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A PA20023 > Pain, Nociception and analgesia 3 > Flashcards

Pain, Nociception and analgesia 3 Flashcards

1
Q

What can Analgesic drugs do

A
  1. Mechanism to sensitise the nociception
  2. Peripheral sensitisation
  3. Central sensitisation- Form of synaptic plasticity
  4. Descending inhibition of nociception
  5. Analgesic drugs could boost descending inhibition, inhibit central sensitisation or peripheral sensitisation
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2
Q

What is peripheral sensitisation

A
  1. Inflammatory immune response
  2. Threshold decreases- more pain
  3. Protects bodies
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3
Q

What is Descending inhibition of nociception

A
  1. Inhibits pain

2. When don’t have time to deal with it

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4
Q

Give some examples of Analgesic drugs

A
  1. Opiate drugs
  2. NSAIDs (non-steroidal anti-inflammatory drugs)
  3. Other analgesics – already used, and in the pipeline
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5
Q

What do opiates do

A
  1. act on opioid receptors

2. mimic endogenous opioids

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6
Q

Give example of opiates

A
  1. Morphine
  2. Heroin (Diamorphine)
  3. Codeine- lower efficacy
  4. Methadone
  5. Pethidine lower efficacy
  6. (Etorphine)- most potent, not clinical use for humans but used in veterinary practice
  7. Fentanyl
  8. Remifentanyl
  9. Butorphanol
  10. Buprenorphine- lower efficacy
  11. Naloxone mu, d, k antagonist- used in case of overdose of opioids
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7
Q

What does the World Health Organisation Pain Ladder suggest to take for different pains

A
  1. Mild pain – NSAIDs e.g. aspirin, ibuprofen
  2. Moderate pain – codeine, buprenorphine
  3. Severe pain – morphine, fentanyl- more effective but more side effects
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8
Q

What type of opioid receptors are most important and where are they found

A
  1. Mu receptors are most important in endogenous anti-nociception
  2. Mu in brain, spinal cord and peripheral
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9
Q

What are side effects of Mu receptor opioids

A
  1. The better the opioid receptors agonist the more euphoria- hard to separate
  2. Respiratory depression- opioid overdose cause
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10
Q

What are side effects of Kappa opioid receptor agonist

A
  1. Dysphoria- miserable

2. Risk of overdose very low

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11
Q

What are side effects of Delta opioid receptor agonist

A
  1. Proconvulsant- risk of fits
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12
Q

What are desirable effects of mu receptor opioids

A
  1. Analgesia
  2. Euphoria
  3. Constipation
  4. Sedation
  5. Cough suppression
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13
Q

What are Undesirable effects of mu receptor opioids

A
  1. Respiratory depression
  2. Euphoria
  3. Constipation (methylnaltrexone)- binds to mu opioid receptor in gut and so agonist can’t bind and cause constipation
  4. Sedation
  5. Nausea & vomiting
  6. Tolerance
  7. Itching
  8. Psychological dependence
  9. Physical dependence
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14
Q

What is tolerance

A
  1. Continued use of a drug requires increased doses for equivalent effect
  2. Analgesic experiment on mice
  3. Does response to morphine first time is much higher than 3 days later- shift to right in potency of morphine
  4. Effect of drug wears off
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15
Q

What is main active ingredient in opium and how was opium first used

A
  1. Main active ingredient in opium is morphine
  2. Codeine as well but morphine is main
  3. Heroin- first attempt at safer drug
  4. Two acetyl groups replace alcohol
  5. But mean they cross blood brain barrier more effectively
  6. Acetyl groups cleaved once passed and left with morphine
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16
Q

Describe routes of administration of opiates

A
  1. Pills
  2. Intravenous injection
  3. Epidural
  4. Transdermal patch
  5. Lollipop
17
Q

What can be taken as pills

A
  1. morphine / codeine
18
Q

What is an intravenous injection

A
  1. patient controlled injection

2. morphine / diamorphine / fentanyl

19
Q

What is an epidural

A
  1. fentanyl / pethidine
  2. way of local delivery just at spinal level
  3. useful for childbirth and surgery
  4. activates opioid receptors in specific part of spinal cord that receives nociceptor input – means doesn’t pass into mothers’ bloodstream and then into babies
20
Q

What is transdermal patch

A
  1. Fentanyl

2. Steady state levels of opioid- if pain is constant it is good

21
Q

What is lollipop

A
  1. Fentanyl- lipophilic so can be delivered through mouth

2. Steady level and then breakthrough level of pain- lollipop along side steady levels of opioid

22
Q

What are Non-steroidal anti-inflammatory drugs (NSAIDS) used for

A
  1. Most widely used therapeutic agents
  2. Over 50 types available
  3. eg. aspirin, ibuprofen, diclofenac, paracetamol
  4. Anti-inflammatory- paracetamol is not
  5. Anti-pyretic
  6. Analgesic
  7. All effects related to decreased prostaglandin synthesis
23
Q

What do prostaglandins do

A
  1. Prostaglandins are part of immune inflammatory response
  2. Various factors try to heal it
  3. Prostaglandins act on Prostanoid receptor which sensitise nociceptors
24
Q

What do NSAIDs inhibit

A
  1. NSAIDs are COX inhibitors
  2. COX- key enzyme in producing prostaglandins
  3. NSAIDS mean less prostaglandins – less peripheral sensitisation
25
Q

What are Disadvantages of NSAIDS

A
  1. PGs involved in many processes
  2. multiple side effects
  3. severe gastric irritation
  4. kidney disorders
    5 paracetamol overdose
  5. Specific COX-2 inhibitors have Less side effects.
26
Q

What do Specific COX-2 inhibitors do

A
  1. COX-1 is widespread throughout the body- leads to gastric side effects
  2. COX-2 is just involved in the inflammatory response- gives desired effect
  3. Traditional block COX-1 and COX-2
  4. Some drugs on market which block COX-2 only
  5. But Vioxx- sudden death syndrome- caused people’s hearts to stop
  6. Not found COX-2 specific that doesn’t have cardiac side effects now
27
Q

What is Neuropathic pain

A
  1. Pain unrelated to peripheral nociception

2. Sometimes called pathological pain – serves no purpose

28
Q

What is neuropathic pain caused by

A
  1. Peripheral nerve damage- (eg. Diabetic neuropathy)
  2. Peripheral nerve terminal damage or infection - (eg. Post-herpetic neuralgia)
  3. Spinal damage
  4. Thalamic stroke
  5. Generally don’t respond to opioids / NSAIDs
29
Q

What are some other analgesic approaches

A
  1. Tricyclic antidepressants (e.g. imipramine)
  2. Antiepileptic drugs (e.g. gabapentin)
  3. Cannabinoid receptor agonists
  4. Glutamate receptor blockers (MK801)
  5. Neurokinin receptor blockers
  6. Nociceptor blockers (TRPV1, P2X3, sodium channel)
30
Q

What do Antiepileptic drugs do

A
  1. Neuropathic pain

2. Unknown mode of action

31
Q

What do Cannabinoid receptor agonists do

A
  1. Central and peripheral effects

2. Neuropathic pain (esp. multiple sclerosis)

32
Q

What do Glutamate receptor blockers (MK801) do

A
  1. Block afferent transmission

2. Severe side effects

33
Q

What do Neurokinin receptor blockers do

A
  1. Block central sensitization

2. In development

34
Q

What do Nociceptor blockers do

A
  1. Block detection of noxious signals

2. In development

A PA20023 (19 decks)

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