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Transcript
THE NEUROSCIENCE OF DRUG ABUSE Presented by Jon Ptachcinski, Samantha Allen, and Melissa Ruminski Basics of Drug Action • • Many drugs work by either activating a neuron within a pathway (excitatory or agonists) or blocking spaces that would ordinarily be available for neurotransmitters (inhibitory or antagonists) Molecular shape mimics chemicals present in your nervous system – Ex. LSD mimics serotonin Tolerance and Addiction What is tolerance to a drug? Tolerance is an increase in the dose of a drug (legal or illegal) in order to achieve the same effect Metabolic or homeostatic Can lead to tolerance-based addiction Tolerance and Addiction Psychological Addiction User gets “hooked” on the effects of the drug Ex. “Being drunk makes me stop worrying about my schoolwork” Ex. “I’m much more effective solving complex problems when I’ve taken acid” Can lead to anxiety, depression, mood swings, failed attempts to quit Physical Addiction User becomes physically dependent on the presence of the drug itself Drug is needed to maintain functioning of their nervous system Removal of the drug leads to withdrawal (effects opposite of the drug) Shakes/tremors Irritability Insomnia ABUSE OF OTC MEDICATIONS Trends in Teen OTC Abuse 10% of teens have abused cough/cold medications 1 in 4 teens know someone that abuses cough/cold medications Most common age 13-16yo Treatment admissions linked to OTC abuse increased >30% from 1993-2003 Most Commonly Abused OTC’s Cough/cold medications Dextromethorphan (DXM): Robitussin Pseudoephedrine (Sudafed) methamphetamine Pain relievers Aspirin NSAIDs (Ibuprofen): Motrin Acetaminophen: Tylenol Motion Sickness pills Dramamine Diet pills/laxatives Sexual performance pills Why Abuse OTC’s? Believed to be safer Easily accessible Cheap Believe additional doses will produce additive effects Dextromethorphan Synthetic cough suppressant compound chemically similar to morphine At high doses, converted to dextrophan (similar to ketamine and PCP) Max dose 120mg/day Abusers consume 360mg or more 100-200mg = mild stimulation 200-400mg = intoxication phase 300-600mg = “out of body” experience 600-1500mg = full dissociate phase Dextromethorphan Side Effects Hallucinations Loss of motor control Impaired judgement Blurred vision Brain damage Cardiac dysrhythmia Pseudoephedrine Used as a decongestant Purchased in large quantities for conversion to methamphetamine Law prohibits the purchase of more than 9g per month Amphetamine side effects Acute Euphoria, increased energy/attentiveness, sweating, loss of appetite, insomnia, agitation, compulsiveness, irritability, DNV Chronic Craving/addiction, weight loss, tooth decay, withdrawalrelated depression Overdose Brain damage, sensation of bugs crawling on skin, rhabdomyolysis, stroke, heart failure, cardiac arrest, hyperthermia NSAIDs (ibuprofen or Motrin) Ibuprofen max dose = 1200mg or 6 tablets Similar signs/symptoms compared to aspirin Less life threatening, typically requiring a massive overdose to be fatal Acetaminophen (Tylenol) Commonly found in many prescription pain medications (vicodin, percocet, darvocet) Max dose = 4000mg/day Acetaminophen is the most common cause of acute liver failure and the leading reason for liver transplants Signs/symptoms of Acetaminophen Overdose May not be present for 24 hours Nausea, vomiting, and sweating at first, followed by a symptom-free period Acute liver failure may take up to 5 days to fully develop Symptoms include hepatic encephalopathy, coma, hypoglycemia, coagulopathy, cerebral edema, acidemia Antidote available but must be administered early Many patients require transplant Mechanism of toxicity: Metabolized in the liver to a reactive intermediate molecule (NAPQI) Normally neutralized by a sulfyhydryl compound in liver (glutathione) Glutathione depletion during overdose, so reactive NAPQI is available to react with sulfyhydrl compounds in cytsol, cell wall, and endoplasmic reticulum liver cell (hepatocyte) destruction Dramamine Max dose 400mg/day Acts as a hallucinogenic and deliriant at doses of 7501200mg Auditory/visual hallucinations Confusion/short term memory loss Coupled lead to paranoia Extreme overdoses lead to tachycardia, heart palpitations, and potentially fatal dysrhythmias Diet pills/laxatives Used to facilitate weight loss Diet pill abuse can cause insomnia, high blood pressure, anxiety, and heart complications Laxative abuse is more common and can cause dehydration, electrolyte imbalance, metabolic acidosis, and physical damage to the GI tract. Laxative abuse is more likely to be fatal Sexual Performance Pills Often used to counteract the effects of alcohol on sexual performance Usually have function related to amphetamines and act as stimulants Can cause potentially fatal cardiac problems in combination with alcohol Key points Don’t recreationally abuse OTC drugs! Follow the directions on all OTC medications! Know what’s in your medications, many are combination products 1-800-222-1222 ABUSE OF PRESCRIPTION MEDICATIONS Trends in Prescription Drug Abuse prescription drugs are the most commonly abused drugs by teens nearly all deaths due to poison in US from 19992004 result from abuse of prescription and illegal drugs nearly 1/5 teens (19% or 4.5 million) report abusing prescription meds Why Abuse Prescription Medications relief of pain/anxiety belief that these drugs are medically safe sleep improvement experimentation help with concentration or alertness easy to obtain Most Commonly Abused Prescription Drugs Opioids CNS Depressants Stimulants Opioids examples: Vicodin (hydrocodone/acetaminophen) Tylenol #3 (acetaminophen with codeine) Oxycontin (oxycodone) Dilaudid (hydromorphone) Kadian (morphine) Opioids Mechanism of action: Mimic the action of endogenous peptides (opiopeptins like enkephalin) Bind at opioid receptors (m, k, d, s, e) in brain loci Effects pain transmission at afferent and spinal cord neurons pain modulation in midbrain and medullary neurons pain reactivity at basal ganglia, hypothalmic, limbic structures, and cerebral cortex neurons Opiods Opioids Therapeutic use Narcotic analgesia Cough suppressant Illicit use Euphoria Dysphoria Apathy/confusion Sedation Attention impairment Adverse effects of opioid abuse Effects of intoxication Respiratory depression Nausea/vomiting Flushing of skin Altered release of hormones Slurred speech Motor retardation Decreased blood pressure when standing Constipation/urinary retention Miosis Withdrawal symptoms Restlessness Trembling Rapid heart rate Sweating Hyperthermia/fever Difficulty breathing Pupil dilation Chills (“goosebumps”) Yawning Runny nose/sneezing Anorexia Muscle pain/cramps Kicking movements CNS Depressants Examples: Barbituates Phenobarbital Amytal Benzodiazepines Xanax (alprazolam) Valium (diazepam) Ativan (lorazepam) Klonipin (clonazepam) CNS Depressants Mechanism of action: Enhance the activity of inhibitory neurotransmitter GABA Slow impulses throughout the body and inhibit motor neurons Effects: Anti-anxiety Sedation CNS Depressants Therapeutic use: Anxiety Sedation Muscle spasms Sleep problems Illicit use: Reduce anxiety Lower amount of alcohol required to become intoxicated Adverse effects of CNS Depressants Effects of intoxication Memory impairment Drowsiness Visual disturbances Confusion Intoxicated appearance Low blood pressure Urinary retention Involuntary eye movements Difficulty breathing Effects of withdrawal Seizures Hallucinations Stimulants Examples: Adderall (amphetamine) Ritalin (methylphenidate) Vyvanse (dislexamfetamine Stimulants Mechanism of action: Increase activity of neurotransmitters (norepinephrine and dopamine) by blocking reuptake, increasing release or inhibiting degrdation Effects: Decrease fatigue Increase alertness Suppress appetite Stimulants Therapeutic use: Illicit use: ADHD Euphoria/mood Narcolepsy enhancement Increased wakefulness Increased physical activity Decreased appetite Depression Adverse Effects of Stimulant Use Effects of intoxication Increased breathing rate Irritability Insomnia Confusion Tremors Anxiety Paranoia Chest pain Aggressiveness Hyperthermia Convulsions Effects of withdrawal Depression Altered mental status Drug craving Fatigue Sleep disorders related to sleeplessness What is Cocaine? Cocaine a stimulant that can be snorted (powder) or smoked (crack) made by drying the leaves of a small tree indigenous to the Andes Mountains in South America to be used, the active compound must 1st be isolated from the leaves in a multi-step chemical reaction Cocaine Powder Crack Cocaine Uses of Cocaine There are 2 main uses for cocaine: Therapeutic: a local anesthetic prior to procedures of the mouth, throat and nose MOA: blocking the conduction of action potentials down the nerves of the peripheral nervous system Without these nerve impulses, the body cannot deliver the message that it is experiencing pain Illicit: a central nervous system (CNS) stimulant resulting in an initial feeling of well-being and euphoria This occurs by blocking the reuptake of several neurotransmitters including serotonin, norepinephrine and dopamine Later on, it will lead to restlessness and motor activity and several other health problems due to overstimulation of nerves Effects on Health CNS Effects At first, stimulates the vomiting center in the brain This is followed by: Respiratory depression leading to respiratory failure Depression of activity in the medulla Large doses can lead to death Also causes an increase in body temperature by effecting the heat-regulating centers of the brain “Cocaine fever” Effects on Health, cont. Cardiovascular Effects Cocaine causes constriction of the blood vessels, increased heart rate and an acute increase in blood pressure This leads to an increased risk for stroke, seizures and heart attacks In the latter stages of the dose, blood pressure falls and death could occur A large IV dose may cause immediate death due to its toxic effects on heart muscle Cocaine Abuse Euphoria is more rapid and intense with smoking “crack” due to its direct path to the brain and users will smoke every 30 minutes to try to maintain this euphoria Monkeys consistently treated with cocaine will ALWAYS choose cocaine over food, for up to 8 days Cocaine produces the highest degree of psychic dependence among all recreational drugs Abruptly stopping after chronic use leads to profound withdrawal symptoms Cocaine Toxic Syndrome Overuse can lead to hallucinations (visual, auditory and tactile) including cocaine “bugs” When using, nasal blood vessels constrict making breathing easier but after effects are finished, the vessels dilate causing a stuffy nose and bleeding Use can lead to states of panic and paranoia What is Marijuana? Marijuana comes from the dried flowering tops of the Cannabis sativa plant The plant is cultivated for its fibers (hemp) and fruit (hempseed) The flowering tops contain molecules called “cannabinoids” which produce the pharmacologic effect associated with smoking marijuana CH3 9 8 7 10 OH 10a 1 2 6a H3C H3C 6 3 O 5 4 9 CH3 -trans-TETRAHYDROCANNABINOL 9 -THC (DRONABINOL) THC is the cannabinoid with major euphoric properties Clinical Uses Antiemetic Used to treat nausea and vomiting associated with chemotherapy in those who don’t experience relief with medication Appetite stimulant Used in AIDS patients who are experiencing anorexia/weight loss Illicit Use People use marijuana because it can elevate mood (euphoria) and cause relaxation and sleepiness It can also lead to spontaneous laughter Side Effects of Marijuana Use CNS Effects Short-term memory impairment and inability to perform tasks the require several mental steps Altered time perception Psychotoxic at high dosages Confusion between past, present and future Hallucinations, paranoia, increased time distortions Chronic users can suffer from amotivational syndrome Side Effects, cont. Cardiovascular Effects Increases heart rate Decreases blood pressure when standing Respiratory Effects Acute use causes bronchodilation Chronic use leads to: Bronchitis, asthma Tar from smoking is more carcinogenic than tobacco tar Causes reddening of the eyes Side Effects, cont. Causes decreased intraocular pressure Used for glaucoma Can cause decreased testosterone levels and reduced sperm formation in males If smoked during pregnancy, it can lead to low birth weight, longer labors and increased risk for infant malformations Studies in animals have shown decreased immune response, but correlation to humans is still unknown Long-term effects These side effects can last much longer than the “high” THC is not eliminated from the body right away because it is stored in fat tissue and is therefore not available for the body to remove from the bloodstream This can affect motor skills necessary for driving Questions?