Brainscape's Knowledge GenomeTM

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


See full index

Pharmacology for Anaesthetists > Opioids > Flashcards

Opioids Flashcards

1
Q

Differentiate opioids from opiates

A

Opiate - drugs derived from opium (e.g. morphine, codeine, heroin)

Opioid - broad class of opiate analogues that have morphine-like activity

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

What is the traditional classification of commonly used opioids?

A

Natural compounds

  1. Codeine
  2. Morphine

Semi-synthetic compounds

  1. Buprenorphine
  2. Hydrocodone
  3. Oxycodone
  4. Naloxone

Synthetic compounds

  1. Fentanil
  2. Alfentanil
  3. Sufentanil
  4. Remifentanil
  5. Tramadol
  6. Meperidine
  7. Methadone
  8. Nalbuphine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the functional classification of commonly used opioids

A

Full Agonists

  1. Codeine
  2. Morphine
  3. Hydrocodone
  4. Oxycodone
  5. Fentanyl
  6. Alfentanil
  7. Sufentanil
  8. Remifentanil
  9. Meperidine
  10. Methadone

Partial agonists

  1. Tramadol
  2. Buprenorphine
  3. Nalbuphine

Centrally acting antagonists
1. Naloxone

Peripherally acting antagonists
1. Methylnaltrexone

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

How is the oral absorption for most opioids and what is the bioavailability for most opioids. Name the exceptions

A

Almost all opioids are well absorbed orally
- Tramadol is 100% absorbed orally

Almost all opioids undergo significant hepatic first pass metabolism and have low-ish bioavailability (30% –> 70%)

  • remifentanyl 0% bioavailability
  • buprenorphine 15% bioavailability
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Compare transmucosal absorption of fentanyl and remifentanil

A

Fentanyl –> slow transmucosal absorption (7 minutes)

Remifentanil –> fast transmucosal absorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the dose of intranasal fentanyl in paediatrics and how long does it take to work?

A

1 - 2 ug/kg (repeat dose of 0.5 - 0.75 ug/kg after 10 - 20 minutes)

Takes about 7 minutes to work

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe the pkA and unionized fraction of NB opioids.

Which opioid is the most important exception to the general trend and what are the implications pf this

A

Opioids are weak bases. Most of them have a pKa close to 8.0 - 9.0

Fentanyl pKa 8.4 9% unionized at pH 7.4

Exception NB

  1. Alfentanil has a pKa of 6.5
    - -> 90% unionized at pH of 7.4 –> Rapid onset
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Fentanyl has an octanol:water coefficient of 717
Alfentanil has an octanol:water coefficient of 128

This means that Fentanyl is significantly more lipid soluble than alfentanil.

Why then is the onset of alfentanil faster than fentanyl

A

Alfentanil has a pKa of 6.5 which means that 90% of it is in its unionized form at physiological pH of 7.4

Fentanyl has a pKa of 8,4 which means that 90% of it is in its ionized form at physiological pH of 7.4

Hence alfentanil is faster

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Why does morphine last longer than fentanyl despite its shorter elimination half life?

A

HIGH OCTANOL:WATER PARTITION CO-EFFICIENT = HIGH LIPID SOLUBILITY

High lipid solubility
–> faster onset (but requires unionized drug so depends also on pKa)

Low lipid solubility
–> Longer duration of action as can’t diffuse out of spinal space/brain.
–> E.g.
Morphine: octanol:water 1.42 + t1/2 = 3 hours
Fentanyl: octanol:water 717 + t 1/2 = 3.5 hours
–> Morphine’s lower lipid solubility means it takes longer to diffuse out of the CNS and therefore has a longer duration of action despite having a shorter t1/2

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

Where are opioids metabolised, what are the exceptions, which agents have active metabolites

A

Hepatic metabolism
Renal excretion of metabolites

Morphine
–> Morphine-6-glucuronide (active)

Heroine
–> Morphine (active)

Codeine
–> Morphine (active)

Oxycodone
–> noroxycodone (active)

Tramadol
–> O - desmethyltramadol (active)

NB
Methadone –> inactive metabolite EDDP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Differentiate factors that stimulate nociceptors vs substances that sensitize nociceptors

A

Stimulating factors:

  1. Mechanical stimuli
  2. Thermal stimuli
  3. Chemical stimuli
    - -> H
    - -> B
    - -> K+
    - -> ACh
    - -> 5 HT
    - -> H+

Sensitising factors:

  1. Prostaglandins
  2. Leukotrienes
  3. Substance P
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Name the two nerve fibres that conduct pain and differentiate these fibres properties

A

A delta

  • Diameter: 4 um
  • Velocity: 40 m/s
  • Synapse: Dorsal horn - Rexed laminae 4 and 5

C fibres

  • Diameter: < 2 um
  • Velocity: 2 m/s
  • Synapse: dorsal horn - Rexed laminae 2 (substantia gelatinosa)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the gate theory of pain

A

A beta touch fibres and descending pathways stimulate inhibitory interneurons that prevent the conduction of nociceptive impulses to the CNS –> i.e. close the gate on C fibres..

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe the sequence of events once opioid receptors are stimulated

A

Seven serpentine transmembrane inhibitory Heterotrimeric G-protein linked receptors

  • -> Inhibition of adenylase cyclase
  • -> Reduced cAMP
  • -> closure V gated Ca channels (increase + ECF)
  • -> K+ efflux (Increase +)

Overall –> increased positive charge outside versus inside –> hyperpolarization of cell membrane –> reduced likelihood of AP generation as resting membrane potential is further away from threshold potential in nociceptive neurons.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Classify the effects of stimulation of different opioid receptors

A

MOP - Analgaesia

     - Respiratory depression
     - Hypotension
     - Constipation
     - Miosis

KOP - Sedation

     - Confusion
     - Miosis

DOP - Analgaesia

     - Respiratory depression
     - Constipation
     - Mood

NOP - Pro-nociceptive

     - Depression
     - Appetite modulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Define context sensitive half time and how it differs from half life

A

Context-sensitive half time is the time required for the plasma concentration of an infused drug to fall to half the concentration when the infusion is stopped.

It is not a number but rather a function of the duration of drug delivery, which is the context.

17
Q

What are the advantages and disadvantages of the use of an intravenous infusion of fentanyl in comparison to morphine

A

FENTANYL
1. EXPENSIVE
2. LONG Context Sensitive Half Time
(due to extensive tissue compartment distribution)
3. CRITICALLY ILL - no accum. active matabolites
4. CRITICALLY ILL - Free fraction increase (PB 80 - 90%)
5. OPIOID WITHDRAWAL more likely (due to high lipid solubility and rapid removal from CNS) –> ICU delirium
6. Beneficial in septic shock - No histamine release

MORPHINE
1. CHEAPER (but increase duration of effect ? longer ICU)
2. Duration INDEPENDENT Context Sensitive Half Time
(due to less extensive tissue compartment distribution)
3. CRITICALLY ILL - accum. of active metabolites
4. CRITICALLY ILL - Free fraction less affected (PB 30 - 25%)
5. OPIOID WITHDRAWAL less likely
6. Beneficial CCF –> Histamine VD

18
Q

What is the intrathecal dose of fentanyl and morphine and how do these differ in onset and duration when intrathecally administered.

Explain the difference in onset and duration

A

Fentanyl 10 - 20 ug

  • Onset: 5 - 10 minutes
  • Duration: 1 - 2 hours

Morphine 0.1 - 0.2mg

  • Onset: 45 minutes
  • Duration: 18 - 24 hours

The mechanism of the above difference relates to significant difference in lipid solubility between the agents

Fentanyl - VERY high lipid solubility

  1. Rapid onset
  2. Rapid offset
  3. Rapid uptake into capillaries = faster clearance CSF

Morphine - Lower lipid solubility

  1. Slower onset
  2. Slower offset
  3. Slower uptake into capillaries = slower clearance CSF
19
Q

Which opioids cannot be administered into the intrathecal space and why

A
  1. Remifentanil (contains glycine buffer)
  2. Morphine IV preparation with preservatives

All substances into intrathecal space must be preservative free

20
Q

How can epidural/intrathecal administration of opioids affect their metabolism and clearance

A

Haemodynamic effects could reduce renal and hepatic blood flow reducing clearance

21
Q

How do the pharmacodynamics of intrathecal versus epidural opioids differ

A

Intrathecal
–> Affects spinal mew opioid receptors + redistributed to the brain stem

Epidural
–> Absorbed systemically to have an effect similar to IV administration

22
Q

List the side effects of intrathecal/Epidural opioid administration

A
  1. Unexpectedly prolonged action
  2. Hypotension
  3. Respiratory depression (with higher spinal levels)
  4. Urinary retention
  5. Pruritis
23
Q

Summarise the cellular events subsequent to activation of opioid receptors

A

Pre-synaptic Seven Serpentine Transmembrane G-protein coupled receptors: mew, kappa, delta, NOP

Activation is INHIBITORY

  1. Gi –> inhibits AC –> Reduced cAMP
    - -> Increased potassium efflux and hyperpolarization
    - -> Reduced calcium conductance and reduced neurotransmitter release

Reduced neurotransmission C fibres

24
Q

Describe the mechanism of opioid induced analgaesia in the spinal cord and brain

A

SPINAL mew receptor effect
- Presynaptic on primary afferent nociceptive neurons

MIDBRAIN mew-receptor effect
(PERIAQUEDUCTAL GREY MATTER)
- Mew agonism here removes GABA-ergic inhibitory tone on descending inhibitory pain pathways
- This increases descending inhibition on the dorsal horn 2nd order neurons

25
Q

Describe the mechanism of opioid induced respiratory depression

A

BRAINSTEM MEW-RECEPTOR EFFECT:
- Decrease rate of firing in the respiratory pacemaker centre (pre-Botzinger complex)

MEDULLARY MEW-RECEPTOR EFFECT:
- Decrease sensitivity of medullary chemoreceptors to hypercapnoea and hypoxia

Pharmacology for Anaesthetists (37 decks)

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