drug abuse 3 Flashcards
what is meant by gateway drug
a drug that leads to the use of harder drugs e.g. cannabis
how do gateway drugs lead to use of harder drugs
the hit might not be enough, users might want a harder and longer hit
users more likely to be exposed to harder drugs esp in countries where softer drugs are illegal, have to obtain them from dealers, friends
they enjoy the pleasurable effects - want to experience more
explain legal highs and their toxicity
very little safety data on legal high toxicity
LD50 and ED50 not known
may contain impurities - enantiomers, cutting agents
mephedrone toxicity - dilated pupils, teeth grinding, poor concentration, hallucinations, discolouration of extremities
polynarcotic toxicity
when narcotic drugs are combined to increase the hit
- when reduced hit is achieved with drug alone
describe narcotic/pharmacological interactions?
benzodiazepines with alcohol and opiates
- inhibits metabolism of opiates - increase concentration- increase potency - increase chance of OD + toxicity
primarily metabolised via 3A4 and glucuronidation
- 3A4 substrates inhibit metabolism - increase effect e.g. antidepressants, antifungals
- 3A4 inducers - increase metabolism, decrease effect e.g. rifampicin, phenytoin, carbamazepine
methadone
- subjected to significant pharmacogenetic variation by 3A4
- Rapid metaboliser phenotypes have to take twice the standard dose
- 3A4 inhibitors increase conc. e.g. fluconazole, ketoconazole, cimetidine, grapefruit juice
- 3A4 inducers will decrease methadone conc. e.g. rifampicin, phenytoin
MDMA
- MDMA metabolites are suicide inhibitors of 2D6
- turn every user into a poor metaboliser phenotype
- metabolism by this pathway is reduced - increase concentration + half life - toxicity particularly in TCAs - leads to tachycardia, hallucinations
- prodrugs lose their efficacy
cannabis toxicity
toxic effect is asphyxiation
toxic dose to psychoactive dose is 40,000:1
little reported toxicity as low chance of fatal overdose, large therapeutic window, and lack of physical dependence and safer withdrawal symptoms
toxic in pregnant women - teratogenic
in adolescents esp males - due to developing brain
ketamine toxicity
low doses - psychoactive properties
- comatose
- neuronal changes
medium to high dose
- slurred speech
- immobilisation
- amnesia
long term causes prefrontal cortex damage
- can increase rate of depression
- impairs cognitive ability + memory
chronic users can develop bladder toxicity
MDMA toxicity
causes serotonergic neurone degeneration
MDMA forms catechol metabolites that form redox cycling quinones which are glutathione conjugated and can be transported across the brain - forming ROS
ROS - occurs due to imbalance between production and ability of cells to detoxify - serotonergic neurones more prone to oxidative stress as serotonin is oxidisable
can also cause PD - via dopaminergic neurone damage
heroin toxicity
LD50 = 75-600mg
occurs due to variation in purity,
cutting agent, co administration with other drugs e.g cocaine
most common SE is constipation
nausea and vomiting - death via aspiration of vomit
respiratory depression - fatal
leukoencephalopathy
methadone toxicity
occurs when co administered with CYP3A4 inhibitors
pinpoint pupils
hypoventilation
sedation
coma
effects are reversible except coma
alcohol toxicity
at low doses 1g/L BAC = 0.1%
- nausea vomiting intoxication
at medium to high doses 3g/L BAC = 0.3%
- stupor (unresponsiveness)
- loss of consciousness
- loss of bladder control
- perturbed heart rhythm
- possibility of death (50% of patients with BAC > 0.4% die)
hepatic steatosis - accumulation of fat in liver - fatty liver
alcoholic hepatitis - inflammation and damage to liver cells - jaundice, abdominal pain, nausea, hepatomegaly
fibrosis - scar tissue formation
cirrhosis - at this point need liver transplant
