Drugs of Abuse 2

Question 1

Types of coke?

Answer 1

Paste, cocaine HCL, crack, freebase

Question 2

cocaine ionised on unionised in stomach?

Answer 2

Usually ionised mostly so not well absorbed

Question 3

1/2 life of coke??

Answer 3

20-90 mins

Question 4

Metabolites of coke? active or inactive?

Answer 4

inactive, ecgonine methyl ester, bezoylecgonine

Question 5

coke is broken down by..? where?

Answer 5

• Broken down by plasma and liver cholinesterases (bloodstream and liver)\

Question 6

HOW DO YOU THINK THAT COCAINE PHARMACOKINETICS CONTRIBUTE TO THE ADDICTIVE POTENTIAL OF THE DRUG?

Answer 6

Fast speed of onset with inhalation (addiction is very closely linked behaviourally with speed of onset) and fast speed of breakdown (loss of euphoric effect quickly as the drug is cleared from the system- want it again and again)

Question 7

How does coke have an anaesthetic effect? Where must it be to do this

Answer 7

Blocks sodium channels within nerves- reduces propagation of APs within that nerve and suppresses sensation of pain
High doses needed for local anaesthetic effect
It can only block Na+ channels when within the membrane or on the cytoplasmic side of the membrane however.

Question 8

Effect of coke on dopamine

Answer 8

 Inhibits reuptake of dopamine from synaptic clefts by blocking dopamine transporters Can also affect NA reuptake transporter and serotonin (5-HT)
 Only low doses needed for this effect

Question 9

Dosage needed of coke for local anaesthetic effect?

Answer 9

High

Question 10

Dosage needed of coke for dopamine effect?

Answer 10

Low

Question 11

DOES COCAINE INFLUENCE DOPAMINE AFFINITY/EFFICACY FOR THE DOPAMINE RECEPTOR?

Answer 11

No, it blocks the reuptake proteins but not the interactions of dopamine at the receptor

Question 12

How does coke cause euphoria

Answer 12

Goes straight to nucleus accumbens and blocks dopamine reuptake transporter to stimulate euphoria, meaning there’s a build up of the dopamine in the synapse

Question 13

Location needed of coke for local anaesthetic effect?

Answer 13

It can only block Na+ channels when within the membrane or on the cytoplasmic side of the membrane however.

Question 14

How does coke cause CVS problem and MI’s

Answer 14

2 major problems:

1. Effects on reuptake- NA related
2. Local anaesthetic effect
   - Increase in NA causes heart to increase work (increases BP as wel)
   - Body requires more oxygen
   - BUT you also get decreased blood flow to the heart e.g. vasoconstriction (endothelin-1 secretion), platelet activation etc.
   - Local anaesthetic effects interfere with rhythm etc

Question 15

How does coke cause hyperthermia

Answer 15

• Cocaine overdose will increase heat production, some of this is sympathetically driven, some is through increased locomotor activity, increased anxiety/agitation, and increased involuntary muscle contraction.

Question 16

How does coke stop heat dissipation

Answer 16

• Cocaine will probably get in the way of vasodilation as its effects are sympathetic, to vasoconstrict
• Enhances sweat production as sweat production is a sympathetic activity
• It elevates the threshold for sweating/cutaneous vasodilation threefold

Question 17

Why is nicotine poorly absorbed buccally even though its pKa is pKa 7.9 (quite high)

Answer 17

cigarette smoke is quite acidic so Nicotine will be heavily ionised in cigarette smoke so will be poorly absorbed buccally

Question 18

why are cigarette replacements not that effective

Answer 18

cigarettes cause a very rapid, very large spike in nicotine, which you don’t get with replacements

Question 19

Nicotine metabolite?

Answer 19

Cotinine

Question 20

1/2 life of nicotine?

Answer 20

1-4hrs

Question 21

What drives the effects of nicotine

Answer 21

interactions with nicotinic cholinergic receptors

Question 22

Euphoria of nicotine?

Answer 22

Acts directly on dopaminergic neurones of the ventral segmental area on nACh receptors (on the neuronal cell body) causing stimulation and dopamine release in the nucleus accumbens

Question 23

CVS effects of nicotine?

Answer 23

increased cardiac work
Increased HR and SV
Reduced blood flow- coronary arterioles and skin arterioles

Question 24

Effect of nicotine on cholesterol related stuff (4)

Answer 24

Increased lipolysis, FFA, VLDL and decreased HDL

Question 25

Effect of nicotine on vascular smooth muscle messengers

Answer 25

• Increased thromboxane A2

- Decreased NO

Question 26

Metabolic effects of nicotine?

Answer 26

Weight loss, people show weight gain following smoking cessation

Question 27

Nicotine and Parkinsons?

Answer 27

Nicotine increases brain CYPs- these metabolise neurotoxins (nicotine has a positive impact on Parkinson’s)

Question 28

Nicotine and Alzheimers?

Answer 28

Chronic nicotine use is associated with decreased beta-amyloid toxicity and decreased amyloid precursor protein (APP) (nicotine has a positive impact on Alzheimer’s)