Drug Interactions
Dual Diagnosis Forum, St Chad’s, Friday 3rd 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……
NAC
……end up as dopamine
in the ‘pleasure centre’
….but too much and it stops being rewarding….
regular use
reduced
response
smoker
alcohol
obesity
cocaine
normal
reponse
smoker
alcohol
obesity
dopamine receptor activity
cocaine
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
Time taken to eliminate a drug depends on
its half life (which is constant):
Amphetamine
Cocaine
Cannabis
Alcohol
Lorazepam
Temazepam
Diazepam
Desmethyl-diazepam
Heroin
Morphine
Codeine
Dihydrocodeine
Methadone
Psilocybin
12 hr (normal urine)
30-90 mins
20-36 hrs
1 hr
12 hrs
8 hrs
32 hrs
65 hrs
3 mins
2-3 hrs
2-4 hrs
4 hrs
15-55 hrs
½-6 hrs
Allow x4-5 half-lives to eliminate a drug
ug/L
Detecting cocaine use…..
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
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
o Opiates: euphoria, analgesia, drowsiness
o Morphine, heroin, codeine, tramadol, buprenorphine
o Stimulants: overactive, talkative, confident
o Ecstasy, amphetamines, cocaine, mephadrone
o Depressants: relaxation, disinhibition
o Cannabinoids, alcohol, benzodiazepines, pregabalin,
gabapentin
o Hallucinogens: altered perception, mood change
o Solvents, GHB/GLB, LSD, ketamine, psylocibin
Agonist and Antagonist Drugs
opiate receptor
Full agonist (eg morphine)
Antagonist (eg naltrexone)
Partial agonist (eg
buprenorphine)
No receptor activity
OPIATES
Heroin
Morphine
Codeine
Tramadol
DF118
Fentanyl
Subutex
OPIATE
mu: analgesia, GABA effects
kappa: analgesia, miosis
sigma: psychosis
GABA
relaxation
coma
DOPAMINE
pleasure
psychosis
Stimulants
Cocaine
Amphetamine
Nicotine
Caffeine
Mephadrone
Ecstasy
DOPAMINE
pleasure
psychosis
GLUTAMATE
overactive
confusion/fits
selection of XTC (MDMA) tablets
cocaine powder
& crack
Spectrum of Stimulant Drug Excitation
Stimulant drugs and psychotic illness may
have a similar effect
Depressants
Alcohol
Benzodiazepines
Gabapentin
Pregabalin
Cannabis
Barbiturates
Hemineverin
Anticonvulsants
CANNABIS receptor
enhances GABA &
DA
GABA
relaxation
coma
DOPAMINE
pleasure
psychosis
Alcohol Neurochemistry
Alcohol
pharmacotherapy
Hallucinogens
LSD
Psylocibin
Mushrooms
Ketamine
GHB/GLB
SEROTONIN
mood
sleep
GLUTAMATE
overactive
confusion/fits
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.
Caused by:
Genetics
Methadone
Alcohol (high BAC)
Antidepressants
Citalopram
Mirtazepine
Amitriptyline
2nd interaction type
‘irregular heart beat’
Statins
Antihistamines
The heart does
not pump blood
properly.
At worst may be
cardiac arrest.
Caused by:
Alcohol misuse
Over eating
Atypical antipsychotics
Clozaril
Olanzapine
Quetiapine
Risperidone
Gabapentin
3rd interaction type
‘metabolism’
Paroxetine (+ SSRIs)
4th interaction type
‘enzyme effects - induction’
Alcohol
Cigarette smoking
Carbamazepine
Phenytoin
Rifampicin
Phenobarbitone
Cabbage
Broccolli
Brussels sprouts
Cauliflower
Charbroiled meats
Oregano
General (CYP450)
Cimetidine/Ranitidine
Diazepam
SSRI antidepressants
Some anti virals
St John’s Wort
(herbal antidepressant)
4th interaction type
‘enzyme effects - blockers’
Chamomile
Grapefruit juice
Specific
Disulfiram
Metronidazole
As with
antipsychotics,
antidepressant effects
are not usually
specific.
Some also have a
generalised enzyme
blocking effect.
enzyme blocking
Blocks alcohol
metabolism
Blocks dopamine
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.