Drugs of Abuse 2 – Cocaine and Nicotine Flashcards Preview

Y2 LCRS 1 - Pharmacology and Therapeutics - Laz > Drugs of Abuse 2 – Cocaine and Nicotine > Flashcards

Flashcards in Drugs of Abuse 2 – Cocaine and Nicotine Deck (24)
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1
Q

What are the four different forms of cocaine and how are theymade?

A

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)

2
Q

Which route of administration of cocaine gives the fastest absorption?

A

Smoking (though IV gives a higher bioavailability)

3
Q

Why is cocaine very slowly absorbed in the GI tract?

A

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

4
Q

What is the half-life of cocaine?

A

20-90 mins

5
Q

Where is cocaine metabolised and what is it metabolised into?

A

Liver – inactive metabolites: ecgonine methyl ester+ benzoylecgonine
Plasma – it can be metabolised by plasma cholinesterases so it doesn’t last long in the plasma

6
Q

Which factors affect the addictive potential of a drug?

A

The speed at which you associate the euphoria with taking the drug and the speed with which the effects are lost

7
Q

Explain how cocaine can act as a local anaesthetic.

A

Cocaine blocks sodium channels and hence inhibits nerve transmission

8
Q

By what mechanism does cocaine exert its most profound effects?

A

Inhibition of monoamine transporters – leads to an accumulation of monoamines (e.g. dopamine) at the synapse

9
Q

How does cocaine cause euphoria?

A

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

10
Q

What are the differences between the effects of low dose cocaine and high dose/chronic cocaine use?

A

Low dose – positive reinforcement – more energetic, need less sleep, more sociable, more talkative
High dose – negative/stereotypical effects – exhaustion, irritability, hostility, insomnia

11
Q

Describe how cocaine is associated with a significantly increased cardiovascular risk.

A

Cocaine causes an increase in sympathetic output (NOTE: noradrenaline is also a monoamine)
This leads to vasoconstriction, thus causing an increase in cardiac work
It will also activate platelets and promote atherosclerosis, leading to thenarrowing of vessels and decreased oxygen supply to the heart
This could lead to myocardial infarction

12
Q

How can cocaine prompt seizures?

A

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

13
Q

What percentage of a cigarette is particulate and what percentage is volatile?

A

5% particulate

95% volatile

14
Q

Why is the nicotine delivery via a cigarette so effective?

A

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

15
Q

Which matter contains most carcinogenic elements?

A

Volatile

16
Q

Why is the cigarette not particularly efficient in delivering nicotine to the body?

A

Cigarette smoke is acidic whereas the pKa of nicotine prefers a more alkaline environment
This means that the nicotine in cigarette smoke becomes ionised and, hence, it is less easily absorbed

17
Q

Describe the metabolism of nicotine. What is the product?

A

Nicotine is metabolised by CYP2A6 in the liver

This produces COTININE, which is then excreted in the urine

18
Q

What is the half-life of nicotine?

A

1-4 hours

19
Q

Describe how nicotine causes euphoria.

A

Nicotine binds to nicotinic acetylcholine receptors on the cell bodies of dopaminergic neurones in the ventral tegmental area and stimulates sodium influx
This leads to an increase in the firing rate of the dopaminergic neurones, hence, more dopamine secretion

20
Q

How does nicotine increase cardiovascular disease risk?

A

Nicotine causes an increase in sympathetic drive – increased heart rate and stroke volume, so more cardiac work
Vasoconstriction of coronary arterioles – reduces oxygen delivery to the myocardium
In addition it also promotes atherosclerosis and increases thromboxane A2 (hence increases platelet activity)
All of these factors increase oxygen demand and decrease oxygen supply

21
Q

What effect does nicotine have on metabolism?

A

It increases metabolism

So chronic smokers often find that they gain weight after quitting

22
Q

Explain how nicotine reduces the risk of Parkinson’s disease.

A

Nicotine increases the activity of the CYP450 enzymes in the brain, so it is better able at removing neurotoxins that have the potential to contribute to the onset of Parkinson’s disease

23
Q

Explain how nicotine reduces the risk of Alzheimer’s disease.

A

Chronic nicotine diminishes some of the proteins that contribute to
Alzheimer’s disease (decrease in beta-amyloid toxicity, decrease in amyloid precursor protein)

24
Q

Explain how caffeine can cause mild euphoria.

A

Adenosine acts via adenosine receptors to decrease dopamine release and decrease D1 receptor function
Caffeine is an adenosine receptor antagonist so it will remove the inhibitory effect of adenosine
However, the inhibitory effect of adenosine is very minimal so caffeine will not cause a significant rise in dopamine release