Drugs of Abuse: Cocaine and nicotine

Question 1

What is the therapeutic form of cocaine and how is it administered?

Answer 1

• cocaine HCL

- i.v, oral, intranasal

Question 2

What is crack cocaine?

Answer 2

-precipitate with alkaline solution e.g. baking soda

inhaled

Question 3

What is freebase cocaine?

Answer 3

-dissolve in non-polar solvent e.g. ammonia and ether

inhaled

Question 4

Why does cocaine have prolonged action?

Answer 4

• 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

Question 5

Which route of administration has the fastest onset?

Answer 5

• smoking is slightly faster than IV
• snorting is moderately fast
• oral has a slow onset

Question 6

What is the bioavailability like compared to smoking for IV?

Answer 6

-IV is very high

Question 7

Where is cocaine metabolised and what into?

Answer 7

• the liver and into inactive metabolites such as ecgonine methyl ester and benzolecgonine

Question 8

What breaks down cocaine in the body?

Answer 8

• 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

Question 9

When can cocaine still act as a local anaesthetic?

Answer 9

• at high doses

- it blocks sodium channels and hence nerve conduction, which leads to local anaesthetic effects

Question 10

What receptor does cocaine have its most profound effects?

Answer 10

• block monoamine transporters

Question 11

What is the action of dopamine at monoaminergic neurones?

Answer 11

• 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

Question 12

What is the difference between low dose vs high dose cocaine?

Answer 12

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

Question 13

What are the two main effects of cocaine on the heart?

Answer 13

• 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

Question 14

What effect does cocaine have on the brain?

Answer 14

• prompt seizures
• reduce blood flow to the brain
• heat build up
• linked to the development of epilepsy

Question 15

How does cocaine lead to hyperthermia?

Answer 15

• it inhibits cutaneous vasodilation

- it enhances sweat production

Question 16

What are the ways of nicotine administration?

Answer 16

• spray 20-50%
• gum 50-70%
• cigarette 20%
• patch 70%

Question 17

Which has the most rapid onset of action?

Answer 17

cigarette< spray< gum < patch

Question 18

how is nicotine broken down?

Answer 18

• in the liver into cotinine

then cleared in the river fairly rapidly

Question 19

What effect does nicotine have on the dopaminergic neurone?

Answer 19

• it increases the amount of dopamine released in the synapse

Question 20

What effect does nicotine have on the heart?

Answer 20

• increase in sympathetic activity
• increase heart rate and stroke volume
• vasoconstriction of the coronary arterioles reducing oxygen delivery to the myocardium

promote atherosclerosis

Question 21

What does nicotine do to your metabolism?

Answer 21

-increases it

Question 22

WHat effect does nicotine have on Parkinsons disease?

Answer 22

-increases brain CYPs, therefore increases the brains ability to metabolise neurotoxins

Question 23

What effect does nicotine have on alzheimers disease?

Answer 23

• decreases B-amyloid toxicity
• decreases amyloid precursor protein

both are proteins that contribute to alzheimers

Question 24

How does caffeine contribute to euphoria?

Answer 24

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