Cocaine and nicotine Flashcards
What sort of compound is nicotine?
Alkaloid
In what part of the cigarette is nicotine present?
Dissolved in tar/ particulate matter which makes up 5% of the cigarette
How much nicotine is present in 1 typical cigarette
9-17mg
What % of nicotine in a cigarette will reach the bloodstream?
20%
Why is there no buccal absorption of nictotine?
Smoke = acidic
Nicotine has a pKa of 7.9 - therefore pushed towards ionised form and not absorbed
Compare the levels of nicotine in the blood produced by a cigarette vs a replacement method
Cigarette = spike and then persists at intermediate level Replacement = constant intermediate level
Where is nicotine metabolised, what is its main breakdown product and where is this excreted?
Liver, cotinine, urine
Why does nicotine stimulate the mesolimbic system?
nAChR agonist
Binds to nAChR In VTA to stimulate DA release in NA
Recall the 4 key effects of nicotine on the CVS
nAChR agonism –> increased sympathetic output –>
- Increased cardiac work
- reduced flow in coronary arterioles due to vasoconstriction
- Worsening effect on lipid profile
- Increases TXA2 –> increased platelet aggregation
Recall and explain the 3 possible benefits of nicotine
- Depresses weight gain
- Increases brain cytochromes for cytotoxin metabolism so reduces Parkinson’s risk
- Decreases beta-amyloid toxicity –> reduced risk of Alzheimer’s
What was the main method of cocaine administration prior to crack cocaine?
Cocaine HCl - but this breaks down when heated
How is crack cocaine produced?
Cocaine HCl is precipitated with an alkaline solution and dissolved in a non-polar solvemt
Where is crack cocaine absorbed when taken orally, and why?
Small intestine as pKa is 8.7
What is the half-life of crack cocaine?
20-90 minutes
Why is the half life of cocaine so short?
Metabolised in liver and also by cholinesterases in blood
What is cocaine metabolised to produce?
2 inactive metabolite
Why do the pharmacokinetics of cocaine make it so addictive?
Super-fast onset when inhaled = powerful reinforcer
Fast breakdown causes people to binge
What is the major clinical use of cocaine, and what is the method of action?
Local anaesthetic
Blocks Na+ channels in nerves at HIGH DOSE
What is the main low-dose effect of cocaine in the brain?
Reuptake inhibition of 5HT, DA and NA - prolonging effect of DA in NA and thus producing euphoria
Other than euphoria, recall 3 short-term effects of cocaine
Stimulant
Sleep disturbance
Increased aggression and self-esteem
How does tolerance to cocaine develop?
Exhaustion of mediator stores as no DA is re-uptaken so there is no substrate for DA production
Recall 3 CVS side effects of cocaine use
SNS output increase –> work increased
Endothelin 1 upregulation –> coronary spasm
Thrombocytophilia
What is the most common side-effect of cocaine use and why is this?
Seizures
Induced by hyperpyrexic effect increasing cellular activity in the brain
