14: Drugs of Abuse 2: Nicotine + Cocaine Flashcards
Explain the ROA of Cocaine
- IV, Oral, Intranasal
- paste (80% cocaine)
- Cocaine HCL (dissolved in Acid solution)
- Inhalation
- Crack —> HCL precipitation with alkaline soluction
- Freebase’ - dissolve in non-polar solvent (e.g. ammonia + ether)
Explain the Bioavailibilty of Cocaine and explain the differences with different ROA
- IV –> 100% bioavailable
- Inhalation –> Same speed of onset but less bioavailable
- PKa = 8.7
- Smoke acidic –> will be ionised when smoking
Explain the metabolism of Cocaoine
- 75-90% rapidly metabolised to produce inactive metabolides
- By Liver and plasma cholinesterasese
What is the t1/2 of cocaine
Short t1/2 -
20-90 min
Why is cocaine so addictive?
- Fast onset after administration –> association between high and substance
- Fast clearing from blood –> 2nd dose to restore euphoria
Summarise the immediate effects of Cocaine
- Local Anestetic
- Euphoria
3.
How does Cocaine act as an local Anestetic
At higher doses
- blocks Na+ channels –> disruption of AP
- Most effective from inside the cell
- diffuses into the cell and blocks channel from inside in its charged form (more effective
- pH outside= 7.4, pH inside= 7 (PKa= 8.7) –> more unionised outside –> diffuses into cell–> gets inonised in cell
How does Cocaine induce Euphoria?
At lower doses:
By inhibition the Reuptake of Neurotransmitters
- Noradrenaline
- Serotonin
- Dopamine
What are the Cardiovascular effects of Cocaine?
Compex effects due to
- Increased SNS
- direct increase in Adrenaline + NA
- centrally increase of SNS activity
- increase platelet activation –> Atherosclerosis
- Increase in Myocardial oxygen demand –> Myocardial infarction
- Increased Inflammtion
- Decreased Na+ transport –> Arrythmias + sudden death
Explain the effects of Cocaine on temperature regulation
Cocaine increases
- muscle activity and agitation leadint to
- Hyperthermia
- muscle activity and agitation leadint to
Additionally it inhibits the central regulatory mechanisms for heat control so it
- inhibits cuntaneous vasodilation
- increases central threshold for thermoregulation
It also increases sweat production but that can’t really cope with the other effects
Explain the consequences of a cocaine induced hyperthermia
In cool/ normal environments: totally fine
BUT: in hot environments (e.g. clubs) might be fatal when overdosing
In which form does nicotine gets inhaled?
Nicotine= plant based alkaloid gets smokes in particular matter(as particle) of cigaret (5%) together with tar
What are the ROA of Nicotine?
- Spray (PO,
- Gum
- Cigarettes
- Patches
What is the bioavailability of the different ROA of nicotine?
Why do they differ so much?
- Nicotine spray – 1mg 20-50%
- Nicotine Gum – 2-4mg Nicotine 50-70%
- Cigarettes – 9-17mg nicotine 20%
- Nicotine Patch – 15-22mg/day 70%
pKa 7.9. –> Cigarette smoke is acidic ie no buccal absorption for cigarette smoke (acidity neglectable for alveolar absorbtion)
What are the differnet times of onset for the effects of nicotine after administration?
Why is nicotine so addictive?
- In cigarettes: quick onset
- quick metabolism into an inactive metabolite –> need quick 2nd cigarette to maintain dose
Explain the metabolism of nicotine
Metabolised by Hepatic CYP2A6 –> into Cotinine (70-80%)
What is the t1/2 of nicotine?
1-4 hours (slower than cocain because ther is no plasma enzyme, but only hepatic metabolism)
Explain the Pharmacodynamics of Nicotine
It is a nicotinic receptor agonist
How does Nicotine induce Euphoria?
By binding to the Nicotinic receptor it directly stimmulates dopaminergic receptors+ the release of dopamine
What are the effects of Nicotine fon the CVS?
It has the same effects as cocain
- increases SNS activity directly and indirectly leadint to
- atherosclerosis (via platelet activation)
- increased oxygen demand
- MI
+ a negative effect on lipid profile
- increase in Free Fatty Acids, VLDL, LDL
Explain the effects of nicotine of metabolic rate
Nicotine increases metabolic rate – >
prevents weith game
Explain the effect of nicotine on Alzheimers and Parkinsons
Might be beneficial:
In Parkinsons:
- increases neural activity from cytochormes p450 → decreased levels of neurotoxins
in Alzheimers
- decrease in ß-amyloid toxicity
- decrease in amyloid precursor protein
Explain tbe effects of Caffeine on Dopamine release
- Adenosine blocks Dopamine (via the stimmulation of inhibitory A1 receptors)
- Caffeine –> blocks Adenosine
- increased Dopamine release
