Wk 25 - Pain 3 Flashcards
What is an analgesic?
Any drug that selectively relieves from pain w/o blocking the conduction of nerve impulses or affect consciousness
What do damaged tissues release?
- Prostaglandins
- Thromboxanes
- Leukotriene
- From arachidonic acid
What is arachidonic acid metabolised by?
- Cyclooxygenase to prod prostaglandins
- Lipoxygenase to prod leukotrienes
What are prostaglandins?
- Mediate inflammation, immune response + muscle constriction/relaxation
- Regulated blood flow + play role in formation of blood clots
- Inc pain + cause fever
What are leukotrienes?
Potent proinflammatory mediators implicated in asthma + RA
What are the 3 enzymes that synthesize prostaglandins?
- Cox 1: constitutive enzyme, GI mucosa, kidneys + platelets
- Cox 2: non constitutive, tissues
- Cox 3: brain, spinal cord + heary, associated in mechanism of paracetamol action
Outline the main mechanism of NSAIDs
Inhibit COX enzymes -? red PG production
What are the types of NSAIDs?
- Selective COX2: celecoxib, etoricoxib, roceoxib
- Non selective COX1 + 2: ibuprofen, naproxen, diclofenac, aspirin
What is acetaminophen indicated for?
- Mild-mod pain
- Red fever
- Mod-severe in conjunction w/ opiates
- Headache, arthritis, sore throat, colds, muscle aches
What are the properties of acetaminophen?
Antipyretic + analgesic - Inhibit cyclooxygenase
What are endorphins?
- Endogenous opioid neuropeptides + peptide hormones
- Enkephalins, endorphins + dynorphins
- Prod: CNS + pituitary
The binding of morphine to u-opioid receptors leads to what?
- Closing of voltage sensitive calcium channels
- Stim potassium efflux leading to hyperpolarization
- Red cAMP prod via inhibition of adenylyl cyclase
- Red cell excitability, inhibiting release of substance P, glutamate + GABA
What are the common side effects of morphine?
- Confusion
- Pupillary constriction
- Euphoria
- Hallucination
Outline the effect of benzodiazepine when given w/ methadone
- Benzo = additive CNS depressant
- Prolong CNS depressant effect of methadone
- Treat w/ artificial ventilation or naloxone
What is morphine-6-glucuronide?
- Morphine metabolite
- Binds to u receptor, high affinity for d + low for k
- 20x more potent than morphine
- Don’t cross BBB
- Less s/e: nausea, vom, sedation + respiratory depression
Which morphine metabolite is devoid of analgesic activity?
Morphine-3-glucuronide
What is diamorphine (heroin)?
- Prodrug converted to acetylmorphine + morphine
- Crosses BBB rapidly
- In brain: metabolised to inactive 3-MAM + active 6-MAM then morphine (u agonist tf euphoric + analgesic)
- More OD + poisoning
What happens when diamorphine is used in comparison to oxymorphone?
Larger histamine release:
- Greater high
- Itching when used for 1st time
What is codeine?
- Agonist: u + d w/ weak affinity
- Oral or IM, 6 hrs interval
- Antitussive + anti-diarrhoeal
- Less sedative, less respiratory depression, little euphoria
- Constipation
What is dihydrocodeine?
- Semi-synthetic derivative of codeine
- Selective full agonist of u, low affinity at K + d
- For: pain, severe dyspnea + antitussive
- IV dangerous due to pulmonary oedema + anaphylaxis
- Addiction potential
What is oxycodone?
- U agonist
- Active metabolites: oxymorphone + noroxymorphone
- Poorly crosses BBB
- 2nd line oral + injectable for mod-severe pain
What is tramadol?
- Low affinity for opioid receptors
- Inhibits uptake of NA + 5-HT
- For: mod-severe pain, acute + chronic
Metabolite w/ analgesic effect: o-desmethyltramadol (bind to u)
- Less respiratory + CV depression than morphine
- Less potential for abuse
- Contra-indicated : MAOI + epilepsy
What is methadone?
- For: analgesic + heroin addiction
- High affinity for u, low k + d
- Antagonist at NMDA + Inhibits uptake of NA + 5-HT
- Short duration of analgesia (4-6hrs) given every 8-12 hrs
Outline how to transition from other opioids to methadone
- Rapid: discontinue previous opioid + institution of methadone
- Slow: taper previous opioid + titrate methadone
Outline the interactions of methadone
- Rifampicin, phenobarbital, phenytoin + carb inc methadone metabolism -> inc opioid w/drawal
- Cimetidine, fluconazole,ciprofloxacin + clarithromycin dec metabolism -> enhanced opioid experience
What is buprenorphine?
- For: mod-severe pain + opioid dependence
- Partial agonist + high affinity MOP
- Antagonist + high affinity DOP + KOP
- Penetrates BBB easily
- Higher analgesic potency than morphine: slower dissociation from MOP
- Effects not reversed by naloxone
- Respiratory depression treated w/ doxapram
What are the characteristics of NA?
- Inhibit nociceptive neurons in substantia gelatinosa
- Promote GABA + glycine release by activating a1-adrenoceptor
- Depress glutamate release by activating 12A-adrenoceptor Ad + C fibers
What are clonidine + dexmedetomidine?
- a2-adrenoceptor agonists
- Used: anesthesia + intensive care: sedative, amnestic + analgesic
- Control NA release in spinal cord
What are the side effects of agents that stimulate a2 receptors?
- Hypotension
- Bradycardia
- Sedation
