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بنام خداوند بخشنده مهربان The Drugs of Abuse "Drug-Use Is Life Abuse" The Drugs of Abuse • • • • • • • 1. Sedatives / Hypnotics 2. Hallucinogens 3. PCP (Phencyclidine) 4. Anabolic Steroids 5. Inhalants 6. Opioid 7. Alcohols The Drugs of Abuse • 1. Sedatives / Hypnotics 1. Benzodiazepines • High Potency / Short Acting • Low Potency / Short Acting • Most Addiction Sympt. / Severity -Alperazolam -Lorazepam • -triazolm • Good Temporary Sleepers for Hosp. Patients. -Serax -Temazepam Benzodiazepines • High Potency / Long Acting • Low Potency / Long Acting • Substitute for Short Acting in Withdrawal -Prosom -Klonepin • Addiction In High Doses -Valium -Librium -Tranxene 2. Barbiturates • Short Acting (Highly Lipid Sol.) -Pentobarbital (Yellows) -Secobarbital (Reds) -Amobarbital (Blues) • Long Acting -Phenobarbital -Substitute for Short In Tx. Benzodiazepines Equiv. Doses • • • • • • Alprazolam (Xanax) Triazolam (Halcion) Temazepam (Restoril) Lorazepam (Ativan) Diazepam (Valium) Phenobarbital 1mg 0.25mg 15mg 2mg 10mg 30mg MOA • GABA Receptor CNS Inhibition --Benzos Potentiate GABA --Barbs Potentiate + Agonists • Respiratory Depression --Benzos + Other CNS Depressants --Barbs Alone • Both With Anticonvulsant Activity CNS Inhibition • With Dose: 1. Decreased Anxiety 2. Sedation 3. Amnesia 4. Hypnosis 5. Anesthesia 6. Reduced Reflexes / Respiration 7. Death Metabolism • Benzodiazepines by Liver Microsomal Enzymes, Metabolites May Be Active Extending Half-life. • Barbiturates by Cytochrome P450 Enzymes, Commonly Induced With Resulting Breakdown of Alcohol , Steroids, Fat Soluble Vitamins, and Anticoagulants. Discontinuation. • Return: Of Original Symptoms • Rebound: Intense Orig. Symptoms • Withdrawal: (Long Use, High Dose) -Anxiety, Panic -Paranoia, Hallucinations -Tremor, Seizures, Delirium Depression, Irritability, N&V Withdrawal Timing • Short Acting Barbs --Onset 1/2 Day --Peak 1-3 Days • Short Acting Benzos --Onset 1 Day --Peak 2-4 Days • Long Acting Barbs / Benzos --Onset 2 Days --Peak 5-8 Days Complications • Benzodiazepines -Memory Loss, Amnesia -Ataxia, Incoordination, Vertigo -Diplopia, Dizziness -Impairment in Driving -Depression, Suicidal Ideation • Relatively Contraindicated in Addiction Overdose • Signs & Symptoms: --Slurred Speech, Staggering --Nystagmus, Slow Reaction --Respiratory Depression • Barbiturates: 3-10 Mg / Dl • Benzodiazepines: 1-2 Gm or More --Less With Alcohol !!! Benzo OD Treatment • Flumazenil --Benzo Antagonist --0.2 Mg, Then 0.3 Mg, Then 0.5 Mg, IV, Max 3.0mg --May Precipitate Withdrawal • Supportive Measures --Airway Management, Etc. Detoxification • Gradual Dose Tapering Over Several Days to Weeks • Substitution of Long Acting Form: --Phenobarbital --Use Equivalent Dose and Taper by 30 Mg or 10% Per Day. (Max. 500mg / D) Detoxification-examples • Drug Daily dose PB dose Valium 40mg 30mg/10mg = 120mg Ativan 10mg 30mg/2mg = 150mg • PB is then tapered 10% / d X 10 d • Xanax requires slower tapering “Date Rape Drugs” Rohypnol & GHB Classified as depressants Rohypnol: Flunitrazepam • Benzodiazepine • Indirect GABA agonist – alcohol synergism – p.o. & intranasal administration • Dissolves easily in carbonated drinks – tasteless – odorless • Associated with sexual assaults Rohypnol: Flunitrazepam • Effects same as any benzodiazepine – feeling of well-being – lowered inhibitions – impaired judgment • Unique to Rohypnol – visual disturbances – no memory for period of intoxification(block any memory) GHB: Gamma-hydroxybutyrate • Homemade CNS depressant – “Grievous Bodily Harm” • GABA agonist – precursor – synergism with alcohol • Clear liquid, powder, tablet, capsule GHB: Gamma-hydroxybutyrate • Effects similar to benzodiazepines and barbiturates • Also – loss of consciousness – loss of reflexes – seizures, coma, death • Associated with sexual assault ~ The Drugs of Abuse 2. Hallucinogens Hallucinogens • Alter Mood, Perception, Thinking. • Induce Delusions • Hallucinations Occur Infrequently 1. LSD 2. Psilocybin 3. Mescaline 4. MDMA 5.Marijuana MOA of Hallucinogens • LSD, Psilocybin, Mescaline: – Bind to Post-Synaptic Serotonin5-Hydroxy Tryptamine, (5-HT) Receptors – 5HT Agonists – Rapid Tolerance From Down Regulation of Receptors Occurs Lysergic Acid Diethylamide General specifications: • Very powerful hallocinogen • Alkaloied derivatives from (Psilocybe mexicana) • German word (Lyser Saure Diethylamide) • Ingestion( rote of misuse) LSD Intoxication 8-12hr • At 10-30 Min. -Laugh / Cry -Euphoria -Paranoia -Impair Think. -Panic Attack -Tachycardia -Elev. BP -Tremors • At 2-3 Hours -Hallucination -Synesthesia (Sounds Felt, Colors Heard) -Derealization -Distorted Time / Space -Blurring DDX of LSD Intoxication • • • • • • Delirium, Dementia Schizophrenia Bipolar, Psychotic Disorders Narcolepsy Etoh, Marijuana, PCP Intoxication Antiparkinsonian Drugs Lasting LSD Effects • Few Develop Florid Psychosis -A Pre-existing Disorder? • “Flashbacks” Occur in 16-57% -? CNS Pathology or Memory, Most Mild / Not Incapacitating • Physical Dependence and Withdrawal Do Not Occur Treatment LSD Overdose • “Bad Trip” --Quiet, Safe, Environment --Calm Supportive Friends --’Talk Down’ -Emphasize Effects Are From Drug and Temporary • Valium 10-20mg, Ativan 1-2mg - MDMA (ecstasy) ECSTASY • MDMA(3,4 • • • • • • • • • ETHYLENEDIOXYMETHAMPHETAMINE) ADAM X-TC X- pill SEX- PILL CLARITY ESSENCE STACY LOVER’S SPEED EVE MDMA Effects • By 5HT Activity: --Minimal Hallucinations --Locomotor Hyperactivity --Hyperthermia MOA of MDMA • Increased Levels of 5HT, Dopamine and Norepinephrine by: --Increased Presynaptic Release --Inhibited Reuptake --Increased Dopamine Synthesis --Decreased Breakdown by Monoamine Oxidase Inhibition MDMA Intoxication • 5HT Activation: --Empathy & Insight --Sexsuality --Euphoria --Energy --Self Esteem MDMA Intoxication • Sympathetic Activation: --Diaphoresis --Mydriasis --Tachycardia -Hypertension -Increased Psychomotor Drive - MDMA Neuro. Complications • • • • Confusion, Paranoia, Panic Psychosis, Acute and Chronic Seizures, Status Epilepticus Destruction of Serotonin Neurons With Long Term Use MDMA CV. Complications • • • • • • Hypertension Dysrhythmias Pulmonary Edema Cardiogenic Shock Cerebral Hemorrhage Mesenteric Ischemia MDMA Complications • • • • • • Hyperthermia (>108 F) Muscle Spasm Rhabdomyolysis Acute Hepatic or Renal Failure DIC Death MDMA Treatment • A, B, C’s • Alpha Blockers (Phentolamine) NOT Beta Blockers For Hypertension • Benzodiazepines (Agitation, Seizure) • Rapid Cooling to 39 C (Tepid H2O) • IV Fluids w Bicarb. To Alk. Urine "Shoot for the moon. Even if you miss it, you will land among the stars." Marijuana Cannabis sativa Response Variables • • • • • • Dose Route of administration Setting Experience Expectations Individual vulnerability Route of Administration • Oral • IV • Smoke The High Early stages – Euphoria – Uncontrollable laughter – Time/sense alterations – Depersonalization Late stages – – – – Relaxation Introspective Dreamlike state Difficulty thinking CNS Effects Marijuana causes some parts of the brain, including those governing emotions, memory and judgement to lose balance and control. General CNS Effects Acute – – – – – – – – Short-term memory Confusion Depersonalization Balance/stability Hunger Dry mouth Sharper imagery REM sleep Chronic (Amotivational Syndrome) – Apathy – Dullness – Judgment – Concentration – Memory – Personal appearance and goals Cardiovascular Effects Dose-dependent in pulse rate. Reddening of the Conjunctiva Endocrine Effects Decreases Luteinizing hormone Follicle-stimulating hormone Prolactin Growth hormone Adrenocorticotrophin hormone • • • • testosterone testicular weight spermatogenesis sexual behavior Respiratory Effects Acute: bronchodilator Chronic: bronchoconstriction Medical Marijuana Dronabinol Antiemetic Medical Marijuana Approved – Antiemetic (cancer) – AIDS wasting syndrome Suggested – – – – Glaucoma Pain Asthma Multiple sclerosis The Drugs of Abuse 3. Anabolic Steroids Anabolic Steroids -Types • Long Acting, Given IM: Testosterone Esters Synthetic Nandrolones • Orally Active Forms: --Methyltestosterone --Danazol, Stanozolol --Methandrostenolone, Etc. Anabolics-Metabolism • Protein Bound in Bloodstream • Unbound Forms Must Be Metabolized to Become Metabolically Active • Dihydroxytestosterone (DHT) Is Very Active, Estradiol Also Active Anabolics MOA • Cellular Receptors --Stimulate Intranuclear Effects • Intranuclear Effects -Increase Protein Transcription -Decrease Protein Breakdown • Euphoria / Aggression, Fatigue • But No Increased Aerobic Capacity! Anabolics - Addictive? • Positve Reinforcing Effects: Athletic Performance Physical Appearance Self-confidence • Negative Reinforcing Effects: Fatigue, Depression Decreased Libido, Muscle Pain Headache, Craving Male Complications • • • • Azoospermia Testicular Atrophy Gynecomastia = “Bitch Tits” Erectile Dysfunction Female Complications • May Not Reverse With Stopping: --Hirsuitism --Male Pattern Baldness --Breast Reduction --Clitoral Hypertrophy --Amenorrhea / Dysmenorrhea --Acne --Deepened Voice Behavioral Complications • With Use: --Aggression, Violence --Mania, Hypomania, Panic --Psychotic Symptoms • With Discontinuation: --Depression --Suicidal Ideation Medical Complications • • • • • • Hypertension Serum Lipids: LDL, HDL Myocardial Infarction, Stroke Cholestatic Jaundice Peliosis Hepatitis (Blood Cysts) Liver Cancer Anabolic Use - Diagnosis • Exam: Jaundice, Acne, Facial Edema, HBP, Clitoral Hypertrophy Testicular Atrophy, Hepatomegaly • Lab: Urine Screen, Elevated Glucose, LDL, or Liver Enzymes The Drugs of Abuse 4. PCP (Phencyclidine) PCP - Phencyclidine • A Dissociative Anaesthetic Related to Ketamine • Antagonist at N-methly, D-aspartate (NMDA) Receptor • “Angel Dust”, “Crystal”, “Space Base “ (Combined With Cocaine) PCP Intoxication • Onset 5 Min Smoked, 1 Hr. PO: -Distorted Body Image -Disorientation, Euphoria -Aud./ Vis. Hallucinations -Paranoia, Belligerence -Analgesia, Self-destructive • < 5mg: Ataxia, Nystg, Blank Stare • >20mg: Seizures, Coma, Death PCP - Withdrawal • Can Occur With Only 2 Weeks Use. • Lasts 24-48 Hours • Peaks at 12-16 Hours --Depression --Drug Craving --Increased Appetite --Increased Need for Sleep PCP Complications • Self-destruction (Fractures Not Felt Due to Analgesia) • Injury to Others • Psychosis Lasting 2-3 Weeks • PCP Delirium, Mood Disorders • Acute Psychosis >> Hallucinogens PCP Treatment • Do Not ‘Talk Down’ • Isolate Patient + Restraints • Valium 10-30 Mg PO (If No Other CNS Drugs Present) • Haldol 5 Mg BID (Psychosis) • Acidify Urine The Drugs of Abuse II 5. Inhalants Inhalants - Types • 1. Volatile Organic Compounds: – Hydrocarbons, Fuels, Ethers, Glues, Paints, Aerosols..... • 2. Nitrates: – Volatile Nitrates: Amyl Nitrate, “Poppers,” Etc. • 3. Nitrous Oxide: “Whippets,” Etc. Inhalants - Metabolism • Nitrates and Hydrocarbons Are Metabolized by Liver Microsomal Enzyme Systems. • Some Metabolites Are Active. • Other Inhalants Excreted by Lungs and Kidneys. VOC’s • • • • • • Peak Use 11-13 Yrs (Experiment) Male, Low Economic ‘sniffing’ (From Container) ‘Huffing’ (From a Rag) ‘Bagging’ (Highest Concentration) Act by Disrupting Neural Function VOC’s - Addictive? • Specific Addiction to These Agents Is Relatively Unusual • Highly Rewarding for Some • Use Associated With: -- ASPD 63% - Alcoholism 68% - Later Drug Use 5-10X Risk VOC’s - Consequences • ‘Sudden Sniffing Death’ Cardiac or Respiratory Depr. • Cognitive Loss / Brain Atrophy -Memory / Concentration • Accidents, Falls VOC’s - Consequences • • • • • • Huffers Rash Pneumonitis Myopathy, Neuropathy Kidney Failure Aplastic Anemia AML (Benzene) b. Nitrates • Volatile Nitrates: --Developed for Angina --Vasodilators ”Rush” Sexual Excitement MOA Is CNS Hypoxia, and ? ---- Volatile Nitrates - Effects • CNS: --Euphoria, Disorientation --Headache, Tinnitis --Dizziness, Syncope --Visual “Yellow Haze” • Other: --Tachy / Bradydysrhythmia -- BP, Wheezing --Hemolytic Anemia --Methemaglobinemia c. Nitrous oxide (NO) • Products With NO: – – – – Whipped Cream “Whippets” Cook. Spray Fire Extinguish. Anesthesia Tanks • Adolescents • Those With Gas Available: – Dentistry – Anesthesia Nitrous oxide - Actions • Affects Neuron Membranes to Depress the CNS, and Respiration • 30 X Solubility of Nitrogen in Body • Exhaled Unchanged From Body • Highest Risks Are Asphyxiation, Barotrauma, Pneumomediastinum NO - Acute Effects • CNS: --Euphoria --Headache --Confusion --Syncope --Seizure --Coma • Respiratory: --Asphyxiation --Frostbite --Air Emboli • Misc: --Anemia -- Immunity --Spontaneous Abortion NO - Chronic Effects CNS: --Spinal Cord Degeneration --Numbness --Weakness --Ataxia --Clumsiness Respiratory: Hematologic: --Pneumonitis --Agranulocytosis --Aplastic Anemia Epidemiology • • • • • 12.5% of Us Pop Use Each Year 2% of Us Pop Use on Any 1 Day 1/2 of All Scripts by Primary Drs. Non-medical Use up to 1.9% / Yr. Benzodiazepines Most Common Drug Prescriptions. Epidemiology • Benzodiazepines Replaced Barbiturates • Females / Males = 2 / 1 • Most Over 50 Years Old • Benzodiazepine Over-dose Is Most Common Suicide Attempt. Barbiturates Equivalent Doses: • • • • Butalbital (Fiorinal) Pentobarbital (Yellows) Secobarbital ( Seconal) Phenobarbital 100mg 100mg 100mg 30mg The Drugs of Abuse • • • • • A. MOA B. Intoxication C. Withdrawal D. Complications E. Treatments a.Volatile organics (VOC) • Epidemiology: (1993-4) • 17% of HS grads had used • 3% of these are chronic users