Drug abuse 2

Question 1

What are the different routes of administration for cocaine?

Answer 1

i.v, oral, intranasal

Inhalation

Question 2

What are the different forms of cocaine

Answer 2

‘Paste’ ~ 80% cocaine (organic solvent). i.v, oral, intranasal

‘Cocaine HCl’ - dissolve in acidic solution. i.v, oral, intranasal

‘Crack’ - precipitate with alkaline solution (e.g. baking soda): You then heat the precipitate and inhale the fumes. More lipid soluble. INHALATION

‘Freebase’ - dissolve in non-polar solvent (e.g. ammonia + ether): Essentially purified crack cocaine. INHALATION

Question 3

Describe the pharmacokinetics of cocaine in terms of the different routes of administration.

Answer 3

Slower absorption, prolonged action. Fast absorption, shorter action.
IV and inhalation are both methods where rapid effects of the cocaine can be seen very quickly. Oral is much slower.

pKa *impacts speed of onset = 8.7 – oral cocaine ionized in GIT

(Low means unioised in the stomach so it can be absorbed in the stomach = faster access to drug stream)

Question 4

Describe the metabolism of cocaine

Answer 4

75-90% - ecgonine methyl ester, benzoylecgonine = INACTIVE METABOLITES (75-90% excreted in the urine)

Plasma half life of 20-90 minutes. <90 minutes

Plasma/liver cholinesterase

Question 5

How do you think that cocaine pharmacokinetics contribute to the addictive potential of the drug?

Answer 5

The quick effects of a drug - inhaled drugs means euphoric effects happen quickly. Drives reinforcement

Rapid break down and loss of effect.

Both drives addictive behaviour

Question 6

Describe the pharmacodynamics of cocaine

Answer 6

NA Re-uptake inhibitor at low dose. A high dose its LA.

Sodium channel blocker - can only access the sodium channels within the membrane or on the cytoplasmic side. Cocaine needs to be non-polar when it reaches the membrane

Cocaine blocks monoamine (catecholamine - NA,A and DA) reuptake. This means NA is not removed from the synapse in the sympathetic nervous system = NA effect. Also blocks reuptake of dopamine. Blocks the dopmaine transporter. Powerful dopamine effect –> euphoria

Question 7

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

Answer 7

NO - it just increases the amount of dopamine available.

Question 8

What are the effects of cocaine?

Answer 8

Low dose - positive/reinforcing

• euphoria
• heightened energy
• hyperactive

High dose - Negative/sterotypic. (seen in chronic abuse when you become tolerant)

• irritability
• insomnia
• total anorexia

Dangerous effects:

• Cardiovascular: MI
• Hyperthermia

Question 9

Describe the effects of cocaine on the cardiovascular system?

Answer 9

Draw the diagram

Cocaine increases:

1) sympathetic output
2) catecholamines (reduces NA reuptake)

Has LA effects:

1) decreases Na+ transport –> arrhythmias
2) inflammation (associated with high dose cocaine) –> impairs cardiac function (decreased left ventricular function)

Question 10

Describe how cocaine causes hyperthermia?

Answer 10

Draw the diagram

Heat production: Cocaine overdose increases heat production - overall it causes increased muscular activity –> HEAT

Heat dissipation: Cocaine inhibits cutaneous vasodilation (causing constriction), enhances sweat production.
Cocaine elevates the threshhold for sweating/cutaneous vasodilation three fold.

Question 11

What are the different dosing methods of nicotine?

Answer 11

BA = bioavailability

Nicotine spray - 1mg. BA = 20-50%
Nicotine gum - 2-4mg. BA = 20%
Cigarettes - 9-17mg. BA = 20%
Nicotine patch - 15-22mg/day. BA = 70%

pKa 7.9. Cigarette smoke is acidic (nicotine is ionized) ie
no buccal absorption. Absorption in alveoli independent of pH

Question 12

Why are cigarettes more addictive?

Answer 12

See graph.

Same idea in terms of high dose and quickly.

Question 13

Metabolism of nicotine

Answer 13

In the liver (CYP2A6) it metabolises nicotine to produce inactive metabolites - continine

70-80% is metabolised

Tissue half life = 2-3 hours

Question 14

Describe the pharmacodynamics of nicotine?

Answer 14

Stimulant effect - activating a nicotinic receptor in the SNS. Nicotine binds to a nicotinic receptor on the post synaptic neurone stimulating it.

Euphoria - nicotine binds to a nicotinic receptor on the dopaminergic neurone in VTA stimulating it to release dopamine at the nucleus accumbeens

Question 15

Describe the CVS effects of nicotine?

Answer 15

Same effects with cocaine - sympathetic effects.

Draw diagram

Additional thing - nicotine worsens lipid profile.

Question 16

Describe the metabolic effects of nicotine?

Answer 16

Increases metabolic rate
–> has a catabolic effect decrease fat production. People who stop smoking experience weight gain

decreases appetite

Question 17

How does nicotine affect neurodegenerative disorders?

Answer 17

Parkinson’s Disease; increases brain CP450s → neurotoxins

Alzheimer’s Disease: decreases beta-amyloid toxicity
decreases amyloid precursor protein (APP)

Question 18

Describe caffeine

Answer 18

Adenosine binds to A1 receptor (adenosine receptor) and decreases dopamine release and decreases D1 receptor function. It is negative for euphoria.

Caffeine is an adenosine receptor antagonist - Stimulant. Caffeine can potential cause euphoria by blocking A1 receptor causing dopamine release.