Drug dependence & Drug Abuse
- 1. DRUG DEPENDENCE ANDABUSE Dr. Mahendranath Y 1ST YEAR PG DEPTOFPHARMACOLOGY GMCANANTHAPURAMU 1
- 2. CONTENTS INTRODUCTION DEFINITIONS DOPAMINERGIC PATHWAY THE THREE STAGES OF DEPENDENCE CLASSIFICATION DRUG ABUSECLASSIFICATION PHARMACOT HERAPY CONCLUSION REFERENCES 01 02 03 04 08 07 06 05 09 10
- 3. INTRODUCTION DEFINITION OF DRUG: WHO DEFINED DRUG AS “any substance OR Product that is used OR intended to be used OR explore physiological systems OR pathological states for the benefit of recipient. 3
- 4. TERMINOLOGIES MISUSE: Indiscriminate use of any drug other than CNS stimulant OR depressant. eg: misuse of laxatives, purgatives, antibiotics for viral fever. ABUSE : Usage of drugs for non -therapeutical purpose( pleasure, altered mood & altering consciousness , for body building) misuse of any CNS stimulant or depressant. It produces Drug Seeking Behaviour. This property is referred as “REINFORCING PROPERTIES” 4
- 5. TERMINOLOGIES CRAVING:- Chronic exposure to reinforcing drugs leads to drug addiction which increase in drug seeking behaviour. Asses “ABUSE POTENTIAL”. EUPHORIA:- Primary reinforcing property of drug referred as “ POSITIVE EFFECTIVE STATE”. Person experiences intense feeling of wellbeing, elation , happiness and joy. DYSPHORIA:- RELIEF from “NEGATIVE AFFECTIVE STATE”. profound state of uneasy ,unhappy and dissatisfaction. Strong impulse to continue the drug. 5
- 6. DEFINITION • DEPENDENCE • DRUG DEPENDENCE: Repeated, periodic or continuous use of a drug All types of detrimental effects- to himself and society or career PSYCHOLOGICAL AND PHYSICAL Craving Withdrawal effects • HUFFING • Many self-gratifying drug seekers inhale volatile substances that affect CNS. Eg: paint solvents, nail polish remover, whitener, deodorizers. Active ingredient is TOLUENE AND AMYL NITRITE SUBSTANCE ABUSE / SUBSTANCE DEPENDANCE 6
- 7. PHYSICAL DEPENDENCE 7 Intense craving for the drug eg:- alcohol, opioid. Tolerance Invariably present (pharmacodynamic type). Withdrawal effects are severe. Mainly caused by CNS depressants(opioid, barbiturates) LIFE THREATINIG Withdrawal effects is the actual evidence of physical dependence. ALCOHOL on heavy & prolonged use produces physical.
- 8. PSYCHOLOGICAL DEPENDENCE 8 • psychic/emotional dependence -- CNS stimulants(AMPHETAMINE). • MILD Drug Seeking Behaviour ex: cigarette smoking. • Tolerance may or may not present. • Withdrawal effects are mild which can be tolerated. • positive reinforcement
- 9. DEFINITIONS • TOLERANCE: upon repeated administration, a decreased effect is seen OR larger doses needed to obtain the same effect of previous dose. • CROSS TOLERANCE: once tolerance to primary drug develops, individual also exhibits cross tolerance to related class of drugs EXAMPLE: Morphine and heroin & alcohol and benzodiazepines. • CROSS DEPENDENCE: Ability Of Drug To Suppress The Withdrawal produced by another Drug. • eg:- methadone and heroin. • WITHDRAWAL/ABSTINENCE SYNDROME : Adverse(sometimes life threatening) psychologic and physiologic reactions to abrupt withdrawal of dependence-producing drug. 9
- 10. 10 ACUTE TOLERANCE (TACHYPHYLAXIS):- Tolerance of drug after rapid and repeated administration at shorter intervals. REASONS: 1) It is due to gradual depletion of agonists from the storage vesicles. example: sympathomimetics like amphetamine, tyramine causes depletion of catecholamine's. 2) Change in sensitivity of target cells. example: workers exposed to nitro-glycerine suffers from headache on Monday and it disappears by Friday and again reappears on Monday. “MONDAY DISEASE”
- 11. 11 Acquired tolerance:-divided into three major types A) PHARMACOKINETIC B) PHARMACODYNAMIC C) LEARNED TOLERANCE 1. Pharmacokinetic or dispositional tolerance:- Refers to changes in the distribution, metabolism of a drug after repeated administrations , such that a given dose produces a lower blood concentration than the same dose did on initial exposure. The most common mechanism is an increase in the rate of metabolism of the drug. FOR EXAMPLE:- chronic administration of barbiturates induces hepatic CYPs1A2, 2C9, 2C19, and 3A4, thereby enhancing the metabolism of drugs that are substrates for these enzymes.
- 12. 12 Pharmacodynamic tolerance:- (cellular adaptive) Refers to adaptive changes that have taken place within systems affected by the drug so that response to a given concentration of the drug is altered (usually reduced). Examples: include drug-induced changes in receptor density or efficiency of receptor coupling. Morphine, alcohol, barbiturates.
- 13. 13 Learned Tolerance:- Refers to a reduction in the effects of a drug due to compensatory mechanisms that are acquired by past experiences. One type of learned tolerance is called behavioural tolerance. A common example is learning to walk a straight line despite the motor impairment produced by alcohol intoxication. PARTIAL TOLERANCE: tolerance only to some effects of the drug. Eg:- tolerance to euphoric& sedative effects of morphine but does not develop to miotic & constipating effect.
- 14. DEPENDENCE SUBSTANCE DEPENDENCE : requires at least ≥ 3 following symptoms for diagnosis 1.Tolerance 2.Withdrawal effects(ABSTINENCE SYNDROME) 3.Craving 4.Substance use in larger amounts than intended 5.Withdrawal from social, occupational, recreational activities 6.Considerable time is spent on obtaining drug 7.Continued use despite health , social , economic, family and legal problems 14
- 15. DSM - 4 CRITERIA • SUBSTANCE ABUSE: DSM 4 criteria - ≥1 following symptoms 1. Recurrent substance use resulting in failure to fulfill obligations at work, school, home. Eg; poor performance at work or repeated absence, expulsion from school) 2.Recurrent substance use even in situations where it should not be used eg: driving, operating machine , during surgical procedures. 3. Recurrent substance use despite punitive action eg: punishment for disorderly conduct. 4. Recurrent substance use despite interpersonal or family problems eg: Argument or physical fight with spouse about consequences of drug abuse. NOTE: Coffee, tea, Smoking 10 cigarettes a day without inhalation does not come under substance abuse 15
- 16. 16 ORDER OF ADDICTION:- cocaine> amphetamine>opioids>nicotine>alcohol>cannabinoids>LSD>phencyclidine. GHB and ECTASY have no risk of addiction. MANDRAX :- METHAQUALONE + DIPHENHYDRAMINE Highly addicted and severe physical dependence.
- 17. TERMINOLOGY REBOUND:- Recurrence of symptoms of a disease due to sudden cessation of the drug No craving or Dysphoria after the cessation of drug. EXAMPLE: Recurrence of REBOUND HTN after discontinuation of clonidine or β blocker. RELAPSE:- The recurrence of disease which has been successfully treated earlier. This may occur with similar symptoms of the disease after a gap of certain period due to discontinuation of treatment. 17
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- 19. MESOLIMBIC-DOPAMINEPATHWAY The drug that activates this pathway is liable for addiction. It correlates with pleasure and reward. Composed of ventral tegmental area(MIDBRAIN) & ventral striatum (forebrain) Nucleus accumbens & olfactory tubercle. Addictive drugs dopamine levels. 19
- 20. THE THREE STAGES OF DEPENDENCE 1.Binge / Intoxication stage-Basal Ganglia 2.Withdrawal/Negative effect stage-Extended Amygdala 3.Preoccupation/Anticipation Stage-Prefrontal Cortex 20
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- 24. LEGAL CLASSIFICATION Classification:- 24 LEGAL CLASSIFICATION Schedule I Schedule II Schedule III 1. No officially recognized medical use 2. Lack of safety under medical supervision 3. High abuse potential 4. Cannot be legally produced Examples: LSD,THC,MDMA Schedule IV 1. Officially recognized medical use 2. High abuse potential that lead to severe psychological or physical dependence Examples: Methamphetamine Morphine 1. Officially recognized medical use 2. Abuse potential less than schedule I & II that can lead to moderate or low physical or high psychological dependence Examples: Ketamine, Hydrocodone (<15mg) 1. Officially recognized medical use 2. Low abuse potential compared with schedule III Examples: Alprazolam Diazepam Schedule V 1. Officially recognized medical use 2. Low abuse potential relative to schedule IV 3. Consists preparations containing limited amounts of narcotics Examples: cough syrup with <200mg codeine per 100ml
- 25. DESIGNER DRUGS • Synthetic substances , prepared in clandestine laboratories, that are inexpensive to produce and difficult to detect. • Done by some chemists to avoid Drugs and Narcotic Act regulations and to make huge profits. • Sometimes unpredictable and sometime lethal consequences occur Examples : AMPHETAMINE ANALOGUES - MDMA – 3-4 methylenedioxymethamphetamine (ECTASY). China White – Fentanyl analogue. MPTP- Pethidine analogue- induces parkinsonism by causing lesions in nigrostriatal pathway. 25
- 26. MANAGEMENT • The ultimate goal is to achieve a ‘drug free status’ and to prevent relapse of drug abuse • The former is achieved by pharmacotherapy and latter by rehabilitation psychotherapy and psychosocial interventions. 26
- 27. MANAGEMENT Treatment approach includes : Substitution therapy- by a similar drug having longer t 1/2 Aversive therapy-by a drug that produces unpleasant response after intake of abused drug Antagonist drug- to prevent relapse, once drug free status achieved Anti craving drugs Rehabilitation and psychosocial interventions 27
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- 30. 30 International Classification of Diseases 10th Edition (ICD-10) Classification F10 - Mental and behavioural disorders due to use of ALCOHOL F11 – Mental and behavioural disorders due to use of OPIOIDS F12 – Mental and behavioural disorders due to use of CANNABINOIDS F13. – Mental and behavioural disorders due to use of SEDATIVE HYPNOTICS F14. – Mental and behavioural disorders due to use of COCAINE F15. – Mental and behavioural disorders due to use of other stimulants, including CAFFEINE F16. – Mental and behavioural disorders due to use of HALLUCINOGENS F17. – Mental and behavioural disorders due to use of TOBBACO F18. – Mental and behavioural disorders due to use of VOLATILE SOLVENTS F19. – Mental and behavioural disorders due to MULTIPLE DRUG USE and use of other psychoactive
- 31. DRUGS OF ABUSE 31 Drug abuse is the nonmedical, self- administered use of a drug that is harmful to the user, generally act on the CNS to modify the user’s mental state, although some are used for enhancing physical performance. Common abused drugs include: • CNS stimulants (e.g., cocaine, amphetamines, nicotine), • hallucinogens (e.g., LSD, mescaline, phencyclidine, and marijuana) • general CNS depressants (e.g., ethanol), • sedative–hypnotics (e.g., alprazolam, diazepam) • opioid analgesics (e.g., heroin) • inhalants (e.g., toluene, nitrous oxide, amyl nitrate).
- 32. 32 PSYCHOMOTOR STIMULANT. DERIVATIVES: DEXAMPHETAMINE,METHAMPHETAMINE(CRYSTAL METH OR ICE) MECHANISM OF ACTION: INCREASE PRESYNAPTIC RELEASE OF CATECHOLAMINES DOPAMINE LEVELS INHIBIT DOPAMINE METABOLISM BY BLOCKING MAO-B INHIBIT REUPTAKE OF CATECHOLAMINES. EFFECTS: MOTOR ACTIVITY and PERFORMANCE EUPHORIA ANOREXIA EXCITEMENT REDUCED FATIGUE. OTHER NAMES: SPEEED, BILLY WIZZ, POORMANS COCAINE AMPHETAMINE
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- 34. ADHD 34 NARCOLEPSY CLINICAL FEATURES: DAYTIME SLEEP VIVID NIGHTMARES CATAPLEXY(SUDDEN LOSS OF MUSCLE TONE) METHYPHENIDATE IS USED NON AMPHETAMINE USED FOR NARCOLEPSY: MODAFINIL HYPERKINETIC CHILD DRUGS: DEXAMPHETAMINE METHYLPHENIDATE ATOMOXETINE( NE REUPTAKE INHIBIT) C/I in patients with GLAUCOMA
- 35. 35 Fenfluramine, dexfenfluramine causes marked anorexia. MECHANISM OF ACTION:- Enhancement of 5HT Release . SERIOUS EFFECTS:- INSOMNIA, PULMONARY HTN. NEW DRUG:- Sibutramine MECHANISM OF ACTION:- BLOCK 5HT & NE REUPTAKE AT HYPOTHALAMUS ADVERSE EFFECTS:- INSOMNIA,CONSTIPATION, HR,BP. C/I in CVD patients, caution with SSRI. Weight Reduction
- 36. Summary Of the Effects of Amphetamines 36 Body Increased heartbeat Increased blood pressure Decreased appetite Increased breathing rate Inability to sleep Sweating Convulsions, fever Chest pain Irregular heartbeat Due to overdose Mind Decreased fatigue Increased confidence Increased feeling of alertness Restlessness Increased irritability Fearfulness Distrust of people Behavioral stereotypy Hallucination low dose high dose
- 37. • Aamphetamine toxicity treated with DIAZEPAM(SLOW IV) • FOR PSYCHOTIC AGITATION – HALOPERIDOL • GASTRIC LAVAGE Acidification of urine by administering AMMONIUM CHLORIDE & ASCORBIC ACID This increase elimination of amphetamine in urine. Anti-hypertensive drugs like – LABETOLOL For ARRYTHMIAS - ESMOLOL Treatment typically requires more than one year of Intense intervention consisting of drug abstinence, cognitive, emotional and motivational rehabilitation. Treatment Of Acute Poisoning 37
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- 39. History of Cocaine • SIGMUND FRAUD USED COCAINE FOR TREATMENT OF DEPRESSION, • ALCOHOL & OPIOID ADDICTION • ALBERT NEIMANN extracted cocaine • from coca leaves and named cocaine. • 1904 • 39
- 40. What is it? • Pure cocaine was first isolated from the leaves of the coca bush in 1860. • Contained in small amounts in the leaves of ERYTHROXYLUM (coca) bush • Researchers soon discovered that cocaine numbs whatever tissue it touches. • This lead to it’s use as a local anesthetic. 40
- 41. Where does it come from? • Coca leaves grow on the slopes of the Andes Mountains. • For at least 4,500 years, people in Peru & Bolivia have chewed the coca leaves to lessen hunger & fatigue. • Most of the world’s supply of coca is grown & refined into cocaine in Colombia. 41
- 42. How is it used SNIFFED (15 – 30 min) 42 SMOKED (5-10 min) INJECTED 3 min
- 43. Cocaine Pharmacodynamics • Indirect Agonist for • DA (high affinity) • NE (high affinity) • 5-HT (modest affinity) 43 • Mechanism: – Blocks catecholamine reuptake
- 44. SYSTEMIC EFFECT OF COCAINE 44
- 45. Short-termeffects • Dilated pupils • Increased body temperature, Blood pressure & heart rate • Insomnia • Loss of appetite • Increased energy • Reduced fatigue • Talkativeness 45
- 46. Long-term effects • Paranoia • Depression • Ulcers in the membranes of the nose • Dulled senses of taste & smell • Weight loss, poor health & sexual dysfunction • Loss of social & financial supports • Holes in bony separation between nostrils in nose 46
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- 48. EUPHORIA Positive Reinforcement CRAVING Neuroadaptations Cycle of CocaineAddiction Use This addiction has biological, behavioral & psychological aspects Cocaine Brain Reward Cocaine Seeking Behavior Negative Reinforcement Treatment interventions are designed to reduce euphoria & craving 48
- 49. COCAINE+ HEROIN Concurrent or substitute use • Multiple drug use (nicotine, alcohol, heroin, amphetamines, hallucinogens). • Cocaine + heroin => “speed ball” 49
- 50. COCAETHYLENE • Alcohol inhibits metabolism of cocaine • Alcohol + cocaine chemically react to form coca ethylene • Only known example where body forms new psychoactive compound from two others • Coca ethylene – Similar effects to cocaine – Greater cardiac toxicity than cocaine – 3-5x the half-life of cocaine – associated with seizures, liver damage, compromised immune system 50
- 51. PHARMACOTHERAPIES Treatment of withdrawal: • Alpha-blockers • Chlorpromazine: DA antagonist (also blocks alpha receptors) • Haloperidol (antipsychotic – 50x more potent than chlorpromazine). • Alprazolam (Xanax - benzodiazepine) for panic attacks. • Antidepressants (fluoxetine or desipramine). • Diazepam (Valium) for seizures - binds to benzodiazepine site of GABAa receptor. • Dopamine agonist for withdrawal symptoms. 51
- 52. New Treatment Approaches IMMUNOLOGICAL • Antibodies made against cocaine, to break-down the molecule and stop its effects. • Undergoing Phase III trials in US • An inactive cholera toxin protein – attach inactivated cocaine • Immune system makes antibodies against both • When individual takes cocaine, antibodies bind to it and prevent it from reaching brain – high does not occur, patient loses interest
- 53. 53 Cocaine is known to have a number of effects during pregnancy. elevated risk of placental abruption Due to its vasoconstrictive and hypertensive effects, they are also at risk for haemorrhagic stroke and myocardial infarction. Cocaine is also teratogenic it can cause birth defects and foetal malformations. In-utero exposure to cocaine is associated with behavioural abnormalities, cognitive impairment, cardiovascular malformations, intrauterine growth restriction, preterm birth, urinary tract malformations, and cleft lip and palate. COCAINE IN PREGNANCY
- 54. METHYLXANTHINES Theophylline ( tea) : long-acting, prescribed for night-time asthma Theo bromine: found in cocoa. Caffeine: (short-acting) the most widely consumed found in coffee (200 mg/cup), carbonated soft drinks (60 mg/can), cocoa and chocolate
- 55. MECHANISM OF ACTION 1) It inhibits PHOSPHODIESTERASE enz. → ↑ cAMP 2) Adenosine (A1, A2 and A3) receptors antagonist almost equally, which explains many of its cardiac effects A2 receptors antagonist responsible for CNS stimulation & smooth muscles relaxation ↓calcium in Smooth muscles 55
- 56. Actions 56 a.CNS: decrease in fatigue, increased alertness: 100-200 mg caffeine in 1 or 2 cups of coffees Aanxiety & tremors- 1.5 g of caffeine: 12-15 cups of coffee Spinal cord stimulation: 2-5 g (very high dose) Tolerance can rapidly develop Withdrawal symptoms: feeling of fatigue & sedation. b. CVS: at high dose of caffeine +ve inotropic and chronotropic effects on the heart, ↑CO c. Diuretic action: mild ↑ urinary output of Na+, Cl- and K+ d.Gastric mucosa: all methylxanthines stimulate secretion of HCl c.Respiratory smooth muscle: bronchodilator, Rx asthma replaced by β-agonists, corticosteroids.
- 57. Pharmacokinetics 57 The methylxanthines are well absorbed orally. Caffeine distributes throughout the body, including the brain. The drugs cross the placenta to the fetus and is secreted into the mother's milk. All are metabolized in the liver, generally by the CYP1A2 pathway, the metabolites are then excreted in the urine. Adverse effects Moderate doses: insomnia, anxiety, agitation High doses: emesis, convulsion Lethal dose (10 gm of caffeine): cardiac arrhythmia Suddenly stop: lethargy, irritability, headache
- 58. GAMMA-HYDROXYBUTYRIC ACID (GHB) 58 1st introduced as a general anesthetic Colourless and odourless DATE RAPE DRUG Max absorption is oral route Peak effect with in 1 hour and lasts for 4 hours Liquid ecstasy ,liquid x. Pharmacology – GHB-receptors are present on both pre-and postsynaptic neurons, thereby inhibiting GABA release Binding site – GABAB receptor( agonist) Available in salt form.
- 59. Side effects of GHB • Loss of conscience • Coma • Seizures • Inhibition • Dizziness • Loss of memory • Loss of coordination • Nausea 59
- 60. BE CAREFULAT ALL TIMES!!! Serious side effects when mixed with alcohol Death due to respiratory depression. Detected in HAIR and URINE(≤ 4 HOURS) Other date rape drug: FLUNITRAZEPAM (roofies) Medically used in Narcolepsy cataplexy 60
- 61. NICOTINE 61 - - Most dangerous dependence producing drug -2nd after alcohol
- 62. NICOTINE • Nicotine, in mild to moderate doses, is a central nervous system stimulant. • It enhances central cholinergic receptors (activated by acetyl choline). • The dependence-producing effects of nicotine appear to be modulated by dopamine (nicotinic-cholinergic receptors lie on dopamine neurons, nicotine increases dopamine). 62
- 63. MOA 63
- 64. NICOTINE 64 Most common route – smoking Oral ingestionn. ACTION some degree of euphoria and arousal improves attention, learning, problem solving, and reaction time Toxic dose - respiratory paralysis and severe hypotension
- 65. TOLERANCE ,DEPENDENCE, WITHDRAWAL 65 Some evidence for tolerance Best feeling after a day of abstinence Strong dependence Mild withdrawal symptoms • Irritability Anxiety Restlessness Impatience • depression
- 66. At higher doses • * Seizures • * Hypotension • * Respiratory arrest can develop • Long term effects:- 66
- 67. Hazardsof smoking • In pregnant women, nicotine crosses the placenta freely and is in the amniotic fluid and umbilical cord blood of neonates. • Sustained exposure of the fetus causes: *Slow growth in utero and lower than average birth weights. *Increased incidences of newborns with persistent pulmonary hypertension. 67
- 68. Rx of nicotine addiction 68 Nicotine substitution - Gum - Transdermal patch - Nasal spray - Electric cigarettes All these do not achieve peak nicotine level – but suppress the withdrawal
- 69. 69 ANTI SMOKING DRUGS cytisine VARENICLINE:PARTIAL NICOTINIC AGONIST(α4β2nAchR) S/E:SUICIDAL TENDENCY Dose of 0.5mg OD initially then 1mg BD from day 8 to 6months BUPROPION SR :NE DA REUPTAKE INHIBITOR S/E: SEIZURES DOSAGE: 150-300mg BD PO 2ND LINE DRUGS: CLONIDINE MISCILLANEOUS: RIMONABANT(CB1 ANTAGONIST)
- 70. PSYCHOTOMIMETIC 70 LYSERGIC ACID DIETHYLAMIDE MESCALINE PHENCYCLIDINE CANNABINOIDS Molecular target- 5-HT2AR – Gq receptor Hallucinogens
- 71. HALLUCINOGENS - Also called psychedelics or psychomimetics - Classicsynthetic hallucinogens - LSD - Some “designer” amphetamines (i.e. MDA, MDMA) - Classicnatural hallucinogens - Psilocybin (“magic mushrooms”) - Mescaline - Schedule I Drugs based on the FDA classification system - Salvia- most powerful natural hallucinogen. Legal. Grows throughout the Americas, including the US.In mint family. 71
- 72. WHAT IS LSD? LSD is the most commonly used synthetic Hallucinogen synthesized by HOFMANN (1938). - LSD is a white or clear, odorless, water-soluble crystal that can be crushed into a powder and dissolved. - The most common form of LSD is as a liquid that has been transferred onto a small paper square known as “blotter” - Experiences on LSD are known as “trips” onset of action in 1 hour and peak effect in 2-4 hours. 72
- 73. LSDTRIP - 1st hour of trip – anxiety,tingling feelings, nausea, colors appear brighter - 3rd hour – peak - Extreme visual, open and closed eyes, hallucinations. Vivid colors and seeing things that are not there. - Can go from periods of giddiness, to extreme insight. - Can become extremely paranoid, especiallywhen put in a situation with people who are not tripping. 73
- 74. 74 - The most common dangers of LSD result from bad trips, including terrifying thoughts and feelings, disorientation from time & space, fear of losing control, and fear of death. Can cause unpredictable long-lasting adverse neuropsychiatric effects, relatively long-lasting psychosis, severe depression or schizophrenia-like syndromes, especially in heavy or long-term users or in people with an underlying mental illness SHORT- TERM EFFECTS LONG-TERM EFFECTS
- 75. Flashback(HPPD) • Flashback – An unexpected relived experience from a hallucination. • A flashback occurs suddenly, often without warning, and may occur within a few days or more than a year after hallucinogen use. • Both frequent users and one-time experimenters can find themselves on another trip when they least expect it. • While driving a car, swimming, playing sports. 75
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- 77. 77 • MDMA (3,4-Methylenedioxymethamphetamine):- • also known as Ecstasy (E, X, or XTC), molly (U.S.), Mandy ( U.K) • A psychoactive drug with stimulant and psychedelic effects that used as a recreational drug. • Drugs sold under the street names ecstasy, molly, or Mandy are often advertised as pure MDMA, but are often mixed with multiple other drugs. • MDMA can cause feelings of euphoria (extreme happiness) and altered sensations. • side effects include insomnia, nausea, rapid heartbeat, and addiction. • RAVE DRUG / CLUB DRUG/ PARTY DRUG • EFFECT TIME 3-6 HOURS • NEUROTOXIC
- 78. Mescaline • Mescaline – A hallucinogen obtained from a small spineless cactus Peyote. • From earliest recorded time, peyote has been used by natives in northwestern Mexico as a part traditional riots. • Least potent psychotomimetic and does not produce sympathomimetic action • The drug is usually taken orally, without chewing, although it can still be smoked, or even injected. • It’s chemical structure is close to that of an amphetamine (stimulant). 78
- 79. PSILOCYBIN MUSHROOMS • How are they taken? • Eaten raw • Cooked in food • Brewed in tea • Dried and ingested • Street names: • Magic mushrooms • “Shrooms” • How long does a trip last? • 5-6 hours 79
- 80. Psilocybin Mushrooms Effects • Nausea • Dilated pupils • Tightness in the neck • Induce sensory hallucinations • Hear things that are not real Effects caused by shrooms begin about 30 min after consumption and last nearly 5 hours. During this period, laughing is somewhat uncontrollable and visual hallucinations caused by organic objects are typical. Psilocybin acts by affinity to serotonin 5-HT receptors. 80
- 81. JIMSONWEED Jimsonweed - A common name for a plant known botanically as Datura stramonium, which has been used as a medicine and intoxicant for centuries. • It’s name comes from colonial Jamestown, where settlers became very ill after mistakenly eating it in a salad. • It is found in most of the continental United States • Also called pod or thorn apple • After ingestion it causes hallucinations. • Severe toxicity includes seizures arrhythmias and coma • Rx includes gastric lavage, activated charcoal. 81
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- 83. AYAHUASCA • Ayahuasca – A plant-based hallucinogen that users ingest as a drink containing a combination of plant products. • For centuries the Amazonian Indians have been drinking it. • The Indians believe it cleanses body and mind and enables communication with spirits. • Common Names: • Caapi • Yage • Vegetal 83
- 84. BUFOTENINE • Bufotenine - A poisonous hallucinogenic alkaloid obtained from the skin glands of toads of the genus Bufo. • Found in the skin of psychoactive toads. • Orally taken by licking the toads skin. • Now there are ways to extract the poison from the toad by milking it under the chin. It can then be created in a substance to be smoked. • HARMINE AND NUTMEG have psychotomimetic effects. 84
- 85. CANNABINOIDS Cannabis Sativa (Hemp) Cannabis indicia GATEWAY DRUG Psychoactive agent = ∆9 Tetrahydocannabinol (THC) Found in all parts of the plant, but concentrated in the sticky resin(charas) secreted from the flowing tops of ♀ plants. WORLDS MOST POPULAR DRUG OF ABUSE The herb was called GANJIKA in Sanskrit 85
- 86. HASH OIL: It obtained by extracting THC from Hashish or Marijuana in oil. Clear pale yellow / green to brown black colour. THC concentration 15-30%. GANJA: Buds and flowering top of female plant. BHANG: Cut and dried large leaves & stem of plants. 6 86
- 87. 87 MARIJUANA - Dried and crumbled leaves, small stems, flowing tops of the plant - Usually smoked in joints, pipes, bongs, - also grass, pot,weed,reefer. - THC content varies… SINSEMILLA: pollination prevented (↑ potency) The Gang Bong: The 4 barrel brain blaster!
- 89. Common Routes- CANNABINOIDS 89 Smoking Oral ingestion Cannabis tea Cannabis+alcohol = green dragon
- 90. PHARMACOLOGY OF CANNABIS 11- hydroxyl ∆9-THC.(active form) Typical Joint contains approximately 0.5 – 1g of cannabis - If THC content = 4%... joint with 1g of cannabis contains 40 mg of THC Burning marijuana results in vaporisation of THC→ absorption into the lungs Only about 20% of original THC is absorbed: Breathing isn’t optimal – can be increased by breath holding Increased high with 15 s breath hold vs. 7 s 90
- 91. NEUROPHARMACOLOGY • Primary constituent is ∆9-THC. • ∆9-THC is rapidly converted to is active form 11- hydroxy ∆9-THC. • THC and its metabolite are highly fat soluble(lipophilic). • There are two type of cannabinoid receptor CB1 and CB2. • CB1 mainly present in brain and mediate psychological effects. • CB2 associated with immune system and modulate inflammatory responses. • CB1 AND CB2 belongs to G protein coupled receptor. 11 91
- 92. ACTIONS - CANNABIS 92 DURING SEDATIVE PHASE: IMPAIRED CONCENTRATION LSD LIFE EFFECTS IMPAIRED SHORT TERM MEMORY MOOD SHIFTS. - DURING STIMULATORY PHASE: lasts for 2 hours. EUPHORIA TALKTIVENSS, APPETITE FEELING OF WELL-BEING. MOOD TRIPS WILL BE SEEN. PERIPHERAL EFFECTS: TACHYCARDIA BLOODSHOT EYES IOP BRONCHODILATATION AMOTIVATION SYNDROME. RUNNING AMOK CHRONIC POISONING
- 93. TOLERANCE ,DEPENDENCE, & WITHDRAWAL 93 Tolerance develops rapidly Withdrawal syndrome – mild Restlessness Irritability Insomnia APPETITE PSYCHOLOGICAL DEPENDENCE NO FATAL OVERDOSE REPORTING TILL NOW. PLASMA TESTOSTERONE AND SPERM COUNT.
- 94. most Commonly. CANNABIS WITHDRAWAL Benzodiazepines are prescribed Dronabinol(cannabis receptor agonist) synthetic THC (20-60 mg/day) for 7-10 days depending on duration of withdrawal symptom. Mostly used in cancer patients to relieve emesis caused by cisplatin Along with NABILONE it increases appetite in HIV patients RIMONABANT (20 mg/day) CB1 receptor antagonist used to treat addiction. 94
- 95. PSYCHOSOCIAL ASPECT: 95 Motivational enhancement therapy (MET). Cognitive behavior therapy (CBT). Contingency management (CM). Family and system intervention. Combined psychosocial treatment.
- 96. ALCOHOL – ETHANOL 96 Most commonly abused drug in the world 70% INDIAN adults have experienced alcohol Absolute alcohol is 99% ethanol All Standard Beverages contain 40% ALCOHOL INDIAN STANDARD in BREATH ANALYSER IS more than 35mg in 100ml IS GUILTY. Minimum age for consumption is 21 years.
- 97. Alcohol Breakdown • Alcohol ADH(alcohol dehydrogenase) × FOMEPAZOLE • Acetaldehyde ALDH(ALDEHYDE) • × DISULFIRAM • EXTRA HEPATIC • Acetic acid and water 97
- 98. 98 FOMEPIZOLE
- 99. Effect ofalcoholon thebrain • * Alcohol is a CNS suppressant. • It exerts this suppressant effect in a descending manner, where higher cortical centers are inhibited first, resulting in euphoria and then disinhibit ion.( 200-300mg) • In larger doses≥ 300mg lower vital centers are inhibited, leading to hypotension and respiratory depression. 99
- 100. Effectofalcoholonneurotransmitters * It is found that ion channel activities associated with acetyl choline, serotonin and GABA receptors are enhanced by alcohol. • Ion channel activities associated with glutamate receptors are inhibited. • * Death is due to central respiratory depression or inhalation of vomitus(500mg/dl) 100
- 101. Alcohol on neurotransmitter systems neurotransmitt er acute intoxication alcohol withdrawal Gamma aminobutyri c acid (GABA) N-methyl-d- aspartate (NMDA) excitatory glutamate receptors 101
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- 103. Alcohol Intoxication 20-99mg% loss of muscular coordination, change in behavior 100-199mg% ataxia, mental impairment 200-299mg% obvious intoxication, nausea and vomiting 300-399mg% severe dysarthria and amnesia 400-600mg% coma occurs 600-800mg% decreased respirations and blood pressure, often fatal. 103
- 104. Withdrawal Signs and Symptoms • Tremor • Agitation • Autonomic changes (BP, HR, Temp.) • Seizures • Sensorium changes (eg, hallucinations, confusion) 104
- 105. Withdrawal Syndrome Stage 1 • Begins within 24 hours • Lasts up to 5 days • 90% of cases do not go beyond stage 1 • Other symptoms include depressed mood, anxiety, diaphoresis, headache, nausea/vomiting, etc. 105
- 106. Withdrawal Syndrome Stage 2 • Mostly untreated or undertreated in stage 1 • Same signs and symptoms in stage 1 only more severe • Hallmark is visual hallucinations (generally perceived as benign) • Usually occurs 48 hours after last drink 106
- 107. Withdrawal Syndrome Stage 3 • Usually occurs 72 hours after last drink • Delirium Tremens (acute reversible organic psychosis) has 2% mortality • Lacks insight into hallucination, often disoriented and labile • Seen in persons with severe alcoholism and/or significant medical problems 107
- 108. Alcohol withdrawal - clinical presentation 1. Minor withdrawal – vegetative symptomps 2. Major withdrawal – 1 +hallucinations, seizures + disordered consciousness= Delirium tremens 108
- 110. 110 In case of alcohol intoxication, pupils are contracted, but on external painful stimulation of the person, e.g. by pinching or slapping, causes pupil to dilate followed by slow constriction again. This is called as McEwan’s sign and if this is positive, it is suggestive of alcoholic coma. McEwan's SIGN
- 111. 111 MARCHIAFAVA–BIGNAMI DISEASE : is a progressive neurological disease of alcoholism, characterized by corpus callosum demyelination and necrosis and subsequent atrophy.
- 112. Treating withdrawal glucose electrolytes 50–100 mg of thiamine daily 25–50 mg of chlordiazepoxide or 10 mg of diazepam given PO every 4–6 h on the first day, with doses then decreased to zero over the next 5 days search for evidence of liver failure, gastrointestinal bleeding, cardiac arrhythmia, infection 112
- 113. Medications for Rehabilitation Drug Dosage MOA BENIFIT REMarks NALTREXONE 50–150 MG/D BLOCKING OPIOID SHORTEN G ALLELE OF ORALLY, RECEPTORS, DECREASE SUBSEQUENT THE AII8G ACTIVITY IN THE DOPAMINE- RELAPSES POLYMORPHISM RICH VENTRAL TEGMENTAL REWARD SYSTEM ACAMPROSAT 2 G/D DIVIDED INHIBITS NMDA RECEPTORS DECREASING E INTO THREE MILD ORAL DOSES SYMPTOMS OF PROTRACTED WITHDRAWAL. DISULFIRAM, 250 MG/D. PRODUCES VOMITING AND AVERSION CAN BE AUTONOMIC NERVOUS THERAPY DANGEROUS SYSTEM INSTABILITY IN THE WITH HEART PRESENCE OF ALCOHOL AS DISEASE, A RESULT OF RAPIDLY STROKE, RISING BLOOD LEVELS OF DIABETES THE FIRST METABOLITE OF MELLITUS, OR ALCOHOL, ACETALDEHYDE HYPERTENSION 113
- 114. 114 Used as a palliative care drug in patients suffering with cancer to get relief from pain and nausea
- 115. Fetalalcoholsyndrome • It occurs when fetuses are exposed in utero to alcohol by their mothers' drinking alcohol. • This syndrome is the leading cause of mental retardation in the United States. • Women with alcohol related disorders have a 35 percent risk of having a child with deficits. 115
- 116. 116
- 117. Opioids – God's own medicine 117
- 118. OPIOIDS 118 • Opioids are highlyaddicting. • Formsof Opioids include opium,morphine, heroin, codeine and some analgesic opiate derivatives.
- 119. AcuteeffectsofOpioids 119 • 1.Centralnervoussystemeffects:Opioidsare centralnervoussystem suppressants (endogenousopioid receptors). Theireffectsinclude: * Analgesia * Mood changes * "Mental clouding" * Sedation * Centralnauseaandvomiting • 2.Gastrointestinaleffects:CTZstimulation. • 3.Pupillaryconstriction(miosis):3rd nervestimulation. • 4.Bradycardia:vagalstimulation. • 5.Respiratorydepression.
- 120. Over dose of opiates 120 Severeintoxication is diagnosed by the triad of: • 1- Coma • 2- Pinpoint pupils • 3- Respiratory depression. • It is amedical emergency that requires immediate attention.
- 121. OpioidsWithdrawalSyndrome • Centralnervoussystemsymptomsinclude restlessness,irritability andinsomnia • Gastrointestinalsymptomsareanorexia,vomiting, abdominal colics, and diarrhea • Cutaneousandmucocutaneoussymptoms include lacrimation, rhinorrhea and piloerection alsoknow as “GOOSEFLESH” • OpioidsCraving 121
- 122. 122 Section Divider Withdrawal As the body gets used to a regular dose of opioids, it slows production of natural opioids When the dose is not taken, the body experiences uncomfortable withdrawal symptoms
- 123. Medications for Opioid Use Disorder • Maintenance therapy • 3 FDA approved medications • Methadone • Buprenorphine • Naltrexone • Detox – management of withdrawal • Inpatient vs. outpatient 123
- 124. 124 OPIOID ABUSE IN PREGNANCY An infant withdrawing from methadone can have sleeping difficulties, seizures and a higher risk of dying from Sudden infant death syndrome. Methadone withdrawal occurs after 7–14 days. If a child is premature they have a lower risk of severe symptoms. It may be because preterm infants may have been exposed to the drug. An infant born with heroin dependency is more likely to be premature and have meconium staining. Heroin withdrawal is seen within 48–72 hours of the birth.
- 125. 125 Symptoms of withdrawal may begin as early as 24 to 48 hours after birth, or as late as five to 10 days. Symptoms of withdrawal in full-term babies. Tremors (trembling) Irritability (excessive crying) Sleep problems High-pitched crying Tight muscle tone Neonatal Abstinence Syndrome
- 126. PHENCYCLIDINE 126 Also called “ ANGEL DUST” MOA: NON COMPETITIVE ANTAGONISM OF NMDA RECEPTOR. TOXICITY: MILD:- (1-5mg) causes ALOCHOL like effect MODERATE:-(5-10mg) causes distortion of space and time HIGH : (≥ 10mg) causes VIVID HALLUCINATIONS OVER DOSE: RESPIRATORY DEPRESSION / SEIZURES TREATMENT: MECHANICAL VENTILATION FOR RESP DEPRESSION FOR SEIZURES BENZODIAZEPINES FOR PSYCHOTIC EFFECTS ANTIPSYCHOTICS
- 127. KETAMINE 127 PHENCYCLIDINE DERIVATIVE DISSCOCIATIVE ANESTHESIA PEAK ONSET:- IM:- ≤ 5 MIN, IV:- ≤ 1 MIN VIVID DREAMS AND HALLUCINATIONS UNIQUE DRUG USED AS HYPNOTIC, ANALGESIA AND AMNESIC EFFECTS DRUG ABUSE: HIGH DEPENDANCE AND TOLERANCE IS SEEN OVERDOSING:100-250mg CAUSES “K- HOLE”. ≥ 250mg RESPIRATORY DEPRESSION REINFORCEMENT SEEN IN MONKEYS CHRONIC EXPOSURE CAUSES SHIZOPHRENIA LIKE STATE.
- 128. 128 INVESTIGATION
- 129. 129 AYURVEDIC HERBS TO TREAT DRUG ADDICTION Radix Pueraria showed the most promising efficacy for alcoholism Thunbergia laurifolia can protect against alcoholic liver toxicity. Withania somnifera and Salvia miltiorrhiza can reduce morphine tolerance and alcohol intake respectively. Asafoetida extract is suitable for the use in the abstinence treatment of subjects addicted to opioid, morphine, marijuana.
- 130. 130 Ginseng extract inhibited tolerance and dependence on morphine passion flower used in the management of symptoms associated with detoxification. Caulis Sinomenii effective for TREATING drug dependence Peganum harmala plays a role in eliminating some of the withdrawal symptoms. Chamomile extract can reduce chronic and acute withdrawal symptoms Valerian is commonly used for the treatment of insomnia and anxiety
- 131. IMMUNOPHARMACOTHERAPY 1. A novel approach to pharmacotherapy which is largely pharmacokinetic. 2. Uses highly specific antibodies to sequester the drug of interest while it is still in blood stream, thus preventing drug reaching brain. 3. Active immunization : antigenic drug protein conjugate administration leading to activation of immune cells causing generation of antibodies to drug protein conjugate. 4. Passive immunization:: injection of pre-generated anti-bodies, typically of monoclonal type. 131
- 132. IMMUNOTHERAPY 5. Successful active immunization with VACCINES in animals for cocaine ,nicotine , phencyclidine, methamphetamine, heroin. 6. Two nicotine vaccines under clinical trials • NicVAX & NIC002 : safe &tolerated in Phase I & II BUT FAILED Phase III 7. Cocaine vaccine(TA-CD)-marginal results in promoting abstinence 8. Another cocaine and heroin vaccine are in different stages of preparation 132
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- 134. 134 THE NARCOTIC DRUG AND PSYCHOTROPIC SUBSTANCE ACT – 1985 Prevention of Illicit Trafficking in Narcotic Drugs and Psychotropic Substances Act- 1988
- 135. CONCLUSION • Medications currently on the market for the treatment of addiction open a window on the opportunities to facilitate treatment and provide a means for evaluating future medications. • The potential for the development of future medications for the treatment of addiction is significant on a number of fronts. A combination of excellent, validated animal models of addiction and an enormous surge in our understanding of the neurocircuits and neuropharmacological mechanisms involved in the development and maintenance of addiction reveal numerous possible targets. • Recent success with acamprosate , naltrexone, varenicline, and buprenorphine should provide some indication that expanded directions are merited in the addiction field. 135
- 136. REFERENCES 1.Sharma HL, Sharma KK. Principles of pharmacology.3rd edition; 2017. 2.Koob, G.F.,Arends, M.A.,Moal, M.L. 2nd edition ; 2014, Drugs, Addiction, and the Brain 3.Murthy, Pratima et al. “Substance Use and Addiction Research in India.” Indian Journal of Psychiatry 52.Suppl1 (2010): S189–S199. 4.Goodman and gillmann 13 th edition drug dependance and drug abuse. 136
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- 138. THANK YOU • SAY NO TO DRUGS 138