Transcript The Drugs of Abuse II

‫بنام خداوند بخشنده مهربان‬
The Drugs of Abuse
"Drug-Use Is Life Abuse"
The Drugs of Abuse
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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
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-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
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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
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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
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MDMA (ecstasy)
ECSTASY
• MDMA(3,4
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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
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MDMA Neuro. Complications
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Confusion, Paranoia, Panic
Psychosis, Acute and Chronic
Seizures, Status Epilepticus
Destruction of Serotonin Neurons
With Long Term Use
MDMA CV. Complications
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Hypertension
Dysrhythmias
Pulmonary Edema
Cardiogenic Shock
Cerebral Hemorrhage
Mesenteric Ischemia
MDMA Complications
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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 ?
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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
c. Nitrous oxide (NO)
• Products With NO:
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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
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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:
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Butalbital (Fiorinal)
Pentobarbital (Yellows)
Secobarbital ( Seconal)
Phenobarbital
100mg
100mg
100mg
30mg
The Drugs of Abuse
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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