Description of common drugs of abuse

1. Ethanol, Drug Use disorders
& addiction
Dr. M. Ahsan (MBBS, MD)

2. An arrested man was told, in a police station by a doctor, that he was drunk.
The man asked, ‘Doctor, could a drunk man stand up in the middle of this room,
jump into the air, turn a complete somersault, and land down on his feet?’
The doctor was injudicious enough to say, ‘Certainly not’ – and was then and there
proved wrong (Worthing C L. 1957 British Medical Journal i:643)
The introduction of the breath-analyzer, which has a statutory role only in road
traffic situations, has largely eliminated such professional humiliations.

3. Introduction
• Drug use for non-medical purposes (abused, misused, used for
recreational purposes) presents a range of social problems, all of
which have important pharmacological dimensions

4. Definition
Drug abuse:
• Intentional use of excessive drugs for purposes other than the
indication for which the drug was prescribed.
• It can be persistent or sporadic

5. Definition
Drug addiction:
• Compulsive drug use characterized by overwhelming involvement
with the use of drug.
• Procuring the drug and using it take precedence over other activities

6. Definition
Drug habituation:
• Less intensive involvement with the drug, so that withdrawal
produces only mild discomfort.

7. Drug dependence
• It is a state in which use of drugs for personal satisfaction is given a
higher priority than other basic needs, often in face of known risks to
health.
Types :
• Psychological dependence
• Physical (Physiological) dependence

8. Dependence
• Psychological dependence :
• It is said to have developed when the individual believes that optimal
state of well being is achieved only through the actions of drug

9. Dependence
• Physical dependence :
• Physical dependence implies that repeated exposure to a drug
induces adaptive changes in the body so that tolerance occurs and
discontinuation results in a withdrawal reaction

10. Basic neurobiology of drug abuse
• Every addictive drug causes its own spectrum of acute effects, but all
induce strong feelings of euphoria and reward
• With repetitive use, addictive drugs induce adaptive changes such as
tolerance (ie, escalation of dose to maintain effect)
• Once the abuse drug is no longer available, signs of withdrawal become
apparent
• Relapse is very common in addicts after a successful withdrawal

11. Basic Neurobiology: Dopamine Hypothesis of
Addiction
• The mesolimbic dopamine system is the prime target of addictive
drugs:
• As a general rule, all addictive drugs activate the mesolimbic
dopamine system
Mesolimbic system:
 This system originates in the ventral segmental area (VTA) and projects to the nucleus
accumbens, the amygdala, the hippocampus, and the pre-frontal cortex.
 Most projection neurons of VTA are dopamine-producing neurons
 When the dopamine neurons of the VTA begin to fire in bursts, large quantities of
dopamine is released in the nucleus accumbens and the prefrontal cortex

12. Common pathway of
drugs of addiction on the
dopaminergic neurones
Increasing evidence suggests that
drugs of addiction all act by
modulating dopaminergic
transmission in the medial forebrain
bundle. (MFB)
(Mesolimbic system is a component
of MFB)

13. Basic Neurobiology: Tolerance & Withdrawal
• With chronic exposure to addictive drugs, the brain shows signs of
adaptation: this phenomenon is called tolerance
• For example, if morphine is used at short intervals, the dose has to be
progressively increased over the course of several days to maintain
rewarding or analgesic effects.
• Adaptive changes become fully apparent once drug exposure is
terminated. This state is called withdrawal and is observed to varying
degrees after chronic exposure to most drugs of abuse

14. Basic Neurobiology:
Addiction: A disease of maladaptive learning
• Addiction is characterized by a high
motivation to obtain and use drug despite
negative consequences.
• With time, drug use becomes compulsive
(“wanting without liking”)
• Even after successful withdrawal: Individuals
have a high risk of relapse
Relapse is triggered by one of the following:
Re-exposure to addictive drug
Stress
Setting that recalls prior drug use (eg. People,
places, or drug paraphernalia)
• A neutral stimulus can motivate
addiction-related behaviour and
act as a “trigger” when it is
paired with drug use :
This phenomenon may involve
synaptic plasticity in the target
nuclei of the mesolimbic
projection
(Synaptic plasticity is involved in learning &
memory)

15. Commonly abused substances
• Amphetamine
• Cocaine
• MDMA
• Synthetic cathinone (bath salts)
Stimulants
• LSD
• Marijuana
• Synthetic cannabinoids
Hallucinogens
• Ethanol
• Prescription drugs (particularly opioids)
Other drugs of
abuse

16. Ethanol
• Alcohol is the most commonly abused substance in modern society
MOA:
• Enhanced effect of the inhibitory neurotransmitter GABA
• Increased release of endogenous opioids
• Altered levels of serotonin and dopamine

17. Ethanol
• At low doses, ethanol is a selective CNS depressant (decreased
inhibition), resulting in drunken behaviour
• At high doses, it is a general CNS depressant, resulting in coma and
respiratory depression
Ethanol is a major cause of fatal automobile
accidents, drownings, and fatal falls and is a
related factor in many hospital admissions

18. Stimulatory and depressant effects of acute alcohol
ingestion

19. Other effects of acute alcohol ingestion

20. Other effects of acute alcohol ingestion
(contd)

21. Ethanol
• Ethanol is highly lipid soluble
…….rapidly absorbed from stomach and duodenum
• Food decreases absorption
• Peak levels are attained in 20 minutes to 1 hr after ingestion
• 95% Ethanol is metabolized by alcohol dehydrogenase and then by
aldehyde dehydrogenase in liver
• Remainder is excreted in breath, sweat and urine

22. Ethanol
Ethanol
Acetaldehyde
Acetate
Alcohol dehydrogenase
Aldehyde dehydrogenase
Al low doses, ethanol is metabolized by
first order kinetics
When blood level exceeds 15 – 40
mg/dL/hr, it follows zero-order kinetics
Reason: enzymatic processes are
saturated
Responsible for
toxicity
Genetic
deficiency of
aldehyde
dehydrogenase
causes flushing,
headache and
nausea after
small amounts of
alcohol due to
accumulation of
acetaldehyde (as
seen in Japanese)
Breath sample can be used to
determine blood alcohol levels:
There is a constant blood-to-breath
ratio of 2100:1

23. Ethanol
Chronic ethanol abuse can
cause profound hepatic,
cardiovascular, pulmonary,
hematologic, endocrine,
metabolic and CNS damage

24. Effects of chronic alcohol use

25. Effect of chronic alcohol use (contd)
Chronic alcohol use has profoundly negative psychosocial impact

26. Ethanol
• Sudden cessation of ethanol ingestion in patients with physical
dependence can precipitate withdrawal symptoms:
Tachycardia
Sweating
Tremor
Anxiety
Agitation
Acute psychotic attack (delirium tremens)
Hallucination
Convulsions
In 6 hours
In 72 hours
Withdrawal symptoms are
managed with symptomatic care,
benzodiazepines and long-term
addiction treatment

27. Treatment of alcohol dependence
• Disulfiram:
• Disulfiram blocks the oxidation of acetaldehyde
to acetic acid by inhibiting aldehyde
dehydrogenase
• This results in the accumulation of acetaldehyde
in the blood, causing flushing, tachycardia,
hyperventilation, and nausea.
• Patient abstains from alcohol to prevent the
unpleasant effects of disulfiram induced
acetaldehyde accumulation
• Naltrexone:
Competitive and
long-acting opioid
antagonist
• Acamprosate:
Acts on NMDA
receptors
Decreases
cravings

29. Prescription drug abuse
Commonly abused prescription drugs:
• Opioids
• Benzodiazepines

30. Opioids
• Most commonly abused opioids:
Morphine
Heroin (diacetylmorphine)
Codeine
Oxycodone
Meperidine abuse is common among health professionals
All these drugs induce strong
tolerance and dependence
The withdrawal syndrome may be very severe (except for codeine) :
intense dysphoria, nausea or vomiting, muscle aches, lacrimation,
rhinorrhea, mydriasis, piloerection, sweating, diarrhea, yawning, and fever

31. Opioids: treatment
Treatment of overdose:
• Opioid antagonist: Naloxone
• Naloxone administration also provokes an acute withdrawal symptoms in a
dependent person
Treatment of opioid addiction:
• Long acting opioid: Methadone, Levomethadone OR
• Partial agonist: Buprenorphine
• Oral methadone is administered as a substitute for the opioid of abuse, and the patient is then
slowly weaned from methadone. The withdrawal syndrome with Methadone is milder but more
protracted (days to weeks) than that with other opioids

32. Cocaine
Obtained from Erythroxylum coca
MOA:
• Cocaine inhibits the reuptake of NE into the
adrenergic neuron  increased availability of NE
at the synapse
• Stimulates pleasure center in the brain (due to
inhibition of reuptake of dopamine and serotonin)

33. Cocaine
• It is a CNS stimulant
• Patient presents to emergency
with:
Agitation/Paranoia
Convulsions
Hyperthermia
Chest pain
Management:
• Benzodiazepine (lorazepam)
…helps to calm the agitated patient,
treat and prevent convulsions
• Cooling the patient
…hyperthermia is major cause of
cocaine mortality
• Symptomatic supportive care

34. Amphetamine
• Amphetamines act by enhancing the release of biogenic amines from
nerve terminals
• Clinical effects are similar to cocaine
• Effects may last longer with less euphoria
• Treatment is similar to cocaine

35. MOA: Cocaine & Amphetamine

36. Methylenedioxymethamphetamine
• MDMA is also known as ‘ecstacy’ or ‘Molly’
• It is a hallucinogenic amphetamine with profound serotonin releasing
property
• Common in rave parties and with social offenders
• MDMA abuse can cause profound hyperthermia, altered mental
status, and movement disorders known as the ‘serotonin syndrome’
• Like amphetamines, MDAM can cause ‘bruxism’ and ‘trismus’

37. Mechanism of action of MDMA
• Because of its unique serotonin properties,
the term “empathogen,” meaning
“generating a state of empathy” was first
coined for MDMA
• Many users describe a sense of well-being
and social interactivity, and sexual offenders
take advantage of this

38. Methylenedioxymethamphetamine
Treatment:
• Benzodiazepines: help to calm and cool the patient.
• Neuromuscular blockers: to control excessive movement and heat
generation.
• Cyproheptadine (serotonin antagonist): to treat serotonin syndrome
• Endotracheal intubation

39. Lysergic Acid diethylamide (LSD)
• LSD produces its psychedelic effects through serving as a potent partial agonist at
5-HT2A receptors.
• Aside from the very colorful hallucinations, the drug is also responsible for mood
alterations, sleep disturbances, and anxiety.
• Repeated use rapidly produces tolerance through down-regulation of the
serotonin receptors.
• LSD may cause tachycardia, increased blood pressure and body temperature,
dizziness, decreased appetite, and sweating.
• Loss of judgment and impaired reasoning are associated with use of LSD.
• This can sometimes be an exaggerated effect with extreme panic, which is known
by individuals as a “bad trip,” and may lead to suicide.

40. Marijuana
• Cannabis sativa is the plant most often used for its hallucinogenic properties
• Marijuana is the most frequently used illicit drug – (dried flowers, leaves,
stems and seeds of the cannabis plant).
• The main psychoactive alkaloid contained in marijuana is Δ9-
tetrahydrocannabinol (THC)
• Cannabinoid or CB1 receptors: targets for THC
• When CB1 receptors are activated by marijuana, the effects produced include
physical relaxation, hyperphagia (increased appetite), increased heart rate,
decreased muscle coordination, conjunctivitis, and minor pain control

41. Marijuana
• The half-life of THC is about 4 hours.
• The onset of effects of THC after smoking marijuana occurs within
minutes and reaches a maximum after 1–2 hours
The most prominent effects are euphoria and
relaxation

42. Effects of
Marijuana

43. Marijuana
• The justification of medicinal use of marijuana was examined by the Institute of
Medicine (IOM) of the National Academy of Sciences in its 1999 report,
Marijuana & Medicine …. This continues to be a controversial issue
• Marijuana has been used to help in the treatment of:
chemotherapy-induced nausea and vomiting
cachexia secondary to cancer and AIDS
epilepsy
chronic pain,
multiple sclerosis
anxiety.
Dranabinol: Synthetic THC
prescribed to treat emesis and to
stimulate the appetite.
Nabilone: Δ 9 -THC analog, used for
adjunctive therapy in chronic pain
management.

44. Drugs and sport
• Drugs are frequently used to enhance performance in sport
• Detection can be difficult when the drugs or metabolites are closely related to
endogenous substances, or when the drug can be stopped well before the event.
• Detection of levels of the naturally occurring compound above a “benchmark”
indicates potential doping.
Mass spectrometry: to detect the isotope content of compounds might enable differentiation of
natural and synthetic steroids
Other indirect methods: Testosterone and its related compound, epitestosterone, are both
eliminated in urine.
The ratio of testosterone to epitestosterone increases with use of anabolic steroids and can be
used to detect anabolic steroid use

45. Use of illicit drugs in
sport

46. Summary: Drugs Used to treat dependence
and addiction

47. Summary: Drugs Used to treat dependence
and addiction

48. Thank you

49. References
Goodman, L. S., Brunton, L. L., Chabner, B., & Knollmann, B. C.
(2011). Goodman & Gilman's pharmacological basis of therapeutics.
New York: McGraw-Hill.
Katzung, B. G., Masters, S. B., & Trevor, A. J. (2017). Basic & clinical
pharmacology. New York: McGraw-Hill Medical.
Whalen, K., Finkel, R., & Panavelil, T. A. (2015). Pharmacology (Sixth
edition.). Philadelphia: Wolters Kluwer.
Bennet PN, Brown MJ, Sharma P. (2012). Clinical Pharmacology.
Churchill Livingstone, Elseivier