Drugs of Abuse 2 Flashcards
Types of coke?
Paste, cocaine HCL, crack, freebase
cocaine ionised on unionised in stomach?
Usually ionised mostly so not well absorbed
1/2 life of coke??
20-90 mins
Metabolites of coke? active or inactive?
inactive, ecgonine methyl ester, bezoylecgonine
coke is broken down by..? where?
- Broken down by plasma and liver cholinesterases (bloodstream and liver)\
HOW DO YOU THINK THAT COCAINE PHARMACOKINETICS CONTRIBUTE TO THE ADDICTIVE POTENTIAL OF THE DRUG?
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)
How does coke have an anaesthetic effect? Where must it be to do this
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.
Effect of coke on dopamine
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
Dosage needed of coke for local anaesthetic effect?
High
Dosage needed of coke for dopamine effect?
Low
DOES COCAINE INFLUENCE DOPAMINE AFFINITY/EFFICACY FOR THE DOPAMINE RECEPTOR?
No, it blocks the reuptake proteins but not the interactions of dopamine at the receptor
How does coke cause euphoria
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
Location needed of coke for local anaesthetic effect?
It can only block Na+ channels when within the membrane or on the cytoplasmic side of the membrane however.
How does coke cause CVS problem and MI’s
2 major problems:
- Effects on reuptake- NA related
- 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
How does coke cause hyperthermia
- 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.
How does coke stop heat dissipation
- 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
Why is nicotine poorly absorbed buccally even though its pKa is pKa 7.9 (quite high)
cigarette smoke is quite acidic so Nicotine will be heavily ionised in cigarette smoke so will be poorly absorbed buccally
why are cigarette replacements not that effective
cigarettes cause a very rapid, very large spike in nicotine, which you don’t get with replacements
Nicotine metabolite?
Cotinine
1/2 life of nicotine?
1-4hrs
What drives the effects of nicotine
interactions with nicotinic cholinergic receptors
Euphoria of nicotine?
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
CVS effects of nicotine?
increased cardiac work
Increased HR and SV
Reduced blood flow- coronary arterioles and skin arterioles
Effect of nicotine on cholesterol related stuff (4)
Increased lipolysis, FFA, VLDL and decreased HDL
