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

How do drugs and medicines work?

Receptors & neurotransmitters receptor

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……..

How is it that effects are specific?

Which receptors do different groups of drugs work at?

Classification of Psychoactive Drugs oOpiates: euphoria, analgesia, drowsiness oMorphine, heroin, codeine, tramadol, buprenorphine oStimulants: overactive, talkative, confident oEcstasy, amphetamines, cocaine, mephadrone oDepressants: relaxation, disinhibition oCannabinoids, alcohol, benzodiazepines, pregabalin, gabapentin oHallucinogens: altered perception, mood change oSolvents, GHB/GLB, LSD, ketamine, psylocibin

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

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

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

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

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

Alcohol Neurochemistry Alcohol pharmacotherapy

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

What are the main kinds of interaction between drugs?

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

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

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

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

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

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

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.

Blocks dopamine metabolism Blocks alcohol metabolism

Coffee Break

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.