Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Human Function II > HUF 2-64&65 Pain: drug overview > Flashcards

HUF 2-64&65 Pain: drug overview Flashcards

1
Q

Pain

A
  • Actual or potential tissue damage => unpleasant sensory and emotional experience
  • Psychical adjunct of imperative protective reflex
  • Stimulus
    => Signal generation and transduction
    => Signal transmission
    => Signal modulation
    => Pain perception
  • Physiologic pain: acute, protective (withdrawal reflex)
  • Pathologic pain: chronic, diseases (RA, DM neuropathy)
    => Neuropathic pain (nerve damage / altered expression of receptors or channels at nerve endings)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Physiologic pain (nociceptive pain)

A
  • Somatic (skin surface, ms, joints, tendons)
  • Visceral (internal organs)
  • External stimuli
  • Nociceptors located on peripheral endings of 1° sensory neurons (pain fibres)
  • Postoperative pain
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Peripheral signal transduction and sensitisation of pain

A
  • Neuronal depolarisation => AP
  • Direct result of stimuli activating nociceptors
  • ↑ Nociceptor sensitivity (lower activation threshold)
    OR ↑ Na+/Ca2+ influx, ↑ Ca2+ release
    (phosphorylation by protein kinase)
    => Signal enhanced (freq, duration)
    => Peripheral sensitisation (SP, BK, PG, Histamine)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Signal conduction of pain

A
  • Thinly myelinated Aδ
  • Unmyelinated C
  • AP propagaion: VGNC opening => depolarisation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Signal transmission of pain

A
  • Various laminae of dorsal horn
  • Both pre- and post-synaptic sides contain receptors, ion channels and transporters => alter transmission
  • Aβ: non-nociceptive, sensitive to rubbing, light pressure
  • Lamina II: substantia gelatinosa - inteneurons that receive inputs from Aδ, C and Aβ fibres
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Central sensitisation of pain

A
  • ↑ receptor/channel expression and phosphorylation
    => ↑ neuronal response to stimuli
    => Easier to generate AP (↓ threshold)
    => Short term OR long term (altered gene expression) sensitisation
    e.g. Role of PG
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Signal relay control at spinal cord of pain

A

Gate control theory
- Nociceptive signals travel via Aδ and C fibres to SG
- Non-nociceptive signals travel via Aβ to SG
- Interneurons in SG are inhibitory
* Absence of Aβ
=> Aδ and C transmit inhibitory signals to SG
=> Suppress SG activity
=> Smaller inhibitory outputs for further projection
=> ↑ Pain perception
* Greater stimulation on SG by Aβ
=> Greater inhibitory outputs for further projection
=> Negate small stimulatory signal that causes pain perception

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Signal modulation of pain

A
  • Descending inhibition
  • Periaqueductal gray (targets of opioids)
  • Locus ceruleus (NA)
  • Nu raphe magnus (5-HT)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

2 Descriptions of pathologic painL allodynia, hyperalgesia

A

Allodynia: pain elicited by stimulus that normally should not cause pain

Hyperalgesia: ↑ pain response produced by stimulus that normally causes lighter pain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Treatment choices according to characteristics of pain

A
  • Pain etiology severity, duration, mechanism, treatment effectiveness
  • WHO Pain Relief Ladder for Cancer Pain
    1. Better pain control: higher steps => descend to lower steps afterwards
    2. Pain not controlled: lower steps => move upward
  • Adjuvants: steroids, anxiolytics, antidepressants, antiepileptics, Na+ channel blockers, Ca2+ channel blockers, NMDA receptor blocker
  • Opioids, non-opioids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Paracetamol

A
  • Weak (~50%) COX1 and COX2 inhibitory activity
  • Much stronger analgesic than anti-inflammatory effect
  • Comparable efficacy to aspirin in treating tension headache; slower onset
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Opioid analgesics and related drugs

A
  • Narcotic analgesics = opioid analgesics
  • Opiate: structurally related compounds to morphine
  • Opioid: any compound with properties of opiate
  • Endogenous opioids enkephalin, endorphin, dynorphin
  • Opioid antagonists: Naloxone, Naltrexone
  • Opioid receptor subtypes: μ, δ, κ, ORL1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Opioid receptors: structural characteristcs

A
  • G1 coupled
  • From homodimers or heterodimers e.g. μ-δ
  • Receptor selectivity dependent on positioning of extracellular loops (favour some agonists over others0
  • Receptor internalisation and subsequent tolerance for μ and δ receptors differentially induced depending on agonist and binding duration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Functional effects of opioid receptors

A

μ

  • Analgesia: supraspinal, spinal, peripheral
  • Respiratory depression
  • Pupil constriction
  • Reduced GI motility
  • Euphoria
  • NO dysphoria and hallucination
  • Sedation
  • Physical dependence

δ

  • Spinal analgesia
  • Respiratory depression
  • Reduced GI motility

κ

  • Analgesia: spinal, peripheral
  • Dysphoria and hallucination
  • Sedation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Points to note on functional effects of opioid receptors

A
  1. Analgesic effects may be diminished (tolerance)
    => May display hyperalgesia after prolonged use
  2. Supraspinal effects
    - Analgesia and reduced affective component of pain (limbic system; related to euphoria)
  3. ↓ Sensitivity of respiratory centres and respiratory rhythm generator
    => Highly fatal in acute opioid poisoning
  4. Miosis: diagnostic of opioid poisoing; resistant to opioid tolerance
  5. Opioid withdrawal symptoms: runny nose, restlessness aggression, shivering, irritability, diarrhoea
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Proposed mechanisms of consequences of chronic opioid use

A
  1. Flawed internalisation-recycling process
    => Fewer new, sensitive receptors on call membrane
    + Impaired receptor-2nd messenger signalling
    => Tolerance
    => Hyperalgesia (↑ pain transmission)
  2. Persisting AC activity even after drug removal
    - ↑ AC expression
    => ↑ cAMP
    => ↑ excitatory NT release; Changes in signalling, synaptic structures and channel expression (e.g. NMDA)
    => Withdrawal symptoms; Hyperalgesia (↑ pain transmission)
17
Q

Principal sites of opioid analgesic actions

A

Brain: inhibit GABAergic interneuronal activity in PAG, LC and NRM (↓ Ca2+ influx)
=> Less Cl- influx to postsynpatic descending neurons
=> Descending neurons are under less inhibition
=> Stronger signal to suppress pain (↑ 5-HT, NE, opioid)

Spinal cord:
1. ↓ Ca2+ influx
=> inhibit presynaptic NT release (e.g. GLU)
2. ↑ K+ efflux and ↓ response of postsynaptic neuron to excitatory NT
=> inhibit postsynaptic neuronal activities

18
Q

Morphine

A
  • Juice of opium poppy seed pod
  • Strong μ agonist; δ, κ agonist
  • Analgesic: IV, IM, SC, oral (less potent)

PK
1. Not as lipophilic as fentanyl or methadone
=> Fewer % drug permeates BBB
2. Glucuronidation
- 10% becomes morphine-6-glucuronide (more potent, longer t1/2 = 6-8 h)
- More is metabolised to morphine-3-glucuronide
=> Neuro-excitatory effect

19
Q

Codeine

A
  • Poppy seed pod
  • Methyl-morphine
  • Weaker μ agonist than morphine; less potent
  • Low risk of dependence
  • Analgesic (moral orally active than morphine)
  • Antitussive (dose of no analgesic effect) - Codeine + Paracetamol

PK

  • Converted to morphine by CYP2D6
  • Potential risks in 2D6*2x2 individuals
  • Less prone to first-pass metabolism than morphine
  • t1/2 = 2-4h (similar to morphine)
20
Q

Buprenorphine

A
  • Very weak partial μ agonist, high affinity; κ antagonist
  • Analgesic in naive persons (more potent than morphine at lower doses)
  • Withdrawal symptoms in chronic opioid users (dissociation of stronger opioids; symptoms less severe than methadone)
  • Analgesic; opioid dependence treatment (IV, sublingual, transdermal)
  • Combined with naloxone => minimise abuse

PK

  • Metabolised by CYP3A4
  • Long t1/2 = 12h (high receptor affinity)
  • Highly lipid-soluble
  • Respiratory depression not easily reversed by naloxone
21
Q

Pethidine

A
  • Strong μ agonist (weaker and less potent than morphine)
  • Analgesic (short term)

PK
- t1/2 = 2-4h
- Highly lipophilic
- First-pass metabolism (converted by CYP2D6/3A4 to norpethidine with longer t1/2 = 15-20h)
=> Delirium (confusion), seizures if pethidine is used for >48h

  • Antimuscarinic => delirium (confusion)
  • Blocks 5-HT reuptake
    ∴ DDI with MAOI, SSRI => Serotonin syndrome (delirium, hyperthermia, convulsions, death)
22
Q

Fentanyl

A
  • Strong μ agonist
  • More potent than morphine
  • Analgesic, general anaesthetic (IV, parenteral, transdermal)
  • High potential for abuse and risk of overdose and death with transdermal patches
  • Transdermal patch: slow inset ~12h later, prolonged duration
  • NOT induce histamine release => less hypotensive effect

PK

  • Short t1/2 = 1-2h; fast onset and offset
  • Highly lipid-soluble
  • Metabolised by CYP3A4 to inactive metabolites
23
Q

Methadone

A
  • Strong μ agonist (no significant depression and less euphoric)
  • Analgesia; management of opioid dependence
  • Orally active; buccal mucosa
  • Tolerance; withdrawal slightly more severe and prolonged than buprenorphine

PK
- Orally active
- Long t1/2 = 40h
- Converted to inactive metabolites mainly by CYP2D6 (rifampicin) and 3A4 (phenytoin, rifampicin)
=> May precipitate withdrawal symptoms after enzyme induction

  • QT prolongation
  • Block NMDA receptor and monoamine reuptake
    => Used for neuropathic pain and hyperalgesia (opioid rotation)
24
Q

Pentazocine

A
  • Weak partial μ agonist / weak μ antagonist, full κ agonist
  • Withdrawal symptoms in chronic opioid users
  • (Rarely) analgesic: κ agonism; combined with naloxone to minimise abuse
  • Dysphoria at high doses
  • Does NOT reverse morphine-induced respiratory depression
  • Tachycardia, HT
  • Buprenorphien and Pentazocine at high doses may displace other μ agonists
    => Precipitate withdrawal symptoms
25
Q

Tramadol

A
  • Weak μ agonist; low potency
  • Analgesic (effect equiv. to Morphine or Pethidine in mild-to-moderate pain)

PK

  • t1/2 = 6h
  • CYP3A4, 2D6 => active demethylated Tramadol - μ agonist
  • Seizure
  • Inhibit monoamine reuptake
    => Analgesic effect; DDI with MAOI and SSRI
26
Q

Heroin and Etorphine

A

Heroin (diamorphin)

  • Very potent μ, δ and κ agonist
  • Converted to Morphine and 6-acetylmorphine
  • Very rapid onset - penetrate BBB easily

Etorphine

  • Very potent μ, δ and κ agonist
  • No legitimate use in humans
  • Immobilise large animals
27
Q

Opioid antagonists: Naloxone, Naltrexone

A
  • High affinity at μ receptor; block δ and κ

Naloxone

  • Short t1/2 = 1-2h
  • IV, IM, intranasal spray
  • Antidote for acute opioid poisoning (need continual monitoring to prevent relapse)

Naltrexone

  • Long t1/2 = 10h
  • Given orally
  • Maintenance treatment for opioid dependence

Human Function II (35 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions