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بخشنده خداوند بناممهربان
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The Drugs of Abuse
"Drug-Use Is Life Abuse"
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The Drugs of Abuse
• 1. Sedatives / Hypnotics
• 2. Hallucinogens
• 3. PCP (Phencyclidine)
• 4. Anabolic Steroids
• 5. Inhalants
• 6. Opioid
• 7. Alcohols
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• 1. Sedatives / Hypnotics
The Drugs of Abuse
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1. Benzodiazepines
• High Potency / Short Acting
• Most Addiction Sympt. / Severity
-Alperazolam-Lorazepam
• -triazolm
• Low Potency / Short Acting
• Good Temporary Sleepers for Hosp. Patients. -Serax -Temazepam
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Benzodiazepines
• High Potency / Long Acting
• Substitute for Short Acting in Withdrawal
-Prosom-Klonepin
• Low Potency / Long Acting
• Addiction In High Doses
-Valium-Librium-Tranxene
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2. Barbiturates
• Short Acting (Highly Lipid Sol.)-Pentobarbital (Yellows)-Secobarbital (Reds)-Amobarbital (Blues)
• Long Acting -Phenobarbital-Substitute for Short In Tx.
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Benzodiazepines Equiv. Doses
• Alprazolam (Xanax) 1mg
• Triazolam (Halcion) 0.25mg
• Temazepam (Restoril) 15mg
• Lorazepam (Ativan) 2mg
• Diazepam (Valium) 10mg
• Phenobarbital 30mg
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MOA
• GABA Receptor CNS Inhibition --Benzos Potentiate GABA --Barbs Potentiate + Agonists
• Respiratory Depression --Benzos + Other CNS
Depressants --Barbs Alone• Both With Anticonvulsant Activity
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CNS Inhibition
• With Dose:1. Decreased Anxiety
2. Sedation 3. Amnesia
4. Hypnosis 5. Anesthesia6. Reduced
Reflexes / Respiration 7. Death
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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.
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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
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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
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Complications
• Benzodiazepines-Memory Loss, Amnesia -Ataxia, Incoordination,
Vertigo -Diplopia, Dizziness -Impairment in Driving -Depression,
Suicidal Ideation
• Relatively Contraindicated in Addiction
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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 !!!
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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.
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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)
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Detoxification-examples
• Drug Daily dose PB doseValium40mg 30mg/10mg
= 120mgAtivan 10mg
30mg/2mg = 150mg
• PB is then tapered 10% / d X 10 d• Xanax requires slower tapering
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“Date Rape Drugs” Rohypnol & GHB
Classified as depressants
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Rohypnol: Flunitrazepam
• Benzodiazepine
• Indirect GABA agonist– alcohol synergism– p.o. & intranasal administration
• Dissolves easily in carbonated drinks – tasteless– odorless
• Associated with sexual assaults
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• 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)
Rohypnol: Flunitrazepam
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• Homemade CNS depressant– “Grievous Bodily Harm”
• GABA agonist– precursor– synergism with alcohol
• Clear liquid, powder, tablet, capsule
GHB: Gamma-hydroxybutyrate
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• Effects similar to benzodiazepines and barbiturates
• Also– loss of consciousness– loss of reflexes – seizures, coma, death
• Associated with sexual assault ~
GHB: Gamma-hydroxybutyrate
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The Drugs of Abuse
2. Hallucinogens
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Hallucinogens
• Alter Mood, Perception, Thinking.
• Induce Delusions
• Hallucinations Occur Infrequently
1. LSD
2. Psilocybin
3. Mescaline
4. MDMA
5.Marijuana
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MOA of Hallucinogens
• LSD, Psilocybin, Mescaline:– Bind to Post-Synaptic Serotonin- 5-
Hydroxy Tryptamine, (5-HT) Receptors
– 5HT Agonists
– Rapid Tolerance From Down Regulation of Receptors Occurs
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Lysergic Acid Diethylamide
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General specifications:
• Very powerful hallocinogen
• Alkaloied derivatives from (Psilocybe mexicana)
• German word (Lyser Saure Diethylamide)
• Ingestion( rote of misuse)
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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
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DDX of LSD Intoxication
• Delirium, Dementia
• Schizophrenia
• Bipolar, Psychotic Disorders
• Narcolepsy
• Etoh, Marijuana, PCP Intoxication
• Antiparkinsonian Drugs
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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 andWithdrawal Do Not Occur
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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
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MDMA (ecstasy)
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ECSTASY
• MDMA(3,4 ETHYLENEDIOXYMETHAMPHETAMINE)
• ADAM • X-TC • X- pill • SEX- PILL• CLARITY• ESSENCE• STACY• LOVER’S SPEED• EVE
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MDMA Effects
• By 5HT Activity: --Minimal Hallucinations
--Locomotor Hyperactivity--Hyperthermia
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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
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MDMA Intoxication
• 5HT Activation:--Empathy & Insight
--Sexsuality--Euphoria
--Energy--Self
Esteem
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MDMA Intoxication
• Sympathetic Activation:--Diaphoresis
--Mydriasis--Tachycardia
--Hypertension --Increased Psychomotor Drive
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MDMA Neuro. Complications
• Confusion, Paranoia, Panic
• Psychosis, Acute and Chronic
• Seizures, Status Epilepticus
• Destruction of Serotonin Neurons With Long Term Use
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MDMA CV. Complications
• Hypertension
• Dysrhythmias
• Pulmonary Edema
• Cardiogenic Shock
• Cerebral Hemorrhage
• Mesenteric Ischemia
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MDMA Complications
• Hyperthermia (>108 F)
• Muscle Spasm
• Rhabdomyolysis
• Acute Hepatic or Renal Failure
• DIC
• Death
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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
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"Shoot for the moon. Even if you miss it, you will land among the stars."
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Marijuana
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Cannabis sativa
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Response Variables
• Dose
• Route of administration
• Setting
• Experience
• Expectations
• Individual vulnerability
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Route of Administration
• Oral• IV• Smoke
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The High
Early stages– Euphoria
– Uncontrollable laughter
– Time/sense alterations
– Depersonalization
Late stages– Relaxation
– Introspective
– Dreamlike state
– Difficulty thinking
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CNS Effects
Marijuana causes some parts of the brain, including those governing emotions, memory and judgement to lose balance and control.
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General CNS EffectsAcute
– 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
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Cardiovascular Effects
Dose-dependent in pulse rate.
Reddening of the Conjunctiva
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Endocrine Effects
Luteinizing hormone
Follicle-stimulating hormone
Prolactin
Growth hormone
Adrenocorticotrophin hormone
• testosterone• testicular weight• spermatogenesis• sexual behavior
Decreases
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Respiratory Effects
Acute: bronchodilator
Chronic: bronchoconstriction
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Medical Marijuana
Dronabinol Antiemetic
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Medical Marijuana
Approved– Antiemetic (cancer)
– AIDS wasting syndrome
Suggested– Glaucoma
– Pain
– Asthma
– Multiple sclerosis
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The Drugs of Abuse
3. Anabolic Steroids
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Anabolic Steroids -Types
• Long Acting, Given IM: Testosterone EstersSynthetic Nandrolones
• Orally Active Forms:--Methyltestosterone--Danazol, Stanozolol--Methandrostenolone, Etc.
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Anabolics-Metabolism
• Protein Bound in Bloodstream
• Unbound Forms Must Be Metabolized to Become Metabolically Active
• Dihydroxytestosterone (DHT) Is Very Active, Estradiol Also Active
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Anabolics MOA
• Cellular Receptors--Stimulate Intranuclear Effects
• Intranuclear Effects-Increase Protein Transcription -Decrease Protein Breakdown
• Euphoria / Aggression, Fatigue• But No Increased Aerobic Capacity!
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Anabolics - Addictive?
• Positve Reinforcing Effects:Athletic Performance
Physical AppearanceSelf-confidence
• Negative Reinforcing Effects:Fatigue, DepressionDecreased Libido, Muscle Pain
Headache, Craving
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Male Complications
• Azoospermia
• Testicular Atrophy
• Gynecomastia = “Bitch Tits”
• Erectile Dysfunction
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Female Complications
• May Not Reverse With Stopping: --Hirsuitism--Male Pattern Baldness --Breast Reduction --Clitoral Hypertrophy--Amenorrhea / Dysmenorrhea--Acne--Deepened Voice
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Behavioral Complications
• With Use:--Aggression, Violence--Mania, Hypomania, Panic--Psychotic Symptoms
• With Discontinuation:--Depression--Suicidal Ideation
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Medical Complications
• Hypertension
• Serum Lipids: LDL, HDL
• Myocardial Infarction, Stroke
• Cholestatic Jaundice
• Peliosis Hepatitis (Blood Cysts)
• Liver Cancer
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Anabolic Use - Diagnosis
• Exam: Jaundice, Acne, Facial Edema, HBP, Clitoral Hypertrophy Testicular Atrophy, Hepatomegaly
• Lab: Urine Screen, Elevated Glucose, LDL, or Liver Enzymes
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The Drugs of Abuse
4. PCP (Phencyclidine)
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PCP - Phencyclidine
• A Dissociative Anaesthetic-Related to Ketamine
• Antagonist at N-methly, D-aspartate (NMDA) Receptor
• “Angel Dust”, “Crystal”, “Space Base “ (Combined With Cocaine)
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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
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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
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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
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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
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The Drugs of Abuse II
5. Inhalants
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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.
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Inhalants - Metabolism
• Nitrates and Hydrocarbons Are Metabolized by Liver Microsomal Enzyme Systems.
• Some Metabolites Are Active.
• Other Inhalants Excreted by Lungs and Kidneys.
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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
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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
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VOC’s - Consequences
• ‘Sudden Sniffing Death’Cardiac or Respiratory Depr.
• Cognitive Loss / Brain Atrophy-Memory / Concentration
• Accidents, Falls
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VOC’s - Consequences
• Huffers Rash
• Pneumonitis
• Myopathy, Neuropathy
• Kidney Failure
• Aplastic Anemia
• AML (Benzene)
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b. Nitrates
• Volatile Nitrates:--Developed for Angina--Vasodilators--”Rush”--Sexual Excitement --MOA Is CNS Hypoxia, and ?
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Volatile Nitrates - Effects
• CNS: --Euphoria, Disorientation --Headache, Tinnitis
--Dizziness, Syncope --Visual “Yellow Haze”
• Other: --Tachy / Bradydysrhythmia -- BP, Wheezing --Hemolytic Anemia
--Methemaglobinemia
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c. Nitrous oxide (NO)
• Products With NO:– Whipped Cream “Whippets”– Cook. Spray– Fire Extinguish.– Anesthesia Tanks
• Adolescents • Those With Gas Available:
– Dentistry– Anesthesia
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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
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NO - Acute Effects• CNS: --Euphoria --Headache
--Confusion --Syncope--Seizure --Coma
• Respiratory: --Asphyxiation--Frostbite --Air Emboli
• Misc: --Anemia -- Immunity--Spontaneous Abortion
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NO - Chronic Effects
CNS: --Spinal Cord Degeneration
--Numbness --Weakness
--Ataxia
--Clumsiness
Respiratory: --PneumonitisHematologic: --Agranulocytosis
--Aplastic Anemia
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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.
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Epidemiology
• Benzodiazepines Replaced Barbiturates
• Females / Males = 2 / 1
• Most Over 50 Years Old
• Benzodiazepine Over-dose Is Most Common Suicide Attempt.
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Barbiturates Equivalent Doses:
• Butalbital (Fiorinal) 100mg
• Pentobarbital (Yellows) 100mg
• Secobarbital ( Seconal) 100mg
• Phenobarbital 30mg
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The Drugs of Abuse
• A. MOA
• B. Intoxication
• C. Withdrawal
• D. Complications
• E. Treatments
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a.Volatile organics (VOC)
• Epidemiology: (1993-4)
• 17% of HS grads had used
• 3% of these are chronic users
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