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Pain Flashcards

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1
Q

What is pain?

A

Subjective experience

Both sensory and emotional components

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2
Q

Which nerves carry pain information?

A

C fibre

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3
Q

Where does pain information travel in the spinal cord?

A

Lateral spinothalamic tract

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4
Q

Where does the information go to in the brain?

A

Nerve travelling in the lateral spinothalamic tract synapses in the thalamus

The thalamo cortical tracts send information to the sensory cortex

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5
Q

What are the three main targets for pain therapy?

A

Site of injury

C-fibre

Sensory cortex

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6
Q

Which drugs target the site of injury to reduce pain?

A

Anti-inflammatory drugs

Like COX inhibitors

Target bradykinin, prostaglandin, ATP and H+ build up

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7
Q

Which drugs target the C fibre to reduce pain?

A

Local anaesthetics

Like sodium channel blockers (cocaine)

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8
Q

Which drugs target the sensory cortex to reduce pain?

A

General anaesthetics

Like anaesthetic gases (NO, halothane)

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9
Q

What suggests there is an endogenous mechanism underlying pain?

A

Don’t feel pain during fight or flight

Could be as a result of the endogenous mechanism underlying response

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10
Q

What is the gate control theory of pain?

A

Explains how there are two pathways involved in pain sensation that antagonise each other

Painful stimuli travel through the a-delta and c fibre
Non-painful stimuli travel through the a-beta fibres

At the spinal cord, non painful inputs close the nerve gates to painful inputs

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11
Q

What stimuli travel through the a-delta and c fibres?

A

Painful stimuli

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12
Q

What stimuli travel through a-beta fibres?

A

Nonpainful stimuli

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13
Q

What is the action of the a-delta and c fibes?

A

Open the pain gate

Leads to transmission of pain

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14
Q

What is the action of a-beta fibres?

A

Close the pain gate

Blocks transmission of pain

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15
Q

What is different between c-fibres and a-delta fibres?

A

C-fibres are sensory neurons with no myelination, impulses travel very slowly

A-delta fibres are myelinated and work on a much more local way to transfer the stimuli faster

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16
Q

What happens when the pain fibres reach the dorsal horn of the spinal cord?

A

Synapse with the nerve going up the spinothalamic tract

Cross to go to the thalamus

Split either:

  • into the sensory motor area for localisation
  • limbic system for more emotional aspect of pain
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17
Q

What was the first sodium channel blocker developed to inhibit pain?

A

Cocaine - local pain reliever

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18
Q

What is the name of the main pain-relieving drugs?

A

Analgesics

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19
Q

What is the effect of analgesics?

A

Modify the transmission of pain

Modify the subjective perception of the painful stimulus

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20
Q

What are opioids?

A

Drugs derived from the milky fluid of unripe poppy seedpods (opium)

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21
Q

What is the active ingredient of opium?

A

Morphine

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22
Q

When was the structural formula of morphine identified?

A

1925

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23
Q

When was morphine first isolated from opium?

A

1804

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24
Q

How was morphine modified to make heroine?

A

Synthetic acetylation

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25
What, apart from analgesia, are the effects of opioids?
Cough suppression - interacts with CNS causing cough Pupil constriction Constipation Euphoria Itching Vomiting Respiratory depression - respiratory center no longer sensitive to CO2
26
What are the two categories of opioid drugs?
Morphine and related compounds Synthetic analogues of morphine
27
Examples of related compounds to morphine
Heroine Codeine
28
Examples of synthetic analogues of morphine
Methadone Fentanyl Pethidine
29
How do opioids work?
Bind to opioid receptors These are g-protein linked Gi - decrease intracellular cAMP and increase activity of K+ channels Inhibits presynaptic transmitter release and reduce postsynaptic excitability
30
What are the types of opioid receptors?
y (miu) d k Most important in pain = miu
31
Where are opioid receptors found on the neurons of the dorsal horn?
Presynaptically
32
What are the effects of analgesics on opioid receptors?
Agonists
33
What are the endogenous opioids in the body?
Met-enkephalin Leu-enkephalin Dynorphin Endorphin
34
How are the effects of analgesics reversed?
Some are structurally related to morphine and act as partial agonists with antagonist activity Some are full antagonists
35
Which precursor do endogenous opioids derive from?
POMC Expressed in tissues like the pituitary Catalysed by peptidases
36
Which receptors does enkephalin work on?
Miu Delta Kappa
37
Which receptors does endorphin work on?
Miu Delta
38
Which receptors does Dynorphin work on?
Kappa
39
What behaviour do opioid receptor knockouts experience?
Modulation of stress-induced nociception Lack of social attachment Non-alcohol dependent
40
Where are opidergic neurons mainly located?
Periaqueductal grey matter In the brain stem - midbrain Anterior to the ventricle
41
How do opidergic neurons inhibit pain?
Inhibit the neurons at the dorsal horn carrying the pain reception Activates the descending pathways that inhibit pain transmission in the dorsal horn Inhibit the activation of nociceptive afferents in the tissues
42
Why are opioids used in diarrhea?
Reduces peristalsis Leading to constipation Don't want to prevent diarrhea for a long time, since we want to remove the agent causing the diarrhea
43
How do opidergic neurons inhibit the neurons in the dorsal horn carrying pain?
Through binding to pre-synaptic membrane of neurons carrying pain This prevents the release of NT and inhibits neural transmission
44
How do opioids cause euphoria?
Bind to miu-receptors These mediate well-being
45
Signs of opioid overdose
Unconscious Respiratory depression Pupillary constriction
46
What leads to death by opioid overdose?
Respiratory depression
47
What is tolerance?
Person's diminished response to a drug Occurs when a drug is used repeatedly Body adapts to the continued presence of the drug
48
What are the two mechanisms of opioid tolerance?
Downregulation of surface receptors Desensitisation of signalling pathways
49
How do opioids cause downregulation of surface receptors?
Causes a decreased efficacy of intracellular mechanisms controlling the movement of receptors
50
Remedy for opioid overdose
Naloxone Opioid receptor antagonist
51
Which mechanisms have been developed to deal with opioid withdrawal?
Inhibiting pain through cox inhibitors Local or general anaethesia Endogenous anti-pain mechanisms
52
What causes the respiratory depression by opioids?
miu-receptors reduce the sensitivity of the respiratory center to CO2
53
What causes the nausea and vomiting by opioids?
Stimulation of the chemoreceptor trigger zone in the medulla
54
Which drug can be used to replace opioid addiction?
Methadone
55
What are the four stages of anaesthesia?
Analgesia - still conscious Excitement - inhibition cortical inhibition Surgical anaesthesia - reflexes disappear, respiratory depression Medullary depression - respiratory arrest and cardiovascular collapse
56
What is the action of anaesthetics?
Analgesia - suppress pain inputs Loss of consciousness - effect on spinothalamic tract Short term amnesia - effect on hippocampus
57
What are the two main categories of anaesthetics?
Inhalation Intravenous
58
How is the potency of inhalational anaesthetics expressed?
Minimum alveolar concentration required to produce surgical anaesthesia Represents the dry dose required The higher the MAC the less efficient the inhalational anaesthetic is
59
What is the MAC for NO?
100%
60
What is the MAC for halothane?
1%
61
When is NO used?
Pregnancy Don't want patient to be completely unconscious
62
What is the mechanism of action of inhalation anaesthetics?
Not known Does not have a well-defined receptor There is no clear structure-activity relationship Known to potentiate inhibitory transmission through GABA receptors
63
What is the relationship between the lipid solubility of inhalatory agents and potency?
Potency is well correlated with lipid solubility
64
What is the blood-gas partition coefficient?
Describes the lipid solubility of a drug The lower the coefficient the higher the solubility The more rapid the effect
65
What results in the characteristic sustained CNS depression following anaesthesia?
In long surgical procedures, the inhalation agents are taken up into adipose tissue Slow release from this leads to respiratory depression
66
Types of inhalation anaesthetic agents used today
Ether Nitrous oxide Halothane
67
Who are inhalational anaesthetics advised against?
Patients with heart conditions Cause cardiovascular collapse due to inhibition of excitable tissues
68
How are intravenous anaesthetics different to inhalation anaesthetics?
Specifically target receptors
69
What are the two main receptor targets of intravenous anaesthetics?
GABA NMDA
70
How do intravenous agents target GABA receptors?
Act as agonists Bind to the chloride channels and hyperpolarises the membranes Mimic the effects of GABA
71
Examples of IV anaesthetics targetting GABA
Barbituates Profolol
72
How do IV anaesthetics target NMDA receptors?
Antagonists Block the receptor for being excitatory
73
Example of an IV anaethetic that targets NMDA
Ketamine
74
Why is Ketamine not a very commonly used anaesthetic?
Causes dissociative anaesthesia Does not always cause anaesthesia So patients often have distant memories of what happened
75
When is ketamine used?
Children Patients with heart conditions
76
Who discovered anaesthetics?
Ether Day Ether vaporiser
77
Are anaesthetics often given singularly?
No Other factors are given prior, after or during recovery following anaesthesia Because anaesthesia is not ideal
78
What do local anaesthetics do?
Inhibit pain in a localised area of the body
79
Mechanism of action of local anaesthetics
Block voltage-gated Na+ channels in the cell membrane
80
What are the three states a sodium channel can be found in?
Resting Activation Inactivation
81
Which states of the sodium channel do local anaesthetics mostly act on?
Open or inactive
82
Which neurons do local anaesthetics mostly act on?
Small fibres are blocked more easily Pain sensation is therefore blocked before other sensory inputs Usually block large fibre diameters less effectively
83
Describe the specificity of local anaesthetics
It is not possible to achieve local anaesthesia without loss of other sensory modalities
84
What form does the drug have to be in to generate local anaesthesia?
Lipid-soluble, uncharged form In order to cross through the cell membrane
85
What type of molecule are most local anaesthetics?
Weak bases
86
What was the first local anaesthetic developed?
Cocaine
87
Example of a modern anaesthetic
Lidocaine
88
Uses of local anaesthetics
Antidysrhythmics Epilepsy

Pharmacology (13 decks)

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