Drugs of abuse 1/general Flashcards
What is another name for the drugs of abuse
Psychoactive drugs
Essentially, why are psychoactive drugs abused
To cause euphoria- they do this by hijacking (predominately dopaminergic) reward pathways in the brain.
mesolimbic dopaminergic pathway – the central reward pathwa
Outline the central reward pathway
Medial forebrain bundle (myelinated fibres) → Ventral tegmental area (VTA)- dopaminergic neurones. → Nucleus Accumbens (NAcc)
Dopamine release from NAcc vital for ‘rewarding’ effect (End point for drugs of abuse)
Outline the methods of administration for the drugs of abuse
§ Methods of administration:
o Intranasal – slow absorption.
§ Mucous membranes of nasal sinus.- gets into venous system this way- right side of heart- pulmonary circulation- left side of heart – brain
o Oral – very slow absorption.- stomach- S.I- hepatic portal system – liver -right side of heart — etc
o Inhalational – rapid absorption.
o Intravenous – rapid absorption.
Why is smoking quicker than I.V
Smoking brings the drug to the alveoli where it easily crosses the alveoli and enters the pulmonary circulation ( the alveoli are designed to filter everything)
There is a shorter distance from the pulmonary circulation to the heart and then to the brain than from the site of IV injection to the heart and then to the brain
For the various drug administration routes, which administration routes will result in a faster onset of euphoria
Ascending order on onset of euphoria – Oral < Intranasal < IV < inhalational
Outline the different classifications for the drugs of abuse
Narcotics/Painkillers – opiate like drugs e.g. heroin
Depressants – ‘downers’
e.g. alcohol, benzodiazepines (valium), barbiturates
Stimulants – ‘uppers’
e.g. cocaine, amphetamine (‘speed’), caffeine
metamphetamine (‘crystal meth’)
Miscellaneous – e.g. Cannabis, Ecstasy (MDMA)
Why is cannabis classed as miscellaneous
It has various pharmacological properties
such as- hallucinogenic, depressant
Ecstasy has hallucinogen and stimulant properties.
Where does cannabis come from
§ The cannabis is the plant, the hashish/resin is the trichomes (glandular hairs that contain the highest concentration of THC) and the hash oil is the solvent extract.
What are the active components of the cannabis sativa plant
Cannabinoids (there are over 60 of them in the plant)
Over 400 other compounds found in Cannabis Sativa.
What are the key cannabinoids
§ Cannabis contains over 400 compounds with >60 being cannabinoids.
o Delta9-THC is the most potent cannabinoid. (THC= Tetrahydrocannabinol)
o Positive aspects of smoking weed are from cannabidiol – experts believe a balance between these two (cannabidiol vs. delta9-THC) is needed.
How has the dosing of THC in cannabis changed
60’s + 70’s: ‘Reefer’ – 10mg THC
21st Century: ‘Skunkweed/Netherweed’
- 150mg THC - 300mg THC (+ hashish oil)
This increase in THC has been at the expense of cannabidiol- which is thought to offset the negative effects of THC.
o The negative effects are more pronounced than the positive effects
Hence cannabis production is becoming more pro-psychotic.
Describe the difference in bioavailability of the different routes of administration of cannabis
Oral – 5-15% reaches the bloodstream
delayed onset/slow absorption
first pass metabolism
Inhalation – 25-35% reaches the bloodstream
The rest is exhaled or not reached the lungs due to shallow inspiration.
Route of administration massively influences the bioavailability of the drug.
Describe the accumulation of cannabis in different tissues over a period of time
Cannabis is very lipid soluble
However, the fat is a very poorly diffused tissue, and so the cannabis will mostly accumulate in the highly perfused tissues (i.e the brain).
However, as the brain is highly perfused, it will also leave the brain just as easily, so its accumulation in the brain rises and falls rapidly.
As it is very lipid soluble, but fat is poorly perfused (2% of cardiac output)- the cannabis will slowly accumulate in the fatty tissue.
The cannabis stored in fat- can also re-enter the bloodstream- complicating its pharmacokinetics.
Describe the cannabis stored in fatty tissue
Subsequently, intensive accumulation occurs in less vascularised tissues and finally in body fat, the major long-term storage site, resulting in concentration ratios between fat and plasma of up to 104 : 1. The exact composition of the material
accumulated in fat is unknown, among them being unaltered THC and its hydroxy metabolites. A substantial proportion of the deposit in fat seems to consist of fatty acid conjugates of 11-OH-THC.
How long will the effects of cannabis last after smoking a joint
Around 30 days (because of the storage in adipocytes)
Describe how cannabis is metabolised in the liver
Phase 1 reactions normally remove the reactive functional group, to then conjugate it in phase 2 reactions to make the compound more soluble and therefore easier to excrete.
However, in phase 1 metabolism, cannabis is metabolised to 11-hydroxy-THC, which is more potent than THC.
What happens to this metabolite of cannabis produced by the Liver
It is excreted in the bile into the GI tract but then it undergoes enterohepatic cycling (as it is lipid soluble) and re-enters the blood stream where it can exert its physiological effects