Drugs and Behaviour Final Flashcards
Production of Alcohol
Fermentation: Yeast + sugar (grapes or grains) → Alcohol.
Distillation: Heating fermented liquid → Capturing vapor → Higher alcohol concentration (e.g., spirits).
History of Alcohol-Ancient Use
Evidence of alcohol use 9,000 years ago (China); Greeks, Egyptians, and English known for beer, wine, mead.
History of Alcohol-North America
Early drinking culture, Prohibition (14 years), then fluctuating consumption.
Measuring Alcohol Levels and Tools
Blood Alcohol Concentration (BAC):
mg alcohol/100 ml blood or percentage (e.g., 0.08% = 80 mg/100 ml).
SI Unit: mmol/L (e.g., 80 mg/100 ml = 17.4 mM).
Measurement Tools: Breathalyzer (BrAC), blood tests.
Pharmacokinetics of Alcohol
Absorption: Mostly in small intestine (slower with food).
Distribution: Alcohol is water-soluble (affects body composition impact — more fat → higher BAC).
Metabolism:
Liver processes 90–98% of alcohol: Ethanol → Acetaldehyde → Acetate.
Kinetics: Originally thought to be zero-order (constant rate), now understood to be dose-dependent first-order kinetics.
Rate of metabolism depends on: Drinking experience, sex, genetics, age, food intake.
Neurotransmitter Affected By Alcohol
GABA: Enhances inhibition → Relaxation, sedation.
Glutamate: Suppresses excitation → Cognitive impairment.
Dopamine: Increases reward → Euphoria, craving.
Opioids: Enhances pleasure and reinforcement.
Long-Term Changes of Alcohol
Chronic alcohol use increases glutamate sensitivity and reduces dopamine receptors, contributing to tolerance and dependence.
Positive and Negative Effects of Alcohol
Positive Effects: Mood improvement, stress relief (at low doses).
Negative Effects: Disinhibition, memory impairment, reduced motor coordination, slower reaction times, poor decision-making.
Stages of Intoxication
Initial Euphoria: Talkativeness, excitement.
Increasing BAC: Poor cognition, sensory dulling.
High BAC: Blackouts, stupor, nausea, alcohol poisoning.
Lethal Risk: Respiratory failure (e.g., Amy Winehouse case).
Short Term Health Impacts of Alcohol
Accidents, alcohol poisoning, impaired driving.
Long Term Health Impacts of Alcohol
Liver Damage: Fatty liver → Cirrhosis (50% of alcohol-related deaths).
Nervous System Disorders: Korsakoff’s syndrome, epilepsy, dementia.
Cancer: Alcohol is genotoxic (e.g., linked to breast cancer).
Reproductive Health: Impotence (males), menstrual disruption (females).
Fetal Alcohol Spectrum Disorder (FASD): Severe developmental issues.
Alcoholism as a Disease
DSM-5 Diagnosis: Alcohol Use Disorder (AUD).
Genetic Factors: ADH/ALDH enzyme variations.
Tolerance: Metabolic, pharmacodynamic, behavioral.
Withdrawal: Minor (early) to severe (late-stage) symptoms.
Types of Alcoholism
Type I: Late onset, environmental stressors, psychological risk.
Type II: Early onset, high genetic risk, impulsivity.
Treatment of Alcoholism
Behavioral Therapy: Support groups (e.g., Alcoholics Anonymous).
Medications:
Acamprosate: Reduces cravings.
Disulfiram: Induces unpleasant effects when drinking.
Naltrexone: Reduces the pleasurable effects of alcohol.
Natural Opioids
Derived from the opium poppy (limited production window of ~10 days per year).
Morphine: Most abundant, used in pain management.
Codeine: Isolated in 1821, now derived from morphine.
Thebaine: Used to synthesize oxycodone and other opioids.
Hydrocodone: Most commonly prescribed opioid in the U.S.
Synthetic & Semi-Synthetic Opioidsc
Heroin: Semisynthetic derivative of morphine.
Meperidine & Fentanyl: Fully synthetic, potent opioid receptor stimulants (fentanyl is 30–50x more potent than heroin).
Designer Drugs: MPPP, China white, and krokodil have serious side effects.
History of Opium Use
Used since ancient Sumerians (called the “joy plant”).
Spread from the Mediterranean to the Middle East, Africa, and Asia.
1600s: Widespread addiction in Britain, leading to the 1868 Pharmacy Act.
U.S.: Morphine was the dominant opioid; heroin was invented in 1898 by Heinrich Dreser for Bayer and marketed as a non-addictive pain reliever. Banned in the U.S. in 1924.
Routes of Administration for Opiods
Oral: Common for prescription opioids but less effective.
Inhalation: “Chasing the dragon” (heroin use).
Injection: Rapid onset, high abuse potential.
Transdermal & Nasal: Used for medical and recreational purposes.
Pharmacokinetics of Opioids
Absorption & Distribution:
Readily cross the Blood-Brain Barrier (BBB), except morphine (low lipid solubility).
Concentrate in the brain, lungs, kidneys, and liver.
Metabolism & Elimination:
Liver metabolism: Two phases involving cytochrome P450 enzymes.
Genetic differences and substances (e.g., St. John’s wort) can affect metabolism.
Pharmacodynamics of Opioids
Opioid receptors (identified in the 1970s) are activated by endogenous neuropeptides (endorphins, enkephalins, dynorphins).
Classical receptors: Mu (µ), Kappa (κ), Delta (δ).
Non-classical: Opioid receptor-like 1 (ORL-1).
Opioid receptor agonists inhibit neuron activity via G-protein-coupled mechanisms.
Opioid Receptor Action
Pure Agonists: Fully activate µ receptors (e.g., morphine, fentanyl).
Partial Agonists: Partially activate µ receptors (e.g., buprenorphine).
Pure Antagonists: Block µ receptors (e.g., naloxone, naltrexone).
Mixed Agonist-Antagonists: Act as agonists on some receptors while blocking others (e.g., pentazocine).
Principal Effects of Opioids
Analgesia (Pain Relief):
Reduce nociceptor excitability.
Bind to µ, δ, and κ receptors in pain-transmitting regions.
Reward System & Addiction:
Opioids increase dopamine release in the brain’s reward pathways.
Dynorphin activation may counteract reward, increasing κ-receptor binding.
Opioids Effects on Animals
Self-administration: Animals readily self-administer opioids.
Discriminative Stimulus Properties: Rats differentiate opioids quickly; tolerance develops in 1–3 days.
Conditioned Place Preference (CPP): Rats prefer locations where they received heroin, demonstrating its reinforcing effects.
Opioids Effects on Humans
Euphoria: Common in experienced users.
Cognitive & Performance Effects: Sedation, low attention, impaired memory.
Mood Changes: Positive moods followed by negative ones.
Abuse Liability: Opioids have high addiction potential.
Epidemiology (Trends) in Opioids
Global use: 0.7% of adults.
U.S. use: 3.8% of adults; increasing heroin use.
Teen use: ~10% of high school seniors and college students report prescription opioid use.
Acute Lethal Effects of Opioids
Respiratory depression, seizures, overdose risk (higher when combined with other depressants like alcohol).
Chronic Effects of Opioids
Financial burden, malnutrition, infections from intravenous use.
Hyperalgesia: Increased sensitivity to pain due to long-term opioid use.
Years of Potential Life Lost (YPLL)
Measurement of premature death impact due to opioid overdose.
What is Opioid Dependence and Overdose
Tolerance: Rapid development, requiring increasing doses.
Withdrawal: Flu-like symptoms, agitation, cravings.
Overdose Symptoms: Weak pulse, bluish skin, severe respiratory depression.
Medication Treatment Options for Addiction and Withdrawal Opioids
Methadone: Long-acting, prevents withdrawal, blocks euphoric effects.
Buprenorphine: Partial agonist, lower overdose risk.
Naltrexone/Naloxone: Antagonists that block opioid effects.
Detoxification:
Abrupt detox: Sudden discontinuation.
Maintenance therapy: Transitioning to long-acting opioid substitutes.
History of Cannabis
Originated in Central Asia and spread globally.
Used in ancient Egypt, China, and India for medicinal purposes.
1839: William O’Shaughnessy found cannabis helpful for convulsions, pain, and appetite stimulation.
1913: U.S. criminalized it → later classified as a Schedule I drug.
Now, there’s a slow move toward legalization for medical and recreational use.
Cannabinoids (Active Compounds in Cannabis)
Phytocannabinoids (Plant-based):
Δ9-THC: Causes psychoactive effects (euphoria, appetite stimulation).
CBD: Not psychoactive, but has medical benefits.
Endocannabinoids (Body-produced):
Anandamide & 2-AG → Activate CB1 & CB2 receptors in the brain & body.
Pharmacokinetics of Cannabis
Absorption & Duration:
Inhalation (faster) vs. Oral (slower, longer effects).
THC accumulates in fat stores, leading to prolonged effects.
Receptors:
CB1 (Brain): Affects mood, memory, movement.
CB2 (Body): Modulates pain & inflammation.
Physiological & Behavioral Short Effects of Cannabis
Euphoria, relaxation, altered time perception, possible paranoia.
Physiological & Behavioral Long Effects Cannabis
Memory issues, reduced motivation, possible withdrawal.
Mecical Uses of Cannabis
Treats pain, nausea (chemo), epilepsy, appetite loss (HIV/AIDS).
Harmful Effects of Cannabis
Respiratory risks (smoke toxins, mixed cancer evidence).
“Amotivational syndrome” (reduced drive, especially in adolescents).
Increased ER visits since legalization.
Hallucinogens Effects
Alter thought, perception, and mood without addiction risk.
Hallucinogens Types
Indolamines (serotonin-like): LSD, mushrooms.
Phenethylamines (dopamine/norepinephrine-like): MDMA, mescaline.
Mechanism and Risk of Hallucinogens
Mechanism: Act on serotonin receptors in the brain.
Risks: Bad trips, panic attacks, flashbacks.
MDMA History
Synthesized in 1914, later banned in 1985 but popular in raves.
Effects and Risk of MDMA
Emotional: Euphoria, bonding, trust (oxytocin release).
Physical: Increased body temperature, dehydration, hyperthermia risk.
Neurotoxic: Damages dopamine & serotonin systems, linked to Parkinson’s.
Overdose risk: Due to overheating & electrolyte imbalance.
Dissociative Anesthetics Effects and Risks (PCP & Ketamine)
Dissociation:
Feeling detached from body/reality.
Memory issues, psychosis at high doses.
Tolerance & withdrawal:
Lethal in high doses.
Dangerous for pregnant women.
Depression
A common mental disorder affecting emotions, cognitions, and behaviour
Symptoms range from lethargy to sadness and despair
Monoamine Hypothesis
Linked to reduced serotonin, norepinephrine, and dopamine
Glucocorticoid Theory
HPA-axis dysfunction and cortisol influence dopamine systems changes
DSM-5 Criteria for Major Depressive Disorder
At least 5 symptoms present for 2+ weeks, including either :
Depressed mood
Loss of interest/pleasure
Other symptoms
appetite/ weight changes, sleep disturbances, fatigue, feelings of worthlessness, suicidal thoughts, etc
Must cause significant distress/impairment and not be due to another condition
First Generation Antidepressants
Monoamine Oxidase Inhibitors (MAOIs): Block MAO enzyme, increasing monoamine levels
Tricyclic antidepressants (TCAs): Inhibit serotonin and norephrine reuptake
Second Generation Antidepressants
Selective Serotonin Reuptake Inhibitors (SSRIs) (e.g., Prozac): Increase serotonin availability
Third-Generation Antidepressants
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): Affects both serotonin and norepinephrine
Pharmacokinetics of Antidepressants
Readily absorbed, cross blood-brain barrier
Metabolized in the liver; TCAs interact significantly with alcohol
Variable half-lives, genetic factors influence drug longevity
Pharmacodynamics of Antidepressants
MAOIs: Block monoamine oxidase to increase monoamine levels
TCAs: Block reuptake transporters for serotonin and norepinephrine
SSRIs/SNRIs: Reduce serotonin/norepinephrine reuptake.
Effects & Side Effects of Antidepressants
No euphoric effects; not commonly abused.
Impact personality, sleep, and performance.
Risks: Increased suicidality, withdrawal symptoms.
Anxiolytics & Sedative Hypnotics
Used for anxiety disorders (e.g., GAD, PTSD, OCD).
Work primarily through GABA-A receptor modulation.
Types of Sedative Hypnotics
Barbiturates: High dependency risks, replaced by safer alternatives.
Benzodiazepines: Lower risk than barbiturates but still addictive.
Non-Benzodiazepines (Z-Drugs): Used primarily for sleep disorders.
Pharmacokinetics of Sedative Hypnotics
Absorbed differently based on lipid solubility.
Highly lipid-soluble substances cross the blood-brain barrier quickly.
Half-life varies significantly between drugs.
Pharmacodynamics of Sedative Hypnotics
Binds to the GABA-A receptor and changes the receptor response to stimuli.
It enhances the inhibitory effects of GABA, reduces anxiety, and promotes sleep.
Effects & Risks of Sedative Hypnotics
Affect sleep (reduce REM, withdrawal leads to rebound insomnia).
Can cause memory impairment (especially with alcohol).
Risk of dependency and withdrawal symptoms.
Overdose potential, especially with alcohol.
Alcohol Withdrawal Syndrome (Causes, Treatments and Symptoms)
Caused by the adaptation of the GABA-Glutamate system.
Symptoms: Tremors, muscle weakness, tachycardia, appetite loss.
Treatment: Benzodiazepines can be administered to reduce withdrawal severity.
Psychotic Disorders
A group of severe mental illnesses affecting thought, emotion, and behavior.
Symptoms include loss of contact with reality, hallucinations, and delusions.
Common Types of Psychotic Disorders
Schizophrenia: Long-term disorder with hallucinations, delusions, and behavioral changes.
Schizoaffective Disorder: Features both schizophrenia and mood disorder symptoms.
Others: Schizophreniform disorder, delusional disorder, substance-induced psychosis.
Schizophrenia Contributions and Trends
Affects ~1% of the population.
Genetic and environmental factors contribute.
Schizophrenia Positive and Negative Symptoms
Positive Symptoms: Hallucinations, delusions, disorganized speech.
Negative Symptoms: Lack of affect, reduced speech, social withdrawal.
Neurological Differences of Schizophrenia
Enlarged lateral and third ventricles.
Decreased tissue volume and excessive synaptic pruning.
Impacts multiple areas of the brain such as Frontal lobe, Limbic system, Hippocampus ect.
Dopamine Hypothesis of Schizophrenia
Excessive dopamine in the limbic system causes positive symptoms.
D1 receptor dysfunction in the prefrontal cortex contributes to negative symptoms.
Issues: Delayed medication effects, variability in drug responses.
Glutamate Hypothesis of Schizophrenia
NMDA receptor dysfunction contributes to symptoms.
Overactive excitatory response in early life may lead to schizophrenia.
Issues: Blocking NMDA has other severe neurological consequences.
Other Theories of Schizophrenia
Involvement of serotonin, GABA, acetylcholine, and histamine.
Schizophrenia likely results from multiple neurotransmitter imbalances.
Early Treatments of Antipsychotic Drugs
Malaria-induced fever therapy for neurosyphilis.
Insulin-shock therapy and electroconvulsive therapy.
Frontal lobotomies were common before antipsychotics.
Discovery of Antipsychotics
Henri Laborit found chlorpromazine effective in calming agitated patients.
Led to widespread use in psychiatric hospitals, reducing restraints and convulsive therapy.
Antipsychotic Medications
Reduce psychotic symptoms by affecting dopamine and serotonin signaling.
Taken orally, slowly metabolized, and excreted.
High therapeutic index, but low compliance due to side effects.
Typical (First-Generation) Antipsychotics
Developed before 1975, primarily block D2 receptors.
Highly effective but cause severe side effects (e.g., Parkinsonian symptoms, tardive dyskinesia).
Delayed treatment effects suggest complex mechanisms.
Atypical (Second-Generation) Antipsychotics
Bind less strongly to D2 receptors; also affect 5-HT receptors (especially 5-HT2A).
Fewer motor side effects but still cause weight gain and metabolic changes.
Motor Effects of Antipsychotics
Parkinsonian symptoms, tremors, muscle rigidity.
Cognitive & Emotional Effects of Antipsychotics
Self-doubt, emotional numbing, sedation.
Some users report impaired cognition and performance.
Physical Effects of Antipsychotics
Sleep disturbances, weight gain, temperature regulation issues.
Males: Reduced sexual interest
Females: Menstrual irregularities.
Long-Term Use of Antipsychotics
Tolerance is minimal; withdrawal is rare due to slow drug release.
Patients often stop taking medication, leading to relapse.
No clear evidence that atypical antipsychotics are superior to typical ones.
Non-Psychotic Uses of Antipsychotics
Prescribed for dementia, anxiety, hyperactivity, agitation, depression, and Tourette’s.
Raises concerns about overuse, especially in non-psychotic conditions.
Use in Developmental Disorders of Antipsychotics
Commonly prescribed for “difficult behaviors” even without psychiatric diagnoses.
Ethical concerns over sedation for ease of caregiving rather than treatment.
Use in Dementia Patients of Antipsychotics
Controversial due to increased risk of death from cardiovascular issues.
Some argue use is justified in palliative care to reduce distress.
