Analgesic Drugs Flashcards
(117 cards)
1
Q
How may the analgesics NSAIDs reduce nociception and pain?
A
- Act at site of injury to decrease nociceptor sensitisation in inflammation.
2
Q
How may the analgesics - local anaesthetics, reduce nociception and pain?
A
- Block nerve conduction.
3
Q
How may the analgesics - opioids and some anti-depressants, reduce nociception and pain?
A
Suppress transmission of nociceptive signals in dorsal horn of spinal cord.
4
Q
How may the analgesics - opioids reduce nociception and pain?
A
Activate/potentiate descending inhibitory controls.
- Suppress transmission of nociceptive signals in dorsal horn of spinal cord.
5
Q
How may the analgesics - anti-epileptics, reduce nociception and pain?
A
- Target ion channels that are upregulated in nerve damage.
6
Q
Give examples of strong opioids.
A
- Morphine, oxycodone, hydromorphone, heroin, fentanyl.
7
Q
Give examples of weak opioids.
A
- Codeine, tramadol, dextropropoxyphene.
8
Q
Give examples of NSAIDs.
A
- Aspirin, diclofenac, ibuprofen, indometacin, naproxen.
9
Q
What is an opiate?
A
Substance extracted from opium OR of similar structure to substances in opium.
10
Q
What is an opioid?
A
ANY agent (including endogenous peptides) that act upon opioid receptors.
11
Q
How do nociception and pain differ?
A
- Pain is the awareness of suffering.
- Nociception may occur in absence of pain and vice versa.
12
Q
Why is pain perception highly variable?
A
For same degree of nociceptor activity, more or less pain may be perceived depending on level of concurrent innocuous sensory input and behavioural context.
13
Q
Pain is triggered by what?
A
- Nociceptor stimulation (C- and Aδ- fibres).
14
Q
How may nociceptor stimulation (C- and Aδ-) be reduced?
A
Simultaneous excitation of low threshold mechanoreceptors (LTMs: Aβ-fibres).
15
Q
Describe the Gate Control Theory of Melzack and Wall.
A
Nerve impulses stimulated by injury are influenced in the spinal cord by other nerve cells which act as gates to either prevent or facilitate the passage of these impulses.
16
Q
Certain neurones within the Substantial Gelatinosa are thought to be excited by both large diameter (Aβ) sensory axons and unmyelinated (C/Aδ-) nociceptive axons.
To where do these project?
A
The spinothalamic tract.
17
Q
Inputs to projection neurones within the Substantial Gelatinosa are inhibited by?
A
An interneurone.
18
Q
What excites the interneurone that inhibits input to projection neurones within the Substantial Gelatinosa?
A
Aβ axon.
19
Q
What inhibits the Aβ axon that excites the interneurone responsible for inhibiting input to projection neurones within the Substantial Gelatinosa.
A
C/Aδ-.
20
Q
What is the overall outcome of the gate control theory?
A
Activity in nociceptive axon maximally excites the projection neurone, allowing nociceptive signals to rise to the brain.
21
Q
Supraspinal anti-nociception is relayed via which pathways and from where?
A
Descending pathways from the brainstem.
22
Q
What brain regions are involved in pain perception and emotion?
A
- Cortex.
- Amygdala.
- Thalamus.
- Hypothalamus.
23
Q
The brain regions involved in pain perception and emotion project back to the brainstem and spinal cord to modify?
A
Afferent input.
24
Q
Excitation by electrical stimulation of the Periaqueductal grey (PAG) region produces what?
A
Profound analgesia.
25
The periaqueductal grey (PAG) area may be excited by what - other than electrical stimulation?
- Endogenous opioids (enkephalins).
| - Morphine and related compounds.
26
How do endogenous opioids, morphine and related compounds cause excitation of the periaqueductal grey area?
By inhibiting inhibitory GABAergic interneurones i.e. disinhibition.
27
What causes excitation of Nucleus raphe magnus?
Morphine.
28
Opioid action is mediated by?
G-protein-coupled opioid receptors.
29
G-protein-coupled opioid receptors preferentially signal to?
Gi/o.
30
G-protein-coupled opioid receptors preferentially signal to Gi/o to produce?
- Inhibition of opening of voltage-activated Ca2+ channels.
- Opening of K+ channels.
- Inhibition of adenylate cyclase.
31
How does opioid action inhibit opening of voltage-activated Ca2+ channels?
- By suppressing excitatory neurotransmitter release from nociceptor terminals.
- Mediated by Gi/oβγ subunit.
32
How does opioid action openq K+ channels?
- Suppresses excitation of projection neurones.
| - Mediated by Gi/oβγ subunit.
33
What mediates opioid action in the inhibition of adenylate cyclase?
- Mediated by Gi/oα subunit.
34
Opioid receptors are distributed throughout the nervous system. Name the three traditional classes.
- μ (mu/ mop).
- δ (delta/ dop).
- κ (kappa/ kop).
35
Decribe the following opioid receptor.
| - μ (mu/ mop).
- Responsible for most analgesic action of opioids.
| - Also responsible for some major adverse s/e.
36
Decribe the following opioid receptor.
| - δ (delta/ dop).
- Contributes to analgesia but activation can be pro-convulsant.
37
Decribe the following opioid receptor.
| - κ (kappa/ kop).
- Contributes to analgesia at spinal and peripheral level.
| - Activation associated with sedation, dysphoria and hallucinations.
38
What effect do opioids have on the following system:
| - Respiratory?
- Apnoea.
39
What effect do opioids have on the following system:
| - Cardiovascular.
- Orthostatic hypotension.
40
What effect do opioids have on the following system:
| - Gastrointestinal.
- Nausea, vomiting, constipation, increased intrabiliary pressure.
41
What effect do opioids have on the following system:
| - Central nervous system.
- Confusion, euphoria, dysphoria, hallucinations, dizziness, myoclonus, hyperalgesia (with excessive use).
42
Describe the mechanism that results in the following effect of opioids:
- Apnoea.
- Blunting of medullary respiratory centre to CO2 (hypercapnic response).
- Involves μ (mu/ mop) and δ (delta/ dop) receptors.
43
Describe the mechanism that results in the following effect of opioids:
- Orthostatic hypotension.
- Reduced sympathetic tone and bradycardia (via actions on medulla).
- Histamine-evoked vasodilation.
- Morphine, but NOT all opioids cause mast cell degranulation which can trigger bronchospasm in asthmatics.
44
Which opioids cause mast cell degranulation that can trigger bronchospasm in asthmatics?
Morphine.
45
Describe the mechanism that results in the following effect of opioids:
- GI s/e: nausea, vomiting, constipation, increased intrabiliary pressure.
- Act on chemoreceptor trigger zone (CTZ - outside the BBB).
- -> Increased smooth muscle tone and decreased motility via enteric neurones.
- Involves μ (mu/ mop) and δ (delta/ dop) receptors.
46
Describe the mechanism that results in the following effect of opioids:
- CNS s/e: confusion, euphoria, dysphoria, hallucinations, dizziness, myoclonus, hyperalgesia.
- Varying degrees dependent upon specific opioid drug and the receptor subtypes activated.
47
How does analgesia provided by opioid agonists mainly occur?
Through prolonged activation of μ-opioid receptors.
48
Where is morphine metabolised?
In the liver.
49
How is morphine metabolised?
In the liver by Glucuronidation at 3 and 6 positions.
50
Morphine is metabolised into what?
Inactive M3G and analgesic active M6G.
51
Morphine is excreted by what?
The kidneys.
52
When may morphine be given IV?
In acute severe pain as incremental doses in high dependency areas.
53
In chronic pain, what administration of morphine is most appropriate?
Oral.
- Immediate: Oramorph.
- Sustained release: MST Continus.
54
Specialist administration of morphine by epidural and intrathecal routes provides what?
Profound analgesia.
55
What is Diamorphine?
- 3,6-diacetylmorphine.
| - Heroin.
56
How does diamorphine differ from morphine?
More lipophilic than morphine.
57
What is the benefit of administering Diamorphine via IV?
- Rapid onset of action as it enters CNS rapidly.
58
What is codeine?
A naturally occurring weak opioid for mild/moderate pain.
59
How is codeine metabolised?
In the liver by demethylation (in small amounts).
60
Codeine undergoes hepatic metabolisation into?
Morphine by CYP2D6 and CYP3A4.
61
What useful properties in addition to analgesia does codeine possess?
- Anti-diarrhoeal (but may cause constipation).
| - Anti-tussive.
62
What semi-synthetic derivatives of codeine have higher potency?
- Oxycodone.
| - Hydrocodone.
63
Which drug is 75-100x more potent than morphine?
Fentanyl.
64
When is Fentanyl given and how?
IV to provide analgesia in maintenance anaesthesia.
65
Fentanyl is suitable for which forms of administration in chronic pain states, but not in acute pain?
- Transdermal.
| - Buccal.
66
When is pethidine used?
Acute pain esp. labour.
67
Pethidine has rapid onset of action when given in which form?
IV, IM or SC.
68
Why is pethidine not suitable for controlling chronic pain?
Rapid onset, but short duration of action.
69
Pethidine should not be used in conjunction with what?
MAO inhibitors.
70
Pethidine used in conjuntion with MAO inhibitors will cause what?
- Excitement, convulsions and hyperthermia.
71
What is a neurotoxic metabolite of pethidine?
Norpethidine.
72
Norpethidine, the neurotoxic metabolite of Pethidine, maycause what?
Seizures.
73
Buprenorphine is a partial agonist, useful in what types of pain?
Chronic pain.
74
How is buprenorphine administered to those with chronic pain?
Patient controlled injection systems.
| - Injection or sublingually.
75
Describe the onset and duration of action of Buprenorphine.
Slow onset but long duration of action.
76
Describe tramadol.
- Weak μ-receptor agonist.
| - Opioid.
77
How is Tramadol thought to exert significant analgesic action?
By potentiation of descending serotonergic and adrenergic systems.
78
How is tramdol administered?
Orally.
79
Tramadol use should be avoided in patients with which condition?
Those with epilepsy.
80
Describe methadone.
Opioid.
- Weak μ-agonist of phenylheptylamine class.
- Action at K+ channels, NMDA glutamate receptors and some 5-HT receptors.
81
How is methadone adminstered?
orally.
82
Describe the duration of action and half-life of methadone.
- Long duration of action.
| - Plasma half-life >24hours.
83
Methadone can be useful in treating patients with which conditions?
- Chronic pain in terminal cancer.
| - Withdrawal from strong opioids e.g. heroin.
84
Etorphine is used in who?
Large animals - elephants, rhinos.
| Reversed by diprenorphine.
85
Generally, the more addictive opioids with abuse potential have which kind of half-life?
Shorter half-life opioids tend to be more addictive than those with long half-lives.
86
Name an antagonist of opioids.
- Naloxone.
- Naltrexone.
- Alvimopan.
- Methylnaltrexone.
87
How does naloxone work?
As a competitive antagonist at μ-receptors.
88
What is naloxone used for?
To reverse opioid toxicity.
| - i.e. respiratory +/or neurological depression.
89
How is naloxone administered?
Incrementally IV.
IM or SC if IV not practical.
90
Naloxone has a short half-life. Why is this important?
- Opioid toxicity can recur due to strong opioid agonsts with a longer duration of action.
- Titrate individual dose and frequency to that required to reverse opioid toxicity. MUST monitor effect closely and do NOT leave patient unattended.
91
In opioid addicts, Naloxone may trigger what?
Acute withdrawal response.
92
In patients requiring high dose opioid analgesia regularly, Naloxone may trigger what?
Acute withdrawal response.
93
If pethidine is given to a mother during labour, and the newborn has opioid toxicity, what may be administered?
Naloxone.
94
What advantage does Naltrexone have over Naloxone?
- Oral availability.
| - Much longer half-life.
95
Describe the action of the opioid antagonists: Alvimopan and Methylnaltrexone.
- Do not enter CNS.
| - Reduce GI effects of surgical and chronic opioid agonist use.
96
Non-selective NSAIDs have which actions?
- Analgesic.
- Antipyretic.
- Anti-inflammatory.
97
Non-selective NSAIDs actions are largely due to what?
Inhibition of synthesis and accumulation of prostaglandins by cyclo-oxygenase (COX) enzymes COX-1 and COX-2.
98
Prostaglandins cause what symptoms?
- Hyperalgesia.
- Allodynia.
- Pain.
99
COX-2 is induced where and by what?
Locally at sites of inflammation by various cytokines.
100
Therapeutic benefit of NSAIDs mainly derives from?
Inhibition of COX-2.
101
Why do NSAIDs decrese recruitent of leukocytes?
These produce inflammatory mediators.
102
Why do NSAIDs suppress prostaglandin activity on nociceptors?
Prostaglandins act on peripheral terminals of nociceptors to decrease activation threshold.
103
If NSAIDs cross the BBB, what are they able to do?
Suppress production of pain-producing prostaglandins in the dorsal horn of the spinal cord.
104
Why is paracetamol not an NSAID?
Lacks anti-inflammatory activity and only acts centrally.
105
Why do NSAIDs have limited analgesic efficacy?
Multiple signalling pathways cause nociceptor sensitisation.
106
Why can nephrotoxicity arise as a result of long-term NSAID administration?
COX-2 is inhibited, but constitutively expressed by the kidney.
107
Inhibition of COX-2 by NSAIDs can have what effect in renal disease?
Compromise renal haemodynamics.
108
Why is the use of selective COX-2 inhibitors limited?
They are prothrombotic.
109
Treatment of neuropathic pain?
- Gabapentin and Pregabalin (anti-epileptics).
- Amitryptyline, Nortryptiline and Desipramine (TCAs).
- Carbamazepine.
110
Neuropathic pain does not respond to?
- NSAIDs.
| - Opioids unless in high doses.
111
How do Gabapentin and Pregabalin help in neuropathic pain?
Reduce cell surface expression of subunit α2δ of some voltage-gated Ca2+ channels that are upregulated in damaged sensory neurones.
112
Reduction of cell surface expression of α2δ by gabapentin and pregabalin presumably has what effect on neurotransmitters?
Decreases neurotransmitters e.g. Glutamate and substance P from central terminals of nociceptive neurones.
113
Gabapentin is often used in which condition?
Migraine prophylaxis.
114
Pregabalin is often useful in which condition?
Painful diabetic neuropathy.
115
Action of Amitriptyline, Nortryptiline and Desipramine in neuropathic pain?
Act centrally by decreasing reuptake of noradrenaline.
116
Action of Carbamazepine in neuropathic pain?
Blocks subtypes of voltage-activated Na+ channels upregulated in damaged neve cel.
117
First line treatment to control pain intensity and frequency of attacks in trigeminal neuralgia?
Carbamazepine.
