بخشنده خداوند بناممهربان

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

• 1. Sedatives / Hypnotics

The Drugs of Abuse

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

Benzodiazepines

• High Potency / Long Acting

• Substitute for Short Acting in Withdrawal

-Prosom-Klonepin

• Low Potency / Long Acting

• 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) 1mg

• Triazolam (Halcion) 0.25mg

• Temazepam (Restoril) 15mg

• Lorazepam (Ativan) 2mg

• Diazepam (Valium) 10mg

• Phenobarbital 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. Anesthesia6. 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 doseValium40mg 30mg/10mg

= 120mgAtivan 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

• 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

• 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 ~

GHB: Gamma-hydroxybutyrate

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 Serotonin- 5-

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 andWithdrawal 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 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

Cardiovascular Effects

Dose-dependent in pulse rate.

Reddening of the Conjunctiva

Endocrine Effects

Luteinizing hormone

Follicle-stimulating hormone

Prolactin

Growth hormone

Adrenocorticotrophin hormone

• testosterone• testicular weight• spermatogenesis• sexual behavior

Decreases

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 EstersSynthetic 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 AppearanceSelf-confidence

• Negative Reinforcing Effects:Fatigue, DepressionDecreased 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: --PneumonitisHematologic: --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) 100mg

• Pentobarbital (Yellows) 100mg

• Secobarbital ( Seconal) 100mg

• Phenobarbital 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