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

 Psychological Dependenc (Habituation) addiction.  Drug necessary to maintain user’s sense of well- being  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

 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.

 Drugs that activate G Protein-Coupled Receptors Opioids Cannabinoids γ -hydroxybutyric acid (GHB) LSD, mescaline  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

OPIATES  Opiates are drugs that are derived from the Poppy Plant and are Central Nervous System (CNS) depressants.  The most common opiates are:  Opium  Heroin  Morphine  Codeine  Opiates are known by several different names:  Smack  Chiva  Morf  H H H H  H H H H  Soapium  Flower  Poppy  Hazel

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

 Acts on μ, κ and delta opioid receptors

 Effects  Analgesia  CNS depression  Euphoria  Drowsiness  Apathy  Antidiarrheal action  Antitussitive action

 Nausea/Vomiting  Constipation  Itchy Skin  Sleepiness  Loss of Sex Drive  Altered Mental Process  Absence of Stress  Overdose/Death  Impaired Vision  Collapsed Veins  Menstrual Irregularities  Liver Damage  Kidney Damage  Lung Damage  Brain Damage  Immune System Damage

 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)

 Overdose  Management  Naloxone  Treatment of opioid addiction  Long acting opioids

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

 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.

 LSD  Mescaline  Psilocybin

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

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

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

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

 Nicotine  Smoking of tobacco through different routes.  Agonist of nicotinic acetylcholine receptor (nAChR),role in cognitive processes.  Rewarding effect of nicotine requires involvement of VTA in which (nAChR) are expressed on dopamine neurons.  Nicotine withdrawal : irritability, sleep problems.

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

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

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

 Street names  Angel dust  Peace Pill  Hog  Krystal  Animal tranquilizer  Used as veterinary anesthetic

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

 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.

 Produce  euphoria  hyperactivity  alertness  sense of enhanced energy  anorexia

 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

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

 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

 Transdermal nicotine patches for smoking  Baclofen is a GABA B receptor agonist  Rimonabant is inverse agonist of CB 1 receptors