drug abuse 4

Question 1

what is pethidine used for?

Answer 1

class A synthetic opioid

used for relief of pain in child birth and labour

intrathecal administration

slows down labour
- pain of contractions is designed to decrease time b/w contractions
- inhibiting pain reduces this positive feedback
- prolongs child birth

Question 2

pethidine metabolism and addiction

Answer 2

norpethidine - nerutoxic form
pethidinic acid and norpethidinic acid - inactive forms

same effects as heroin
heavy users appear slow and confused
develop tolerance over time
- need bigger and bigger doses

not a problem in UK - as its limited to use in labour

OD cannot be treated with naloxone

Question 3

illegal therapeutic use examples

Answer 3

cannabis and MS:
- MS - autoimmune myelination disease - myelin sheath is destroyed
- anecdotal reports suggest cannabis is effective at pain relief and treating spasticity associated with MS
- various trials have shown conflicting results

cannabis oil and childhood epilepsy:
- many patients have severe epilepsy - up to 100 seizures a day
- anecdotal evidence shows cannabis extracts (cannabis oil) can relieve seizure symptoms in otherwise untreatable patients
- however its use in children has neurological development concerns - associated with 9-THC
- CBD has no neurological toxicity
- UK GOV allowed 20 day license for its use in April 2019

MDMA and PD:
- PD characterised by degeneration of dopaminergic neurones of substantia nigra
- gives rise to motor and non-motor symptoms
- anecdotal reports that MDMA can dramatically reduce uncontrollable arm and leg movements
- however other evidence suggests single dose MDMA can cause toxicity - serotonergic degeneration
- systemic administration leads to release of ROS
- catechol metabolites can form redox-cycling quinones which can be glutathione conjugated and transported across brain to form ROS
- also thought to cause PD later on in life due to dopaminergic damage
- suicide inhibitors of CYP2D6
- effects last for 7-10 days as you have to wait for more 2D6 to be synthesised as cannot induce synthesis

Question 4

what classes of drugs will MDMA interact with?

Answer 4

antipsychotics - chlorpromazine
- cognitive depression
- coma
- respiratory arrest

antidepressant e.g. TCAs
- hallucinations
- tachycardia
- respiratory arrest
- coma
- death

Question 5

describe therapeutics based upon drugs of abuse?

Answer 5

sativex
- used for pain and spasticity in MS and analgesia in advanced cancer patients
- mix of THC and CBD
- approved in UK in 2019
- CBD - pharmacological effect
- THC - psychotropic effect

epidiolex
- treatment of dravet and lennox gastaut syndrome - severe forms of epilepsy
- only CBD, no THC
- reduces seizures upto 40% in some children
- expensive - costs 5000-10000 per patient per year

nabilone
- synthetic cannabanoid similar to THC
- for nausea and vomiting in patients undergoing cancer chemotherapy
- UK approved in 1982

MDMA based therapies for PD:
- MDMA analogues still under test
- none have been developed and transferred from pre clinical to phase 1 trials
- very toxic - suicide inhibitors
- UWA-101 - lead compound better at improving L-dopa effect than MDMA, not psychoactive - hasn’t progressed into phase 3 due to toxicities