Drugs of abuse: Cocaine and nicotine

Question 1

How is cocaine metabolised?

Answer 1

75-90% broken down into inactive metabolites: ecgonine methyl ester and benzoylecgonine.
Half-life = 20-90 minutes.
Plasma/liver cholinesterases.

Question 2

What are the 2 major effects of cocaine on the body?

Answer 2

Local anaesthetic- blocks sodium channels at high doses.
Reuptake inhibition at low doses- dopamine, serotonin, noradrenaline are not removed from the synapse- more commonly seen.

Question 3

Does cocaine influence dopamine affinity or efficacy for the dopamine receptor?

Answer 3

No- blocks reuptake protein. Affinity and efficacy are related to interactions at the receptor. Number of dopamine molecules in synapse increased, more complexes formed, but same affinity and efficacy.

Question 4

How does cocaine stimulate euphoria?

Answer 4

Binds to dopamine transporter in the nucleus accumbens, inhibits reuptake of dopamine from the synapse, causing euphoria. Very direct effect.

Question 5

What are the positive/reinforcing effects of cocaine?

Answer 5

Mood amplification- euphoria and dysphoria
Heightened energy
Sleep disturbance, insomnia
Restlessness
Talkativeness
Anger, anorexia, inflated self-esteem, etc.

Question 6

What are the negative/stereotypic effects of cocaine?

Answer 6

Tolerance to euphoric effects.
Irritability, hostility, anxiety, fear, withdrawal
Extreme energy or exhaustion
Rambling
Delusions of grandiosity
Total insomnia
Usually associated with chronic cocaine bingeing.

Question 7

What effects does cocaine have on the cardiovascular system?

Answer 7

Increases sympathetic output and catecholamines: increased HR, BP and contractility, increased oxygen demand; coronary spasm/vasoconstriction and increased platelet adherence/thrombus leads to decreased oxygen supply. Results in ischaemia, infarction and death.
Decreases sodium transport and has a local anaesthetic effect at high doses: decreased left ventricular function (also due to ischaemia and infarction), combined with arrhythmia, QRS prolongation and QT prolongation leads to death.

Question 8

What effects does cocaine overdose have on the CNS?

Answer 8

Seizures
Vasoconstriction
Hyperpyrexia

Question 9

What are nicotine cigarettes made up of?

Answer 9

95% volatile: nitrogen, carbon monoxide/dioxide, benzene, hydrogen cyanide.
5% particulate: alkaloids (nicotine itself) dissolved in tar droplets when heated.

Question 10

What are the routes of administration for nicotine?

Answer 10

Cigarettes (inhalation)
Nicotine spray
Nicotine gum
Nicotine patch

Question 11

What is the pKa of nicotine?

Answer 11

7.9- heavily ionised in acidic cigarette smoke

Question 12

How is nicotine metabolised?

Answer 12

In the liver by hepatic CYP2A6 (70-80%), converted to inactive metabolite, cotinine.
Half-life = 1-4 hours.

Question 13

How does nicotine cause euphoria?

Answer 13

Stimulates nicotinic acetylcholine receptors in ventral tegmental area leading to dopamine release in nucleus accumbens.

Question 14

What are the cardiovascular effects of nicotine?

Answer 14

Autonomic stimulation.
Increased sympathetic stimulation
Increased HR and SV
Vasodilation
Atherogenic effects (poor lipid profile, increased thromboxane, etc.)
Cardiovascular disease

Question 15

How does nicotine affect metabolism?

Answer 15

Increases metabolic rate

Decreases appetite

Question 16

How might chronic nicotine affect Parkinson’s disease?

Answer 16

Increased brain CYPs which metabolise neurotoxins.

Positive impact.

Question 17

How might chronic nicotine affect Alzheimer’s disease?

Answer 17

Decreased beta-amyloid toxicity and amyloid precursor protein.
Positive effect on progression.

Question 18

Can caffeine cause euphoria?

Answer 18

Yes- it is a stimulant.

Blocks adenosine receptor and thus increases dopamine release.