Drugs of abuse 2: Cocaine and nicotine

Question 1

Where does cocaine come from?

Answer 1

It is a plant based alkaloid coming from the erythroxylum coca plant

Question 2

What part of the plant contains cocaine?

Answer 2

The leaves

Question 3

How is cocaine paste made?

Answer 3

Plant leaves are mushed up with an inorganic solvent- this allows extraction of about 80% of the cocaine

Question 4

What is the therapeutic form of cocaine?

Answer 4

Cocaine HCl- you take the paste and dissolve it in an acidic solution and then extract the cocaine HCl

Question 5

What is the most famous route of cocaine abuse?

Answer 5

Intranasal

Question 6

Why is cocaine not smoked?

Answer 6

Cocaine HCl breaks down when it’s smoked

Question 7

What is crack?

Answer 7

Precipitate cocaine with an alkaline solution - can be smoked

Question 8

What is freebase?

Answer 8

Purer form of crack that is dissolved in non-polar solvent and you can extract the slightly purer form of cocaine

Question 9

How does the rate of onset of cocaine vary between smoked or IV?

Answer 9

Indistinguishable- smoking is slightly faster

Question 10

How does bioavailability of cocaine vary between smoked or IV?

Answer 10

IV has a much higher bioavailability whereas you lose a lot of the drug when you smoke it

Question 11

Why does oral have a slow rate of onset?

Answer 11

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

Question 12

Where is cocaine mainly metabolised?

Answer 12

In the liver

Question 13

How is cocaine metabolised?

Answer 13

Metabolised into inactive metabolites and these metabolites are cleared in the urine relatively quickly

Question 14

Apart from in the liver, how else can cocaine be metabolised?

Answer 14

By cholinesterase’s- there are plasma cholinesterases so it can be broken down as soon as it gets into the blood

Question 15

What affects how addictive a drug is?

Answer 15

How quickly euphoric effect is associated with taking drug

How quickly effect is lost

Question 16

In high doses, cocaine is used as a local anaesthetic, how does it have anaesthetic effects?

Answer 16

It blocks sodium channels and blocks nerve conduction leading to local anaesthetic effect

Question 17

What is cocaine’s most profound effect as a drug?

Answer 17

It can block monamine transporters

Question 18

How does cocaine lead to euphoria?

Answer 18

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

Question 19

Where are dopamine transporters found?

Answer 19

End of the dopaminergic neurone- presynaptic membrane

Question 20

What effect does cocaine have on the cardiovascular system?

Answer 20

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

Question 21

How does cocaine increase sympathetic output?

Answer 21

Increases duration of noradrenaline in synapse and stimulates sympathetic nerves

Question 22

What effect can cocaine have in the brain?

Answer 22

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

Question 23

Where does nicotine come from?

Answer 23

It is a plant based compound coming from nicotiana tabacum

Question 24

What percentage of a cigarette is nicotine?

Answer 24

5%

Question 25

Why is the delivery system via a cigarette very effective?

Answer 25

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

Question 26

What other methods apart from smoking are there for nicotine delivery?

Answer 26

Spray, gum and patches

Question 27

How effective are cigarettes at delivering nicotine?

Answer 27

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

Question 28

Why do people chain smoke?

Answer 28

In an attempt to maintain a high blood nicotine level- drug gives a rapid onset of action but effects are lost pretty quickly

Question 29

How is nicotine metabolised?

Answer 29

It is broken down into cotinine in the liver and then cleared relatively rapidly in the urine

Question 30

What receptors does nicotine bind to?

Answer 30

Nicotine acetylcholine receptors

Question 31

What happens when nicotine binds to its receptors?

Answer 31

It activates the receptor and stimulates sodium influx

Question 32

Where are nicotinic acetylcholine receptors found in the ventral segmental area?

Answer 32

On the cell bodies of the dopaminergic neurones

Question 33

How does nicotine increase dopamine secretion?

Answer 33

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

Question 34

What effect does nicotine have on the cardiovascular system?

Answer 34

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

Question 35

What effect does nicotine have on metabolic rate?

Answer 35

It increases it- smokers tend to put on weight once they stop smoking

Question 36

What effect does nicotine have on the brain?

Answer 36

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

Question 37

How does adenosine affect dopamine function?

Answer 37

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

Question 38

How does caffeine affect dopamine function?

Answer 38

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