Analgesic Drugs

Question 1

What is the difference between an opiate and an opioid?

Answer 1

an opiate is a substance extracted from opium or similar in structure whereas opioids are any agent which acts upon the opioid receptors

Question 2

How do NSAIDs work?

Answer 2

decrease nociceptor sensitization in inflammation

Question 3

What is segmental ant-nociception?

Answer 3

gate control theory

Question 4

What is supraspinal anti-nociception?

Answer 4

descending pathways from brainstem

Question 5

What areas of hte brain are involved in pain perception and emotion?

Answer 5

cortex, amygdala, thalamus and hypothalamus

Question 6

What areas of hte brainstem are invovled in supraspinal anti-nocicpetion?

Answer 6

periaqueductal grey and nucleus raphe magnus; locus coeruleus

Question 7

What happens in response to electrical stimulation in the PAG?

Answer 7

profound analgesia

Question 8

How do opioids work on the PAG?

Answer 8

cause excitation by disinhibition

Question 9

Where do axons from the nucleus raphe magnus and locus coeruleus project via?

Answer 9

dorsolateral funiculus

Question 10

What neurotransmitters does the nucelus raphe magnus use?

Answer 10

5-HT and enkephalins

Question 11

What neurotransmitter does the locus coeruleus use?

Answer 11

noradrenaline

Question 12

What type of receptor are opioid receptors?

Answer 12

GPCR which couple to Gi/o

Question 13

What is the effect of activation of the opioid receptors?

Answer 13

inhibition of opening of Ca channels presynptically and opens K channels postsnyaptically

Question 14

How does inhibition of Ca channels by opioids contribute to analgesia?

Answer 14

suppresses excitatry neurotransmitter release from nociceptor terminals

Question 15

How does opening of K channels by opioids contribute to analgesia?

Answer 15

suppresses excitation of projection neurons

Question 16

What are the types of opioid receptor?

Answer 16

mu; delta; kappa and ORL

Question 17

What type of opioid receptor is responsible for most of the analgesic action of opioids?

Answer 17

mu receptors

Question 18

What problem does mu receptor activation cause?

Answer 18

respiratory depresssion; constipation; euphoria; sedation and dependece

Question 19

What is the problem with activation of delta receptors?

Answer 19

proconvulsant

Question 20

Where does kappa contribute to analgesia?

Answer 20

spinal and peripheral levels

Question 21

What is kappa receptor activation associated with?

Answer 21

sedation; dysphoria and hallucinations

Question 22

What happens with ORL1 activation?

Answer 22

anti-opioid effect

Question 23

What is fentanyl used for?

Answer 23

providing analegsia in maintenance anaesthesia

Question 24

Why is buprenorphine useful in chronic pain?

Answer 24

long duration of action

Question 25

What should pethidine not be used with?

Answer 25

MAO inhibitors as cause convulsions and hyperthermia

Question 26

Who should tramadol be avoided in?

Answer 26

epileptics

Question 27

What type of agents are more likely to be abused?

Answer 27

short half-life are more addictive

Question 28

How does tramadol work?

Answer 28

weak um agonist; potentiates descending serotonergic and adrenergic systems

Question 29

How does methadone work?

Answer 29

weak m agonist; works at potassium channels; NMDA receptors and some 5-HT receptors

Question 30

What is naloxone?

Answer 30

competitive antagonist at um receptors (a little at kappa and delta)

Question 31

What is the use of naloxone?

Answer 31

reverse opioid toxicity

Question 32

Why is the short half life of naloxone important?

Answer 32

opioid toxicity can recur to strong opioid agonists with a longer duration of action

Question 33

What enzyme converts phospholipis to arachiodonic acid?

Answer 33

phospholipase A2

Question 34

What enzyme converts arachiodonic acid to endoperoxides?

Answer 34

COX 1 and COX 2

Question 35

What are the 3 products of endoperoxides?

Answer 35

prostaglandins; thromboxane A and prostacyclin (PGI2)

Question 36

What is the function of prostaglandins?

Answer 36

hyperalgesia by sensitising nocieptive neurons

Question 37

What is the function of thromboxane-A2?

Answer 37

platelet aggregation and vasoconstriction

Question 38

What is the function of prostacyclin?

Answer 38

platelet disaggregation and vasodilation

Question 39

Name some COX2 selective inhibitors?

Answer 39

etoricoxib; celecoxib and lumiracoxib (COXIBs)

Question 40

When is COX2 induced?

Answer 40

during inflammation

Question 41

What causes GI toxicity in COX inhibition?

Answer 41

COX-1 inhibition

Question 42

When do cells generate prostaglandins?

Answer 42

in reponse to mechanical, thermal or chemical injury

Question 43

Why do NSAIDs have limited analgesic efficacy?

Answer 43

mulitple signalling pathways not involving arachidonic acid metabolism also cause nociceptor sensitisation

Question 44

Why does long-term administration of non-selective NSAIDs produce GI damage?

Answer 44

prostaglandins produced by COX-1 protect against the acid/pepsin environment

Question 45

What is the problem with selective COX-2 inhibitors?

Answer 45

prothrombotic

Question 46

What can cause neuropathic pain?

Answer 46

trigeminal neuralgia; diabetic neuropathy; post-herpetic neuralgia; phantom limb pain

Question 47

What drugs are effective in neuropathic pain?

Answer 47

gabapentin and pregabalin; TCAs; carbamzepine

Question 48

How do gabapentin and pregabalin work?

Answer 48

reduce cell surface expression of some voltage-gated Ca channels which are upregulatedi n damaged sensory neurones which reduces neurotransmitters from central terminals

Question 49

How does carbamazepine work?

Answer 49

blocks subtypes of voltage-activated Na channels that are upregulated in damaged nerve cells