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Pharmacology > Pain > Flashcards

Pain Flashcards

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
Q

What, apart from analgesia, are the effects of opioids?

A

Cough suppression - interacts with CNS causing cough

Pupil constriction

Constipation

Euphoria

Itching

Vomiting

Respiratory depression - respiratory center no longer sensitive to CO2

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26
Q

What are the two categories of opioid drugs?

A

Morphine and related compounds

Synthetic analogues of morphine

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27
Q

Examples of related compounds to morphine

A

Heroine

Codeine

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28
Q

Examples of synthetic analogues of morphine

A

Methadone

Fentanyl

Pethidine

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29
Q

How do opioids work?

A

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

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30
Q

What are the types of opioid receptors?

A

y (miu)

d

k

Most important in pain = miu

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31
Q

Where are opioid receptors found on the neurons of the dorsal horn?

A

Presynaptically

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32
Q

What are the effects of analgesics on opioid receptors?

A

Agonists

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33
Q

What are the endogenous opioids in the body?

A

Met-enkephalin

Leu-enkephalin

Dynorphin

Endorphin

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34
Q

How are the effects of analgesics reversed?

A

Some are structurally related to morphine and act as partial agonists with antagonist activity

Some are full antagonists

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35
Q

Which precursor do endogenous opioids derive from?

A

POMC

Expressed in tissues like the pituitary

Catalysed by peptidases

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36
Q

Which receptors does enkephalin work on?

A

Miu

Delta

Kappa

37
Q

Which receptors does endorphin work on?

A

Miu

Delta

38
Q

Which receptors does Dynorphin work on?

A

Kappa

39
Q

What behaviour do opioid receptor knockouts experience?

A

Modulation of stress-induced nociception

Lack of social attachment

Non-alcohol dependent

40
Q

Where are opidergic neurons mainly located?

A

Periaqueductal grey matter

In the brain stem - midbrain

Anterior to the ventricle

41
Q

How do opidergic neurons inhibit pain?

A

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
Q

Why are opioids used in diarrhea?

A

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
Q

How do opidergic neurons inhibit the neurons in the dorsal horn carrying pain?

A

Through binding to pre-synaptic membrane of neurons carrying pain

This prevents the release of NT and inhibits neural transmission

44
Q

How do opioids cause euphoria?

A

Bind to miu-receptors

These mediate well-being

45
Q

Signs of opioid overdose

A

Unconscious

Respiratory depression

Pupillary constriction

46
Q

What leads to death by opioid overdose?

A

Respiratory depression

47
Q

What is tolerance?

A

Person’s diminished response to a drug

Occurs when a drug is used repeatedly

Body adapts to the continued presence of the drug

48
Q

What are the two mechanisms of opioid tolerance?

A

Downregulation of surface receptors

Desensitisation of signalling pathways

49
Q

How do opioids cause downregulation of surface receptors?

A

Causes a decreased efficacy of intracellular mechanisms controlling the movement of receptors

50
Q

Remedy for opioid overdose

A

Naloxone

Opioid receptor antagonist

51
Q

Which mechanisms have been developed to deal with opioid withdrawal?

A

Inhibiting pain through cox inhibitors

Local or general anaethesia

Endogenous anti-pain mechanisms

52
Q

What causes the respiratory depression by opioids?

A

miu-receptors reduce the sensitivity of the respiratory center to CO2

53
Q

What causes the nausea and vomiting by opioids?

A

Stimulation of the chemoreceptor trigger zone in the medulla

54
Q

Which drug can be used to replace opioid addiction?

A

Methadone

55
Q

What are the four stages of anaesthesia?

A

Analgesia - still conscious

Excitement - inhibition cortical inhibition

Surgical anaesthesia - reflexes disappear, respiratory depression

Medullary depression - respiratory arrest and cardiovascular collapse

56
Q

What is the action of anaesthetics?

A

Analgesia - suppress pain inputs

Loss of consciousness - effect on spinothalamic tract

Short term amnesia - effect on hippocampus

57
Q

What are the two main categories of anaesthetics?

A

Inhalation

Intravenous

58
Q

How is the potency of inhalational anaesthetics expressed?

A

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
Q

What is the MAC for NO?

A

100%

60
Q

What is the MAC for halothane?

A

1%

61
Q

When is NO used?

A

Pregnancy

Don’t want patient to be completely unconscious

62
Q

What is the mechanism of action of inhalation anaesthetics?

A

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
Q

What is the relationship between the lipid solubility of inhalatory agents and potency?

A

Potency is well correlated with lipid solubility

64
Q

What is the blood-gas partition coefficient?

A

Describes the lipid solubility of a drug

The lower the coefficient the higher the solubility

The more rapid the effect

65
Q

What results in the characteristic sustained CNS depression following anaesthesia?

A

In long surgical procedures, the inhalation agents are taken up into adipose tissue

Slow release from this leads to respiratory depression

66
Q

Types of inhalation anaesthetic agents used today

A

Ether

Nitrous oxide

Halothane

67
Q

Who are inhalational anaesthetics advised against?

A

Patients with heart conditions

Cause cardiovascular collapse due to inhibition of excitable tissues

68
Q

How are intravenous anaesthetics different to inhalation anaesthetics?

A

Specifically target receptors

69
Q

What are the two main receptor targets of intravenous anaesthetics?

A

GABA

NMDA

70
Q

How do intravenous agents target GABA receptors?

A

Act as agonists

Bind to the chloride channels and hyperpolarises the membranes

Mimic the effects of GABA

71
Q

Examples of IV anaesthetics targetting GABA

A

Barbituates

Profolol

72
Q

How do IV anaesthetics target NMDA receptors?

A

Antagonists

Block the receptor for being excitatory

73
Q

Example of an IV anaethetic that targets NMDA

A

Ketamine

74
Q

Why is Ketamine not a very commonly used anaesthetic?

A

Causes dissociative anaesthesia

Does not always cause anaesthesia

So patients often have distant memories of what happened

75
Q

When is ketamine used?

A

Children

Patients with heart conditions

76
Q

Who discovered anaesthetics?

A

Ether Day

Ether vaporiser

77
Q

Are anaesthetics often given singularly?

A

No

Other factors are given prior, after or during recovery following anaesthesia

Because anaesthesia is not ideal

78
Q

What do local anaesthetics do?

A

Inhibit pain in a localised area of the body

79
Q

Mechanism of action of local anaesthetics

A

Block voltage-gated Na+ channels in the cell membrane

80
Q

What are the three states a sodium channel can be found in?

A

Resting

Activation

Inactivation

81
Q

Which states of the sodium channel do local anaesthetics mostly act on?

A

Open or inactive

82
Q

Which neurons do local anaesthetics mostly act on?

A

Small fibres are blocked more easily

Pain sensation is therefore blocked before other sensory inputs

Usually block large fibre diameters less effectively

83
Q

Describe the specificity of local anaesthetics

A

It is not possible to achieve local anaesthesia without loss of other sensory modalities

84
Q

What form does the drug have to be in to generate local anaesthesia?

A

Lipid-soluble, uncharged form

In order to cross through the cell membrane

85
Q

What type of molecule are most local anaesthetics?

A

Weak bases

86
Q

What was the first local anaesthetic developed?

A

Cocaine

87
Q

Example of a modern anaesthetic

A

Lidocaine

88
Q

Uses of local anaesthetics

A

Antidysrhythmics

Epilepsy

Pharmacology (13 decks)

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