Drugs of Abuse 2 Flashcards
What are the four different forms of cocaine and how are they made?
Cocaine paste –this is simply the plant (erythroxylum coca) mushed up in a solvent
Cocaine HCl – therapeutic form of cocaine: you take the cocaine paste and dissolve it in an acidic solution
Crack – cocaine is precipitated with an alkaline solution (e.g. baking soda)
Freebase – slightly purer form of crack: you take crack and dissolve it in a non-polar solvent (e.g. ammonia and ether)
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
Quick onset + Short half life = really fucking addictive
Explain how cocaine can act as a local anaesthetic.
Cocaine blocks sodium channels and hence inhibits nerve transmission (Only occurs at relatively high dose)
By what mechanism does cocaine exert its most profound effects?
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 – positive reinforcement – more energetic, need less sleep, more sociable, more talkative
High dose – 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)
This leads to vasoconstriction, thus causing an increase in cardiac work 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
(NOTE: Vasoconstriction of vessels in septum leads to snorted cocaine fucking up the septum)
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
How can cocaine cause Hyperthermia?
Cocaine overdose triggers agitation and sympathetic driven locomotor activity increase as well as involuntary muscle contraction, all increasing heat production.
It also increases the temperature threshold that triggers sweating and cutaneous vasodilation (also inhibits extent of vasodilation and enhances sweating) meaning a rapid, maintained increase in temperature.
What percentage of a cigarette is particulate and what percentage is volatile?
5% particulate (Alkaloid including nicotine)
95% volatile
Which matter contains most carcinogenic elements?
Volatile
