DRUG ABUSE Self administration of drug or drugs

DRUG ABUSE Self administration of drug or drugs in manner not in accord with accepted medical or social patterns

Drug Abuse Psychological Dependenc (Habituation) addiction. Drug necessary to maintain user’s sense of wellbeing Physical Dependence, dependence Physical symptoms if intake is reduced

Addiction Compulsive, relapsing drug use despite negative consequences, at times triggered by cravings. Includes Tolerance (dose has to be progressively increased to maintain rewarding or analgesic effect) Psychological dependence Physical dependence Compulsive use

Molecular Mechanism of Action Mesolinbic dopamine system is the prime target of addictive drugs. The system originates in the ventral tegmental area (VTA). Drug of abuse are rewarding and reinforcing.

Classification of drugs of abuse Ø Drugs that activate G Protein-Coupled Receptors Opioids Cannabinoids γ-hydroxybutyric acid (GHB) LSD, mescaline Ø Drugs that bind to ionotropic receptors and ion channels Nicotine Alcohol Benzodiazepines Phencyclidine, ketamine

Drugs that bind to transporters of Biogenic Amines Cocaine Amphetamine Ectasy Ø

OPIATES ¹Opiates are drugs that are derived from the Poppy Plant and are Central Nervous System (CNS) depressants. ¹The most common opiates are: ØOpium ØHeroin ØMorphine ØCodeine ¹Opiates are known by several different names: N Smack N Soapium N Chiva N Poppy N Flower N Hazel N Morf NH

Narcotics Examples Opium Morphine Heroin Codeine Oxycodone (Percodan) Meperidine (Demerol) Propoxyphene (Darvon) Talwin Fentanyl

Mechanism of Action Acts on μ, κ and delta opioid receptors

Effects Analgesia CNS depression Euphoria Drowsiness Apathy Antidiarrheal action Antitussitive action

åAbsence of Stress åAltered Mental Process åLiver Damage åNausea/Vomiting åCollapsed Veins åKidney Damage åSleepiness åLung Damage åConstipation åBrain Damage åItchy Skin åMenstrual Irregularities åImmune System Damage åImpaired Vision åLoss of Sex Drive åOverdose/Death

Narcotics Overdose Mild to Moderate Lethargy Pinpoint pupils Bradycardia Hypotension Decreased bowel sounds Flaccid muscles u Severe F Respiratory depression F Coma F Aspiration F Seizures with certain compounds (meperidine, propoxyphene, tramadol)

Narcotics Overdose Management Naloxone Treatment of opioid addiction Long acting opioids

Narcotics Withdrawal Insomnia Restlessness Irritability Anorexia Tremors Back, extremity pain Watery eyes Yawning Rhinorrhea Sneezing Diarrhea Diaphoresis Resembles Severe Influenza

Cannabinoids Marijuana (Tetrahydrocannabinol (THC) Endogenous cannabinoids (Anandamide) Act on CB 1 receptors, presynaptically and inhibit the release of glutammate or GABA Leading to disinhibition of dopamine neurons. Onset of effects: within minutes Effects: Euphoria, relaxation, visual distortions, drowsiness, diminished coordination and memory impairment.

Hallucinogens LSD Mescaline Psilocybin

Produce altered/enhanced sensation Increased dose does not intensify effect Mechanism of action Act on 5 HT 2 A receptor------G proteins -----IP 3 ---intracellular calcium---- increase glutamate release.

Signs and symptoms Anxiety, excitement Nausea, vomiting Tachycardia, tachypnea

Hallucinogens Moderate Intoxication Tachycardia Mydriasis Diaphoresis Short attention span Tremor Hypertension Hyperreflexia Fever

Hallucinogens Life-threatening toxicity (rare) Seizures Severe hyperthermia Hypertension, arrhythmias Agitated Diaphoretic, hyperreflexic Untreated hyperthermia can lead to hypotension, coagulopathy, rhabdomyolysis and multiple organ failure

Drugs that mediate their effects via ionotropic receptors Ø Ø Nicotine Smoking of tobacco through different routes. Agonist of nicotinic acetylcholine receptor (n. ACh. R), role in cognitive processes. Rewarding effect of nicotine requires involvement of VTA in which (n. ACh. R) are expressed on dopamine neurons. Nicotine withdrawal : irritability, sleep problems.

Treatment Slowly absorbable form of nicotine. Cytisine, varenicline (partial agonists) Act by occupying n. ACh. Rs on dopamine neurons of the VTA. Bupropion + behavioural therapy

Benzodiazepines and barbiturates Anxiolytic and sleep medications Abused for their EUPHORIC effects GABAA receptors on interneurons, disinhibition of mesolimbic dopamine system-----rewarding effects. Withdrawal symptoms include Irritability, insomnia, photophobia, depression, muscle cramps and even seizures.

Ketamine and Phencyclidine General anesthetic Non-competitive antagonism of NMDA receptor. Increased blood pressure, impaired memory function & visual alterations. ‘Club drugs’ and sold as ‘angel dust’

Phencyclidine (PCP) Street names Angel dust Peace Pill Hog Krystal Animal tranquilizer Used as veterinary anesthetic

Inhalants Examples Nitrates , ketones , aliphatic and aromatic hydrocarbons Gases (freon, halon fire extinguishing agent) Metallic paints Sniffing Huffing Bagging

Drugs that bind to transporters of biogenic amines Examples Cocaine Amphetamines Benzedrine (bennies) Dexedrine (dexies, copilots) Methamphetamine (ice, black beauties) Ephedrine Caffeine Ritalin

Cocaine local anesthetic used to treat depression Block of dopamine transporter, by increasing conc in nucleus accumbens Increased risk of intracranial haemorrhage, ischemic stroke, myocardial infarction and seizures.

Amphetamines Produce euphoria hyperactivity alertness sense of enhanced energy anorexia

Stimulants Overdose signs/symptoms Euphoria, restlessness, agitation, anxiety Paranoia, irritability, delirium, psychosis Muscle tremors, rigidity Seizures, coma Nausea, vomiting, chills, sweating, headache Elevated body temperature Tachycardia, hypertension Ventricular arrhythmias

Stimulants Withdrawal Drowsiness Profound depression (“cocaine blues”) Increased appetite Abdominal cramps, diarrhea, nausea Headache

Ectasy Include derivatives of amphetamine related compound methylene-dioxymethaamphetamine (MDMA) Increases extracellular concentration of serotinin Long term cognitive impairement in heavy users of MDMA. Withdrawal lead to depression

Treatment of addiction Transdermal nicotine patches for smoking Baclofen is a GABAB receptor agonist Rimonabant is inverse agonist of CB 1 receptors