Drugs of Abuse: Cocaine and nicotine Flashcards
What is the therapeutic form of cocaine and how is it administered?
- cocaine HCL
- i.v, oral, intranasal
What is crack cocaine?
-precipitate with alkaline solution e.g. baking soda
inhaled
What is freebase cocaine?
-dissolve in non-polar solvent e.g. ammonia and ether
inhaled
Why does cocaine have prolonged action?
- relatively high pKa =8.7, so in the stomach the drug means largely ionised
- this slows down the rate of absorption of cocaine from the stomach
- this means it has prolonged action
Which route of administration has the fastest onset?
- smoking is slightly faster than IV
- snorting is moderately fast
- oral has a slow onset
What is the bioavailability like compared to smoking for IV?
-IV is very high
Where is cocaine metabolised and what into?
- the liver and into inactive metabolites such as ecgonine methyl ester and benzolecgonine
What breaks down cocaine in the body?
- plasma/liver cholinesterase
- half life of 20-90 mins
-it can be metabolise din the blood as well as the liver
if you have a rapid speed of onset it gives a very powerful addictive component and it is rapidly cleared form the body
When can cocaine still act as a local anaesthetic?
- at high doses
- it blocks sodium channels and hence nerve conduction, which leads to local anaesthetic effects
What receptor does cocaine have its most profound effects?
- block monoamine transporters
What is the action of dopamine at monoaminergic neurones?
- normally dopamine is released into the synapse and has an effect on the receptors
- this is then removed from the synapse by monoamine transporter
-cocaine is a monoamine transporter blocker so dopamine remains in the synapse for longer- euphoria
What is the difference between low dose vs high dose cocaine?
Low dose has a positive reinforcing effect and tends to have the effects that people like e.g. more energy, euphoria, less need for sleep, more talkative, inflated self-esteem
High dose has negative effects - exhaustion, irritability, hostility, insomnia
What are the two main effects of cocaine on the heart?
- increases sympathetic output
- leads to vasoconstriction which also activates platelets - this decreases oxygen supply to the heart
this leads to increased risk of myocardial infarction
What effect does cocaine have on the brain?
- prompt seizures
- reduce blood flow to the brain
- heat build up
- linked to the development of epilepsy
How does cocaine lead to hyperthermia?
- it inhibits cutaneous vasodilation
- it enhances sweat production
What are the ways of nicotine administration?
- spray 20-50%
- gum 50-70%
- cigarette 20%
- patch 70%
Which has the most rapid onset of action?
cigarette< spray< gum < patch
how is nicotine broken down?
- in the liver into cotinine
then cleared in the river fairly rapidly
What effect does nicotine have on the dopaminergic neurone?
- it increases the amount of dopamine released in the synapse
What effect does nicotine have on the heart?
- increase in sympathetic activity
- increase heart rate and stroke volume
- vasoconstriction of the coronary arterioles reducing oxygen delivery to the myocardium
promote atherosclerosis
What does nicotine do to your metabolism?
-increases it
WHat effect does nicotine have on Parkinsons disease?
-increases brain CYPs, therefore increases the brains ability to metabolise neurotoxins
What effect does nicotine have on alzheimers disease?
- decreases B-amyloid toxicity
- decreases amyloid precursor protein
both are proteins that contribute to alzheimers
How does caffeine contribute to euphoria?
Adenosine activates the adenosine receptor
Adenosine receptors negatively impact on dopamine function
Adenosine will decrease dopamine release and it will decrease D1 receptor function
In general, adenosine will try to diminish the euphoric effects
Caffeine is an ADENOSINE RECEPTOR ANTAGONIST - so it prevents the negative effects of adenosine on the dopaminergic neurones
