Drugs of Abuse - Cocaine and Nicotine

Question 1

What is Cocaine?

Answer 1

An Alkaloid drug coming from the Erythroxylum coca plant leaves

Question 2

What are the four most common forms of Cocaine?

How are they made?

Answer 2

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

Question 3

How can Cocaine be administered?

Answer 3

Cocaine paste and HCL: IV, Orally, Intranasally - NOT SMOKED

Crack and Freebase - can be smoked as they don’t thermally decompose

Question 4

What method of Cocaine administration gives the fastest onset?

(rank them all)

Answer 4

Smoking = IV

Intranasally

Orally

Question 5

Which method of Cocaine administration gives the highest Bioavailability and why?

Answer 5

IV, more than smoking as you lose a lot of the drug when smoked

Question 6

Why does oral absorption of Cocaine take so long?

Answer 6

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

Question 7

Where is cocaine metabolised?

Answer 7

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

Question 8

Name two significant factors that decide the addictive potential of a drug:

Answer 8

Speed of onset

How quickly effects are lost

Question 9

How addictive is Cocaine?

Answer 9

Probably the most addictive drug on the planet because of its powerful euphoric effects that come on quickly and leave quickly

Question 10

How can Cocaine act as a local anaesthetic?

Answer 10

Blocks sodium channels - blocking nerve conduction

Question 11

What is the main method of action of Cocaine?

Answer 11

It’s a Monoamine Transporter Blocker

It prevents monoamines from being removed from the synapse prolonging effects

e.g. Dopamine - euphoria

Question 12

What are Monoamines?

Answer 12

Neurotransmitters containing a single amine group:
Dopamine

(Nor)adrenaline

Seratonin

Question 13

Where does Cocaine act to produce Euphoria?

Answer 13

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

Question 14

What are the differences in the effects of low-dose and high-dose Cocaine?

Answer 14

Question 15

What are the two main actions of Cocaine on the Cardiovascular system?

Answer 15

Increases Sympathetic output - increase duration of NA in synapse

SNS stimulation causes Vasoconstriction and Activates Platelets

Question 16

What are the long-term consequences of the actions of Cocaine on the Heart?

Answer 16

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

Question 17

What are the Consequences of Cocaines LA properties on the CVS?

Answer 17

It will interfere with any underlying heart issues e.g. Arrhythmias

Together with its other effects, this significantly increases the risk of MI

Question 18

What are the possible long-term effects of Cocaine on the Brain?

Answer 18

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

Question 19

Where does Nicotine come from?
How much of this drug makes up a Cigarette?

Answer 19

Nicotiana tabacum

5% of a cigarette

Question 20

How does smoking a Cigarette get Nicotine into the lungs?

Answer 20

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

Question 21

How much Nicotine is absorbed from a Cigarette?

Answer 21

20% Not efficient

(9-17mg)

Question 22

Why are Cigarettes not particularly efficient?

Answer 22

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)

Question 23

Describe Nicotine Metabolism:

Answer 23

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)

Question 24

What does Nicotine do?

Answer 24

It binds to Nicotinic ACh receptors (dur)

Causes Na influx (agonising them)

Question 25

How does Nicotine cause ‘euphoria’?

Answer 25

Binds to the nACh receptors on the Dopaminergic VTA neurones stimulating them

Increased Dopamine secretion at the NAcc

Question 26

What are the effects of Nicotine on the CVS?

(4 main things)

Answer 26

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

Question 27

What happens to Chronic smokers when they quit nicotine?

Answer 27

They tend to put on weight - Nicotine appears to increase the BMR

Question 28

What are some effects of Nicotine on Neurological diseases?

Answer 28

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

Question 29

What is the effect of Adenosine and Adenosine receptors on the reward pathway?

Answer 29

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

Question 30

What is the effect of Caffeine on the Euphoric effects of the Reward pathway?

Answer 30

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)