Analgesic Drugs Flashcards
What is the difference between an opiate and an opioid?
an opiate is a substance extracted from opium or similar in structure whereas opioids are any agent which acts upon the opioid receptors
How do NSAIDs work?
decrease nociceptor sensitization in inflammation
What is segmental ant-nociception?
gate control theory
What is supraspinal anti-nociception?
descending pathways from brainstem
What areas of hte brain are involved in pain perception and emotion?
cortex, amygdala, thalamus and hypothalamus
What areas of hte brainstem are invovled in supraspinal anti-nocicpetion?
periaqueductal grey and nucleus raphe magnus; locus coeruleus
What happens in response to electrical stimulation in the PAG?
profound analgesia
How do opioids work on the PAG?
cause excitation by disinhibition
Where do axons from the nucleus raphe magnus and locus coeruleus project via?
dorsolateral funiculus
What neurotransmitters does the nucelus raphe magnus use?
5-HT and enkephalins
What neurotransmitter does the locus coeruleus use?
noradrenaline
What type of receptor are opioid receptors?
GPCR which couple to Gi/o
What is the effect of activation of the opioid receptors?
inhibition of opening of Ca channels presynptically and opens K channels postsnyaptically
How does inhibition of Ca channels by opioids contribute to analgesia?
suppresses excitatry neurotransmitter release from nociceptor terminals
How does opening of K channels by opioids contribute to analgesia?
suppresses excitation of projection neurons
What are the types of opioid receptor?
mu; delta; kappa and ORL
What type of opioid receptor is responsible for most of the analgesic action of opioids?
mu receptors
What problem does mu receptor activation cause?
respiratory depresssion; constipation; euphoria; sedation and dependece
What is the problem with activation of delta receptors?
proconvulsant
Where does kappa contribute to analgesia?
spinal and peripheral levels
What is kappa receptor activation associated with?
sedation; dysphoria and hallucinations
What happens with ORL1 activation?
anti-opioid effect
What is fentanyl used for?
providing analegsia in maintenance anaesthesia
Why is buprenorphine useful in chronic pain?
long duration of action
What should pethidine not be used with?
MAO inhibitors as cause convulsions and hyperthermia
Who should tramadol be avoided in?
epileptics
What type of agents are more likely to be abused?
short half-life are more addictive
How does tramadol work?
weak um agonist; potentiates descending serotonergic and adrenergic systems
How does methadone work?
weak m agonist; works at potassium channels; NMDA receptors and some 5-HT receptors
What is naloxone?
competitive antagonist at um receptors (a little at kappa and delta)
What is the use of naloxone?
reverse opioid toxicity
Why is the short half life of naloxone important?
opioid toxicity can recur to strong opioid agonists with a longer duration of action
What enzyme converts phospholipis to arachiodonic acid?
phospholipase A2
What enzyme converts arachiodonic acid to endoperoxides?
COX 1 and COX 2
What are the 3 products of endoperoxides?
prostaglandins; thromboxane A and prostacyclin (PGI2)
What is the function of prostaglandins?
hyperalgesia by sensitising nocieptive neurons
What is the function of thromboxane-A2?
platelet aggregation and vasoconstriction
What is the function of prostacyclin?
platelet disaggregation and vasodilation
Name some COX2 selective inhibitors?
etoricoxib; celecoxib and lumiracoxib (COXIBs)
When is COX2 induced?
during inflammation
What causes GI toxicity in COX inhibition?
COX-1 inhibition
When do cells generate prostaglandins?
in reponse to mechanical, thermal or chemical injury
Why do NSAIDs have limited analgesic efficacy?
mulitple signalling pathways not involving arachidonic acid metabolism also cause nociceptor sensitisation
Why does long-term administration of non-selective NSAIDs produce GI damage?
prostaglandins produced by COX-1 protect against the acid/pepsin environment
What is the problem with selective COX-2 inhibitors?
prothrombotic
What can cause neuropathic pain?
trigeminal neuralgia; diabetic neuropathy; post-herpetic neuralgia; phantom limb pain
What drugs are effective in neuropathic pain?
gabapentin and pregabalin; TCAs; carbamzepine
How do gabapentin and pregabalin work?
reduce cell surface expression of some voltage-gated Ca channels which are upregulatedi n damaged sensory neurones which reduces neurotransmitters from central terminals
How does carbamazepine work?
blocks subtypes of voltage-activated Na channels that are upregulated in damaged nerve cells
