drugs of abuse 2 Flashcards
What is the origin of cocaine? what are the active ingredients?
Originate from coca plants-can extract active ingredient-cocaine
been used since at least 6th century
Coca-cola-brain elixir (cocaine and caffeine)
can be made to paste -80% cocaine => cocaine HCL => can be taken oral/intranasal (but cant heat)
cocaine HCL can be made to
->crack->freebase -then can be inhaled
Describe the pharmacokinetics of cocaine?
IV-very high intake/bioavailability
Smoked/nasal/oral are low (lowest in smoked-but fasted)
Why-pKa of cocaine is high (8.7)-very ionised in stomach (poorly absorbed)-doesnt diffuse well in lung either, or mucous membrane
effects/conc peak in 30 min-very fast for iv/smoked-slower in nasal-slower again in oral
What metabolites are made from cocaine? Where? how fast? Does it contribute to how addictive it is?
can be metabolised in blood
CHolinesterases- makes ecogonin methyl ester benzoylecgonine-inactive metabolites
=> disappears very fast
Cocaine acts very fast-reward very fast so nice
Because metabolised so fast-get a great effect but dissapears fast-drives wanting more
What does cocaine do in the body? (site of targets/etc)
high dose: Works as a local anaesthetic-blocks sodium channels-dysrupts actions potentials in nerves and pain
(to be most effective, cocaine must diffuse in the nerve, then block the Na channel from the inside-can do that because of its pKa-on outside tends to be more unionized-can diffuse-but with inside pH-more ionised and cant leave-and also when charged can blocks Na channels better)
lower dose: Blocks mono-amine reuptake-what normally removes nor-adrenaline from the synapse-so increase conc of norA-(also works on Serotonine/dopamine-general reuptake in general) –doesnt increase affinity or efficacy
What effects does low dose cocaine have on the body?
Euphoria-blocks dopamine transpoter between VTA and NAcc-> dopamine lives longer in synapse and increase reward system activation
mild/moderate doses:
higher energy, insomnia, more talktative, anger, anorexia
positive reinforcement of mood
High dose-mostly negative effects: irritability, exhaustion, total insomnia, compulsive motor effects, rambling
CVD issues
Hyperthermia
What are the CVD effects of cocaine
CVD effects: from increase adrenaline effects- increase Cathecolamines effect (and central SNS activation)-HR, contractility, BP high, –, decrease na transport (reduce muscle effectivness)-and can increase inflammation
can lead to endothelial injury, constant high demand ofheart (O2 use high)-vessels are narrowing and the heart O2 use keep increasng (and Na transport down cause Left ventricule to work less) => MI
How does cocaine affect hyperthermia
More in cocaine overdose
Overdose increase agitation, locomotor activity, involuntary muscle contraction => all generate a lot of heat (body temp up)
Body counteracts with seat, vasodilation,etc => but if environement is hot as well-cause hyperthermia–can cause death
sweat and vasodilation are mainly ACh controlled-so cocaine doesnt help-even seem to inhbit the vasodilation (actually does increase sweat a bit)-but rised central threshold for heat
What is the origin of nicotine? And routes of intake (and bioavailability)
Plant blased-alkaloid
Cigarettes are mode of-95% volatile parts (nitrogen/C)/benzene) and 5% particules (alkaloids + tar)
Can be taken as spray, gum, cigarette, patches
spray-20/50%-mucous
gum-50/70%-mucous membrane
smoking-20%-acidic smoke means its ionised-hard to diffuse into
Nicotine patch-70%-through skin direct to blood
fastest-cigartette, spray
Gum inhaler/tablet -much slower speed of onset
peak effect is very short-so need to smoke a lot to keep levels high
How is nicotine metabolised?
Metabolised very fast to inactive metabolite-(cotinine)-like cocaine its cleared very fast
But nicotine isnt metabolised in the blood-just liver
Describe what effects nicotine has on your body
well binds the nicotinic receptor -the ones that ACh binds to
In all ganglias of ANS-drives the ANS
the volatile matter has cancinogenic effects and stuff-
Euphoria-nicotine stimulates the VTA nerve and activates it-more dopamine in synapse and activation CVD effects (only nicotine): Increase FFA, increase VLDL/LDL-cause artherosclerosis Combine with Sympathetic output increase-high BP/HR/Contract -> very similar to what cocaine does
Increase metabolic rate-prevents weight gain (and people tend to gain weight when they stop smoking)
Some evidence that it has positive effectsnof parkinsons (increase brain CYP-/alzheimers (decrease B-amyloid toxicity) –way to treat it?
how does caffeine work
Stimulant-interferesed with adenosine (neurotransmitter)—adenosine blocks reward pathway, and caffeine blocks adenosine
How is alcohol units define and give alcohol content?
Absolute amount abvx0.78 =g alcohol/100ml
%ABV x Volume /1000
1 unit=1mml or 8g of absolute alcohol
“low risk”-less than 14 units/week (and not more than 8 units in one sitting)
relation to blood levels will depend on you body weight-
What is the pharmacokinetics of administration of alcohol?
20% taken in by the stomach, and 80% in the the intestine
If you have a full stomach-alcohol will join food and not reach intestine as fast. On an empty stomachs, goes straight through and gets absorbed faster
faster you drink the less time to metabolise to get drunkfaster
How is alcohol 1st phase metabolised? Why do we become tolerant to alcohol? Why are women more affected
only 90% is metabolised
In the liver (85%) - done by alcohol dehydrogenase 75% and mixed function oxidase (25) -if throw too much can work-> both produce acetaldehyde (very toxic)-
tolerance increases as liver upregulated Mixed function oxidase
15% is removed via the GIT-via the stomach alcohol dehydrogenase (never reaches systemic)-women have less of that (and also have less body water-less to dilute in)
What happens in the second phase of alcohol metabolism
Acetaldehyde is very bad-thought that most bad effects of alcohol are caused by this
Aldehyde dehydrogenase metabolises it to acetic acid
Disulfiram-inhbits aldehyde dehydro and cause a lot of bad side effects-cause aversion to alcohol
Common genetic polymorphism is asian-blocks AD more and get more nauseous easier
