Drugs of abuse & their Pharmacological aspect
- 1. Presented by : Dr. Tara Chand (JR2) Dr. Pulkit (JR1) Drugs of Abuse Moderator : Dr. Charu Jain Professor SMS Medical college, Jaipur
- 3. Good news is : And Drug abuse is a preventable behaviour Drug addiction is a treatable disease
- 10. llicit drugs include mar ij uana/hashish, cocaine (including crack), heroin, hallucinogens, inhalants, or prescription type psychotherapeutics used nonmedically
- 11. Relative potential for physical dependence of commonly abused substances
- 12. Case scenario A 35-year-old man with a history of cocaine abuse smokes crack cocaine and consumes alcohol at a party. Shortly afterward, he becomes agitated, anxious, and begins to exhibit rapid heart rate (tachycardia), high blood pressure (hypertension), and a high body temperature (hyperthermia). He also complains of chest pain. His behavior becomes increasingly erratic and alarming, prompting his friends to call emergency medical services.
- 13. 1. Cocaine : Routes of Administration: • Snorted (powder form – cocaine hydrochloride) • Injected (dissolved powder) • Smoked (crack cocaine – Alkaloid form, not destroyed by heat) • Oral: Poor bioavailability
- 14. Effects: • Euphoria (“rush”) followed by dysphoria (“crash”) • CNS stimulation: Agitation, hyperactivity, paranoia • Addictive potential: High Toxicity & Complications: • Neurologic: Seizures (due to CNS stimulation) • Cardiac: ◦ Chest pain (vasoconstriction, coronary spasm) ◦ Arrhythmias ◦ Infarction risk • Hyperthermia: Due to CNS Stimulation & vasoconstriction • Pulmonary damage (especially from smoked crack) • Immunosuppression: From adulterants like levamisole → agranulocytosis • Cocaethylene (formed when combined with alcohol): Cardiotoxic
- 15. Treatment of Toxicity: 1. Benzodiazepines (e.g., lorazepam): ◦ Calms agitation ◦ Prevents/controls seizures ◦ Reduces hyperthermia 2. Cooling measures: Manage hyperthermia 3. Short-acting antihypertensives: Control BP 4. Anticonvulsants: If seizures persist 5. Supportive care: Airway, breathing, hydration Addiction Potential: • High • Due to rapid "high" and subsequent crash → reinforcement cycle
- 16. Comparison with Cocaine • Similar Behavioral Effects: Both cause euphoria, increased alertness, and potential for addiction. • Different Mechanisms: ◦ Cocaine: Primarily blocks reuptake of neurotransmitters. ◦ Amphetamine: Primarily releases stored neurotransmitters and inhibits MAO. 2. Amphetamine :
- 17. • Amphetamines are primarily used to treat ADHD, narcolepsy, and as appetite suppressants for obesity. • Atomoxetine is an alternative for ADHD that isn’t addictive. • Modafinil and armodafinil are effective for narcolepsy with less potential for abuse compared to traditional stimulants. • Chronic use of these drugs can lead to dependence and tolerance, limiting their long-term effectiveness.
- 18. 3. MDMA : Class: Hallucinogenic amphetamine. Primary Effect: Profound serotonin release, leading to euphoria, empathy, and enhanced tactile sensation (popular at raves and clubs). Nickname: Often called an "empathogen" due to its emotional effects.
- 19. • Negative Effects: ◦ Dehydration and renal failure (early MDMA deaths). ◦ Water intoxication and hyponatremia from excessive water intake. ◦ Bruxism (teeth grinding) and jaw clenching (trismus), leading to use of pacifiers and lollipops. Dangerous Complications: • Serotonin Syndrome: ◦ Hyperthermia, altered mental status, and movement disorders. ◦ Can be life-threatening if untreated. Treatment of MDMA Toxicity: 1. Benzodiazepines: To calm and cool the patient. 2. Severe Hyperthermia: Treated with neuromuscular blockers and intubation. 3. Serotonin Syndrome: Managed with Cyproheptadine (oral serotonin antagonist, limited by oral availability).
- 20. 4. Synthetic Cathinones : Cathinone is the psychoactive component of Khat, an evergreen shrub native to East Africa and the Arabian Peninsula. Synthetic cathinones are artificially created analogs and are sold under various names, including “bath salts” or “pond water cleaner”. Synthetic cathinones are not easily detected on urine toxicology screens Examples of Synthetic Cathinones: • Methcathinone • Butylone • Methylene dioxypyrovalerone (MDPV) • Naphyrone Mechanism of Action: • Synthetic cathinones increase the release and inhibit the reuptake of catecholamines (dopamine, norepinephrine, epinephrine), similar to cocaine and amphetamines. Treatment is similar to the emergent treatment of amphetamines and cocaine.
- 21. LSD • Lysergic acid diethylamide • Mechanism of Action: LSD acts as a potent partial agonist at the 5-HT2A receptors , leading to Psychedelic effects. • This drug is also responsible for mood alterations , Loss of judgement and impaired reasoning sometimes associated with extreme panic , which is known as ‘Bad trip’ . •Physical side effects include : 1 Tachycardia 2 Hypertension. 3 Hyperthermia. 4 Loss of appetite
- 22. Marijuana • Cannabis plant ( Cannabis Sativa) • The main psychoactive alkaloid contained in marijuana is Δ9-tetrahydrocannabinol (THC) • Mechanism of action • THC binds to Cannabinoid receptors (CB1) in Brain. •Acute Pharmacological effects : When CB1 receptors are activated by marijuana, the effects produced include physical relaxation, hyperphagia (increased appetite), increased heart rate, decreased muscle coordination, conjunctivitis, and minor pain control
- 23. Marijuana • Marijuana stimulates the amygdala, causing the user to have a sense of novelty to anything the user encounters through an enhancement of sensory activity. For this reason, heavy users have a down-regulation in their CB1 receptors, leaving them with a feeling of boredom when not taking the drug. • The effects of marijuana on γ-aminobutyric acid (GABA) in the hippocampus diminish the capacity for short-term memory in users. • Dronabinol (THC) is approved by US FDA for HIV/AIDS Induced Anorexia and Chemotherapy induced nausea and vomiting ( not in India)
- 24. Ethanol • It is a major cause of fatal automobile accidents, drownings, and fatal falls and is a related factor in many hospital admissions.
- 25. Ethanol • Mechanism of Action : Ethanol exerts its effects by enhancing the effects of the inhibitory neurotransmitter GABA, inducing the release of endogenous opioids, and altering levels of serotonin and dopamine • Metabolism : In Liver . It is metabolized by zero-order elimination at approximately 15 to 40 mg/dL/h.
- 26. Ethanol • There is a constant blood-to-breath ratio of 2100:1, a breath sample can be used to determine blood alcohol concentrations (BAC) . Permissible BAC for Drink and Drive is 30mg/dl in India. • Management of Toxicity :Acute Ethanol Toxicity • Medical management of acute ethanol toxicity includes symptomatic supportive care and the administration of thiamine and folic acid to prevent/treat Wernicke encephalopathy and macrocytic anemia.
- 28. Ethanol • Drugs used in the treatment of alcohol dependence: • Disul f iram blocks the oxidation of acetaldehyde to acetic acid by inhibiting aldehyde dehydrogenase . This results in the accumulation of acetaldehyde in the blood, causing flushing, tachycardia, hyperventilation, and nausea. • Naltrexone is a long-acting opioid antagonist that should be used in conjunction with supportive psychotherapy. • Acamprosate is an agent used in alcohol dependence treatment programs with an as-yet poorly understood mechanism of action.
- 29. Prescriptiondrugabuse • Commonly abused prescription drugs include opioids, benzodiazepines, and barbiturates
- 30. Opioids : Acute overdose/poisoning → IV Naloxone (Antidote) Maintenance (Detoxi fi cation phase: To prevent withdrawal) 3 opioids Bupernorphine,Methadone, Tramadol >> Non Opoids- Clonidine, Lofexidine Prevent relapse (Abstinence), DOC: Oral Naltrexone ◦ Tolerance does not develop to 3 effects of opioids • Constipation • Convulsions • Constructed pupil (Meiosis)
- 31. Tobacco • World No Tobacco Day 31 may : “Unmasking the Appeal : Exposing Industry Tactics on Tobacco and Nicotine Products” 1. Tobacco use is a major risk factor for many chronic diseases, including cancer, lung disease, cardiovascular disease and stroke. It is one of the major causes of death and disease in India and accounts for nearly 13.5 lakh deaths every year. India is also the second largest consumer and producer of tobacco. 2. Nearly 26.7 crore adults (15 years and above) in India (29% of all adults) are users of tobacco, according to the Global Adult Tobacco Survey India, 2016-17. The most prevalent form of tobacco use in India is smokeless tobacco and commonly used products are khaini, gutkha, betel quid with tobacco and zarda. Smoking forms of tobacco used are bidi, cigarette . 3. It leads not only to loss of lives but also has heavy social and economic costs. The total costs attributed to tobacco use from all diseases in India in the year 2017-18 for persons aged 35 years and above amounted to INR 177 341 crore (Union govt healthcare expenditure - 48878 crore in 2017-18).
- 32. Tobacco 1. Active Compound: Nicotine is an alkaloid derived from the tobacco plant. (Nicotiana tabacum) 2. Mechanism of Action : Nicotine binds to Nicotinic Acetylcholine Receptors (nAchRs) in the Ventral tegmental area of the brain — stimulates Dopaminergic neurons —feeling of reward ,pleasure or euphoria. 3. Pharmacological effects System Effects 1 Cardiovascular. Increase in HR & BP 2 GI track. Increase in GI Motility 3 Endocrine. Increase in Blood glucose 4 Muscular. Tremors . 4 Metabolism : CYP2A6 -Cotinine 5 Therapeutic use — Nicotine replacement therapy : Patches , Gums , Lozenges , Nasal sprays , Inhalers
- 34. Thank you