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  • Slide 13: Cocaine binding to uptake pumps; inhibition of dopamine uptake Now, show what happens when cocaine is present in the synapse. Cocaine (turquoise) binds to the uptake pumps and prevents them from removing dopamine from the synapse. This results in more dopamine in the synapse, and more dopamine receptors are activated.
  • Slide 16: Positron emission tomography (PET) scan of a person on cocaine Cocaine has other actions in the brain in addition to activating reward. Scientists have the ability to see how cocaine actually affects brain function in people. The PET scan allows one to see how the brain uses glucose; glucose provides energy to each neuron so it can perform work. The scans show where the cocaine interferes with the brain's use of glucose - or its metabolic activity. The left scan is taken from a normal, awake person. The red color shows the highest level of glucose utilization (yellow represents less utilization and blue shows the least). The right scan is taken from a cocaine abuser on cocaine. It shows that the brain cannot use glucose nearly as effectively - show the loss of red compared to the left scan. There are many areas of the brain that have reduced metabolic activity. The continued reduction in the neurons' ability to use glucose (energy) results in disruption of many brain functions.
  • Slide 11: Localization of cocaine "binding sites" When a person smokes or snorts cocaine, it travels quickly to the brain. Although it reaches all areas of the brain, it concentrates in some specific areas. These are highlighted with the turquoise sprinkles; the VTA, the nucleus accumbens and the caudate nucleus (lighter turquoise since the caudate is inside the hemisphere). Point out that cocaine concentrates especially in the reward areas that you have just discussed. Cocaine accumulation in other areas such as the caudate nucleus can explain other effects such as increased stereotypic behaviors (pacing, nail-biting, scratching, etc..)
  • Slide 21: Localization of THC binding sites When a person smokes marijuana, the active ingredient, cannabinoids or THC, travels quickly to the brain. Point to the areas where THC (magenta) concentrates. The VTA, nucleus accumbens, caudate nucleus, hippocampus, and cerebellum are highlighted. THC binds to THC receptors that are concentrated in areas within the reward system as well as these other areas. Indicate that the action of THC in the hippocampus explains its ability to interfere with memory and actions in the cerebellum are responsible for its ability to cause incoordination and loss of balance.
  • Drugsofabuse

    1. 1. DRUGS OF ABUSE www.freelivedoctor.com
    2. 2. Definitions <ul><li>I. Drug abuse. </li></ul><ul><li>II. Drug dependence. </li></ul><ul><li>A) Psychological dependence. </li></ul><ul><li>B) Physiological dependence. </li></ul><ul><li>III. Drug addiction. </li></ul><ul><li>IV. Drug tolerance. </li></ul>www.freelivedoctor.com
    3. 3. www.freelivedoctor.com
    4. 4. www.freelivedoctor.com
    5. 5. www.freelivedoctor.com
    6. 6. I. Drug abuse <ul><li>Inappropriate and usually excessive, self-administration of a drug for non-medical purposes. </li></ul><ul><ul><li>Abused drugs exert their effects in the CNS. </li></ul></ul><ul><ul><li>Compulsive drug-seeking behavior . </li></ul></ul><ul><ul><li>Preoccupation with the procurement and use of the drug may be so demanding as to decrease the users productivity. </li></ul></ul><ul><ul><li>Prolonged abuse may cause chronic toxicity. </li></ul></ul>www.freelivedoctor.com
    7. 7. II. Drug dependence <ul><li>Repetitive use of substances that produce an optimal state of well being because of their positive reinforcing effects in the CNS. </li></ul><ul><ul><ul><li>A) Psychological dependence. </li></ul></ul></ul><ul><ul><ul><li>B) Physical dependence. </li></ul></ul></ul>www.freelivedoctor.com
    8. 8. II. Drug dependence <ul><li>A) Psychological Dependence </li></ul><ul><ul><ul><li>Motivational component: great subjective need, compulsion, drive to get the drug. </li></ul></ul></ul><ul><ul><ul><li>Will take drug periodically. </li></ul></ul></ul><ul><ul><ul><li>Although physical dependence for a drug may not occur, “drug-seeking behavior” is present. </li></ul></ul></ul><ul><ul><ul><li>Habituation; Just &quot;like&quot; the drug; Drug effects serve as “positive reinforcers”. </li></ul></ul></ul><ul><ul><ul><li>No tolerance increase. </li></ul></ul></ul>www.freelivedoctor.com
    9. 9. II. Drug dependence <ul><li>B) Physiological Dependence </li></ul><ul><ul><li>The body needs the drug for normal physiological function. </li></ul></ul><ul><ul><li>Tend to increase dose because of tolerance. </li></ul></ul><ul><ul><li>Withdrawal Symptoms/Absence Syndrome (negative reinforcement). </li></ul></ul><ul><ul><ul><ul><li>Predictable group of signs and symptoms resulting from abrupt removal of a drug. </li></ul></ul></ul></ul><ul><ul><li>Psychological dependence is also present. </li></ul></ul>www.freelivedoctor.com
    10. 10. III. Drug addiction <ul><li>The drug-use and drug-seeking behavior of dependent individuals is maintained by the reinforcing central activity of the drug despite its negative social, psychological and physical consequences. </li></ul><ul><li>Physiological and psychological dependence is present. Physiological changes have occurred. Symptoms of withdrawal, will be involved. </li></ul><ul><li>High tendency to relapse. </li></ul>www.freelivedoctor.com
    11. 11. IV. Drug tolerance <ul><li>After chronic use, the same amount of drug is insufficient to cause the desired effect and thus, more drug is used. </li></ul><ul><li>A compensatory response. </li></ul>Drug Dose EFFECT Normal Tolerance www.freelivedoctor.com
    12. 12. IV. Drug tolerance <ul><li>A) Innate Tolerance </li></ul><ul><ul><li>1. Sensitivity </li></ul></ul><ul><ul><li>2. Insensitivity </li></ul></ul><ul><li>B) Acquired Tolerance </li></ul><ul><ul><li>1. Pharmacokinetic or metabolic </li></ul></ul><ul><ul><li>2. Pharmacodynamic or functional </li></ul></ul><ul><ul><li>3. Learned or behavioral </li></ul></ul>www.freelivedoctor.com
    13. 13. IV. Drug tolerance <ul><li>C) Tachyphylaxis </li></ul><ul><li>Rapid development of tolerance to the drug after a few doses or a single administration. </li></ul>Blood Pressure Time 1X 2X 1X desensitized tolerance activated www.freelivedoctor.com
    14. 14. V. Cross-dependence <ul><li>When a drug is administered to achieve the same outcome as that of another drug. </li></ul><ul><ul><ul><li>i.e. heroin  methadone. </li></ul></ul></ul><ul><ul><ul><li>In a heroin user, methadone can be substituted for heroin in preventing the withdrawal syndrome. </li></ul></ul></ul>www.freelivedoctor.com
    15. 15. VI. Cross-tolerance <ul><li>When an individual has become tolerant to a drug and requires higher than normal doses of a second drug to have its effects. </li></ul><ul><ul><ul><ul><li>i.e. Barbiturates  BDZ. </li></ul></ul></ul></ul><ul><li>Amphetamine  cocaine. </li></ul><ul><li>BARBs or BDZs  Anesthetics. </li></ul>www.freelivedoctor.com
    16. 16. VI. Cross-tolerance <ul><li>In general there is cross-dependence and cross-tolerance between drugs of the same class, but not between drugs in different classes. </li></ul><ul><li>Exceptions: </li></ul><ul><li>Sedative-hypnotics and volatile intoxicants. </li></ul><ul><li>LSD and phenylethylamines, but not with other hallucinogens . </li></ul>www.freelivedoctor.com
    17. 17. VII. Co-administration/Co-abuse <ul><li>Many of these drugs are used in combination with other drugs from one or more categories. </li></ul><ul><ul><ul><li>Alcohol and Heroin </li></ul></ul></ul><ul><ul><ul><li>Nicotine and Alcohol </li></ul></ul></ul><ul><ul><ul><li>Speed balls  cocaine + heroin </li></ul></ul></ul><ul><ul><ul><li>Cocaine + BDZs </li></ul></ul></ul><ul><ul><ul><li>Heroin and BARBs </li></ul></ul></ul><ul><li>Be aware of the possibility of combination of drugs when treating withdrawal or overdose, each drug will require a specific treatment. </li></ul>www.freelivedoctor.com
    18. 18. Because of the diverse character of these drugs, there is no “single reason” for their use, nor is there an “addictive personality&quot;. <ul><li>IT IS NOT NECESSARY TO HAVE A PREEXISTING EMOTIONAL OR PSYCHIATRIC PROBLEM TO BECOME DRUG DEPENDENT!!! </li></ul>www.freelivedoctor.com
    19. 19. VIII. Toxicology <ul><li>A ) Tissue and organ toxicity </li></ul><ul><li>Acute use </li></ul><ul><li>Respiratory depression --- narcotics, inhalants, barbiturates. </li></ul><ul><li>Cardiovascular effects and seizures --- cocaine, amphetamines. </li></ul><ul><li>Arrhythmias --- volatile intoxicants. </li></ul><ul><li>Lack of motor coordination  Accidents (car accidents, big machinery accidents)  death --- alcohol, narcotics, stimulants, PCP, marihuana, hallucinogens, CNS depressants. </li></ul><ul><li>S </li></ul>www.freelivedoctor.com
    20. 20. VIII. Toxicology <ul><li>Chronic use </li></ul><ul><li>Abnormal neuronal activity --- ALL </li></ul><ul><li>Liver damage --- alcohol. </li></ul><ul><li>Increase incidence of lung, breast, gastrointestinal and rectal cancer, and cardiovascular diseases --- tobacco. </li></ul><ul><li>Pregnancy complications and babies born dependent --- narcotics. </li></ul>www.freelivedoctor.com
    21. 21. VIII. Toxicology <ul><li>B) Psychic toxicity </li></ul><ul><li>Acute use </li></ul><ul><li>Bad trips, flashbacks --- hallucinogens, CNS stimulants. </li></ul><ul><li>Mood liability --- marihuana, hallucinogens, PCP. </li></ul><ul><li>Panic attacks --- cocaine, amphetamines, marihuana, hallucinogens, PCP. </li></ul><ul><li>Chronic use </li></ul><ul><li>Reality distortion --- alcohol, hallucinogens, stimulants . </li></ul>www.freelivedoctor.com
    22. 22. VIII. Toxicology <ul><li>C) Behavioral toxicity </li></ul><ul><li>Acute use </li></ul><ul><li>Lack of motivation. </li></ul><ul><li>Lack of judgment. </li></ul><ul><li>Loss of concentration. </li></ul><ul><li>Violence  death. </li></ul>Alcohol, narcotics, stimulants, PCP, marihuana, hallucinogens, CNS depressants. www.freelivedoctor.com
    23. 23. VIII. Toxicology <ul><li>Chronic use </li></ul><ul><ul><li>Amotivational syndrome </li></ul></ul><ul><ul><li>Loss of productivity. </li></ul></ul><ul><ul><li>Decrease hygiene. </li></ul></ul><ul><ul><li>Decrease health. </li></ul></ul><ul><li>Alcohol, narcotics, stimulants, PCP, marihuana, hallucinogens, CNS depressants. </li></ul>www.freelivedoctor.com
    24. 24. VIII. Toxicology <ul><li>D) Associated Diseases </li></ul><ul><ul><li>Infections </li></ul></ul><ul><ul><ul><li>AIDS </li></ul></ul></ul><ul><ul><ul><li>Venereal diseases </li></ul></ul></ul><ul><li>E) Others: </li></ul><ul><ul><li>Tobacco-related fires. </li></ul></ul><ul><ul><li>Toxicity due to bad batches of drug can produce permanent damage such as Parkinson-like disorders --- heroin (MPTP). </li></ul></ul>www.freelivedoctor.com
    25. 25. I. Animal Studies <ul><li>Drug-self administration </li></ul><ul><li>Drugs as reinforcers in animals. </li></ul><ul><li>High correlation with </li></ul><ul><li>human dependence </li></ul><ul><li>liability. </li></ul>www.freelivedoctor.com
    26. 26. Morphine/Heroin <ul><li>Self-Administration </li></ul>www.freelivedoctor.com
    27. 27. THE REWARD CENTER OF THE BRAIN www.freelivedoctor.com
    28. 28. THE MESOLIMBIC DOPAMINERGIC REWARD PATHWAY www.freelivedoctor.com
    29. 29. II. Brain Reward System <ul><li>Changes in brain function => Reward=> Craving </li></ul><ul><li>Involve the Dopaminergic System </li></ul><ul><ul><ul><ul><li>Mesolimbic pathway :Ventral tegmental area (VTA), medial forebrain bundle, nucleus accumbens and the prefrontal cortex. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Nigrostriatal pathway: Sustantia nigra, striatum. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Mesocortical pathway: VTA, cingulate and frontal CTX. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Tubero-Infundibular: Arcuate N. in hypothalamus. </li></ul></ul></ul></ul>www.freelivedoctor.com
    30. 30. THE DOPAMINERGIC SYSTEM www.freelivedoctor.com
    31. 31. Dopamine Synapse DA L-DOPA Tyrosine Tyrosine www.freelivedoctor.com
    32. 32. www.freelivedoctor.com
    33. 33. Dopamine receptor Dopamine reuptake pump www.freelivedoctor.com
    34. 34. www.freelivedoctor.com
    35. 35. OPIOIDS or NARCOTICS <ul><li>I. Morphine </li></ul><ul><li>II. Codeine </li></ul><ul><li>III. Meperidine </li></ul><ul><li>IV. Methadone </li></ul>www.freelivedoctor.com
    36. 36. OPIOIDS or NARCOTICS <ul><li>I. Morphine, Heroin, Hydromorphone,Oxymorphone. </li></ul><ul><li>A. Pharmacology </li></ul><ul><ul><ul><li>- Heroin is very lipid soluble. </li></ul></ul></ul><ul><ul><ul><li>- Short half-life (t½ = 3 min). </li></ul></ul></ul><ul><ul><ul><li>- Heroin  6-mono-acetyl morphine  morphine </li></ul></ul></ul>www.freelivedoctor.com
    37. 37. OPIOIDS or NARCOTICS <ul><li>Acute effects </li></ul><ul><li>1. Positive Effects </li></ul><ul><li>Desirable </li></ul><ul><li>Subjective </li></ul><ul><li>2. Negative Effects </li></ul><ul><li>Undesirable </li></ul>www.freelivedoctor.com
    38. 38. <ul><li>Desirable Effects : </li></ul><ul><li>Euphoria </li></ul><ul><li>Sedation </li></ul><ul><li>Relief of anxiety and various other forms of distress. </li></ul><ul><li>Analgesia. </li></ul><ul><li>Depression of cough reflex* </li></ul><ul><li>Subjective CNS effects : </li></ul><ul><li>Drowsiness </li></ul><ul><li>Difficulty concentrating </li></ul><ul><li>Apathy </li></ul><ul><li>Decreased physical activity </li></ul><ul><li>Lethargy </li></ul><ul><li>Extremities feel heavy and the body feels warm </li></ul>Undesirable Effects : Dysphoria Dizziness Nausea Vomiting Constipation* Biliary tract spasm Urinary retention www.freelivedoctor.com
    39. 39. OPIOIDS or NARCOTICS <ul><li>B. Acute Toxicity/Overdose </li></ul><ul><li>1.Disruption of central control of peripheral sympathetic activity. </li></ul><ul><li>Brainstem  Respiratory depression  DEATH </li></ul><ul><li> Circulatory depression   BP </li></ul><ul><li>Pupils constricted (miosis), (may be dilated with meperidine or severe hypoxia) </li></ul><ul><li>Nausea and Vomiting </li></ul><ul><li>Pulmonary edema </li></ul><ul><li>Reflexes  </li></ul>www.freelivedoctor.com
    40. 40. OPIOIDS or NARCOTICS <ul><ul><li>2. CNS depression </li></ul></ul><ul><ul><li>Drowsiness  Sedation  Coma </li></ul></ul><ul><ul><li>3. CNS abnormal neuronal activity </li></ul></ul><ul><ul><ul><li>Convulsions -- with propoxyphene or meperidine </li></ul></ul></ul>www.freelivedoctor.com
    41. 41. OPIOIDS or NARCOTICS <ul><li>a. Tissue Toxicity </li></ul><ul><ul><li>- “Heroin lung” with acute overdose. </li></ul></ul><ul><ul><li>- No apparent tissue damage. </li></ul></ul><ul><ul><li>- Acute and chronic drive reduction. </li></ul></ul><ul><ul><li>- Criminal behavior to obtain drugs. </li></ul></ul><ul><ul><li>Unsterile syringes: AIDS, hepatitis, SBE, malaria, tetanus, localized infections, pulmonary infiltration of contaminants, Neuropathies. </li></ul></ul><ul><ul><li>Violent deaths. </li></ul></ul>www.freelivedoctor.com
    42. 42. OPIOIDS or NARCOTICS <ul><li>Treatment of acute toxicity and overdose: </li></ul><ul><ul><li>Naloxone. Opioid antagonist, used to block the actions of opioids in a life-threatening situation of opioid overdose. Given IV. Short half-life (1-2hrs). It precipitates withdrawal. </li></ul></ul><ul><ul><li>Methadone . Used in the detoxification process. It causes a less pronounced euphoria and less severe withdrawal. </li></ul></ul>www.freelivedoctor.com
    43. 43. OPIOIDS or NARCOTICS <ul><li>C. Withdrawal </li></ul><ul><li>Most severe withdrawal of all drugs of abuse. </li></ul><ul><li>Onset related to time-effect curve and t½ of narcotic. </li></ul><ul><li>Not life threatening , no convulsions, no delirium, no disorientation. </li></ul>www.freelivedoctor.com
    44. 44. Opiate Withdrawal <ul><li>6-8 hr =>drug seeking behavior, restless, anxious. </li></ul><ul><li>8-12 hr => Pupils dilated (mydriasis) , reactive to light; increased pulse rate;  blood pressure; yawning; chills; rhinorrhea; lacrimation; piloerection/ gooseflesh; sweating; restless sleep. </li></ul><ul><li>48-72 hrs (peak) => All of the above plus muscular weakness, aches (cramps) and twitches; nausea, vomiting and diarrhea;  temperature;  respiratory rate;  heart rate and blood pressure; dehydration. </li></ul>www.freelivedoctor.com
    45. 45. <ul><li>Used to block autonomic signs and symptoms of withdrawal: </li></ul><ul><ul><ul><li>cramps </li></ul></ul></ul><ul><ul><ul><li>nausea </li></ul></ul></ul><ul><ul><ul><li>vomiting </li></ul></ul></ul><ul><ul><ul><li>tachycardia </li></ul></ul></ul><ul><ul><ul><li>sweating </li></ul></ul></ul><ul><ul><ul><li>hypertension </li></ul></ul></ul>ANS EFFECTS Clonidine Motivational: Pleasure Reward Euphoria NE DA  2-AR Treatment of Sympathetic effects during withdrawal. www.freelivedoctor.com
    46. 46. <ul><li>D. Treatment of Addiction </li></ul><ul><li>Medical Detoxification </li></ul><ul><li>A process whereby individuals are systematically withdrawn from addicting drugs in an inpatient or outpatient setting, typically under the care of a physician. </li></ul><ul><li>Detoxification is sometimes called a distinct treatment modality but is more appropriately considered a precursor of treatment, because it is designed to treat the acute physiological effects of stopping drug use. </li></ul>www.freelivedoctor.com
    47. 47. OPIOID DETOX <ul><li>Heroin </li></ul><ul><li> </li></ul><ul><li>Detoxification with </li></ul><ul><li>methadone (Dolophin ® ) </li></ul><ul><li>↓ </li></ul><ul><li>Reduce to 5mg/day. </li></ul><ul><li>↓ </li></ul><ul><li>Discontinue=> Drug free </li></ul><ul><li> </li></ul><ul><li>Help achieve abstinence </li></ul><ul><li>w/a long-acting opiate </li></ul><ul><li>antagonist naltrexone </li></ul><ul><li>(Trexan ®) </li></ul><ul><li> </li></ul><ul><li>Maintenance </li></ul><ul><li>w/ methadone </li></ul><ul><li>(6-8 mg/day). </li></ul><ul><li>Plus: </li></ul><ul><li>Psychosocial approaches. </li></ul><ul><li>Support group </li></ul>www.freelivedoctor.com
    48. 48. OPIOIDS or NARCOTICS <ul><li>Heroin </li></ul><ul><li>Methadone </li></ul><ul><li>N altrexone </li></ul>www.freelivedoctor.com TIME Severity of Withdrawal
    49. 49. OPIOIDS or NARCOTICS <ul><li>Detoxification or Maintenance treatment </li></ul><ul><li>Methadone </li></ul><ul><ul><li>Used for the sequential detoxification and maintenance treatment of opiate dependence. </li></ul></ul><ul><li>b. LAAM (L-  -acetyl methadol, methadyl acetate). </li></ul><ul><ul><li>Structurally similar to methadone. </li></ul></ul><ul><ul><li>Longer-acting opiate. </li></ul></ul><ul><ul><li>Taken orally in liquid form, lasts 72 hrs (visits 3 X a week). </li></ul></ul><ul><ul><li>“ Take home&quot; medication. </li></ul></ul><ul><li>c. Buprenorphine </li></ul><ul><ul><li>Partial opioid agonist which substitutes for low doses of opioids but antagonizes at high doses. </li></ul></ul><ul><ul><li>Can be administered sublingually every 24-48 hrs as an alternative to methadone </li></ul></ul>www.freelivedoctor.com
    50. 50. OPIOIDS or NARCOTICS <ul><li>d. Naltrexone </li></ul><ul><li>Opiate Antagonist </li></ul><ul><ul><li>Causes precipitated abstinence. </li></ul></ul><ul><ul><li>Use only for long-term maintenance of abstinence. </li></ul></ul><ul><ul><li>Long half-life, oral, 3 times a week. </li></ul></ul><ul><ul><li>Major problem in detoxification and maintenance of abstinence is the motivational component of the CNS effect, which is responsible for the “drug craving” sensations, also conditional dependence and social factors play an important role. </li></ul></ul>www.freelivedoctor.com
    51. 51. OPIOIDS or NARCOTICS <ul><li>F. Mechanism of action . </li></ul><ul><ul><li>Opioids act at the Mesolimbic Dopaminergic System </li></ul></ul><ul><ul><li>=> Reward Center of the Brain. </li></ul></ul><ul><ul><li>ACUTE EXPOSURE </li></ul></ul><ul><ul><li>Activation of VTA dopamine neurons </li></ul></ul><ul><ul><li>by i nhibition of GABA release </li></ul></ul><ul><ul><li> </li></ul></ul><ul><ul><ul><li>Desinhibition of Dopamine neurons </li></ul></ul></ul><ul><ul><ul><li> </li></ul></ul></ul><ul><ul><ul><li> DA activity </li></ul></ul></ul><ul><ul><ul><li> </li></ul></ul></ul><ul><ul><ul><li>CHRONIC EXPOSURE </li></ul></ul></ul><ul><ul><ul><li>Deficient VTA-NAC function </li></ul></ul></ul>www.freelivedoctor.com
    52. 52. OPIOIDS or NARCOTICS <ul><li>Opioids normally inhibit neurons in locus coereleus by  conductance of inward rectifying K + channels and a  Na + –dependent inward current through coupling to G i/o =>  AC activity =>  cAMP =>  PKA activity =>  phosphorylation state of CREB and other proteins. Nestler et al., 97 </li></ul>Alterations in the Drug-Addicted State www.freelivedoctor.com
    53. 53. www.freelivedoctor.com
    54. 54. CNS DEPRESSANTS <ul><li> I. Alcohol </li></ul><ul><li>II. Sedative/Hypnotics, Anxiolytics </li></ul><ul><li>All are very addictive and cause withdrawal symptoms (mild anxiety, convulsions, seizures). </li></ul><ul><li>All of these drugs create &quot; lethal potentiation &quot; when combined. </li></ul><ul><li>Alcohol<>Anxiolytics<>Hypnotics<> Anesthetics </li></ul>www.freelivedoctor.com
    55. 55. Alcohol <ul><ul><li>Intake of alcohol begins during adolescence. Ninety percent of high school seniors have tried alcohol during their life times and 30% report daily use. Chronic abuse occurs much later. </li></ul></ul><ul><li>A. Pharmacology </li></ul><ul><ul><li>Alcohol is readily dissolved in water and lipids and thus, distributes very evenly throughout the body. It crosses the blood-brain-barrier as well as the placenta without difficulty. </li></ul></ul>www.freelivedoctor.com
    56. 56. Alcohol <ul><li>B. Acute Intoxication/Overdose </li></ul><ul><li>Loss of inhibition, anxiolysis, sedation, decreased motor coordination.  Slowed and slurred speech, ataxia, nystagmus, drowsiness  coma, confusion; reflexes are low, respiratory depression or apnea, low blood pressure  death. </li></ul>www.freelivedoctor.com
    57. 57. Alcohol <ul><li>Fetal Alcohol Syndrome </li></ul><ul><li>Children exposed to alcohol in utero may exhibit a wide range of developmental disabilities and cognitive and behavioral deficits that reflect damage to the developing neurons. These effects may include: mental retardation, attention deficit disorders, perceptual problems, memory and learning disabilities, and psychomotor dysfunction. Fetal Alcohol Syndrome (FAS), which is characterized by central nervous system impairments, growth retardation and characteristic facial dysmorphology is the most severe, manifestation of alcohol neuratogenesis. </li></ul><ul><li>from NIAAA, Alcohol Alert, No. 13 1991 </li></ul>www.freelivedoctor.com
    58. 58. Alcohol Withdrawal <ul><li>C. Withdrawal Syndrome </li></ul><ul><li>When an alcoholic stops drinking, withdrawal symptoms begin within six to 48 hours and peak about 24 to 35 hours after the last drink. During this period the inhibition of brain activity caused by alcohol is abruptly reversed. Stress hormones are over-produced and the central nervous system becomes over-excited. Depending on severity, withdrawal symptoms may include the following: </li></ul><ul><ul><li>Fever. </li></ul></ul><ul><ul><li>Rapid heart beat. </li></ul></ul><ul><ul><li>Changes in blood pressure either higher or lower. </li></ul></ul><ul><ul><li>Extremely aggressive behavior. </li></ul></ul><ul><ul><li>Hallucinations and other mental disturbances. </li></ul></ul><ul><ul><li>Seizures occur in about 10% of adults during withdrawal, and in about 60% of these patients, the seizures are multiple. The time between the first and last seizure is usually six hours or less. </li></ul></ul><ul><ul><li>About 5% of alcoholic patients experience delirium tremens, which usually develops two to four days after the last drink. </li></ul></ul>www.freelivedoctor.com
    59. 59. Delirium Tremens <ul><li>C. Withdrawal Syndrome (con’t) </li></ul><ul><li>In severe cases, it can develop into: </li></ul><ul><li>“ Delirium Tremens”: </li></ul><ul><li>Insomnia, tremulousness, REM rebound, reflexes are high, weakness, anorexia, orthostatic hypotension, sweating, agitation </li></ul><ul><li>Delirium, vivid auditory and visual hallucinations; convulsions and seizures (probably caused by increase NMDA receptor number and hyperexcitability), may generate “status epilepticus”. </li></ul><ul><li>Disorientation, paranoid delusions, hyperthermia dehydration, cardiovascular collapse. </li></ul><ul><li>Risk of death </li></ul>www.freelivedoctor.com
    60. 60. Alcohol <ul><li>Treatment of Withdrawal </li></ul><ul><li>Benzodiazepines. </li></ul><ul><li>To inhibit nerve-cell excitability in the brain. </li></ul><ul><li>Relieve withdrawal symptoms. </li></ul><ul><li>Help prevent progression to delirium tremens. </li></ul><ul><li>Reduce the risk for seizures. </li></ul><ul><li>Benzodiazepines may be administered intravenously or orally, depending on the severity of symptoms. These drugs vary in how long they are effective. </li></ul><ul><li>diazepam (Valium) alprazolam (Xanax) </li></ul><ul><ul><li>lorazepam (Ativan) midazolam (Versed) </li></ul></ul><ul><li>oxazepam (Serax) </li></ul><ul><li>benzodiazepines are usually not prescribed for more than two weeks or administered for more than three nights per week </li></ul>www.freelivedoctor.com
    61. 61. Alcohol DETOX <ul><li>D. Treatment of Dependence </li></ul><ul><li>Detox Center/Clinic </li></ul><ul><li>Disulfiram (antabuse) * </li></ul><ul><li>CCC (citrate calcium carbamate) * </li></ul><ul><ul><li>*Both of these drugs are acetaldehyde dehydrogenase blockers. </li></ul></ul><ul><ul><ul><li>Drinking alcohol with these drugs produces increased concentration of acetaldehyde and this makes the person sick. </li></ul></ul></ul><ul><ul><ul><li>Sometimes tranquilizers and antidepressants are given to relieve the anxiety. </li></ul></ul></ul><ul><ul><ul><li>DETOX is best in a hospital setting. </li></ul></ul></ul><ul><ul><ul><li>AAA to prevent relapse. </li></ul></ul></ul>www.freelivedoctor.com
    62. 62. Alcohol <ul><li>ETHANOL (CH 3 CH 2 OH) </li></ul><ul><ul><li>Alcohol dehydrogenase  </li></ul></ul><ul><ul><li>ACETALDEHYDE (CH 3 CHO) </li></ul></ul><ul><ul><li>Aldehyde dehydrogenase  === Disulfiram </li></ul></ul><ul><li>  </li></ul><ul><ul><ul><ul><ul><li>ACETYL COENZYME A </li></ul></ul></ul></ul></ul><ul><ul><ul><li>  </li></ul></ul></ul><ul><ul><ul><ul><li>energy citric acid cycle </li></ul></ul></ul></ul><ul><ul><ul><li>  </li></ul></ul></ul><ul><ul><ul><li>carbon dioxide water </li></ul></ul></ul>= www.freelivedoctor.com
    63. 63. Alcohol <ul><li>E. Mechanism of Action </li></ul><ul><ul><li>1. Affects several ion channels: </li></ul></ul><ul><ul><ul><ul><li>a. NMDA receptor => allosteric inhibitor. Physical dependence/withdrawal. Reinforcement. Behavioral desinhibition. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>b. GABA A receptor => allosteric facilitator. Tolerance. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>c. 5-HT 3 receptor => sedative, antianxiety effects. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>d. L-type calcium channel => allosteric modulator. </li></ul></ul></ul></ul>www.freelivedoctor.com
    64. 64. Alcohol <ul><li>2. CNS Control </li></ul><ul><ul><li>a. Alcohol effects in the cerebellum => disturb equilibrium and posture. </li></ul></ul><ul><ul><li>b. Alcohol effects in hippocampus => disturb memory formation and retrieval. </li></ul></ul><ul><ul><li>c. Alcohol in brainstem and medulla => disturb respiratory centers. </li></ul></ul>www.freelivedoctor.com
    65. 65. CNS DEPRESSANTS <ul><li> </li></ul>Alcohol at GABA-A receptors www.freelivedoctor.com
    66. 66. Sedative/Hypnotics <ul><ul><ul><ul><ul><li>I. Barbiturates </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>II. Benzodiazepines </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>III. Methaqualone </li></ul></ul></ul></ul></ul><ul><li>Can be procured readily from illicit sources. </li></ul>www.freelivedoctor.com
    67. 67. Sedative/Hypnotics <ul><li>Pharmacology </li></ul><ul><li>Well absorbed after oral administration </li></ul><ul><li>Form active metabolites </li></ul><ul><li>Patients experience rebound insomnia or anxiety. </li></ul><ul><li>Gross binges of intoxication that last several days. Others ingest large quantities on a daily basis and remain chronically intoxicated. </li></ul><ul><li>They are teratogenic if used during pregnancy (malformations of the limbs, facial features, CNS, heart, skeleton). </li></ul>www.freelivedoctor.com
    68. 68. Sedative/Hypnotics <ul><li>a. Concurrent or substitute use </li></ul><ul><ul><li>May be lethal with other depressants. </li></ul></ul><ul><ul><li>Co-abused with alcohol, amphetamines, cocaine. </li></ul></ul><ul><ul><li>Not likely to abuse narcotics, but not vice-versa. </li></ul></ul><ul><li>b. Tolerance </li></ul><ul><ul><li>- Pharmacodynamic tolerance exists to most CNS depressants. </li></ul></ul><ul><ul><li>- Tolerance of modest degree to the sedative effects but not to the respiratory depressant effects. </li></ul></ul><ul><ul><li>- Cross-tolerance with alcohol, anesthetics and volatile intoxicants . </li></ul></ul>www.freelivedoctor.com
    69. 69. Sedative/Hypnotics <ul><li>c. Acute effects </li></ul><ul><li>Euphoria, impaired judgement, loss of self-control and anterograde amnesic effects. </li></ul><ul><li>Physiological consequences resemble those of alcohol intoxication. Slowed and slurred speech. Drowsiness  coma. Fatal with Barbiturates or mixtures of CNS depressants. Death unlikely with pure benzodiazepines. </li></ul><ul><li>The person may feel a remarkable capability for coping with stress and anxiety, a general feeling of well being, may feel euphoric and stimulated. These effects (euphoria and stimulation) may be due to inhibition of inhibitory pathways, in other words, desinhibition. </li></ul>www.freelivedoctor.com
    70. 70. Sedative Hypnotics <ul><li>I). Barbiturates: </li></ul><ul><ul><ul><li>Used clinically as anticonvulsant, anti-anxiety drugs or preanesthetics. </li></ul></ul></ul><ul><ul><ul><li>Street Names </li></ul></ul></ul><ul><ul><ul><li>Phenobarbital purple hearts </li></ul></ul></ul><ul><ul><ul><li>Pentobarbital yellow jackets </li></ul></ul></ul><ul><ul><ul><li>Secobarbital red devils </li></ul></ul></ul><ul><ul><ul><li>Amobarbital blue angels </li></ul></ul></ul>www.freelivedoctor.com
    71. 71. Sedative Hypnotics <ul><li>II.) Benzodiazepines : </li></ul><ul><li>Used as anxiolytics and hypnotics. </li></ul><ul><ul><li>Flurazepam => sleeping pills. </li></ul></ul><ul><ul><li>Flunitrazepam => “date rape drug”. </li></ul></ul><ul><ul><li>Diazepam (Valium) => tranquilizer. </li></ul></ul><ul><ul><li>Chlordiazepoxide (Librium) => tranquilizer. </li></ul></ul><ul><ul><li>Clonazepam => anticonvulsant. </li></ul></ul><ul><li>They all cause sedation and muscle relaxation. </li></ul><ul><li>Induce sleep (hypnosis). </li></ul><ul><li>Abuse may cause &quot;BDZ-induced aggression&quot;. </li></ul>www.freelivedoctor.com
    72. 72. Respiratory Depression Coma/ Anesthesia Ataxia Sedation Anxiolytic Anticonvulsant DOSE RESPONSE BARBS BDZs ETOH www.freelivedoctor.com
    73. 73. Sedative/Hypnotics <ul><li>Rapid acting barbiturates such as secobarbital or pentobarbital are more widely abused than depressants with a slower onset such as phenobarbital or the benzodiazepines. </li></ul><ul><li>Drugs with half-lives of 8 to 24 hrs produce a rapid evolving, severe withdrawal syndrome. </li></ul><ul><li>Drugs with half-lives of 48 to 96 hrs produce a slow evolving, less severe but longer withdrawal. </li></ul>www.freelivedoctor.com
    74. 74. Sedative Hypnotics <ul><li>III.) Methaqualone (Quaalude) => &quot;Downer&quot;, works as Valium, seriously abused, very addictive. </li></ul><ul><ul><li>Synthesized as part of an Indian program looking for antimalarial drugs. </li></ul></ul><ul><ul><li>In 1965 it was approved for prescription use and placed in Schedule V. </li></ul></ul><ul><ul><li>In 1984 methaqualone was transferred to Schedule I of the CSA. </li></ul></ul>www.freelivedoctor.com
    75. 75. Sedative Hypnotics <ul><li>B. Acute toxicity/Overdose </li></ul><ul><li>Acute Intoxication </li></ul><ul><ul><ul><li>Pupils are normal; BP and respiration are depressed; nystagmus on lateral gaze; tendon reflexes depressed; ataxia; slurred speech; confusion; coma; shock => Risk of Death, particularly with BARBs. </li></ul></ul></ul><ul><li>Treatment of overdose </li></ul><ul><ul><ul><li>Treatment of overdose w/BDZs: flumazenil (BDZ receptor blocker). </li></ul></ul></ul><ul><ul><ul><li>No treatment for Barbiturates. </li></ul></ul></ul>www.freelivedoctor.com
    76. 76. Sedative/Hypnotics <ul><li>C. Withdrawal: </li></ul><ul><li>Minor: tremors; insomnia (REM rebound); high fever; clonic blink. Anxiety and dysphoria. Sleep disturbances. </li></ul><ul><li>12-16hrs: minor symptoms plus abdominal cramps; nausea and vomiting, o. hypotension;  deep tendon reflexes, hyperreflexia. </li></ul><ul><li>24hrs: pronounced weakness, course tremors (“the shakes”), hyperactive reflexes, early illusions and hallucinations. Hyperpyrexia. </li></ul><ul><li>48-72hrs: convulsive seizures (“rum fits”); vivid auditory and visual hallucinations (“the horrors”), formication, agitation, disorientation, delirium, paranoid delusions. </li></ul><ul><li> </li></ul>www.freelivedoctor.com
    77. 77. Sedative/ Hypnotics <ul><li>Hyperthermia, dehydration, electrolyte imbalance, exhaustion, cardiovascular collapse => Threat to life. </li></ul><ul><li>Time of onset and symptoms experienced vary with CNS depressant use, similar to alcohol withdrawal. </li></ul><ul><li>Additive effect of sedative/hypnotics. </li></ul><ul><li>Treatment of withdrawal: </li></ul><ul><li>Drug tapered off slowly to prevent onset of withdrawal (reversible only early in course). </li></ul><ul><li>Stabilization  diazepam, chlordiazepoxide, phenobarbital (cross-dependence). </li></ul><ul><li>Vomiting, nausea, tremor and twitching  Propranolol or clonidine. </li></ul>www.freelivedoctor.com
    78. 78. Sedative Hypnotics <ul><li>D. Mechanism of Action </li></ul><ul><li>Enhance GABAergic Transmission </li></ul><ul><li> Barbiturates </li></ul><ul><ul><li>Prolong the opening of the channel associated with GABA binding, increasing conductance. </li></ul></ul><ul><ul><li>Benzodiazepines </li></ul></ul><ul><ul><li>Facilitates the activity of GABA to open the channel. </li></ul></ul>www.freelivedoctor.com
    79. 79. Sedative Hypnotics <ul><li>The GABA receptor is a pentameric structure that forms a Cl - channel. </li></ul><ul><ul><ul><li>The receptor complex includes distinct binding sites for benzodiazepines, barbiturates and GABA-like substances. </li></ul></ul></ul><ul><ul><ul><li>GABA transmission exerts an inhibitory effect on norepinephrine (NE), dopamine (DA), serotonin (5-HT), and acetylcholine (ACh) pathways. </li></ul></ul></ul>www.freelivedoctor.com
    80. 80. Sedative/Hypnotics <ul><li>Major site of action for these drugs is at GABAergic synapses. </li></ul><ul><li>Inhibitory Synapse. </li></ul><ul><li>GABA-A receptors => Cl - Channels. </li></ul><ul><li>Hyperpolarization. </li></ul>GABA AGONISTS BDZs     BARBs  www.freelivedoctor.com
    81. 81. CNS DEPRESSANTS <ul><li> </li></ul>Alcohol Sedative/hypnotics www.freelivedoctor.com
    82. 82. CNS Stimulants <ul><li>Cocaine, Crack (free base or hydrochloride). </li></ul><ul><li>Amphetamines. </li></ul><ul><li>III. Khat: Cathinone, methcathinone. </li></ul><ul><li>IV. Methylxanthines: caffeine, theophyline, theobromide. </li></ul><ul><li>V. Nicotine </li></ul>www.freelivedoctor.com
    83. 83. Cocaine <ul><li>A. Pharmacology </li></ul><ul><li>Cocaine and the amphetamines have very similar effects on mood, patterns of abuse, the type of dependence produced, and their toxic effects. </li></ul><ul><li>Differences are mainly in the pharmacokinetics (t½ of cocaine is shorter (50-90min) vs longer (5-10hrs) t½ for amphetamines). </li></ul><ul><li>Cocaine-HCl is injected I.V. => “rush” or “flash => euphoria. </li></ul><ul><li>Rate of absorption is limited by local vasoconstriction. Cocaine free base (“crack”, “rock”) is smoked => delivered directly to pulmonary circulation, left heart and brain. </li></ul>www.freelivedoctor.com
    84. 84. Cocaine <ul><li>a. Acute effects </li></ul><ul><li>Causes an initial but temporary euphoria, “rush”. Causes craving within 30 minutes of taking the drug. </li></ul><ul><li>Increase alertness, feeling of elation and well being, increased energy, feelings of competence, increased sexuality. </li></ul><ul><li>The user becomes more talkative, restless and often more irritable. Consciousness is clear, but delusions may occur as well as visual, tactile (formication) and auditory hallucinations. </li></ul><ul><li>These drugs are sympathomimetic, thus, they cause  HR,  BP,  skeletal muscle tension, but musculature of the bronchi and intestines relax. </li></ul>www.freelivedoctor.com
    85. 85. Cocaine <ul><li>Given unlimited access to the drugs, animals will self-administer these drug until they die. </li></ul><ul><li>B. Acute toxicity/Overdose </li></ul><ul><li>“ Runs” – Uninterrupted sequences of stimulant abuse to maintain a continuous state of intoxication, to extend the pleasurable feeling, and to postpone the postintoxication “crash” than ensues as the drug effects subside. </li></ul>www.freelivedoctor.com
    86. 86. Cocaine/Amphetamines <ul><li>“ The Runs” </li></ul>DRUG TAKING CRAVING DRUG TAKING DRUG TAKING CRAVING CRAVING The Blues FATIGUE DEPRESSION HYPERPHAGIA CRASH DRUG TAKING sleep www.freelivedoctor.com
    87. 87. Cocaine <ul><li>Acute tolerance may occur in such people, particularly in those taking the drug I.V., resulting in the need of increasingly larger doses. </li></ul><ul><li>This spiral of tolerance and dose increases continues until the drug is depleted or the person collapses from exhaustion. </li></ul><ul><li>Drug taking and drug seeking take a compulsive character. </li></ul>www.freelivedoctor.com
    88. 88. Cocaine <ul><li>Stimulant overdose results in excessive activation of the sympathetic nervous system and cardiac toxicity. </li></ul><ul><ul><ul><li>tachycardia and hypertension </li></ul></ul></ul><ul><ul><ul><li>myocardial infarction </li></ul></ul></ul><ul><ul><ul><li>cerebrovascular hemorrhage </li></ul></ul></ul><ul><ul><ul><li>Cocaine can cause coronary vasospasms and cardiac dysrhythmias . </li></ul></ul></ul><ul><li>CNS symptoms include anxiety feelings of paranoia and impending doom, and restlessness. </li></ul><ul><li>Users exhibit unpredictable behavior and may become violent. </li></ul>www.freelivedoctor.com
    89. 89. Cocaine <ul><li>Treatment of overdose </li></ul><ul><ul><li>- Beta blockers => for autonomic hyperactivity. </li></ul></ul><ul><ul><li> 1 blockade (Atenolol, metoprolol, esmolol and non-selective : labetolol) . </li></ul></ul><ul><ul><ul><li>This treatment is controversial: Problems with using non-selective  blockers may lead to unopposed  effects =>  BP </li></ul></ul></ul><ul><ul><li>- Nitroglycerine or other nitrites/nitrates  for angina. </li></ul></ul><ul><ul><li>- Calcium channel blockers ( verapamil, diltiazem )  for hypertension. </li></ul></ul><ul><ul><li>- Ice baths  for high fever. </li></ul></ul><ul><ul><li>- Acidify urine  to hasten excretion. </li></ul></ul>www.freelivedoctor.com
    90. 90. Cocaine <ul><ul><li>After the acute toxic effects are handled: </li></ul></ul><ul><ul><li>Antidepressants  for depression </li></ul></ul><ul><ul><li>Haloperidol  for psychosis. </li></ul></ul><ul><ul><li>Alprazolam  for panic attacks. </li></ul></ul>www.freelivedoctor.com
    91. 91. Cocaine <ul><li>E. Mechanism of Action </li></ul><ul><ul><li>Inhibition of DA reuptake => increase of DA concentration in N. accumbens. </li></ul></ul><ul><ul><li>Everywhere else it also causes: </li></ul></ul><ul><ul><ul><li>1. Increase activation of DA receptors. </li></ul></ul></ul><ul><ul><ul><li>2. Negative feedback inhibition. </li></ul></ul></ul><ul><ul><ul><li>3. May also produce dopamine release from nerve endings. </li></ul></ul></ul><ul><ul><ul><li>4. Inhibition of NE and 5-HT reuptake also occurs. </li></ul></ul></ul>www.freelivedoctor.com
    92. 92. Dopamine reuptake inhibitors www.freelivedoctor.com
    93. 93. GLUCOSE METABOLISM normal Red: high activity Blue: low activity www.freelivedoctor.com
    94. 94. www.freelivedoctor.com
    95. 95. Amphetamines <ul><li>d, l-Amphetamine, </li></ul><ul><li>Methylphenidate (Ritalin ®, use to treat attention deficit and hyperactivity disorders in children), </li></ul><ul><li>Phenmetrazine (used to treat obesity), </li></ul><ul><li>Methamphetamine (“crystal”, “speed”, “ICE”). </li></ul><ul><li>methylendioxyamphetamine, (MDA). </li></ul><ul><li>methylenedioxymetamphetamine, (MDMA, ecstasy, XTC). </li></ul><ul><li>A. Pharmacology: </li></ul><ul><ul><ul><li>Used as nasal decongestants (benzedrine, replaced by propylhexedrine). </li></ul></ul></ul><ul><ul><ul><li>Used as antidepressants and to treat obesity (anorectic) => can cause dependence. </li></ul></ul></ul><ul><ul><ul><li>Used to stay awake. </li></ul></ul></ul>www.freelivedoctor.com
    96. 96. Amphetamines <ul><ul><ul><li>Present clinical therapeutic use, only in narcolepsy. </li></ul></ul></ul><ul><ul><ul><li>Amphetamine and methamphetamine -HCl (speed), </li></ul></ul></ul><ul><ul><ul><li>Amphetamine or methamphetamine => I.V. </li></ul></ul></ul><ul><ul><ul><li>D-methamphetamine (“ice”) => smoked like cocaine but has a much longer duration of action. </li></ul></ul></ul><ul><ul><li>Psychological Dependence </li></ul></ul><ul><ul><ul><li>Similar to Cocaine </li></ul></ul></ul><ul><ul><ul><li>May cause hallucinations  MDA, DOM, MDMA </li></ul></ul></ul>www.freelivedoctor.com
    97. 97. Amphetamines Psychoactive: Club Drugs & Inhalants www.freelivedoctor.com
    98. 98. Nicotine <ul><li>A. Pharmacology </li></ul><ul><ul><ul><li>One of the most widely used licit drugs. </li></ul></ul></ul><ul><ul><ul><li>Drug found exclusively in the tobacco plant ( Nicotiana tabacum, serves as a natural insecticide), which is harvested, cured, and manufactured into snuff, chewing tobacco, pipe tobacco, cigars and cigarettes. Nicotine is absorbed best by the lungs and it is distributed rapidly throughout the body. </li></ul></ul></ul><ul><ul><ul><li>It has a half-life of about 30 min. </li></ul></ul></ul><ul><ul><ul><li>Highly lipophylic: Crosses BBB and placenta. </li></ul></ul></ul>www.freelivedoctor.com
    99. 99. Nicotine <ul><ul><li>a. Acute Effects </li></ul></ul><ul><ul><li>-  Fibrinolytic activity </li></ul></ul><ul><ul><li>-  Free fatty acids </li></ul></ul><ul><ul><li>-  Epinephrine and NE release from adrenal gland. </li></ul></ul><ul><ul><li>-  Sympathetic and Parasympathetic activity. </li></ul></ul><ul><ul><li>-  ACTH release from pituitary. </li></ul></ul><ul><ul><li>- depolarization of thermo, mechano, and nociceptors. </li></ul></ul><ul><ul><li>- depolarization of carotid body and other ganglia. </li></ul></ul><ul><ul><li>- depolarization of baroreceptors. </li></ul></ul><ul><ul><li>- depolarization of chemoreceptors in area posterma => Stimulation of emetic centers. </li></ul></ul>www.freelivedoctor.com
    100. 100. www.freelivedoctor.com
    101. 101. Nicotine <ul><li>B. Acute Intoxication </li></ul><ul><ul><li>Respiratory arrest due to blockade of respiratory centers and neuromuscular junctions controlling breathing. </li></ul></ul><ul><li>C. Chronic effects </li></ul><ul><ul><li>Associated diseases: Heart disease, lung disease, cancer, babies with small birth weight, asthma in children, others. </li></ul></ul><ul><li>D. Detoxification treatment </li></ul><ul><ul><li>Smoking therapy => substitution, tapering off: nicotine gum (Nicorette), nicotine patches, nicotine nasal spray. </li></ul></ul>www.freelivedoctor.com
    102. 102. Nicotine <ul><li>E. Withdrawal </li></ul><ul><ul><ul><li>Withdrawal symptoms include nervousness, anxiety, drowsiness, lightheadedness, insomnia, dizziness, tremor, sleep disturbances, decrease inability to concentrate, irritability and an intense craving for tobacco. Other physical symptoms include nausea, headache, constipation and an increase in appetite and increase body weight. </li></ul></ul></ul>www.freelivedoctor.com
    103. 103. Nicotine <ul><li>F. Mechanism of action </li></ul><ul><ul><ul><li>- Its primary site of action is at the nicotinic ACh receptors (peripheral and CNS) where it stimulates at low doses and blocks at high doses. </li></ul></ul></ul><ul><ul><ul><li>- Stimulates release of DA from VTA terminals onto N. accumbens. </li></ul></ul></ul><ul><ul><ul><li>- Presynaptic receptors regulate release of neuro-transmitters: </li></ul></ul></ul><ul><ul><ul><li>NE, EPI, DA, ACh, GABA </li></ul></ul></ul>www.freelivedoctor.com
    104. 104. www.freelivedoctor.com
    105. 105. Proposed Sites of Action of Drugs of Abuse Nicotine acts here www.freelivedoctor.com
    106. 106. Drugs causing hallucinations, delusions or delusions. <ul><li>Psychedelics and hallucinogens </li></ul><ul><li>II. Marihuana (Cannabis) </li></ul><ul><li>Dissociative anesthetics (PCP) </li></ul><ul><li>Anticholinergics </li></ul>www.freelivedoctor.com
    107. 107. Drugs causing hallucinations, delusions or delusions. <ul><li>Psychedelics and hallucinogens. </li></ul><ul><li> Indolamines: Lysergic acid diethylamide (LSD), morning glory seed (LSM), psilocybin, psilocin, ibogaine, dimethyltryptamine (DMT). </li></ul><ul><li> Phenyethylamines: mescaline, bufotenin, dimethoxymethyl-amphetamine (DOM). </li></ul><ul><li>II. Cannabis. Marihuana, delta-9-THC. </li></ul><ul><li>III. Dissociative anesthetics. Ketamine, Phencyclidine (PCP). </li></ul><ul><li>IV. Anticholinergics. Mandrake root, jimson weed, atropine, scopolamine. </li></ul>www.freelivedoctor.com
    108. 108. Hallucinogens <ul><li>A. Pharmacology </li></ul><ul><li>These four classes of drugs are usually considered together because of their prominent feature of intoxication (hallucinations, delusions, illusions), but they differ in almost every aspect: chemical structure, mechanism of action, CNS receptor involved, picture of intoxication, type and seriousness of their toxic effects. </li></ul><ul><li>They occur naturally in plants, mushrooms and in some frogs </li></ul>www.freelivedoctor.com
    109. 109. Hallucinogens <ul><li>a. Acute Effects </li></ul><ul><li>At low doses: </li></ul><ul><ul><li>Euphoria; Changes in affect (mood): anxiety, tension, labile mood; Thought and feeling disorders: perceptual changes (distortion), depersonalization, illusions visual hallucinations, time and visual distortions, synesthesias; nausea, pupils are dilated,  HR,  BP,  temperature,  reflexes, tremors. </li></ul></ul><ul><ul><li>Panic, paranoia. </li></ul></ul>www.freelivedoctor.com
    110. 110. Hallucinogens <ul><li>At high doses: </li></ul><ul><ul><li>Dangerous behavior may cause accidents. </li></ul></ul><ul><ul><li>For the amphetamines: </li></ul></ul><ul><ul><li>Visual hallucinations => convulsions, coma. </li></ul></ul><ul><li>Subjective reason for taking these drugs: </li></ul><ul><li>Allows insight into oneself and new ways of looking at the world. </li></ul><ul><li>Cross-tolerance between LSD and mescaline. </li></ul><ul><li>Usually polydrug users. </li></ul>www.freelivedoctor.com
    111. 111. Hallucinogens <ul><li>B. Acute toxicity/Overdose </li></ul><ul><li>Depends on the individual drug . </li></ul><ul><ul><li>Tissue toxicity. Some are neurotoxic. </li></ul></ul><ul><ul><li>Psychic toxicity. Acute transient psychosis. Flash backs. </li></ul></ul><ul><ul><li>Behavioral toxicity. Distorted behavior, aggressive, violent. </li></ul></ul>www.freelivedoctor.com
    112. 112. Hallucinogens <ul><li>C. Withdrawal </li></ul><ul><li>These drugs do not cause physical dependence, but they have tremendous abuse potential (psychological dependence). </li></ul><ul><li>- Use is occasional. </li></ul>www.freelivedoctor.com
    113. 113. Hallucinogens <ul><li>D. Mechanism of Action </li></ul><ul><ul><li>LSM (from morning glory seeds), LSD (synthetic), mescaline (from the peyote cactus) and psilocybin (from mushrooms) have chemical resemblances to 5-HT, NE and DA. </li></ul></ul><ul><ul><li>Scopolamine is a cholinergic antagonist. </li></ul></ul><ul><ul><li>They all cause hyperarousal of the CNS. </li></ul></ul>www.freelivedoctor.com
    114. 114. Hallucinogens <ul><ul><li>Systems Affected: </li></ul></ul><ul><ul><ul><li>5-HT. Presynaptic agonists. decrease 5-HT transmission. “Cocktail party effect&quot; all sensory information goes in. temporal lobe. Postsynaptic agonists to 5-HT 1A and 5-HT 1C receptors. </li></ul></ul></ul><ul><ul><ul><li>NE. Postsynaptic agonists. increase NE activity in temporal lobe. Produce a lot of “bad trips”. Anxiety and hyperactivity. </li></ul></ul></ul><ul><ul><ul><li>ACh. Pr oduce delirium. Anticholinergic effects. Not addictive. </li></ul></ul></ul>www.freelivedoctor.com
    115. 115. Hallucinogens <ul><li>F. Treatment </li></ul><ul><ul><ul><li>None </li></ul></ul></ul>www.freelivedoctor.com
    116. 116. Proposed Sites of Action of Drugs of Abuse Nicotine acts here Nicotine acts here www.freelivedoctor.com
    117. 117. Marihuana (Cannabis) www.freelivedoctor.com
    118. 118. Marihuana (Cannabis) <ul><li>A. Pharmacology </li></ul><ul><li>From the Indian hemp plant, or Cannabis sativa . </li></ul><ul><li>Medicinal powers => Egyptians. Probably originated in Central Asia. </li></ul><ul><li>Delta-9-tetrahydrocannabinol (THC) is the active ingredient. </li></ul><ul><li>Marihuana, marijuana, bhang, ganja, hashish or charas, sinsemilla, red oil. </li></ul>www.freelivedoctor.com
    119. 119. Marihuana (Cannabis) <ul><li>High lipid solubility but does not dissolve well in water so if taken orally they are absorbed through the digestive system rather slowly. </li></ul><ul><li>Smoking causes 50% of cannabinoids to enter the lungs. Holding the smoke in the lungs maximizes absorption. </li></ul>www.freelivedoctor.com
    120. 120. Cannabis <ul><li>B. Mechanism of Action </li></ul><ul><li>In 1990 the THC receptor was cloned and in 1992 the endogenous cannabimimetic was discovered. </li></ul><ul><li>They named it anandamide (ànanda, in Sanskrit = bliss). </li></ul><ul><li>Anandamide is the ethanolamine of arachidonic acid. </li></ul><ul><li>Cannabinoids as well as anandamide inhibit Adenylate Cyclase (which produces cAMP) both in brain and periphery, via G protein-coupled cannabinoid receptors. </li></ul><ul><li>They also inhibit the N-type calcium channel current, which may affect regulation of neurotransmitter release. </li></ul>www.freelivedoctor.com
    121. 121. Cannabis <ul><ul><li>- Cannabinoids have effects not related to receptor function, including activation of PLA 2 and intracellular calcium mobilization. </li></ul></ul><ul><ul><li>- THC causes the release of serotonin, causes an elevation of ACh and inhibits the synthesis of prostaglandins. </li></ul></ul><ul><ul><li>- They have also been known to influence levels of NE, DA and GABA. </li></ul></ul><ul><ul><li>- THC concentrates in the limbic system, particularly in hippocampus and amygdala and sensory centers for hearing. </li></ul></ul>www.freelivedoctor.com
    122. 122. Cannabis <ul><ul><li>- A new peripheral cannabinoid receptor, with only 44% homology to the brain receptor, has been found in spleen, lymph nodes and leukocytes. Thus, they appear confined to the immune system. </li></ul></ul><ul><ul><li>- Cannabinol, a compound also found in marihuana but with less psychotropic effects seems to have preference for this receptor. </li></ul></ul><ul><ul><li>- Dronabinol. Medicinal grade cannabinol. Approved as an antiemetic. </li></ul></ul>www.freelivedoctor.com
    123. 123. www.freelivedoctor.com
    124. 124. PCP <ul><li>Phencyclidine, Angel Dust, Hog </li></ul><ul><li>A. Pharmacology </li></ul><ul><li>It is a synthetic phenylcyclohexylamine derivative. </li></ul><ul><li>Initially introduced in 1957 as a “dissociative anesthetic”, which caused no loss of consciousness. It was removed from the market for use in humans, but it was used in veterinary practice. </li></ul><ul><li>It is the most commonly used hallucinogenic agent. </li></ul><ul><li>It may be snorted, taken orally, smoked with tobacco, or injected IV. </li></ul><ul><li>Usually gives bad trips. </li></ul><ul><li>Behavior under the influence of the drug may be unpredictable, bizarre and violent. </li></ul>www.freelivedoctor.com
    125. 125. PCP <ul><li>a. Acute effects </li></ul>LOW DOSE Dreamy, carefree state, mood elevation, heightened or altered perception. MODERATE DOSE Inebriation, dissociation, depersonalization, perceptual distortions, diminished pain sensitivity HIGH DOSE All of the above and hallucinations Impaired judgment, Mood swings, Partial amnesia Untoward Effects Ataxia, motor impairment, confusion, disorientation, preoccupation with abnormal body sensations, amnesia, nystagmus, exaggerated mood swings, PANIC Catatonia, “blank” stare, delirium, severe motor impairment, psychotic behavior, hypertensive crisis, meditatio mortis, amnesia. www.freelivedoctor.com
    126. 126. PCP <ul><li>C. Acute toxicity /Overdose </li></ul><ul><li>Intoxication may last 4 to 6 hrs. </li></ul><ul><li>Usually not lethal. </li></ul><ul><li>Treatment of Intoxication/Overdose </li></ul><ul><li>No treatment </li></ul><ul><li>Physical dependence is not clear. </li></ul>www.freelivedoctor.com
    127. 127. PCP <ul><li>D. Mechanism of Action </li></ul><ul><ul><li>Receptors for PCP have been identified and are closely related (if not identical) to opioid sigma receptors. </li></ul></ul><ul><ul><li>PCP acts as an antagonist of NMDA glutamate receptors. </li></ul></ul><ul><ul><li>May block DA reuptake. </li></ul></ul>www.freelivedoctor.com
    128. 128. Solvents/Inhalants <ul><li>Anesthetics, Volatile Intoxicants </li></ul><ul><li>They can be easily and inexpensively obtained legally. One big problem is that they are most likely to be abused by the youngest members of the drug-abusing community. </li></ul><ul><li>Boys as young as 7 and 10 years of age, as well as young teenagers are those most frequently found sniffing glue of gasoline. </li></ul><ul><li>Few studies of these abused substances. </li></ul>www.freelivedoctor.com
    129. 129. Solvents/Inhalants <ul><ul><li>Volatile Solvents </li></ul></ul><ul><ul><li>Aerosols </li></ul></ul><ul><ul><li>Anesthetic agents </li></ul></ul><ul><ul><li>Amyl, butyl, and isobutyl nitrite </li></ul></ul>www.freelivedoctor.com
    130. 130. Solvents/Inhalants <ul><li>Anesthetics, Volatile Intoxicants </li></ul><ul><li>Low-income communities and isolated communities such as Native American reservations and Hispanic enclaves seem particularly affected. Although more afluent communities have also began to deal with the problem (cans of whipped cream have been removed from supermarket shelves). </li></ul><ul><li>Solvents such as toluene may cause permanent neurological damage. </li></ul>www.freelivedoctor.com
    131. 131. Solvents/Inhalants <ul><li>Four major groups of inhalants: </li></ul><ul><ul><li>1. Volatile Solvents : </li></ul></ul><ul><ul><ul><li>“ Glue sniffing”: model cement (airplane glue), lighter fluids, cleaning solutions, lacquer thinners, industrial solvents, esters ketones, gasoline and other petroleum distillates, propane and butane fuel, toluene chlorinated hydrocarbons, etc. </li></ul></ul></ul><ul><ul><ul><li>Toxic solvents such as benzene and carbon tetrachloride have been remove from most products. </li></ul></ul></ul>www.freelivedoctor.com
    132. 132. Solvents/Inhalants <ul><li>2. Aerosols : </li></ul><ul><ul><li>Fluorocarbons and other aerosol propellants. spray paint (containing alcohols), -- particularly dangerous are the products containing chlorofluorocarbons, ketones, organic metals and n-hexane, they cause cardiotoxicity, axonopathies or hepathotoxicity. </li></ul></ul>www.freelivedoctor.com
    133. 133. Solvents/Inhalants <ul><ul><li>3. Anesthetic agents : </li></ul></ul><ul><ul><ul><li>Ethyl ether, chloroform, methylchloride, trichloroethylene and nitrous oxide. Some are contained in oil and grease dissolvers. </li></ul></ul></ul><ul><ul><ul><li>Chloral hydrate. Popular in Queen Victoria's age as sleeping medication, used in drinks. Produces similar effects as the barbiturates. </li></ul></ul></ul>www.freelivedoctor.com
    134. 134. Solvents/Inhalants <ul><ul><li>4. Amyl, butyl, and isobutyl nitrite : </li></ul></ul><ul><ul><ul><li>Amyl nitrite was used since 1867 as a vasodilator to relieve angina pectoris. Available originally in mesh covered glass ampoules, called pearls, and design to be crushed with the fingers. The popping sound that resulted caused them to be referred as &quot;poppers&quot;. Isobutyl nitrite, with similar pharmacological properties is used as a room odorizer. </li></ul></ul></ul>www.freelivedoctor.com
    135. 135. Solvents/Inhalants <ul><li>A. Pharmacology </li></ul><ul><li>The onset of action of most solvents is rapid and their duration is short, with the exception of acetone that has a slower onset and longer duration of action. </li></ul><ul><ul><li>1. Psychological Dependence </li></ul></ul><ul><ul><li>2. Physical Dependence. </li></ul></ul><ul><ul><ul><ul><li>No physiological dependence . </li></ul></ul></ul></ul><ul><li>Alcohol potentiates their effect. </li></ul><ul><li>They seem to disrupt membrane function . </li></ul>www.freelivedoctor.com
    136. 136. Solvents/Inhalants <ul><li>a. Acute Effects </li></ul><ul><li>At low doses these substances generally cause marked euphoria and dizziness (resulting from the hypotension and hypoxia secondary to peripheral venous pooling); slurred speech, ataxia, impaired judgement and feelings of giddiness and drunkenness. Some may experience perceptual distortions. </li></ul><ul><li>At high doses they have a generalized depressant effects upon the CNS. </li></ul><ul><li>Amyl nitrite -- reputed to act as a sexual enhancer (penile vasodilation). </li></ul>www.freelivedoctor.com
    137. 137. Solvents/Inhalants <ul><li>B. Acute toxicology/Overdose </li></ul><ul><li>Photophobia, irritation of the eyes, diplopia, rhinitis, sneezing, coughing, nausea, diarrhea, chest pain, and vague muscle and joint pains. </li></ul><ul><li>Overdose can cause respiratory depression. </li></ul><ul><li>Usually die of asphyxia. </li></ul><ul><ul><li>Halogenated hydrocarbons in some aerosol propellants and cleaning solutions cause cardiac arrest . </li></ul></ul>www.freelivedoctor.com