Drug Dependence andDrug Dependence and
Drug AbuseDrug Abuse
TypeType ExamplesExamples Dependence liabilityDependence liability
Narcotic analgesicsNarcotic analgesics MorphineMorphine...
Drug dependenceDrug dependence
 Dependence is defined as a compulsive cravingDependence is defined as a compulsive cravin...
 dependence is often associated with (i)dependence is often associated with (i)
tolerance to the drug, which can arise by...
Pharmacological approaches to treating drug dependencePharmacological approaches to treating drug dependence
MechanismMech...
Pharmacology of nicotinePharmacology of nicotine
 At a cellular level, nicotine acts on nicotinicAt a cellular level, nic...
Pharmacology of nicotinePharmacology of nicotine
Electroencephalography changes show anElectroencephalography changes sho...
Nicotine is metabolised, mainly in the liver,Nicotine is metabolised, mainly in the liver,
within 1-2 hours. Its inactive...
NicotineNicotine
NicotineNicotine
Effects of ethanolEffects of ethanol
Ethanol acts as a general CNSEthanol acts as a general CNS
depressant, similar to vo...
Effective plasma concentrations:Effective plasma concentrations:
threshold effects: about 40 mg/100 mlthreshold effects:...
Effects of ethanolEffects of ethanol
 Long-term ethanol consumption causes liver disease,Long-term ethanol consumption ca...
Metabolism of ethanol.
Fetal Alcohol SyndromeFetal Alcohol Syndrome
Fetal Alcohol SyndromeFetal Alcohol Syndrome
CannabisCannabis
 Main active constituent is Δ9-tetrahydro cannabinol (THC),Main active constituent is Δ9-tetrahydro cann...
CannabisCannabis
 Anandamide, an arachidonic acid derivative, is anAnandamide, an arachidonic acid derivative, is an
endo...
MarijuanaMarijuana
MarijuanaMarijuana
HallucinogensHallucinogens
LSDLSD
CocaineCocaine
CocaineCocaine
Drug dependence and drug abuse
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Drug dependence and drug abuse

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Drug dependence and drug abuse

  1. 1. Drug Dependence andDrug Dependence and Drug AbuseDrug Abuse
  2. 2. TypeType ExamplesExamples Dependence liabilityDependence liability Narcotic analgesicsNarcotic analgesics MorphineMorphine Very strongVery strong    DiamorphineDiamorphine Very strongVery strong General CNS depressantsGeneral CNS depressants EthanolEthanol StrongStrong    BarbituratesBarbiturates StrongStrong    MethaqualoneMethaqualone ModerateModerate    GlutethimideGlutethimide ModerateModerate    AnaestheticsAnaesthetics ModerateModerate    SolventsSolvents StrongStrong Anxiolytic drugsAnxiolytic drugs BenzodiazepinesBenzodiazepines ModerateModerate Psychomotor stimulantsPsychomotor stimulants AmphetaminesAmphetamines StrongStrong    CocaineCocaine Very strongVery strong    CaffeineCaffeine WeakWeak    NicotineNicotine Very strongVery strong Psychotomimetic agentsPsychotomimetic agents LSDLSD Weak or absentWeak or absent    MescalineMescaline Weak or absentWeak or absent    PhencyclidinePhencyclidine ModerateModerate    CannabisCannabis Weak or absentWeak or absent
  3. 3. Drug dependenceDrug dependence  Dependence is defined as a compulsive cravingDependence is defined as a compulsive craving that develops as a result of repeatedthat develops as a result of repeated administration of the drug.administration of the drug.  Dependence occurs with a wide range ofDependence occurs with a wide range of psychotropic drugs, acting by many differentpsychotropic drugs, acting by many different mechanisms.mechanisms.  The common feature of dependence-producingThe common feature of dependence-producing drugs is that they have a positive reinforcingdrugs is that they have a positive reinforcing action ('reward') associated with activation ofaction ('reward') associated with activation of the mesolimbic dopaminergic pathway.the mesolimbic dopaminergic pathway.
  4. 4.  dependence is often associated with (i)dependence is often associated with (i) tolerance to the drug, which can arise by varioustolerance to the drug, which can arise by various biochemical mechanisms; (ii) a physicalbiochemical mechanisms; (ii) a physical abstinence syndrome, which varies in type andabstinence syndrome, which varies in type and intensity for different classes of drug; (iii)intensity for different classes of drug; (iii) psychological dependence (craving), which maypsychological dependence (craving), which may be associated with the tolerance-producingbe associated with the tolerance-producing biochemical changes.biochemical changes.  Psychological dependence, which usuallyPsychological dependence, which usually outlasts the physical withdrawal syndrome, is theoutlasts the physical withdrawal syndrome, is the major factor leading to relapse among treatedmajor factor leading to relapse among treated addicts.addicts.  Though genetic factors contribute to drug-Though genetic factors contribute to drug- seeking behaviour, no specific genes have yetseeking behaviour, no specific genes have yet been identified.been identified.
  5. 5. Pharmacological approaches to treating drug dependencePharmacological approaches to treating drug dependence MechanismMechanism ExamplesExamples Substitution, to alleviateSubstitution, to alleviate withdrawal symptomswithdrawal symptoms Methadone, used short-term to blunt opiateMethadone, used short-term to blunt opiate withdrawalwithdrawal    Benzodiazepines, to blunt alcohol withdrawalBenzodiazepines, to blunt alcohol withdrawal Long-term substitutionLong-term substitution Methadone substitution for opiate addictionMethadone substitution for opiate addiction    Nicotine patches or chewing gumNicotine patches or chewing gum Blocking responseBlocking response Naltrexone to block opiate effectsNaltrexone to block opiate effects    Mecamylamine to block nicotine effectsMecamylamine to block nicotine effects    Immunisation against cocaine to produce circulatingImmunisation against cocaine to produce circulating antibody (not yet proven)antibody (not yet proven) Aversive therapiesAversive therapies Disulfiram to induce unpleasant response to ethanolDisulfiram to induce unpleasant response to ethanol Modification of cravingModification of craving Bupropion (antidepressant)Bupropion (antidepressant)    Naltrexone (blocks opiate receptors-also of value inNaltrexone (blocks opiate receptors-also of value in treating other addictions)treating other addictions)    Clonidine (α-adrenoceptor agonist)Clonidine (α-adrenoceptor agonist)    Acamprosate (NMDA-receptor antagonist)Acamprosate (NMDA-receptor antagonist)
  6. 6. Pharmacology of nicotinePharmacology of nicotine  At a cellular level, nicotine acts on nicotinicAt a cellular level, nicotine acts on nicotinic acetylcholine receptors, mainly of the α4β2 subtype,acetylcholine receptors, mainly of the α4β2 subtype, to cause neuronal excitation. Its central effects areto cause neuronal excitation. Its central effects are blocked by receptor antagonists such asblocked by receptor antagonists such as mecamylamine.mecamylamine.  At the behavioural level, nicotine produces a mixtureAt the behavioural level, nicotine produces a mixture of inhibitory and excitatory effects.of inhibitory and excitatory effects.  Nicotine shows reinforcing properties, associated withNicotine shows reinforcing properties, associated with increased activity in the mesolimbic dopaminergicincreased activity in the mesolimbic dopaminergic pathway, and self-administration can be elicited inpathway, and self-administration can be elicited in animal studies.animal studies.
  7. 7. Pharmacology of nicotinePharmacology of nicotine Electroencephalography changes show anElectroencephalography changes show an arousal response, and subjects reportarousal response, and subjects report increased alertness, accompanied by aincreased alertness, accompanied by a reduction of anxiety and tension.reduction of anxiety and tension. Peripheral effects of nicotine result mainly fromPeripheral effects of nicotine result mainly from ganglionic stimulation: tachycardia, increasedganglionic stimulation: tachycardia, increased blood pressure and increase gastrointestinalblood pressure and increase gastrointestinal motility. Tolerance develops rapidly to thesemotility. Tolerance develops rapidly to these effects.effects.
  8. 8. Nicotine is metabolised, mainly in the liver,Nicotine is metabolised, mainly in the liver, within 1-2 hours. Its inactive metabolite,within 1-2 hours. Its inactive metabolite, cotinine, has a long plasma half-life andcotinine, has a long plasma half-life and can be used as a measure of smokingcan be used as a measure of smoking habits.habits. Nicotine replacement therapy (chewingNicotine replacement therapy (chewing gum or skin patch preparations) improvesgum or skin patch preparations) improves the chances of giving up smoking, but onlythe chances of giving up smoking, but only when combined with active counselling.when combined with active counselling.
  9. 9. NicotineNicotine
  10. 10. NicotineNicotine
  11. 11. Effects of ethanolEffects of ethanol Ethanol acts as a general CNSEthanol acts as a general CNS depressant, similar to volatile anaestheticdepressant, similar to volatile anaesthetic agents, producing the familiar effects ofagents, producing the familiar effects of acute intoxication.acute intoxication. Several cellular mechanisms areSeveral cellular mechanisms are postulated: inhibition of calcium channelpostulated: inhibition of calcium channel opening, enhancement of GABA actionopening, enhancement of GABA action and inhibitory action at NMDA-typeand inhibitory action at NMDA-type glutamate receptors.glutamate receptors.
  12. 12. Effective plasma concentrations:Effective plasma concentrations: threshold effects: about 40 mg/100 mlthreshold effects: about 40 mg/100 ml (5 mmol/l)(5 mmol/l) severe intoxication: about 150 mg/100severe intoxication: about 150 mg/100 mlml death from respiratory failure: about 500death from respiratory failure: about 500 mg/100 ml.mg/100 ml. Main peripheral effects are self-limitingMain peripheral effects are self-limiting diuresis (reduced antidiuretic hormonediuresis (reduced antidiuretic hormone secretion), cutaneous vasodilatation andsecretion), cutaneous vasodilatation and delayed labor (reduced oxytocindelayed labor (reduced oxytocin secretion).secretion). Neurological degeneration occurs inNeurological degeneration occurs in heavy drinkers, causing dementia andheavy drinkers, causing dementia and peripheral neuropathies.peripheral neuropathies.
  13. 13. Effects of ethanolEffects of ethanol  Long-term ethanol consumption causes liver disease,Long-term ethanol consumption causes liver disease, progressing to cirrhosis and liver failure.progressing to cirrhosis and liver failure.  Moderate ethanol consumption has a protective effectModerate ethanol consumption has a protective effect against ischemic heart disease.against ischemic heart disease.  Excessive consumption in pregnancy causes impairedExcessive consumption in pregnancy causes impaired fetal development, associated with small size, abnormalfetal development, associated with small size, abnormal facial development and other physical abnormalities, andfacial development and other physical abnormalities, and mental retardation.mental retardation.  Tolerance, physical dependence and psychologicalTolerance, physical dependence and psychological dependence all occur with ethanol.dependence all occur with ethanol.  Drugs used to treat alcohol dependence includeDrugs used to treat alcohol dependence include disulfiram (aldehyde dehydrogenase inhibitor),disulfiram (aldehyde dehydrogenase inhibitor), naltrexone (opiate antagonist) and acamprosate (NMDA-naltrexone (opiate antagonist) and acamprosate (NMDA- receptor antagonist).receptor antagonist).
  14. 14. Metabolism of ethanol.
  15. 15. Fetal Alcohol SyndromeFetal Alcohol Syndrome
  16. 16. Fetal Alcohol SyndromeFetal Alcohol Syndrome
  17. 17. CannabisCannabis  Main active constituent is Δ9-tetrahydro cannabinol (THC),Main active constituent is Δ9-tetrahydro cannabinol (THC), though pharmacologically active metabolites may bethough pharmacologically active metabolites may be important.important.  Actions on CNS include both depressant andActions on CNS include both depressant and psychotomimetic effects.psychotomimetic effects.  Subjectively, subjects experience euphoria and a feeling ofSubjectively, subjects experience euphoria and a feeling of relaxation, with sharpened sensory awareness.relaxation, with sharpened sensory awareness.  THC also shows analgesic and antiemetic activity,THC also shows analgesic and antiemetic activity,  Peripheral actions include vasodilatation, reduction ofPeripheral actions include vasodilatation, reduction of intraocular pressure and bronchodilatation.intraocular pressure and bronchodilatation.  Cannabinoid receptors belong to the G-protein-coupledCannabinoid receptors belong to the G-protein-coupled receptor family, linked to inhibition of adenylate cyclase andreceptor family, linked to inhibition of adenylate cyclase and effects on calcium and potassium channel function, causingeffects on calcium and potassium channel function, causing inhibition of synaptic transmission.inhibition of synaptic transmission.
  18. 18. CannabisCannabis  Anandamide, an arachidonic acid derivative, is anAnandamide, an arachidonic acid derivative, is an endogenous ligand for the CNS cannabinoid receptor; itsendogenous ligand for the CNS cannabinoid receptor; its function has not yet been ascertained.function has not yet been ascertained.  Cannabinoids are less liable than opiates, nicotine orCannabinoids are less liable than opiates, nicotine or alcohol to cause dependence but may have long-termalcohol to cause dependence but may have long-term psychological effects.psychological effects.  Nabilone, a THC analogue, has been developed for itsNabilone, a THC analogue, has been developed for its antiemetic property.antiemetic property.  Though cannabinoids are not available for clinical use,Though cannabinoids are not available for clinical use, trials are in progress for symptomatic treatment oftrials are in progress for symptomatic treatment of multiple sclerosis and AIDS.multiple sclerosis and AIDS.
  19. 19. MarijuanaMarijuana
  20. 20. MarijuanaMarijuana
  21. 21. HallucinogensHallucinogens
  22. 22. LSDLSD
  23. 23. CocaineCocaine
  24. 24. CocaineCocaine
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