The document discusses several substance-related disorders including substance abuse, alcohol-related disorders, amphetamine-related disorders, caffeine-related disorders, cannabis-related disorders, cocaine-related disorders, and hallucinogen-related disorders. It provides information on the diagnostic criteria, physiological and psychological effects, mechanisms of action, pharmacokinetics, and treatment approaches for managing withdrawal and dependence for each substance.

2. Substance Abuse
 Substance abuse
 – Use of drug interferes with ability to function
 Fails to meet work or family obligations
 – No physiological dependence
 Substance dependence (addiction)
 – Involves either tolerance or withdrawal
 – Tolerance
 Greater and greater amounts of substance are needed to produce
 the desired effect
 – Withdrawal
 Physiological and psychological consequences when individual
 discontinues or reduces substance use
 – Restlessness, anxiety, cramps, death

3. Alcohol-Related Disorders
 Discontinuation of alcohol in heavy user:
 – Anxiety
 – Depression
 – Weakness
 – Restlessness
 – Difficulty sleeping
 – Muscle tremors
 • Face, fingers, eyelids, other small musculature
 – Elevated BP, pulse, temperature

4. Management of Alcohol
Withdrawal
General Measures
 Seizure precautions with h/o Sz
 Hydration
 Thiamine 100mg IM/IV prior to glucose
 Correct electrolytes—Mg, Ca, K, PO4
 Treat concurrent illnesses

5. Management of AWS
 Benzodiazepines (BDZ)
 Treatment of choice
 Reduce symptoms and decrease risk of Seizurezs
 Phenobarbital
 Narrow therapeutic index
 Carbamazepine
 Effective alternative, less sedation
Mayo-Smith JAMA 1997;278:144-51

6. Choice of Benzodiazepine
 All seem effective for AWS
 Limited comparative data
 All metabolized by liver
 Differences
 Onset of action, half life, routes
 1 or 2 step metabolism; active metabolites
 Long vs shorter acting

7. Long-acting Benzodiazepines
Chlordiazepoxide (Librium®)
 Oral dosing only
 Intermediate onset
 Long-acting parent compound and metabolites
 Smoother withdrawal, less sz, better cognitive fxn
 Potential accumulation in elderly and patients with liver
disease
 [Diazepam]

8. Shorter-acting BDZs
Lorazepam (Ativan®)
 Versatile dosing—PO, IV, IM, SL
 Fast to intermediate onset
 Intermediate half-life, no metabolites
 Less likely to accumulate in elderly or with liver
disease
 Breakthrough sx, met. acidosis, delirium
 [Oxazepam]

9. Benzodiazepines
 Chlordiazepoxide generally preferred
 Indications for Lorazepam
 Elderly
 Established liver disease
 NPO
 Severe w/d requiring frequent or high doses

10. Benzodiazepines
Route of administration
 Oral preferable
Ease of administration
More consistent blood levels
 Sublingual if NPO
(e.g., surgical patients)
 Intravenous
Severe w/d requiring rapid titration or NPO

11. Amphetamine Related
Disorder
 DSM IV
 Amphetamine induced
 Anxiety disorder
 Mood disorder
 Psychotic disorder with delusions
 Psychotic disorder with hallucinations
 Sexual dysfunction

12. Amphetamine Related
Disorder
 Treatment
 None established
 Treat specific symptoms
 Comorbid conditions such as depression may
respond to antidepressants
 Bupropion (Wellbutrin)
 Used after patients withdraw from amphetamines

13. Caffeine-Related Disorder
 Caffeine is an methylxantine
 More potent than other known methylxantines
 Theophyline (Primatene)
 Half-life- 3-10 hrs
 Peak 30-60 minutes
 Crosses BBB
 Adenosine-receptor antagonist

14. Amount of Caffeine
Consumption
Beverages / Food:
 Cup of coffee: 65-120 mg caffeine
 Espresso 1oz shot: 40 mg
 Cup of tea: 40-60 mg
 Can of soda: 30-60 mg
 Red Bull (8.3oz): 80 mg
 Hershey’s milk chocolate almond bar (6oz): 25mg
Over the counter medicines:
 No-Doze: 100 – 200 mg
 Midol: 20-100 mg
 Excedrin: 30-65 mg
Benowitz, 1990
Total consumption of caffeine per person per day is estimated at
210 to 238 mg (Barone and Roberts, 1996)

15. Mechanism of Action
 Three main hypotheses:
1. Mobilization of intracellular calcium
 Biphasic effect on intracellular calcium levels
 *Toxic amounts of caffeine
2. Inhibition of phosphodiesterase
 Inhibition of enzyme that breaks down cyclic adenosine monophosphate
(cAMP)
 *Toxic amounts of caffeine
3. Antagonism of inhibitory presynaptic adenosine receptors
 Caffeine blocks adenosine receptors
 Resulting in the inhibition of the breakdown of cAMP
 Blocking the inhibitory effects of adenosine
Nehlig et al., 1992

16. Pharmacodynamics
Caffeine
Central Nervous System Enhances neurotransmitter release
Stimulates locomotor activity
Decreases cerebral blood flow
Cardiovascular Release of epinephrine (adrenaline) which
Increases heart rate
Increases blood pressure
Increases blood flow to the muscles
Decreases blood flow to skin and inner
organs
Renal Diuresis; stimulates renal release
Vasculature Peripheral: Dilation
Central: Constriction
Gastrointestinal Increases gastric secretions
Respiratory Bronchodilation
Increases respiratory rate
Garrett and Griffiths 1997

17. Pharmacokinetics
 Absorption
 Gastrointestinal tract and stomach
 Rapid rate, peak blood level in 30-60 min.
 Crosses lipid-membrane (not water soluble)
 Distribution
 Diffuses throughout the organism and crosses BBB
 Including placenta and placental BBB
Nehlig et al., 1999; Fredholm et al., 1999

18. Pharmacokinetics
 Metabolism
 Metabolized through liver biotransformation initially by demethylation into
dimethylxanthines.
 *Dimethylxanthines are pharmacologically active and may add to the
effects of caffeine consumption in humans.
 This process is unique to humans, no other animal species metabolizes
caffeine in a similar way
 Half life of caffeine
 Three to eight hours; varies with age and other external factors
 Newborns cannot metabolize caffeine, mainly eliminated by excretion
 Half life 80 +/_ 23 hours
 Smokers, half life is reduced up to 50%
 Pregnant women and those taking oral contraceptive, half life up to 15
hours longer
Nehlig et al., 1999; Fredholm et al., 1999

19. Treatment of Caffeine-Related
Disorders
 Reducing or eliminating caffeine
consumption
 ASA
 Headaches, muscle aches from withdrawal
 Benzodiazepines-rarely required

20. Cannabis-Related Disorders
 Major active ingredient  Physiological
 – THC (delta-9-  – Bloodshot & itchy eyes
 tetrahydrocannabinol)  – Dry mouth and throat
 • Psychological  – Increased appetite
 – Feelings of relaxation and  – Reduced pressure within the
 sociability  eye
 – Rapid shifts of emotion  – Reduced BP
 – Interferes with attention,  – Abnormal heart rate
 memory, and thinking  • May exacerbate preexisting
 – Heavy doses can induce  cardiovascular problems
 hallucinations and panic  – Damage to lung structure and
 – Impairment of skills needed  function
 for driving  – Tolerance may develop
 • Impairment present for
 several hours after ‘high’ has
 worn off

21. Cannabis Withdrawal
 No specific treatment
 Abstinence and support
 Anxiolytics
 Short-term withdrawal symptoms relief
 If depressive disorder is present, treat with
antidepressants

22. Cocaine-Related Disorder
 Alkaloid obtained from coca  Overdose
leaves  – Chills, nausea, insomnia,
 – Reduces pain paranoia, hallucinations, and
 – Produces euphoria  other psychotic symptoms
 – Heightens sexual desire  – Can cause heart attack and
 – Increases self-confidence and death because drug causes
indefatigability  blood vessels to narrow
 Blocks reuptake of dopamine in  • Not all users develop tolerance
mesolimbic areas of brain  – Some become more sensitive
 • May increase risk of OD
 • Usage increased in 70s and 80s
 – Dropped late 80s; rose mid 90s
 In 2003, 2.3 million users over
the age of 12 (SAMHSA, 2004)

23. Cocaine-Related Disorder
 Crack
 – Form of cocaine that become popular in the
 80s
 – Rock crystal that is heated, melted, & smoked
 – Increased popularity because it is cheaper than
cocaine

24. Cocaine-Related Disorder
 Treatment
 No pharmacological treatments produce decreases in
cocaine use comparable to the decreases in opioid use
when heroin users are treated with methadone,
levomethadyl and buprenorphine.
 Methylphenidate (Ritalin),Lithium (Eskalith)
 Cocaine users presumed to have preexisting ADHD and
mood disorders
 Those drugs are useless in patients without the
disorders

25. Cocaine-Related Disorder
 Treatment, cont.
 Many different treatments have been use with
little or no effects
 TCAs
 MAOIs
 SSRIs
 Antipsychotics
 Etc.

26. Hallucinogen-Related Disorders
 Natural and synthetic substances
 Psychedelics or psychomimetics
 Induce hallucinations or disconnection with reality
 Schedule 1 drugs

27. Hallucinogen-Related Disorders
 Naturally occurring
 Psilocybin
 Mushroom
 Mescaline
 Peyote cactus
 Other
 Harmine, harmaline, ibogaine, dymethyltriptamine
(DMT)

28. Hallucinogen-Related Disorders
 LSD
 Synthesized in 1938
 Classic synthetic hallucinogen
 MDMA- erroneously classified as a hallucinogen,
vstructirally related to amphetamines

29. Hallucinogen-Related Disorders
 Treatment
 Symptom specific
 Psychological support
 Hallucinogen intoxication can be treated with
diazepam 20 mg
 Stops LSD effect and associated panic to a stop
within 20 minutes

30. Inhalants-Related Disorders
 Volatile hydrocarbons
 Tolouene
 n-Hexane
 Methyl butyl ketone
 Trichloroethylane
 Dichloromethane
 Gasoline
 Butane

31. Inhalants-Related Disorders
 4 commercial classes
2. Solvents, glues and adhesives
3. Propelants for aerosol sprays
4. Thinners
5. Fuels

32. Inhalants-Related Disorders
 Inhalant-induced pathological conditions
 Intoxication
 Delirium
 Persisting dementia
 Psychotic disorder
 Mood and anxiety disorders
 Disorder not otherwise specified

33. Inhalants-Related Disorders
 Intoxication requires no medical attention
 Effects of intoxication may require attention
 Coma, bronchospasm, laryngospasm, cardiac
arrhythmias, or burns
 Sedation is contraindicated
 Confusion, panic or psychosis
 Severe agitation
 Haloperidol 5mg IM/70 kg bw

34. Nicotine-Related Disorders
 One of the most highly addictive drugs in the
US.

35. Treatment Modalities for
Substance-Related Disorders
• Alcoholics Anonymous
Stimulants •
– Minor tranquilizers
• Disulfiram (Antabuse) – Major tranquilizers
• Other medications for treatment of – Anticonvulsants
alcoholism – Antidepressants
• Counseling • Hallucinogens and Cannabinols
• Group therapy – Benzodiazepines
– Antipsychotics
• Alcohol
– Benzodiazepines
– Anticonvulsants
– Multivitamin therapy
– Thiamine
• Opioids
– Narcotic antagonists
• Naloxone (Narcan)
• Naltrexone (ReVia)
• Nalmefene (Revex)
– Methadone
– Buprenorphine
– Clonidine