Drugs of abuse 2: Cocaine and nicotine Flashcards
Where does cocaine come from?
It is a plant based alkaloid coming from the erythroxylum coca plant
What part of the plant contains cocaine?
The leaves
How is cocaine paste made?
Plant leaves are mushed up with an inorganic solvent- this allows extraction of about 80% of the cocaine
What is the therapeutic form of cocaine?
Cocaine HCl- you take the paste and dissolve it in an acidic solution and then extract the cocaine HCl
What is the most famous route of cocaine abuse?
Intranasal
Why is cocaine not smoked?
Cocaine HCl breaks down when it’s smoked
What is crack?
Precipitate cocaine with an alkaline solution - can be smoked
What is freebase?
Purer form of crack that is dissolved in non-polar solvent and you can extract the slightly purer form of cocaine
How does the rate of onset of cocaine vary between smoked or IV?
Indistinguishable- smoking is slightly faster
How does bioavailability of cocaine vary between smoked or IV?
IV has a much higher bioavailability whereas you lose a lot of the drug when you smoke it
Why does oral have a slow rate of onset?
Cocaine has a relatively high pKa (8.7) so within the stomach it is largely ionised which slows down its absorption- it doesn’t cross the membrane easily but it has prolonged action
Where is cocaine mainly metabolised?
In the liver
How is cocaine metabolised?
Metabolised into inactive metabolites and these metabolites are cleared in the urine relatively quickly
Apart from in the liver, how else can cocaine be metabolised?
By cholinesterase’s- there are plasma cholinesterases so it can be broken down as soon as it gets into the blood
What affects how addictive a drug is?
How quickly euphoric effect is associated with taking drug
How quickly effect is lost
In high doses, cocaine is used as a local anaesthetic, how does it have anaesthetic effects?
It blocks sodium channels and blocks nerve conduction leading to local anaesthetic effect
What is cocaine’s most profound effect as a drug?
It can block monamine transporters
How does cocaine lead to euphoria?
It stops monamines from being removed from synapse so dopamine remains in synapse for longer and you get prolonged effects of dopamine leading to euphoria
Where are dopamine transporters found?
End of the dopaminergic neurone- presynaptic membrane
What effect does cocaine have on the cardiovascular system?
It increases sympathetic output which leads to increase in work that the heart has to do so there is greater demand
Prolonged sympathetic stimulation will cause vasoconstriction and active platelets which promotes atherosclerosis and narrowing of vessels which decreases oxygen supply to the heart
How does cocaine increase sympathetic output?
Increases duration of noradrenaline in synapse and stimulates sympathetic nerves
What effect can cocaine have in the brain?
It can cause seizures as it reduces blood flow to the brain and you also get heat build up in certain parts of the brain- can cause epilepsy
Where does nicotine come from?
It is a plant based compound coming from nicotiana tabacum
What percentage of a cigarette is nicotine?
5%
Why is the delivery system via a cigarette very effective?
When you heat the cigarette, tar within the particulate matter forms lipid droplets- alkaloids dissolve in the tar droplets and then are distributed very well in the lung. The alkaloids then diffuse from the tar across the alveoli
What other methods apart from smoking are there for nicotine delivery?
Spray, gum and patches
How effective are cigarettes at delivering nicotine?
Not particularly efficient- smoke is acidic whereas pKa of nicotine prefers a more alkaline environment so it becomes ionised and isn’t particularly well absorbed
Why do people chain smoke?
In an attempt to maintain a high blood nicotine level- drug gives a rapid onset of action but effects are lost pretty quickly
How is nicotine metabolised?
It is broken down into cotinine in the liver and then cleared relatively rapidly in the urine
What receptors does nicotine bind to?
Nicotine acetylcholine receptors
What happens when nicotine binds to its receptors?
It activates the receptor and stimulates sodium influx
Where are nicotinic acetylcholine receptors found in the ventral segmental area?
On the cell bodies of the dopaminergic neurones
How does nicotine increase dopamine secretion?
It activates the receptor which directly activates the dopaminergic neurone and leads to increased firing rate of the dopaminergic neurone and hence more dopamine secretion
What effect does nicotine have on the cardiovascular system?
It causes an increase in sympathetic activity so it increases cardiac work- heart rate and stroke volume
It also causes vasoconstriction of coronary arterioles thus reducing oxygen delivery to the myocardium which leads to an imbalance between supply and demand and risk of atherosclerosis
What effect does nicotine have on metabolic rate?
It increases it- smokers tend to put on weight once they stop smoking
What effect does nicotine have on the brain?
It provides protection for some neurological systems- it increases the brain’s cytochrome p450 system which increases the brains ability to metabolise neurotoxins which are involved in Parkinson’s.
It also appears to diminish some of the proteins that contribute to Alzheimer’s disease
How does adenosine affect dopamine function?
It negatively impacts dopamine function by activating the adenosine receptor which causes decrease in dopamine release and decreased D1 receptor function so diminishes euphoric effects
How does caffeine affect dopamine function?
It is an adenosine receptor antagonist so prevents negative effects of adenosine on dopaminergic neurone but it’s a very small contributor to this pathway so dopamine increase due to caffeine is small
