
• Street names:
• Magic mushrooms
• “Shrooms”
• How long does a trip last?
• 5-6 hours 79
80. Psilocybin Mushrooms Effects
• Nausea
• Dilated pupils
• Tightness in the neck
• Induce sensory hallucinations
• Hear things that are not real
Effects caused by shrooms begin about 30 min
after consumption and last nearly 5 hours.
During this period, laughing is somewhat uncontrollable and visual
hallucinations caused by organic objects are typical.
Psilocybin acts by affinity to serotonin 5-HT receptors.
80
81. JIMSONWEED
Jimsonweed - A common name for a plant known botanically as Datura stramonium,
which has been used as a medicine and intoxicant for centuries.
• It’s name comes from colonial Jamestown, where settlers became very ill after
mistakenly eating it in a salad.
• It is found in most of the continental United States
• Also called pod or thorn apple
• After ingestion it causes hallucinations.
• Severe toxicity includes seizures arrhythmias and coma
• Rx includes gastric lavage, activated charcoal. 81
83. AYAHUASCA
• Ayahuasca – A plant-based hallucinogen that users ingest as a drink
containing a combination of plant products.
• For centuries the Amazonian Indians have been drinking it.
• The Indians believe it cleanses body and mind and enables
communication with spirits.
• Common Names:
• Caapi
• Yage
• Vegetal 83
84. BUFOTENINE
• Bufotenine - A poisonous hallucinogenic alkaloid obtained from
the skin glands of toads of the genus Bufo.
• Found in the skin of psychoactive toads.
• Orally taken by licking the toads skin.
• Now there are ways to extract the poison from the toad by
milking it under the chin. It can then be created in a substance
to be smoked.
• HARMINE AND NUTMEG have psychotomimetic effects.
84
85. CANNABINOIDS
Cannabis Sativa (Hemp)
Cannabis indicia
GATEWAY DRUG
Psychoactive agent = ∆9 Tetrahydocannabinol (THC)
Found in all parts of the plant, but concentrated in the sticky resin(charas)
secreted from the flowing tops of ♀ plants.
WORLDS MOST POPULAR DRUG OF ABUSE
The herb was called GANJIKA in Sanskrit
85
86. HASH OIL:
It obtained by extracting THC from Hashish or Marijuana in oil.
Clear pale yellow / green to brown black
colour.
THC concentration 15-30%.
GANJA: Buds and flowering top of
female plant.
BHANG: Cut and dried large leaves
& stem of plants. 6
86
87. 87
MARIJUANA
- Dried and crumbled leaves, small stems,
flowing tops of the plant
- Usually smoked in joints, pipes, bongs,
- also grass, pot,weed,reefer.
- THC content varies…
SINSEMILLA:
pollination prevented (↑ potency)
The Gang Bong: The 4 barrel brain blaster!
90. PHARMACOLOGY OF CANNABIS
11- hydroxyl ∆9-THC.(active form)
Typical Joint contains approximately 0.5 – 1g of cannabis
- If THC content = 4%... joint with 1g of cannabis contains 40 mg of THC
Burning marijuana results in vaporisation of THC→ absorption into the lungs
Only about 20% of original THC is absorbed:
Breathing isn’t optimal – can be increased by breath holding
Increased high with 15 s breath hold vs. 7 s
90
91. NEUROPHARMACOLOGY
• Primary constituent is ∆9-THC.
• ∆9-THC is rapidly converted to is active form 11- hydroxy ∆9-THC.
• THC and its metabolite are highly fat soluble(lipophilic).
• There are two type of cannabinoid receptor CB1 and CB2.
• CB1 mainly present in brain and mediate psychological effects.
• CB2 associated with immune system and modulate inflammatory
responses.
• CB1 AND CB2 belongs to G protein coupled receptor.
11
91
92. ACTIONS - CANNABIS
92
DURING SEDATIVE PHASE: IMPAIRED CONCENTRATION
LSD LIFE EFFECTS IMPAIRED SHORT TERM MEMORY
MOOD SHIFTS.
-
DURING STIMULATORY PHASE: lasts for 2 hours.
EUPHORIA
TALKTIVENSS, APPETITE
FEELING OF WELL-BEING.
MOOD TRIPS WILL BE SEEN.
PERIPHERAL EFFECTS: TACHYCARDIA
BLOODSHOT EYES
IOP
BRONCHODILATATION
AMOTIVATION SYNDROME.
RUNNING AMOK CHRONIC POISONING
94. most Commonly.
CANNABIS WITHDRAWAL
Benzodiazepines are prescribed
Dronabinol(cannabis receptor agonist)
synthetic THC (20-60 mg/day) for 7-10 days depending on
duration of withdrawal symptom.
Mostly used in cancer patients to relieve emesis caused by
cisplatin
Along with NABILONE it increases appetite in HIV patients
RIMONABANT (20 mg/day) CB1 receptor antagonist used to treat
addiction. 94
95. PSYCHOSOCIAL ASPECT:
95
Motivational enhancement therapy (MET).
Cognitive behavior therapy (CBT).
Contingency management (CM).
Family and system intervention.
Combined psychosocial treatment.
96. ALCOHOL – ETHANOL
96
Most commonly abused drug in the world
70% INDIAN adults have experienced alcohol
Absolute alcohol is 99% ethanol
All Standard Beverages contain 40% ALCOHOL
INDIAN STANDARD in BREATH ANALYSER
IS more than 35mg in 100ml IS GUILTY.
Minimum age for consumption is 21 years.
97. Alcohol Breakdown
• Alcohol ADH(alcohol dehydrogenase) × FOMEPAZOLE
• Acetaldehyde
ALDH(ALDEHYDE)
• × DISULFIRAM
• EXTRA HEPATIC
• Acetic acid and water
97
99. Effect ofalcoholon thebrain
• * Alcohol is a CNS suppressant.
• It exerts this suppressant effect in a descending manner,
where higher cortical centers are inhibited first, resulting in
euphoria and then disinhibit ion.( 200-300mg)
• In larger doses≥ 300mg lower vital centers are inhibited,
leading to hypotension and respiratory depression. 99
100. Effectofalcoholonneurotransmitters
* It is found that ion channel activities associated with
acetyl choline, serotonin and GABA receptors are enhanced by
alcohol.
• Ion channel activities associated with glutamate receptors
are inhibited.
• * Death is due to central respiratory depression or
inhalation of vomitus(500mg/dl)
100
101. Alcohol on neurotransmitter systems
neurotransmitt er acute
intoxication
alcohol
withdrawal
Gamma
aminobutyri c
acid (GABA)
N-methyl-d-
aspartate
(NMDA)
excitatory
glutamate
receptors
101
103. Alcohol Intoxication
20-99mg% loss of muscular coordination, change in behavior
100-199mg% ataxia, mental impairment
200-299mg% obvious intoxication, nausea and vomiting
300-399mg% severe dysarthria and amnesia
400-600mg% coma occurs
600-800mg% decreased respirations and blood pressure, often
fatal. 103
105. Withdrawal Syndrome Stage 1
• Begins within 24 hours
• Lasts up to 5 days
• 90% of cases do not go beyond stage 1
• Other symptoms include depressed mood, anxiety, diaphoresis,
headache, nausea/vomiting, etc.
105
106. Withdrawal Syndrome Stage 2
• Mostly untreated or undertreated in stage 1
• Same signs and symptoms in stage 1 only more severe
• Hallmark is visual hallucinations (generally perceived as benign)
• Usually occurs 48 hours after last drink
106
107. Withdrawal Syndrome Stage 3
• Usually occurs 72 hours after last drink
• Delirium Tremens (acute reversible organic psychosis) has
2% mortality
• Lacks insight into hallucination, often disoriented and
labile
• Seen in persons with severe alcoholism and/or significant
medical problems
107
110. 110
In case of alcohol intoxication, pupils are contracted, but on
external painful stimulation of the person, e.g. by pinching or
slapping, causes pupil to dilate followed by slow constriction
again. This is called as McEwan’s sign and if this is positive, it
is suggestive of alcoholic coma.
McEwan's SIGN
111. 111
MARCHIAFAVA–BIGNAMI DISEASE :
is a progressive neurological disease of alcoholism,
characterized by corpus callosum demyelination and necrosis and
subsequent atrophy.
112. Treating withdrawal
glucose
electrolytes
50–100 mg of
thiamine daily
25–50 mg of chlordiazepoxide or 10 mg of
diazepam given PO every 4–6 h on the first
day, with doses then decreased to zero
over the next 5 days
search for evidence of liver failure,
gastrointestinal bleeding, cardiac arrhythmia,
infection
112
113. Medications for Rehabilitation
Drug Dosage MOA BENIFIT REMarks
NALTREXONE 50–150 MG/D BLOCKING OPIOID SHORTEN G ALLELE OF
ORALLY, RECEPTORS, DECREASE SUBSEQUENT THE AII8G
ACTIVITY IN THE DOPAMINE- RELAPSES POLYMORPHISM
RICH VENTRAL TEGMENTAL
REWARD SYSTEM
ACAMPROSAT 2 G/D DIVIDED INHIBITS NMDA RECEPTORS DECREASING
E INTO THREE MILD
ORAL DOSES SYMPTOMS OF
PROTRACTED
WITHDRAWAL.
DISULFIRAM, 250 MG/D. PRODUCES VOMITING AND AVERSION CAN BE
AUTONOMIC NERVOUS THERAPY DANGEROUS
SYSTEM INSTABILITY IN THE WITH HEART
PRESENCE OF ALCOHOL AS DISEASE,
A RESULT OF RAPIDLY STROKE,
RISING BLOOD LEVELS OF DIABETES
THE FIRST METABOLITE OF MELLITUS, OR
ALCOHOL, ACETALDEHYDE HYPERTENSION 113
114. 114
Used as a palliative
care drug in patients
suffering with cancer
to get relief from pain
and nausea
115. Fetalalcoholsyndrome
• It occurs when fetuses are exposed in utero to alcohol by
their mothers' drinking alcohol.
• This syndrome is the leading cause of mental retardation in
the United States.
• Women with alcohol related disorders have a 35 percent risk
of having a child with deficits. 115
120. Over dose of opiates
120
Severeintoxication is diagnosed by the triad of:
• 1- Coma
• 2- Pinpoint pupils
• 3- Respiratory depression.
• It is amedical emergency that requires immediate
attention.
122. 122
Section Divider
Withdrawal
As the body gets used to a
regular dose of opioids, it slows
production of natural opioids
When the dose is not taken,
the body experiences
uncomfortable withdrawal
symptoms
123. Medications for Opioid Use Disorder
• Maintenance therapy
• 3 FDA approved medications
• Methadone
• Buprenorphine
• Naltrexone
• Detox – management of withdrawal
• Inpatient vs. outpatient
123
124. 124
OPIOID ABUSE IN PREGNANCY
An infant withdrawing from methadone can have sleeping
difficulties, seizures and a higher risk of dying from Sudden infant
death syndrome. Methadone withdrawal occurs after 7–14 days. If
a child is premature they have a lower risk of severe symptoms. It
may be because preterm infants may have been exposed to the
drug.
An infant born with heroin dependency is more likely to
be premature and have meconium staining. Heroin withdrawal is
seen within 48–72 hours of the birth.
125. 125
Symptoms of withdrawal may begin as early as 24 to 48
hours after birth, or as late as five to 10 days.
Symptoms of withdrawal in full-term babies.
Tremors (trembling)
Irritability (excessive crying)
Sleep problems
High-pitched crying
Tight muscle tone
Neonatal Abstinence Syndrome
126. PHENCYCLIDINE
126
Also called “ ANGEL DUST”
MOA: NON COMPETITIVE ANTAGONISM OF NMDA RECEPTOR.
TOXICITY:
MILD:- (1-5mg) causes ALOCHOL like effect
MODERATE:-(5-10mg) causes distortion of space and time
HIGH : (≥ 10mg) causes VIVID HALLUCINATIONS
OVER DOSE: RESPIRATORY DEPRESSION / SEIZURES
TREATMENT:
MECHANICAL VENTILATION FOR RESP DEPRESSION
FOR SEIZURES BENZODIAZEPINES
FOR PSYCHOTIC EFFECTS ANTIPSYCHOTICS
127. KETAMINE
127
PHENCYCLIDINE DERIVATIVE
DISSCOCIATIVE ANESTHESIA
PEAK ONSET:- IM:- ≤ 5 MIN, IV:- ≤ 1 MIN
VIVID DREAMS AND HALLUCINATIONS
UNIQUE DRUG USED AS HYPNOTIC, ANALGESIA AND AMNESIC EFFECTS
DRUG ABUSE: HIGH DEPENDANCE AND TOLERANCE IS SEEN
OVERDOSING:100-250mg CAUSES “K- HOLE”.
≥ 250mg RESPIRATORY DEPRESSION
REINFORCEMENT SEEN IN MONKEYS
CHRONIC EXPOSURE CAUSES SHIZOPHRENIA LIKE STATE.
129. 129
AYURVEDIC HERBS TO TREAT DRUG ADDICTION
Radix Pueraria showed the most promising efficacy for alcoholism
Thunbergia laurifolia can protect against alcoholic liver toxicity.
Withania somnifera and Salvia miltiorrhiza can reduce morphine
tolerance and alcohol intake respectively.
Asafoetida extract is suitable for the use in the
abstinence treatment of subjects addicted to
opioid, morphine, marijuana.
130. 130
Ginseng extract inhibited tolerance and dependence on morphine
passion flower used in the management of symptoms associated with detoxification.
Caulis Sinomenii effective for TREATING drug dependence
Peganum harmala plays a role in eliminating some of the withdrawal symptoms.
Chamomile extract can reduce chronic and acute withdrawal symptoms
Valerian is commonly used for the treatment of insomnia and anxiety
131. IMMUNOPHARMACOTHERAPY
1. A novel approach to pharmacotherapy which is largely pharmacokinetic.
2. Uses highly specific antibodies to sequester the drug of interest while it is still in
blood stream, thus preventing drug reaching brain.
3. Active immunization : antigenic drug protein conjugate administration leading to
activation of immune cells causing generation of antibodies to drug protein
conjugate.
4. Passive immunization:: injection of pre-generated anti-bodies, typically of
monoclonal type.
131
132. IMMUNOTHERAPY
5. Successful active immunization with VACCINES in animals for cocaine ,nicotine ,
phencyclidine, methamphetamine, heroin.
6. Two nicotine vaccines under clinical trials
• NicVAX & NIC002 : safe &tolerated in Phase I & II BUT FAILED Phase III
7. Cocaine vaccine(TA-CD)-marginal results in promoting abstinence
8. Another cocaine and heroin vaccine are in different stages of preparation
132
134. 134
THE NARCOTIC DRUG AND PSYCHOTROPIC SUBSTANCE ACT – 1985
Prevention of Illicit Trafficking in Narcotic Drugs and Psychotropic Substances Act- 1988
135. CONCLUSION
• Medications currently on the market for the treatment of addiction open a
window on the opportunities to facilitate treatment and provide a means for
evaluating future medications.
• The potential for the development of future medications for the treatment of
addiction is significant on a number of fronts. A combination of excellent,
validated animal models of addiction and an enormous surge in our
understanding of the neurocircuits and neuropharmacological mechanisms
involved in the development and maintenance of addiction reveal numerous
possible targets.
• Recent success with acamprosate , naltrexone, varenicline, and buprenorphine
should provide some indication that expanded directions are merited in the
addiction field. 135
136. REFERENCES
1.Sharma HL, Sharma KK. Principles of pharmacology.3rd edition; 2017.
2.Koob, G.F.,Arends, M.A.,Moal, M.L. 2nd edition ; 2014, Drugs, Addiction, and the
Brain
3.Murthy, Pratima et al. “Substance Use and Addiction Research in India.” Indian
Journal of Psychiatry 52.Suppl1 (2010): S189–S199.
4.Goodman and gillmann 13 th edition drug dependance and drug abuse.
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