Substance Abuse Substance abuse – Use of drug interferes with ability to function      Fails to meet work or family obl...
Alcohol-Related Disorders   Discontinuation of alcohol in heavy user:   – Anxiety   – Depression   – Weakness   – Res...
Management of AlcoholWithdrawal  General Measures    Seizure precautions with h/o Sz    Hydration    Thiamine 100mg IM/...
Management of AWS Benzodiazepines (BDZ)   Treatment of choice   Reduce symptoms and decrease risk of Seizurezs Phenoba...
Choice of Benzodiazepine All seem effective for AWS   Limited comparative data All metabolized by liver Differences  ...
Long-acting Benzodiazepines  Chlordiazepoxide (Librium®)     Oral dosing only     Intermediate onset     Long-acting pa...
Shorter-acting BDZs Lorazepam (Ativan®)    Versatile dosing—PO, IV, IM, SL    Fast to intermediate onset    Intermediat...
Benzodiazepines Chlordiazepoxide generally preferred Indications for Lorazepam   Elderly   Established liver disease  ...
Benzodiazepines Route of administration    Oral preferable      Ease of administration      More consistent blood levels ...
Amphetamine RelatedDisorder DSM IV   Amphetamine induced     Anxiety disorder     Mood disorder     Psychotic disorde...
Amphetamine RelatedDisorder Treatment   None established Treat specific symptoms Comorbid conditions such as depressio...
Caffeine-Related Disorder Caffeine is an methylxantine More potent than other known methylxantines   Theophyline (Prima...
Amount of Caffeine   ConsumptionBeverages / Food: Cup of coffee: 65-120 mg caffeine   Espresso 1oz shot: 40 mg Cup of t...
Mechanism of Action    Three main hypotheses:    1. Mobilization of intracellular calcium        Biphasic effect on intr...
Pharmacodynamics                                 Caffeine        Central Nervous System   Enhances neurotransmitter releas...
Pharmacokinetics Absorption       Gastrointestinal tract and stomach       Rapid rate, peak blood level in 30-60 min.  ...
Pharmacokinetics Metabolism       Metabolized through liver biotransformation initially by demethylation into        dim...
Treatment of Caffeine-RelatedDisorders Reducing or eliminating caffeine  consumption ASA   Headaches, muscle aches from...
Cannabis-Related Disorders   Major active ingredient             Physiological   – THC (delta-9-                     –...
Cannabis Withdrawal No specific treatment   Abstinence and support Anxiolytics   Short-term withdrawal symptoms relief...
Cocaine-Related Disorder    Alkaloid obtained from coca           Overdose    leaves                                   ...
Cocaine-Related Disorder Crack   – Form of cocaine that become popular in the 80s   – Rock crystal that is heated, mel...
Cocaine-Related Disorder Treatment   No pharmacological treatments produce decreases in    cocaine use comparable to the...
Cocaine-Related Disorder Treatment, cont.   Many different treatments have been use with    little or no effects       ...
Hallucinogen-Related Disorders Natural and synthetic substances   Psychedelics or psychomimetics   Induce hallucination...
Hallucinogen-Related Disorders Naturally occurring   Psilocybin     Mushroom   Mescaline     Peyote cactus   Other  ...
Hallucinogen-Related Disorders LSD  Synthesized in 1938  Classic synthetic hallucinogen  MDMA- erroneously classified ...
Hallucinogen-Related Disorders Treatment   Symptom specific   Psychological support   Hallucinogen intoxication can be...
Inhalants-Related Disorders Volatile hydrocarbons   Tolouene   n-Hexane   Methyl butyl ketone   Trichloroethylane   ...
Inhalants-Related Disorders 4 commercial classes2. Solvents, glues and adhesives3. Propelants for aerosol sprays4. Thinne...
Inhalants-Related Disorders Inhalant-induced pathological conditions   Intoxication   Delirium   Persisting dementia  ...
Inhalants-Related Disorders Intoxication requires no medical attention Effects of intoxication may require attention   ...
Nicotine-Related Disorders One of the most highly addictive drugs in the  US.
Treatment Modalities forSubstance-Related Disorders•   Alcoholics Anonymous                  Stimulants             •     ...
Substance abuse[2]
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Substance abuse[2]

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Substance abuse[2]

  1. 1. 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
  2. 2. 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
  3. 3. Management of AlcoholWithdrawal 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
  4. 4. 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
  5. 5. 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
  6. 6. 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]
  7. 7. 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]
  8. 8. Benzodiazepines Chlordiazepoxide generally preferred Indications for Lorazepam  Elderly  Established liver disease  NPO  Severe w/d requiring frequent or high doses
  9. 9. 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
  10. 10. Amphetamine RelatedDisorder DSM IV  Amphetamine induced  Anxiety disorder  Mood disorder  Psychotic disorder with delusions  Psychotic disorder with hallucinations  Sexual dysfunction
  11. 11. Amphetamine RelatedDisorder Treatment  None established Treat specific symptoms Comorbid conditions such as depression may respond to antidepressants  Bupropion (Wellbutrin)  Used after patients withdraw from amphetamines
  12. 12. 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
  13. 13. Amount of Caffeine ConsumptionBeverages / 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): 25mgOver the counter medicines: No-Doze: 100 – 200 mg Midol: 20-100 mg Excedrin: 30-65 mgBenowitz, 1990Total consumption of caffeine per person per day is estimated at210 to 238 mg (Barone and Roberts, 1996)
  14. 14. 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
  15. 15. 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 rateGarrett and Griffiths 1997
  16. 16. 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 BBBNehlig et al., 1999; Fredholm et al., 1999
  17. 17. 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 longerNehlig et al., 1999; Fredholm et al., 1999
  18. 18. Treatment of Caffeine-RelatedDisorders Reducing or eliminating caffeine consumption ASA  Headaches, muscle aches from withdrawal  Benzodiazepines-rarely required
  19. 19. 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
  20. 20. Cannabis Withdrawal No specific treatment  Abstinence and support Anxiolytics  Short-term withdrawal symptoms relief  If depressive disorder is present, treat with antidepressants
  21. 21. 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)
  22. 22. 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
  23. 23. 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
  24. 24. Cocaine-Related Disorder Treatment, cont.  Many different treatments have been use with little or no effects  TCAs  MAOIs  SSRIs  Antipsychotics  Etc.
  25. 25. Hallucinogen-Related Disorders Natural and synthetic substances  Psychedelics or psychomimetics  Induce hallucinations or disconnection with reality  Schedule 1 drugs
  26. 26. Hallucinogen-Related Disorders Naturally occurring  Psilocybin  Mushroom  Mescaline  Peyote cactus  Other  Harmine, harmaline, ibogaine, dymethyltriptamine (DMT)
  27. 27. Hallucinogen-Related Disorders LSD  Synthesized in 1938  Classic synthetic hallucinogen  MDMA- erroneously classified as a hallucinogen, vstructirally related to amphetamines
  28. 28. 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
  29. 29. Inhalants-Related Disorders Volatile hydrocarbons  Tolouene  n-Hexane  Methyl butyl ketone  Trichloroethylane  Dichloromethane  Gasoline  Butane
  30. 30. Inhalants-Related Disorders 4 commercial classes2. Solvents, glues and adhesives3. Propelants for aerosol sprays4. Thinners5. Fuels
  31. 31. Inhalants-Related Disorders Inhalant-induced pathological conditions  Intoxication  Delirium  Persisting dementia  Psychotic disorder  Mood and anxiety disorders  Disorder not otherwise specified
  32. 32. 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
  33. 33. Nicotine-Related Disorders One of the most highly addictive drugs in the US.
  34. 34. Treatment Modalities forSubstance-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

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