Drugs of Abuse 2 – Cocaine and Nicotine Flashcards
What are the four different forms of cocaine and how are theymade?
intranasal, oral, IV:
- Paste-80% cocaine
- cocaine HCL (paste in acidic solution)
inhalational:
- crack
- freebase (dissolved in non polar solvent)
Which route of administration of cocaine gives the fastest absorption?
Smoking (though IV gives a higher bioavailability)
Why is cocaine very slowly absorbed in the GI tract?
Cocaine has a pKa of 8.7 so it is mainly ionised in the stomach meaning that it isn’t very lipid soluble and it isn’t very easily absorbed This does, however, mean that the cocaine has a prolonged action
What is the half-life of cocaine?
20-90 mins
Where is cocaine metabolised and what is it metabolised into?
Liver – inactive metabolites: -ecgonine methyl ester+ benzoylecgonine
Plasma – it can be metabolised by plasma cholinesterases so it doesn’t last long in the plasma
Which factors affect the addictive potential of a drug?
The speed at which you associate the euphoria with taking the drug and the speed with which the effects are lost
Explain how cocaine can act as a local anaesthetic.
high dose: Cocaine blocks sodium channels and hence inhibits nerve transmission
By what mechanism does cocaine exert its most profound effects?
low dose: Inhibition of monoamine transporters – leads to an accumulation of monoamines (e.g. dopamine) at the synapse
How does cocaine cause euphoria?
Cocaine blocks the monoamine transporters at the end of the dopaminergic neurones projecting to the nucleus accumbens – this leads to an accumulation of dopamine in the synapse at the nucleus accumbens –> EUPHORIA
What are the differences between the effects of low dose cocaine and high dose/chronic cocaine use?
Low dose/acute – positive reinforcement – more energetic, need less sleep, more sociable, more talkative these initial effects soon become those below
High dose/chronic – negative/stereotypical effects – exhaustion, irritability, hostility, insomnia
Describe how cocaine is associated with a significantly increased cardiovascular risk.
Cocaine causes an increase in sympathetic output (NOTE: noradrenaline is also a monoamine) ^HR+^contractility, thus causing an increase in oxygen demand Also leads to vasoconstriction- decreased oxygen supply It will also activate platelets and promote atherosclerosis, leading to the narrowing of vessels and decreased oxygen supply to the heart This could lead to myocardial infarction
How can cocaine prompt seizures?
It causes vasoconstriction in various arteries of the brain and it also causes an increase in temperature, which can prompt seizures It is linked to the development of epilepsy
What percentage of a cigarette is particulate and what percentage is volatile?
5% particulate -eg nicotine
95% volatile -eg co2/hcn/benzene
Why is the nicotine delivery via a cigarette so effective?
Heating the cigarette melts the tar so that it forms lipid droplets The alkaloids dissolve in the lipid droplets, which are then widely distributed across the lungs and can be easily absorbed
Describe the metabolism of nicotine. What is the product?
Nicotine is metabolised by CYP2A6 in the liver This produces COTININE, which is then excreted in the urine
Describe how nicotine causes euphoria.
Nicotine binds to nicotinic acetylcholine receptors on the cell bodies of dopaminergic neurones in the ventral tegmental area and stimulates sodium influx This leads to an increase in the firing rate of the dopaminergic neurones, hence, more dopamine secretion
Explain how caffeine can cause mild euphoria.
Adenosine acts via adenosine receptors to decrease dopamine release and decrease D1 receptor function
Caffeine is an adenosine receptor antagonist so it will remove the inhibitory effect of adenosine–>^Dopamine in Nacc
However, the inhibitory effect of adenosine is very minimal so caffeine will not cause a significant rise in dopamine release
