Drug Interactions Dual Diagnosis Forum, St Chads, Friday 3 rd
October Duncan Raistrick, Leeds Addiction Unit Slide 2 Plan for the
Session How drugs/medicines work Classes of drugs/medicines Common
interactions of drugs/medicines Coffee Break Case scenario
discussions Slide 3 How do drugs and medicines work? Slide 4
Receptors & neurotransmitters receptor Slide 5 The big four
neurotransmitters: 1 GABA inhibits 2 Glutamate excites 3 Dopamine
pleasure and psychosis 4 Serotonin (5HT) mood and psychosis Slide 6
All the nice things in life end up as dopamine in the pleasure
centre NAC Slide 7 normal reponse regular use reduced response
smoker alcohol obesity cocaine .but too much and it stops being
rewarding. dopamine receptor activity Slide 8 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 Slide 9 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 Psilocybin-6 hrs Allow x4-5 half-lives to eliminate a drug
Slide 10 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 Slide 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.. Slide 12 How is it that effects are specific? Slide 13
Which receptors do different groups of drugs work at? Slide 14
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 Slide 15 Agonist and
Antagonist Drugs opiate receptor Full agonist (eg morphine) Partial
agonist (eg buprenorphine) No receptor activityAntagonist (eg
naltrexone) Slide 16 OPIATE mu: analgesia, GABA effects kappa:
analgesia, miosis sigma: psychosis GABA relaxation coma DOPAMINE
pleasure psychosis OPIATES Heroin Morphine Codeine Tramadol DF118
Fentanyl Subutex Slide 17 GLUTAMATE overactive confusion/fits
DOPAMINE pleasure psychosis Stimulants Cocaine Amphetamine Nicotine
Caffeine Mephadrone Ecstasy selection of XTC (MDMA) tablets cocaine
powder & crack Slide 18 Spectrum of Stimulant Drug Excitation
Stimulant drugs and psychotic illness may have a similar effect
Slide 19 GABA relaxation coma CANNABIS receptor enhances GABA &
DA DOPAMINE pleasure psychosis Depressants Alcohol Benzodiazepines
Gabapentin Pregabalin Cannabis Barbiturates Hemineverin
Anticonvulsants Slide 20 Alcohol Neurochemistry Alcohol
pharmacotherapy Slide 21 GLUTAMATE overactive confusion/fits
SEROTONIN mood sleep Hallucinogens LSD Psylocibin Mushrooms
Ketamine GHB/GLB LSD ketamine GHB Slide 22 What are the main kinds
of interaction between drugs? Slide 23 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
Slide 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. Slide 25 2nd
interaction type irregular heart beat Caused by: Genetics Methadone
Alcohol (high BAC) Antidepressants Citalopram Mirtazepine
Amitriptyline Statins Antihistamines Slide 26 The heart does not
pump blood properly. At worst may be cardiac arrest. Slide 27 3rd
interaction type metabolism Caused by: Alcohol misuse Over eating
Atypical antipsychotics Clozaril Olanzapine Quetiapine Risperidone
Gabapentin Paroxetine (+ SSRIs) Slide 28 Slide 29 4th interaction
type enzyme effects - induction Alcohol Cigarette smoking
Carbamazepine Phenytoin Rifampicin Phenobarbitone Cabbage Broccolli
Brussels sprouts Cauliflower Charbroiled meats Oregano Slide 30 4th
interaction type enzyme effects - blockers General (CYP450)
Cimetidine/Ranitidine Diazepam SSRI antidepressants Some anti
virals St Johns Wort (herbal antidepressant) Chamomile Grapefruit
juice Specific Disulfiram Metronidazole Slide 31 enzyme blocking As
with antipsychotics, antidepressant effects are not usually
specific. Some also have a generalised enzyme blocking effect.
Slide 32 Blocks dopamine metabolism Blocks alcohol metabolism Slide
33 Coffee Break Slide 34 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. Slide 35 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. Slide 36 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.
Slide 37 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.
