Cannabis Flashcards
How many people does MS affect in the UK? How many people worldwide? Is it more common in males or females?
120,000
2-3 million
Female ratio 2-3:1
Is MS inherited?
More than 100 genes identified, such as HLA-DR
List three risk factors for MS.
EBV infection
Vit D deficiency
Smoking
What are the four clinical courses of MS?
Relapsing-remitting
Secondary progressive
Primary progressive
Progressive-relapsing
What is MS?
MS is a chronic auto-immune-mediated demyelinating disease of the CNS. The onset is usually between 20-40 years of age.
What three major things does MS cause? What type of cells are lost?
Inflammation, demyelination and neurodegeneration
Oligodendrocyte loss
How does the normal ageing atrophy rate compare to the MS one?
0.1% p.a. compared to 0.5-1.35% p.a.
How does the treatment approach differ for…
Attacks
Relapses
Progressive disease?
Attacks treated with steroids
Relapses treated with disease modifying therapy
Progressive disease – currently nothing effective, just symptomatic treatments (baclofen, sativex).
What are the four main mechanisms of MS drugs? Give examples of drugs for each one.
- Pleiotrophic effects (e.g. beta inferons)
- Targeted cell lysis (e.g. alemtuzumab)
- Reduced proliferation (e.g. teriflunomide)
- Anti-migratory (fingolimod, natalizumab)
What do MS treatments mostly rely on?
Direct targeting of pro-inflammatory cells
Interferon beta 1a and 1b:
- How is it administered?
- How does it work?
- What is its efficacy?
- What is the major side effect?
Injection
Blocks viral replication (pleiotrophic effects)
Low efficacy
Can cause flu-like symptoms
Glatiramer acetate (copaxone). Injection.
TERIFLUNOMIDE - Blocks Immune activation & targets rapidly dividing cells and block NF-Κb.
FINGOLIMOD – oral. Sphingosine-1-phosphate receptor modulator Traps cells in the Lymph nodes.
Natalizumab:
- How is it administered?
- How does it work?
- What is its efficacy?
Infusion
Blocks CD49d (blocks the migration of lymphocytes/monocytes into the CNS)
High efficacy
Alemtuzumab:
- How does it work?
- What is its efficacy?
CD52 T and B cell depletion
High efficacy
What are the main symptoms of MS? (9)
Blindness and nystagmus Fatigue Pain Tremor Spasms and spasticity Bladder problems and incontinence Sexual problems Cognitive deficits Motor deficits
What neurotransmission problems are there in MS? (4)
Conduction block
Demyelination
Loss of axons and neurons
Loss of synaptic plasticity
What does “no evidence of disease activity” involve? (4)
No new lesions
No clinical relapses
No worsening of disability
No Brain Atrophy on MRI
List some current anti-spastics.
Baclofen Gabapentin Tizanidine Benzodiazapines Dantrolene Phenol and botulinum toxin
How does baclofen work? What are the main side effects?
GABA B agonist,
Sedation and muscle weakness
How does gabapentin work? What are the main side effects?
GABA analogue - ion channel modulator
Sedation, fatigue and dizziness
How does tizanidine work? What are the main side effects?
Alpha 2 adrenergic agonist
Sedation, dry mouth, hypotension
How does benzodiazepine work? What are the main side effects?
Allosteric GABA A modulation
Sedation and addiction
How does dantrolene work? What are the main side effects?
Muscle relaxant
Sedation and liver damage
How do phenol and botulinum work?
Nerve blocking agents
Anandamide and 2-arachidonyl glycerol are both what?
What do they affect (what parts of the body) and via what receptor?
Endocannabinoids
Immune system - B cells, monocutes, spleen and tonsils
CB 2 receptor
What is anandamide formed from?
What is 2-arachidonoyl glycerol formed from?
What are they BOTH formed by the action of (enzyme)?
NAPE
Arachidonic acid containing diacylglycerol
Phospholipases
What is THC? What does it affect and via what receptor?
Plant cannabinoid
Nervous system (brain, adipose, muscle, liver, GI tract and pancreas)
CB 1 receptor
Where are cannabis receptors located? (5)
Cerebral cortex Striatum Amygdala Hippocampus Cerebellum
What happens if you stimulate CB receptors?
INHIBIT TREMOR & SPASTICITY
What happens if you block CB receptors?
WORSENS SPASTICITY
What is Sativex/Nabiximols? How is it administered?
Mix of botanical cannabis, containing tetrahydrocannabinol and cannabidiol
Sublingual spray
What is sativex used to treat? (2)
Neuropathic pain
MS
Why might cannabis not be an ‘ideal’ treatment?
We can’t dissociate the therapeutic effects from the psychoactive side effects.
What is Rimonabant/Acomplia used for? What is it?
Anti-obesity drug
CB1 Receptor Antagonist
Explain how cannabinoids help with spasticity.
They act via cannabinoid receptors to cause hyper-polarisation, causing inhibition of spasticity. They limit the capacity to generate action potentials. They cause potassium ions to be expelled and an influx of chloride ions to do this.
(Spasticity is due to damage-induced over excitation/lack of neural inhibition.)
What receptor does diazepam work on?
GABA A receptor
What is spasticity due to?
Damage induced over-excitation/lack of neural inhibition
What does the endocannabinoid system regulate?
Synaptic neurotransmission
