Drugs of Abuse 2 – Cocaine and Nicotine 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
75-90% excreted in the urine
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.
When uncharged coacine diffuses into/across the plasma membrane
Cocaine can then block open or closed sodium channels and hence inhibits nerve transmission
By what mechanism does cocaine exert its most profound effects?
It is a reuptake inhibiotr at lower doses
Inhibition of monoamine transporters – leads to an accumulation of monoamines (e.g. dopamine and noradrenaline) 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 stimulates the sympathetic nervous system by:
inhibiting catecholamine reuptake at sympathetic nerve terminals,
stimulating central sympathetic outflow,
and increasing the sensitivity of adrenergic nerve endings to norepinephrine.
This leads to Increased heart rate, contractility and increased bp, therefore increasing the overall demand on the heart and hence increasing myocardial oxygen demand
It also causes coronary 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
In addition, cocaine stimulates the release of endothelin-1, a potent vasoconstrictor, from endothelial cells and inhibits nitric oxide production, the principal vasodilator produced by endothelial cells. This leads to inflammation and consequently endothelial injury and more atherosclerosis
This could lead to myocardial infarction
Cocaine’s effect on decreasing sodium transport can also cause arrhythmias
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
95% volatile
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
Which matter contains most carcinogenic elements?
Volatile
