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CPT (My own) > Opioids > Flashcards

Opioids Flashcards

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1
Q

How is pain stimulated?

A 
Nociceptors stimulated
Release of substance P and glutamate
Afferent nerve stimulated
Fibres decussate
Action potential ascends
Synapse in thalamus
Project to post central gyrus
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2
Q

Name 2 specific pain afferent nerve fibres

A

A Delta fibre

C fibres

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3
Q

What pain do A delta fibres transmit

A

Sharp pain, myelinated

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4
Q

What pain do C fibres transmit?

A

Dull achey pain

Slower transmission

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5
Q

Which of the 2 types of pain afferent fibres need the higher stimulus

A

c fibres

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6
Q

Which specific parts of the dorsal horn do the 1st order synapse at?

A

Lamina 1 and 5

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7
Q

Which tract do the 2nd order neurones pass through?

A

Ascending lateral spinothalamic tract

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8
Q

Where does the 2nd order neurone synapse?

A

Thalamus

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9
Q

Where do 3rd order neurones synapse?

A

Pre-central gyrus

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10
Q

What is the key pain modulator in the peripheral system?

A

Substantia gelatinosa

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11
Q

What is the key pain modulator in the central system?

A

Peri-aqueductal grey

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12
Q

Describe the stimulatory pathway in peripheral pain?

A

Stimulator alpha and c fibres from damaged tissue to lamina 1 in dorsal horn then to the thalamus

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13
Q

Describe the inhibitory pathway in the peripheral pain

A

Inhibitory afferents towards substantial gelatinosa

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14
Q

How does ‘rub it better’ work?

A

Stimulates substantia gelatinosa, inhibiting lamina 1 and 5

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15
Q

How do we modulate pain centrally?

A

Pain afferents from dorsal horn to the thalamus, then stimulator paths to the cortex from then inhibitory stimulus to periaqueductal grey matter,

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16
Q

Give examples of endogenous opioids

A

Enkpehalins
Gynorphins
Beta-endorphins
Seratonin

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17
Q

What part do the endogenous opioids have on central pain modulation?

A

Inhibition from periaquaductal grey matter to dorsal horn

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18
Q

How are endogenous opioids categorised?

A

According to the class of GPCR receptors

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19
Q

What are the 3 classes of opioid receptors?

A

MOP
DOP
KOP

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20
Q

Where are MOP receptors found?

A

Supraspinal

GI tract

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21
Q

Where are DOP receptors found?

A

Wide distribution

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22
Q

Where are KOP receptors found?

A

Spinal cord
Brain
Periphery

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23
Q

What affect does all the endogenous opioids have on cAMP

A

Decreases it

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24
Q

What effect does MOP receptors have on minerals?

A

Outward flux of potassium

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25
What effect does DOP receptors have on minerals?
Influx od calcium
26
What effect does KOP receptors have on minerals?
Efflux od potassium | Influx of calcium
27
What are the examples of MOP opioids?
Enkephalins | Beta endorphins
28
What are the examples of DOP opioids?
Enkephalins
29
What are the examples of KOP opioids?
Dynorphins
30
What is the order of the WHO analgesic ladder?
Simple analgesia- paracetamol NSAIDs - -> Weak opioids-codeine - -> Strong opioid- morphine, fentanyl
31
If the pain is neuropathic which analgesics are used preferentially?
Anticonvulsants Tricyclics Serotonin/NA reuptake inhibitors
32
What is the main receptor subtype with therapeutic effects?
MOP
33
What are uses od opioids?
Mainly to modulate pain Cough Diarrhoea Palliation
34
Describe the absorption go morphine
PO, IV, IM, SC, PR Gut absorption erratic Significant first pass effect- 40% oral bioavailability
35
Describe the distribution of morphine?
Lipophilic therefore rapidly enters all tissues including foetal Struggles to cross the blood brain barrier
36
Describe the metabolism of morphine
Morphine and glucuronic acid --? M6G and M3G which have neuroexcitatory effects
37
Describe the elimination of morphine
Renally
38
Which receptors do morphine have strongest affinity for?
Mu
39
What are the actions of Morphine?
Analgesia | Euphoria
40
What are the side effects of Morphine?
Respiratory depression- medullary res centre less responsive to CO2 Emesis- stimulate chemoreceptor trigger zone GI tract- decreasing motility, increasing sphincter tone CVS Miosis Histamine release- caution in asthmatics
41
Describe the absorption of Fentanyl
IV, epidural, intrathecal, nasal | 80-100% bioavailability
42
Describe the distribution of fentanyl
Highly lipophilic, highly protein bound High level of CNS crossing Has higher distribution than Morphine
43
Describe the metabolism of fentanyl
Hepatic via CYP3A4
44
Describe the elimination of fentanyl
Half life is 6 mins | Renally excreted
45
What is it compared to mirphine in terms of potency?
100 x potency Higher affinity to mu receptors Less histamine release, sedation and constipation
46
What implication does the higher potency of fentanyl have on morphine
Can shift morphine off, smaller side effects
47
What are the actions of fentanyl?
Analgesia | Anaesthetic
48
What are the side effects of fentanyl?
Respiratory depression Constipation Vomiting
49
What is the absorption of codeine?
PO, SC administration sometimes
50
Describe the metabolism of Codeine?
Codeine goes to Morphine via CYP2D6 in the liver CYP2D6 inhibited in Fluoxetine and other SSRI's Variable expression throughout the population, so can have no effect or excessive efefcts
51
Describe the elimination of Codeine
Glucoronidation of morphine and renal excretion
52
Codeine compared to morphine in terms of potency?
1/10th potency
53
What are the actions of Codeine?
Mild- moderate analgesia | Cough depressant
54
What are the side effects of Codeine?
Constipation | Respiratory depression- worse in children
55
Give an example of a mixed agonist-antagonist
Buprenorphine
56
Describe the absorption of Buprenorphine
Transdermal, Buccal, Sublingual
57
Describe the distraction of Buprenorphine
Very lipophilic therefore distributes everywhere including the brain
58
Describe metabolism of Buprenorphine
Hepatic via CYP3A4 | Glucoronidation before biliary excretion
59
Describe the elimination of Buprenorphine
Biliary > Renal Safe in renal impairment Long half life of 37 hrs
60
What is the implications of the long half life?
Works as a patch
61
Compare Buprenorphine to Morphine
Very high affinity for mu receptor--> low Kd Long duration of action Not easily displaced Lower EMax, as partial agonist--> lower efficacy Antagonist at K receptors
62
What are the actions of Buprenorphine?
Moderate to severe pain Especially chronic pain Opioid addiction treatment
63
What are the side effects of Buprenorphine
Respiratory depression Low BP Nausea Dizziness
64
Describe absorption of Naloxone
IV, IM Intranasal, PO Very low oral bioavailability as extensive first pass effect Rapid onset of action Short onset of action
65
Describe the distribution of naloxone
Rapid distribution as very lipophilic
66
Describe the metabolism of Naloxone
Hepatic--> Naloxone-3-glucoronide | Renally excreted
67
Describe the elimination of Naloxone
Duration of action 30-60 mins
68
Compare Naloxone to Morphine
mu>delta>kappa Greater affinity than morphine Affinity less than Buprenorphine
69
What are the actions of Naloxone?
Competitive antagonism of opioid
70
What are the side effects of Naloxone?
Short half life | Slow infusion
71
Why must Naloxone be given in slow infusion?
Allowing the stronger drug to be metabolised and excreted to non toxic levels while the competitive inhibitor that Naloxone is able to bind and compete for receptors
72
What are the 2 mechanisms of opioid tolerance?
Phosphorylation and uncoupling | cAMP production
73
What is the effect of opioid via phosphorylation and uncoupling?
Decreased cAMP which would result to decreased pain via linking with G protein
74
What happens to the phosphorylation and uncoupling process on repeated exposure to opioids?
Results in decreased sensisitivty | Arrestin protein binds to the Mu receptors instead and GPCR is displaced so no more downstream cAMP
75
How does repeated exposure to opioids affect cAMP?
Rebound effect when opioid removed and instead get flood of cAMP Decreased neuronal excitability, increased depolarisation Withdrawal symptoms
76
What can be the effects of opioid overdose?
Mu receptor Variable effects pf doses Respiratory depression most common cause of death Can decrease effects- delta agonists and serotonin agonists
77
What is the treatment of opioid overdose?
Naloxone infusion
78
Explain the process of respiratory depression in overdose?
Drowsyiness decreases breathing--> lowers CO2--> decreased medullary CO2 response--> Decreased respiratory rate --> Increased acidotic state
79
What special considerations are there for opioid prescriptions?
``` Manual laboureres Elderly Asthmatics Biliary tract obstruction Resp diseases Renal impairment Pregnancy ```
80
Why do special considerations need to be made with opioids?
Make you drowsy
81
What are contraindications of opioids?
``` Hepatic failure Acute respiratory distress Comatose Head injuries Raised ICP ```
82
What indications opioids have on palliative care?
Pain | Shortness of breath
83
What side effects are there in opioid usage on palliative care?
Nausea | Constipation

CPT (My own) (6 decks)

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