Drugs of Abuse - Cocaine and Nicotine Flashcards
What is Cocaine?
An Alkaloid drug coming from the Erythroxylum coca plant leaves
What are the four most common forms of Cocaine?
How are they made?
Cocaine paste - Mush up leaves with organic solvent - 80%
Cocaine HCL - take paste and dissolve it in HCL then extract
Crack - Precipitate cocaine with an alkaline solution
Freebase - take Crack and dissolve it in a non-polar solvent (e.g. ammonia + ether) - purer crack
How can Cocaine be administered?
Cocaine paste and HCL: IV, Orally, Intranasally - NOT SMOKED
Crack and Freebase - can be smoked as they don’t thermally decompose
What method of Cocaine administration gives the fastest onset?
(rank them all)
Smoking = IV
Intranasally
Orally
Which method of Cocaine administration gives the highest Bioavailability and why?
IV, more than smoking as you lose a lot of the drug when smoked
Why does oral absorption of Cocaine take so long?
Cocaine has a relatively high pKa (8.7)
So in the acidic stomach, it is largely ionised, so will not pass through membranes that quickly, so absorption takes a while
This does mean that it has prolonged action though
Where is cocaine metabolised?
Mostly in the liver - quickly into inactive metabolites cleared via the urine
Also by Plasma cholinesterases in the blood - active cocaine doesn’t last long in the blood
Name two significant factors that decide the addictive potential of a drug:
Speed of onset
How quickly effects are lost
How addictive is Cocaine?
Probably the most addictive drug on the planet because of its powerful euphoric effects that come on quickly and leave quickly
How can Cocaine act as a local anaesthetic?
Blocks sodium channels - blocking nerve conduction
What is the main method of action of Cocaine?
It’s a Monoamine Transporter Blocker
It prevents monoamines from being removed from the synapse prolonging effects
e.g. Dopamine - euphoria
What are Monoamines?
Neurotransmitters containing a single amine group:
Dopamine
(Nor)adrenaline
Seratonin
Where does Cocaine act to produce Euphoria?
Blocks the MAO on the presynaptic membrane at the synapse between the neurone from the VTE and the NAcc
This increase the amount of dopamine in the synapse - Euphoria
What are the differences in the effects of low-dose and high-dose Cocaine?
What are the two main actions of Cocaine on the Cardiovascular system?
Increases Sympathetic output - increase duration of NA in synapse
SNS stimulation causes Vasoconstriction and Activates Platelets
What are the long-term consequences of the actions of Cocaine on the Heart?
Increased SNS output - Increases the work of Cardiac muscle
Vasoconstriction and Platelet activation - promotes atherosclerosis and vessel narrowing decreasing the O2 supply to the heart
This may lead to tissue ischaemia, MI and Death
What are the Consequences of Cocaines LA properties on the CVS?
It will interfere with any underlying heart issues e.g. Arrhythmias
Together with its other effects, this significantly increases the risk of MI
What are the possible long-term effects of Cocaine on the Brain?
Has been found to prompt seizures
Reduces blood flow to the brain and can cause heat build-up in certain parts that is linked to the development of Epilepsy
Where does Nicotine come from?
How much of this drug makes up a Cigarette?
Nicotiana tabacum
5% of a cigarette
How does smoking a Cigarette get Nicotine into the lungs?
Heating the tobacco the tar melts forming lipid droplets
The alkaloids dissolve in the tar
These droplets are then very well distributed in the lung
How much Nicotine is absorbed from a Cigarette?
20% Not efficient
(9-17mg)
Why are Cigarettes not particularly efficient?
Cigarette smoke is acidic whereas the pKa of Nicotine (7.9) prefers a more alkaline environment
The nicotine becomes ionised so is not particularly well absorbed
(There is no buccal absorbtion)
Describe Nicotine Metabolism:
Liver breaks nicotine down to Cotinine
This is then cleared into the urine relatively rapidly
(Its not as fast as Cocaine, but its still pretty quick which is why its so addictive)
What does Nicotine do?
It binds to Nicotinic ACh receptors (dur)
Causes Na influx (agonising them)
How does Nicotine cause ‘euphoria’?
Binds to the nACh receptors on the Dopaminergic VTA neurones stimulating them
Increased Dopamine secretion at the NAcc
What are the effects of Nicotine on the CVS?
(4 main things)
Nicotine causes an increase in Sympathetic activity
Increases HR and SV
Causes vasoconstriction of coronary arterioles - decreases O2 supply
Promotes atherosclerosis
Increases Thromboxane A2 - increases platelet activity
This imbalance between Cardiac Supply and Demand leads to Cardiovascular disease
What happens to Chronic smokers when they quit nicotine?
They tend to put on weight - Nicotine appears to increase the BMR
What are some effects of Nicotine on Neurological diseases?
Nicotine increase the brain’s Cytochrome P450 system
There are more CP450s to metabolise neurotoxins - these are involved in Parkinson’s - Lower rate of Parkinson’s
Chronic nicotine also appears to diminish some of the proteins contributing to Alzheimer’s
What is the effect of Adenosine and Adenosine receptors on the reward pathway?
Adenosine activates Adenosine receptors on the Dopaminergic VTA neurones synapse with the NAcc (Pre and Post-synaptic)
These decrease Dopamine release and decrease D1 receptor function
Adenosine diminishes Euphoric effects
What is the effect of Caffeine on the Euphoric effects of the Reward pathway?
Caffeine antagonises the Adenosine receptors
Prevents the negative effects of Adenosine on Dopamine release and reception
(Very small effect as Adenosine doesn’t do much anyway)
