Wk 25 - Pain 3

Question 1

What is an analgesic?

Answer 1

Any drug that selectively relieves from pain w/o blocking the conduction of nerve impulses or affect consciousness

Question 2

What do damaged tissues release?

Answer 2

• Prostaglandins
• Thromboxanes
• Leukotriene
• From arachidonic acid

Question 3

What is arachidonic acid metabolised by?

Answer 3

• Cyclooxygenase to prod prostaglandins

- Lipoxygenase to prod leukotrienes

Question 4

What are prostaglandins?

Answer 4

• Mediate inflammation, immune response + muscle constriction/relaxation
• Regulated blood flow + play role in formation of blood clots
• Inc pain + cause fever

Question 5

What are leukotrienes?

Answer 5

Potent proinflammatory mediators implicated in asthma + RA

Question 6

What are the 3 enzymes that synthesize prostaglandins?

Answer 6

• 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

Question 7

Outline the main mechanism of NSAIDs

Answer 7

Inhibit COX enzymes -? red PG production

Question 8

What are the types of NSAIDs?

Answer 8

• Selective COX2: celecoxib, etoricoxib, roceoxib

- Non selective COX1 + 2: ibuprofen, naproxen, diclofenac, aspirin

Question 9

What is acetaminophen indicated for?

Answer 9

• Mild-mod pain
• Red fever
• Mod-severe in conjunction w/ opiates
• Headache, arthritis, sore throat, colds, muscle aches

Question 10

What are the properties of acetaminophen?

Answer 10

Antipyretic + analgesic - Inhibit cyclooxygenase

Question 11

What are endorphins?

Answer 11

• Endogenous opioid neuropeptides + peptide hormones
• Enkephalins, endorphins + dynorphins
• Prod: CNS + pituitary

Question 12

The binding of morphine to u-opioid receptors leads to what?

Answer 12

• 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

Question 13

What are the common side effects of morphine?

Answer 13

• Confusion
• Pupillary constriction
• Euphoria
• Hallucination

Question 14

Outline the effect of benzodiazepine when given w/ methadone

Answer 14

• Benzo = additive CNS depressant
• Prolong CNS depressant effect of methadone
• Treat w/ artificial ventilation or naloxone

Question 15

What is morphine-6-glucuronide?

Answer 15

• 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

Question 16

Which morphine metabolite is devoid of analgesic activity?

Answer 16

Morphine-3-glucuronide

Question 17

What is diamorphine (heroin)?

Answer 17

• 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

Question 18

What happens when diamorphine is used in comparison to oxymorphone?

Answer 18

Larger histamine release:

• Greater high
• Itching when used for 1st time

Question 19

What is codeine?

Answer 19

• Agonist: u + d w/ weak affinity
• Oral or IM, 6 hrs interval
• Antitussive + anti-diarrhoeal
• Less sedative, less respiratory depression, little euphoria
• Constipation

Question 20

What is dihydrocodeine?

Answer 20

• 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

Question 21

What is oxycodone?

Answer 21

• U agonist
• Active metabolites: oxymorphone + noroxymorphone
• Poorly crosses BBB
• 2nd line oral + injectable for mod-severe pain

Question 22

What is tramadol?

Answer 22

• 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

Question 23

What is methadone?

Answer 23

• 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

Question 24

Outline how to transition from other opioids to methadone

Answer 24

• Rapid: discontinue previous opioid + institution of methadone
• Slow: taper previous opioid + titrate methadone

Question 25

Outline the interactions of methadone

Answer 25

• Rifampicin, phenobarbital, phenytoin + carb inc methadone metabolism -> inc opioid w/drawal
• Cimetidine, fluconazole,ciprofloxacin + clarithromycin dec metabolism -> enhanced opioid experience

Question 26

What is buprenorphine?

Answer 26

• 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

Question 27

What are the characteristics of NA?

Answer 27

• Inhibit nociceptive neurons in substantia gelatinosa
• Promote GABA + glycine release by activating a1-adrenoceptor
• Depress glutamate release by activating 12A-adrenoceptor Ad + C fibers

Question 28

What are clonidine + dexmedetomidine?

Answer 28

• a2-adrenoceptor agonists
• Used: anesthesia + intensive care: sedative, amnestic + analgesic
• Control NA release in spinal cord

Question 29

What are the side effects of agents that stimulate a2 receptors?

Answer 29

• Hypotension
• Bradycardia
• Sedation