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Drug Interactions

Drug Interactions. Dual Diagnosis Forum, St Chad’s, Friday 3 rd October Duncan Raistrick, Leeds Addiction Unit. Plan for the Session. How drugs/medicines work Classes of drugs/medicines Common interactions of drugs/medicines Coffee Break Case scenario discussions.

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Drug Interactions

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  1. Drug Interactions Dual Diagnosis Forum, St Chad’s, Friday 3rdOctober Duncan Raistrick, Leeds Addiction Unit

  2. Plan for the Session • How drugs/medicines work • Classes of drugs/medicines • Common interactions of drugs/medicines Coffee Break • Case scenario discussions

  3. How do drugs and medicines work?

  4. Receptors & neurotransmitters receptor

  5. The big four neurotransmitters: 1 GABA – inhibits 2 Glutamate – excites 3 Dopamine – pleasure and psychosis 4 Serotonin (5HT) – mood and psychosis

  6. NAC All the nice things in life…… ……end up as dopamine in the ‘pleasure centre’

  7. ….but too much and it stops being rewarding…. regular use reduced response smoker alcohol obesity cocaine normal reponse smoker alcohol obesity cocaine dopamine receptor activity

  8. What happens to drugs in your body? Parent Drug Unchanged Drug Metabolites typically drugs are broken down and made water soluble to pass in urine

  9. Time taken to eliminate a drug depends on its half life (which is constant): Amphetamine 12 hr (normal urine) Cocaine 30-90 mins Cannabis 20-36 hrs Alcohol 1 hr Lorazepam 12 hrs Temazepam 8 hrs Diazepam 32 hrs Desmethyl-diazepam 65 hrs Heroin 3 mins Morphine 2-3 hrs Codeine 2-4 hrs Dihydrocodeine 4 hrs Methadone 15-55 hrs Psilocybin ½-6 hrs Allow x4-5 half-lives to eliminate a drug

  10. Detecting cocaine use….. Clinical screening threshold 300 ug/L ug/L UK Workplace screening threshold 150 ug/L Limit of quantitation 10 ug/L Limit of detection 4 ug/L

  11. Poppy Seed Defence if reporting cut offs set too low then ‘false’ positives – too high ‘false’ negatives Contains 1.5mg morphine 0.1mg Codeine Implications for child protection, prescribing, occupational risks……..

  12. How is it that effects are specific?

  13. Which receptors do different groups of drugs work at?

  14. Classification of Psychoactive Drugs • Opiates: euphoria, analgesia, drowsiness • Morphine, heroin, codeine, tramadol, buprenorphine • Stimulants:overactive, talkative, confident • Ecstasy, amphetamines, cocaine, mephadrone • Depressants: relaxation, disinhibition • Cannabinoids, alcohol, benzodiazepines, pregabalin, gabapentin • Hallucinogens: altered perception, mood change • Solvents, GHB/GLB, LSD, ketamine, psylocibin

  15. opiate receptor Antagonist (eg naltrexone) No receptor activity Agonist and Antagonist Drugs Full agonist (eg morphine) Partial agonist (eg buprenorphine)

  16. OPIATES Heroin Morphine Codeine Tramadol DF118 Fentanyl Subutex OPIATE mu: analgesia, GABA effects kappa: analgesia, miosis sigma: psychosis DOPAMINE pleasure psychosis GABA relaxation coma

  17. DOPAMINE pleasure psychosis Stimulants Cocaine Amphetamine Nicotine Caffeine Mephadrone Ecstasy GLUTAMATE overactive confusion/fits cocaine powder & crack selection of XTC (MDMA) tablets

  18. Spectrum of Stimulant Drug Excitation Stimulant drugs and psychotic illness may have a similar effect

  19. Depressants Alcohol Benzodiazepines Gabapentin Pregabalin Cannabis Barbiturates Hemineverin Anticonvulsants GABA relaxation coma CANNABIS receptor enhances GABA & DA DOPAMINE pleasure psychosis

  20. Alcohol Neurochemistry Alcohol pharmacotherapy

  21. SEROTONIN mood sleep LSD Hallucinogens LSD Psylocibin Mushrooms Ketamine GHB/GLB ketamine GLUTAMATE overactive confusion/fits GHB

  22. What are the main kinds of interaction between drugs?

  23. For example PSYCHOSIS and drugs causing psychosis: Opiates Dextromoramide Pentazocine Stimulants Cocaine Amphetamine Depressants Alcohol Cannabis Hallucinogens LSD Ketamine Mushrooms 1st interaction type‘same effect’

  24. Antipsychotics all block dopamine. All have effects at other receptors which gives each its individual profile. Olanzapine is most likely to cause metabolic syndrome.

  25. Caused by: Genetics Methadone Alcohol (high BAC) Antidepressants Citalopram Mirtazepine Amitriptyline Statins Antihistamines 2nd interaction type‘irregular heart beat’

  26. The heart does not pump blood properly. At worst may be cardiac arrest.

  27. Caused by: Alcohol misuse Over eating Atypical antipsychotics Clozaril Olanzapine Quetiapine Risperidone Gabapentin Paroxetine (+ SSRIs) 3rd interaction type‘metabolism’

  28. Alcohol • Cigarette smoking • Carbamazepine • Phenytoin • Rifampicin • Phenobarbitone • Cabbage • Broccolli • Brussels sprouts • Cauliflower • Charbroiled meats • Oregano 4th interaction type‘enzyme effects - induction’

  29. General (CYP450) • Cimetidine/Ranitidine • Diazepam • SSRI antidepressants • Some anti virals • St John’s Wort • (herbal antidepressant) • Chamomile • Grapefruit juice • Specific • Disulfiram • Metronidazole 4th interaction type‘enzyme effects - blockers’

  30. As with antipsychotics, antidepressant effects are not usually specific. Some also have a generalised enzyme blocking effect. enzyme blocking

  31. Blocks alcohol metabolism Blocks dopamine metabolism

  32. Coffee Break

  33. Table 1 Tracy is a 27yr old woman who works in estate agent office. She goes out weekends and uses a lot of recreational drugs – she feels depressed and lacking confidence at work the next week and has taken to using some GBH to perk her up when she takes clients to see properties. Her GP has prescribed her citalopram (an SSRI antidepressant) and she has asked her to prescribe some diazepam. What are the pharmacological possibilities.

  34. Table 2 John is a 45yr old man who was diagnosed with schizophrenia in his early twenties. He is prescribed olanzapine 15mg daily and wants to have this increased because he is using quite a bit of cannabis and drinking to help him cope with his ‘voices’ and to help him overcome his anxiety about going out of the house. A few years ago he broke his arm and he still get pain and when it is bad his GP treats this with tramadol. What are the pharmacological possibilities.

  35. Table 3 Julie is a 24yr old who has been told that she has a personality disorder. She was sexually abused in her early life and has repeatedly taken up in relationships with violent men. She has used most illicit drugs and is prescribed methadone 120mg from a drugs service. She sees her drugs worker with a story that she is being followed and is scared. She is drinking 3L cider daily and is wanting some help. What are the pharmacological possibilities.

  36. Table 4 Dave is a 42yr old man who has a long history of prescription opiate misuse, drinking and depression. His life fell apart 3yrs ago when he lost his job and his wife left him. He became homeless. Dave is in hospital where he started treatment with rifampicin for tuberculosis. Dave is hopeful that he can be rehoused and wants help to get over his substance misuse. What are the pharmacological possibilities.

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