Most widely used drug is?
11% of aussiesin the past year
33% in in thei rlifetime
Psychactive constituent of effectiveness of cannabis?
Δ9 - tetrahydrocannabinol (THC)
What is the endocannabinoid system?
- neurochemical system
- consisting of multiple receptors known as CB1, (cannabinoid) CB2, etc
Describe CB1 and its properties?
- Responsible for the effects that THC has on the body
- Most receptors are presynaptic
Pharmacology of CB1
- metabotropic (they are g protein coupled) - require the G protein that can inhibit Ca2+ channels (which is critical for neurotransmitting signalling)
Brief outcome what CB does when activated?
CB receptors activated by Gio coupled receptors inhibit Ca2+ channels and adenylate cyclase. This triggers a cascade of events which leads to transformation of ATP to protein kinase A, which causes phosphorylation of some cell functions to change the purpose of it.
What are the naturally occuring ligans/chemicals which interact with the CB receptors?
- Anandamide (anand-bliss)
- 2-arachidonyl glycerol (2-AG)
- these act as retrograde messengers
Outline the synthesis of Cannabinoids?
- Created on demand.
- Cleaved from acid derivatives in the lipid membrane of the cell wall.
- They are released from the post synaptic cells to interact with the pre-synaptic CB1 receptors (this is reverse to a typical reaction!)
- An important neurotransmitter
- too much of it kills nerves cells via excitement, so it is regulated homeostatically
How does THC interact inside the synapse area?
- Δ9-THC imitates the annbinoid and interacts with the CB1 receptor in the presynaptic nerve
- This in turn inhibits the release of further glutamate via homeostasis
Symptoms and Effects of cannabis
- Cognitive impairment
- "munchies" or appetite stimulation
- Rare reports of hallucinations
Where are the general areas of cannabinoid receptors ?
Yellow are the concentrations of CB1
- CPu (corda putnem)
Hippocampus is involved with?
ie cannabis will cause memory loss
Where are the cannabinoid receptors in the brain stem?
- this means its hard to overdose on cannabis
Opoid vs cannaboid?
- both metabotropic
- both have similar effects in the cell
Cocaine - background / epidemiology
- derived from coca plant
- 1.0% of australins have used it in the past 12 months
- 4.7% used in lifetime
Pharmalogical effects of cocaine
- Euphoria (short lived)
- HR and BP increased
- Increased motor activity
- Local anaestetic reactions
- Overdose: tremors and convulsions, with respiratory depression (eg maradonna)
- Psychotic episodes and/or damage to heart with chronic usage
Mechanism of action of Cocaine
- Blocks monoamine uptake (eg dopamine) after reaction back into the presynaptic nerve
- This increases synaptic DA, NA and 5-HT levels in the synapse
- It does inhibit calcium channels to cause anaesthesia, but only in the brain.
Mechanism of action of Cocaine in synapse (IMAGE)
List Dopamine pathways
- Nigrostriatal Dopamine Pathway (from substantiao niagra)
- Tuberoinfundibular dopamine pathway
Ecstasy otherwise known as?
- 3.4% of australians have used it in the last 12 months
- 7.5% used in lifetime
Why aren't clinical studies done on ecstacy?
- illegal drug
Effects of MDMA on person
- Closeness to others (oxytocin, which is also released at birth)
- emotional clarity
- Involuntary teeth clenching
5-HT also known as
Location of 5-HT in brain?
- raphe nucleus, Striatum, Hypothalamus, Hippocampus, Medulla
Mechanism of 5-HT
- pushes 5-HT out of presynaptic cell
- blocking 5-HT transporter recycling mechanism
- This results in 5-HT increase in synapse
- sensory and pain transmissinn
Neurotoxicity is associated with which drug?
via 5-HT released.
Neurotoxicity effects on the persion in regards to temperature?
Hyperthermia in warm environments
Hypothermia in cold environments
Heroin via syringe
Actions of opoids
- Respiratory depression (as there are many respiratory depression (cause of death pCO2 - pCO2 is needed for you to breathe)
Heroin - mechanism of action? (IMAGE)
Inhibits neuron function
What drug does heroin differentiate into?
- morphine . allows bypass of blood/brain barrier
What is the heroin drought?
- Occured in the 2000's
- Asian suppliers had poor weather conditions, and drug syndicates focused on other drugs
- china has an increased share
- 1.1 billion smokers.
- Slowly declining
- associated with many major deaths due to the tar (combustion mechanism)
- Nicotine the only active constituent
- Increased alertness, sensory and motor performance improved, increased heart rate/BP, less apetite
- extremely addictive
Nicotine / Tobacco mechanisms of action
- ligand guided ion channel
- nicotine reacts with nicotinic acetylocholine receptor (these are channels between synaptic cleft and cytoplasm)
- nicotine binds and opens the channel. The channel influx of Na+ comes in and hyperpolarises the cell.
Characteristics of addiction
- compulsive drug seeking
- repetitive drug use
- tolerance of drug
- withdrawal symptom