Analgesia Flashcards
What are the modes of action of analgesics?
Act at side of injury to decrease nociceptor sensitization
Suppress nerve conduction by blocking/ inactivating voltage-activated sodium channels
Suppress synaptic transmission of nociceptive signals in the dorsal horn of the spinal cord
Activate or potentiate descending inhibitory controls
Targeting ion channels upregulated in nerve damage
Examples of strong opioids
Morphine Oxycodone Hydromorphone Heroin Fentanyl
Examples of weak opioids
Codeine
Tramadol
Dextropropoxyphene
Examples of NSAIDs
Aspirin Diclofenac Ibuprofen Indomethacin Naproxen
What are endogenous peptides?
Endorphine which act upon opioid receptors
What mediates the supraspinal antinociception pathway?
Descending pathways from the brainstem
Which areas of the brain are involved in pain perception?
Cortex
Amygdala
Thalamus
Hypothalamus
What are important brainstem regions in the regulation of pain?
Periaqueductal grey area of midbrain around the 4th ventricle
Locus ceruleus of the pons
Nucleus raphe magnus of the medulla
Where will activated PAG neurones project?
Nucleus Raphe Magnus (NRM) to excite 5-HT and enkephalinergic neurones which project to the dorsal horn resulting in suppression of nociceptive transmission
Which neurotransmitter will the locus coeruleus utilise in regulation of pain?
Noradrenergic neurones which project to the dorsal horn
What are the different types of opioid receptors?
Mu
Delta
Kappa
What is the function of Mu?
Responsible for the majority of analgesic action of opioids but also the major adverse side effects
What is the function of delta?
Contributes to analgesia but also can be a proconvulsanat
What is the function of kappa?
Contributes to analgesia at the spinal and peripheral level and activation assoc with sedation, dysphoria and hallucinations
What is the major resp effect of opioids and what is the mechanism?
Apnoea
Blunting of medullary resp centre to CO2 involving Mu and delta receptors
What is the major CV effect of opioids and what is the mechanism?
Orthostatic hypertension
Reduced sympathetic tone and bradycardia via actions on medulla
Histamine evoked vasodilation
Morphine can cause mast degranulation which can trigger bronchospasm in asthmatics
What is the major GI effects of opioids and what are the modes of action?
N+V, constipation, increased intrabiliary pressure
Actions on CTZ
Increased smooth muscle tone, decreased motility via enteric neurones
Involves Mu and Delta receptors
What are the major CNS effects of opioids and what are the modes of action?
Confusion, eurphora, dysphoria, hallucinations, dizziness, myoclonus and hyperalgesia
Occurs to different degrees dependent upon the specific opioid drug and receptor subtypes activated
How is morphine metabolised and where?
Liver
Glucuronidation at the 3 and 6 hydroxyl positions
What is the impact of glucuronidation at the 3 and 6 positions of morphine?
3 - inactive drug
6 - active analgesic that is excreted renally
What is the difference between morphine and diamorphine?
Diamorphine is more lipophilic than morphine
Rapid onset of action (enters CNS)
How is codeine metabolised and where?
Hepatic metabolism by demethylation to morphine by cytochrome p450
What are common side effects of codeine?
Anti-diarrhoeal
Antitussive
What are the semi-synthetic derivatives of codeine?
Oxycodone
Hydrocodone
Is fentanyl more or less potent than morphine?
75-100x more potent
When is fentanyl commonly given?
IV to provide analgesia in maintenance anaesthesia
When is pethidine used?
Acute pain, particularly labour
Which drugs can pethidine not be used in conjunction with?
MAO inhibitors as will cause excitement, convulsions and hyperthermia
What is the mode of action of tramadol?
Weak Mu receptor agonist
Analgesic action by potentiation of descending serotonergic and adrenergic systems
What condition can you NOT give tramadol?
Epilepsy
What is the mode of action of methadone?
Weak Mu agonist of the phenylheptylamine class with additional actions at other sides in the CNS, including potassium channels, NMDA glutamate receptors and 5-HT receptors
What is the mode of action of naloxone?
Competitive antagonist at Mu receptors used to reverse opioid toxicity
What is important clinically about naloxone?
MUST monitor the effect of naloxone carefully, titrating the individual dose, and frequency to that required to reverse opioid toxicity
What is the difference between naloxone and naltrexone?
Naltrexone has oral availability and a much longer half life
What benefits do NSAIDs result in?
Analgesic
Antipyretic
Anti-inflammatory
What is the mode of action of NSAIDs?
Inhibit the synthesis and accumulation of prostaglandins by COX enzymes COX-1 and COX-2
What is the difference between COX-1 and COX-2?
COX-1 is constitutively active
COX-2 is induced locally at sites of inflammation by various cytokines
How do NSAIDs reduce pain and inflammation?
Suppress the decrease in activation of threshold of peripheral terminals of nociceptors caused by prostaglandins
Decrease recruitment of leukocytes that produce inflammatory mediators
If cross BBB; suppress the production of pain-producing prostaglandins in the dorsal horn of the spinal cord
Why can NSAIDs result in GI damage?
PGE2 produced by COX-1 protects against the acid/pepsin environment of the stomach
What is neuropathic pain?
Trigeminal neuralgia
Diabetic neuropathy
Postherpetic neuralgia
Phantom limb pain
What are the treatment options for neuropathic pain?
Gabapentin and pregabalin (antiepileptics)
Amitriptyline (antidepressants)
Carbamezapine
What is the mode of action of gabapentin/pregabalin in pain modulation?
Reduction in surface expression of calcium channels which are upregulated in damaged sensory neurones
Causes a decrease of neurotransmitters such as glutamate and substance P from the central terminal sof nociceptive neurones
In what condition is gabapentin frequently used?
Migraine prophylaxi
In what condition is pregabalin frequently used?
Painful diabetic neuropathy
What is the mode of action of tricyclics in modulation of pain?
Act centrally by decreasing the uptake of NA
What is the mode of action of carbamazepine in the modulation of pain?
Blocks subtypes of voltage activated Na+ channels that are upregulated in damaged nerve cells
In what condition is carbamazepine commonly used?
1st line to control pain intensity and frequency of attacks in trigeminal neuralgia
