Mechanisms of Anaesthesia Flashcards
Which type of analgesia blocks nerve conduction?
Local anaesthetics
Where do delta receptors act as analgesics?
Spinal
Peripheral
Which type of opioid receptors are associated with sedation dysphoria and hallucinations?
Kappa
What are the respiratory effects of opioids?
Apnoea
What are the cardiovascular effects of opioids?
Orthostatic hypotension
How can morphine cause asthma attacks?
Causes mast cell degranulation which triggers bronchospasms
How do opioids cause nausea?
Act on CTZ outside the BBB
Decrease motility via enteric neurons via mu and delta receptors
What are the GI side effects of opioids?
Nausea
Vomiting
Constipation
Increased intrabilliary
What are the CNS effects of opioids?
Confusion, euphoria, dysphoria, hallucinations, dizziness, myoclonus
How is morphine metabolised?
Glucorinidation at 3 and 6 position to M3G and M6G
M6G excreted by the kidney
Which is the active metabolite of morphine?
M6G
Is oxycodone more/less potent than morphine?
3x more
What is diamorphine mostly used for?
Severe post op pain
Labour
Which is more lipophilic morphine or diamorphine?
Diamorphine
What is codeine metabolised to and how?
Via p450s in hepatic metabolism
To morphine
How is fentanyl given?
IV
Transdermal or buccal in chronic pain
How do opioids works as analgesics?
Act to open inhibit VGCCs and open K+ channels on projection neurons of nociceptors
Which receptor is responsible for most of the analgesic action of opioids?
Mu
Describe the onset of action of pethidine
Rapid (when given IV, IM, s/c)
Which metabolite of pethidine causes seizures?
Norpethidine
What is the problem with use of pethidine in labour?
Very potent so causes resp depression in babies
What is buprenorphine?
Long acting partial agonist of opioids
How is buprenorphine administered?
Injection
Sublingual
What is tramadol
Weak mu opioid receptor agonist
What is though to be the main mechanism of action of tramadol?
Potentiates the descending serotonin system
And adrenergic system from the LC
Other than opioid receptors where does methadone act?
K channels
NMDAR
5HT recs
How is methadone administered?
Oral
What is methadone used for?
Addiction
Cancer
What is naloxone?
Competitive antagonist of mu receptors (kappa and delta a lil)
What is naloxone mainly used for?
Reversal of opioid toxicity
Why does the use of naloxone in opioid overdose need to be monitored?
Has a short half life
Some opioids still acting
What are alvimopan and methylnaltrexone used for?
Reduce the GI effects of chronic opioid use
Outline the mechanism of action of NSAIDs
Inhibits COX-1 and COX-2 to reduce the synthesis and accumulation of prostaglandins
Outline the production pathway of prostaglandins
Phospholipids converted to arachidonic acid by phospholipase A
Arachidonic acid converted to endoperoxides which COX1 and 2
Endoperoxdies to prostaglandins isomerase
Prostaglandin isomerase to prostaglandins
Which group of drugs selectively inhibids COX-2?
coxibs
Why is COX2 sometimes selectively inactivated?
Bc COX2 is induced locally at sites of inflammation by various cytokines
Most of the therapeutic benefit comes from this
What do NSAIDs decreased recruitment of?
Leukocytes
What occurs if NSAIDs cross the BBB?
suppress the production of pain producing prostaglandins in the dorsal horn
Why do NSAIDs have limited analgesic activity?
Multiple signalling pathways do not involve arachidonic acid metabolism
What might long term administration of non-selective NSAIDs cause?
GI damage
Nephrotoxicity
Why do kidneys get damaged with NSAIDs?
COX-2 constitutively expressed by kidney
Why is the use of coxibs limited?
They are prothrombotic
What is the proposed pathology behind neuropathic pain?
Down regulation of mu opioid receptors following injury
How does gabapentin act?
Reduces cell surface expression of an alpha2delta-1 group in the VGCC of sensory neurons
To decrease the weirdly high amount of neurotransmitters released
What is the first line treatment of neuropathic pain?
Tricyclic antidepressants
Give examples of tricyclic antidepressants
Amitriptyline
Nortryptyline
Desipramine
How do tricylic antidepressants work?
Act centrally by decreasing the reuptake of noradrenaline (and 5HTfor venlafaxine)
How does carbamazepine work?
Blocks VGNCs which are upregulated in damaged nerve
