The big four neurotransmitters: 1 GABA – inhibits 2 Glutamate – excites 3 Dopamine – pleasure and psychosis 4 Serotonin (5HT) – mood and psychosis
All the nice things in life…… ……end up as dopamine in the ‘pleasure centre’ NAC
normal reponse regular use reduced response smoker alcohol obesity cocaine ….but too much and it stops being rewarding…. dopamine receptor activity
Parent Drug Metabolites Unchanged Drug What happens to drugs in your body? typically drugs are broken down and made water soluble to pass in urine
Time taken to eliminate a drug depends on its half life (which is constant): Amphetamine12 hr (normal urine) Cocaine30-90 mins Cannabis20-36 hrs Alcohol1 hr Lorazepam12 hrs Temazepam8 hrs Diazepam32 hrs Desmethyl-diazepam65 hrs Heroin3 mins Morphine2-3 hrs Codeine2-4 hrs Dihydrocodeine4 hrs Methadone15-55 hrs Psilocybin½-6 hrs Allow x4-5 half-lives to eliminate a drug
Clinical screening threshold 300 ug/L UK Workplace screening threshold 150 ug/L Limit of quantitation 10 ug/L Limit of detection 4 ug/L Detecting cocaine use….. ug/L
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……..
4th interaction type ‘enzyme effects - blockers’ General (CYP450) Cimetidine/Ranitidine Diazepam SSRI antidepressants Some anti virals St John’s Wort (herbal antidepressant) Chamomile Grapefruit juice Specific Disulfiram Metronidazole
enzyme blocking As with antipsychotics, antidepressant effects are not usually specific. Some also have a generalised enzyme blocking effect.
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.
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.
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.
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.