PH 179 Lecture 2: Drug Abuse and Public Health Concerns

PH 179 Lecture 2: Drug Abuse and Public Health Concerns

Overview of Lecture Content

  • Examination of various substances:

    • Alcohol (including methanol, diethylene glycol)

    • Magic mushroom

    • Fentanyl

    • Marijuana (cannabis)

Definition of Drug Abuse

  • Definition:

    • The harmful or excessive use of psychoactive substances, including:

    • Alcohol

    • Tobacco

    • Marijuana

    • Prescription drugs

    • Characteristics:

    • Causes significant impairment in health, social, or occupational functioning

    • Acts on the central nervous system (CNS, brain)

  • Distinction between legal and illegal drugs

Academic Reference

  • Gable, R. S. (2006). Acute toxicity of drugs versus regulatory status.

    • In J. M. Fish (Ed.), Drugs and Society: U.S. Public Policy, pp. 149-162

Alcohol Consumption Statistics

  • Gallons of ethanol consumed per person in the U.S. (Years: '77 to '21):

    • Increasing trend in ethanol consumption observed across various years.

    • Source: National Institute on Alcohol Abuse and Alcoholism

  • Underage Drinking Statistics from 2022:

    • Alcohol use by age group (in %):

    • 12-17 years: 61.2%

    • 18-20 years: 53.4%

    • 21-25 years: 36.3%

    • 26+ years: 31.6%

    • Survey conducted on 71,369 respondents aged 12 and older in the U.S.

Alcohol (Ethanol) – Effects and Toxicity

  • Temporary Effects (Acute Toxicity):

    • Relaxation and euphoria (CNS depressant)

    • Impaired coordination and balance

    • Slurred speech

    • Slowed reaction time

    • Potential for death due to excessive ingestion (CNS depression)

  • Delayed Effects (Chronic Toxicity):

    • Hangover and headache

    • Dependency and withdrawal symptoms (both physical and mental)

    • Gastrointestinal damage

    • Liver damage (cirrhosis)

    • Cancer (classified as an IARC group 1 carcinogen)

Mechanisms of Action of Ethanol

  • Acute Toxicity Mechanisms:

    • Activates inhibitory neurons

    • Inhibits excitatory neurons, leading to CNS depression

    • Ethanol's ability to penetrate the blood-brain barrier (BBB)

  • Metabolism of Ethanol (Chronic Toxicity):

    • Breakdown of Ethanol leading to toxic metabolites

Acetaldehyde Toxicity

  • Pathological Effects:

    • Acetaldehyde, a toxic metabolite, promotes DNA mutation via:

    • DNA adduct formation

    • Cross-linking with proteins, lipids, and DNA

    • Source: Jayakody and Jin (2021) Appl. Microbiol. Biotech.

  • Clinical Consequences of Alcohol Consumption and Liver Damage:

    • Formation of DNA adducts leading to:

    • Mutations

    • Loss of protein synthesis

    • Enzyme function failure

    • Membrane integrity loss

    • Tumor development

    • Necrosis

    • Major metabolism occurs in the liver

Stages of Alcohol-Induced Liver Damage

  • Health Stages:

    • Healthy liver

    • Fatty liver (reversible with abstinence)

    • Alcoholic hepatitis (partial reversibility)

    • Alcoholic cirrhosis (irreversible)

  • Alcohol Tolerance and Risk of Liver Damage:

    • Aldehyde dehydrogenase 2 (ALDH2) variants affect enzyme activity

    • Presence of one copy of ALDH2*2 results in slower alcohol metabolism

    • Presence of two copies leads to alcohol intolerance

Methanol and Diethylene Glycol Toxicity

  • Methanol (CH₃OH) Toxicity and Mechanism:

    • Leads to severe acidosis

    • Causes optic nerve damage resulting in blindness

  • Diethylene Glycol Toxicity Concerns:

    • Historical pediatric deaths due to contaminated cough syrup noted in multiple countries (2023-2025)

    • Clinical symptoms include:

    • Nausea and vomiting

    • Abdominal pain

    • Acute kidney failure (1-3 days post-ingestion)

    • Neurological symptoms like lethargy leading to coma

    • Treatment:

    • Preventing metabolism using Fomepizole (alcohol dehydrogenase inhibitor) and ethanol

    • Hemodialysis to remove DEG from the body

Public Health Concerns

  • Clinical Symptoms of DEG Toxicity:

    • Nausea, vomiting, abdominal pain, diarrhea

    • Following with acidosis, acute kidney failure

    • Neurological effects manifest late (<10 days)

  • Prognosis:

    • Dependent on ingestion amount, with possibility of lifelong dialysis for survivors

  • Historical Context of DEG Poisoning:

    • Notable incidents spanning decades (1937-2019) highlighting the persistent risk of DEG contamination in various products

Fentanyl and its Public Health Impact

  • Fentanyl (Synthetic Opioid):

    • Defined as a powerful synthetic opioid, 50-100x stronger than heroin and morphine

    • Estimated LD50 ≈ 0.03 mg/kg (2 mg for an adult)

    • Rapid onset and half-life of 2-4 hours

  • Effects and Clinical Symptoms:

    • Positive effects: relaxation, euphoria, sedation

    • Negative effects: drowsiness, dizziness, nausea, respiratory depression

  • Overdose Mechanism:

    • Causes respiratory failure leading to death

Mechanisms of Action and Neurotransmitter Effects

  • Neurotransmitters and Reward Circuitry:

    • Fentanyl affects the ventral tegmental area (VTA) increasing dopamine release leading to euphoria

  • Fentanyl Overdose Death Statistics:

    • Reported in the UK and the U.S., correlated with opioid prescription practices and shifts in drug availability

Marijuana (Cannabis) and its Public Health Concerns

  • Legal Status and Access:

    • Legal for recreational use in many states (e.g., California)

    • Access for individuals 21+ or with physician recommendations for medicinal use

  • Marijuana's Toxicity and Effects:

    • THC binds to cannabinoid receptors altering neurological functions impacting memory, learning, and heart rate

    • Associated health risks: anxiety, psychosis, cardiovascular problems

  • Long-Term Effects on Youth:

    • Heavy marijuana use linked to poor educational outcomes, decreased job satisfaction, potential for lifelong consequences

Summary of Drug Abuse Mechanisms

  • Alcohol: Activates GABA receptors and inhibits NMDA receptors, leading to CNS depression

  • Magic Mushrooms: Mimic serotonin and increase serotonin signalling, leading to altered states of perception and mood

  • Fentanyl and Opioids: Bind to opioid receptors leading to inhibition of respiratory function during overdose

  • Marijuana (THC/CBD): Binds to cannabinoid receptors altering neurotransmitter release and impacting various CNS functions

Ethical and Social Considerations

  • Personal and Community Implications:

    • Risks of progression towards more potent drug use

    • Public safety concerns relating to impaired state driving, legal issues, and community health costs

    • Potential for addiction and increased healthcare burdens

Conclusion

  • Drug abuse presents significant public health challenges through its mechanisms of action, societal impacts, and long-term health consequences.