Opiods

Question 1

What are the components of pain

Answer 1

Psychological: perception of pain affected by mood

Physiological: perception of pain affected by nociceptors

Question 2

How do opioids affect pain

Answer 2

Produce euphoria thus increase pain tolerance

Act on opioid receptors thus reduce pain transmission

Question 3

What is the process of pain pathway

Answer 3

Pain detected by nociceptor
Signal transmission down C fibres
C fibres synapse with secondary neurones in dorsal horn (substantia gelatinosa)
Release of neurotransmitter Substance P
Pain transmitted to Thalamus + PMC and perceived

Question 4

What are the types of gate control of pain

Answer 4

By A fibres via Inhibitory interneurones
Descending inhibition via inhibitory interneurones

Inhibitory interneurones release enkephalins that inhibit pain transmission bw C fibres and secondary neurones

Question 5

What are the types of endogenous opioids

Answer 5

Enkephalins
Endorphins
Dynorhin

Question 6

What are the types of opioid receptors

Where are they found

Answer 6

Mu - supraspinal (brain)
Kappa - spinal
Delta - widespread

Question 7

What is the mechanism of action of opioids

Answer 7

Opioids bind to opioid receptors
Opioid receptors are GPCRs
Expressed pre-synaptic and post-synaptic membranes of pain neurones
1. +very coupled to K channels - hyperpolarisation, inhibit Ca influx
2. Negatively coupled to AC - reduced cAMP, inhibit Ca influx
3. Directly inhibit Ca channels - inhibit Ca influx
Reduced intracellular[Ca] - reduce Substance P release

Question 8

What are the different pharmacodynamics of opioids

Answer 8

Agonist - morphine
Partial agonist - buprenorphine
Agonist/antagonist - Nalbuphine
Antagonist - Naloxone

Question 9

What is mechanism of action of Partial agonists

Answer 9

Have lower efficacy - produce partial response on binding

But has higher affinity than agonists - Acts as an antagonist of agonists

Question 10

What is mechanism of action of Nalbuphine

Answer 10

Agonist at delta receptor
Partial agonist at kappa receptor
Antagonist at mu receptor
Thus produce analgesia without euphoric effects

Question 11

What is route of admin of opioids

Answer 11

Oral
SC
Slow IV

Question 12

What are PK properties of morphine

Answer 12

25% oral bioavailability - oral admin not effective

T0.5 - 4 hours

Phase II metabolism (glucuronidation)
MGG is active metabolite
Metabolites have long T0.5 - metabolites in urine to screen for opioid misuse

Question 13

What are PK properties of diamorphine

Answer 13

90% oral bioavailability
Lipid soluble
Cross BBB

T1/2 - 5mins

Metabolism -
ester bond hydrolysed rapidly
Convert to active metabolite - morphine
Thus allows high dose of morphine to enter CNS rapidly

Question 14

What are PK properties of methadone

Answer 14

T1/2 - 20hrs

Thus used for chronic pain and maintenance therapy for opioid dependence

Question 15

What are PK properties of codeine

Answer 15

T1/2 - 2hrs

CYP 206 metabolism - polymorphic thus efficacy varies in population

Question 16

What are clinical indications of opioids

Answer 16

Analgesia:
Moderate - severe pain
Especially Chronic or visceral pain

Question 17

What are indications of morphine

Answer 17

Analgesia - palliative for Terminal illness

Diarrhoea

Question 18

What are indications of diamorphine

Answer 18

Analgesia - terminal illness, epidural

Question 19

What are indications for methadone

Answer 19

Analgesia

Maintenance therapy for opioid dependence (longer acting but less euphoric opioid)

Question 20

What are indications of Tramadol

Answer 20

Analgesia
Serotonergic and NA-ergic activity
Thus analgesia with euphoric effects

Question 21

What are indications of Tapentadol

Answer 21

Analgesia:
Mu receptor specific
NA reuptake inhibitor
Thus analgesia with euphoric effects

Question 22

What are artificial opioids

Answer 22

Fentanyl

Pethidine

Question 23

What are indications of Fentanyl

Answer 23

Anaesthesia

1000x more potent

Question 24

What are indications of Pethidine

What caution do you need to take

Answer 24

Analgesia in labour

Do not give frequent repeat dosing - risk of convulsions

Question 25

What are indications of naloxone

Answer 25

Opioid overdose

Respiratory depression

Question 26

How do you administer naloxone

Answer 26

IV

Repeat dosing every 2 mins until response

Question 27

What receptor is the side effects mediate by

Answer 27

Mu

Question 28

What are the side effects of opioids

Answer 28

N+V
Constipation
Miosis
Hyperalgesia
Drowsiness
Hypotension 
Respiratory depression 
Tolerance 
Dependence

Question 29

What medications do you prescribe with opioids to minimise side effects

Answer 29

Anti emetics

Laxatives

Question 30

Why do you get respiratory depression with opioid overdose

Answer 30

Reduced sensitivity to pCO2
Thus reduced signalling in response to change in pH/pCO2
Occurs in dependence + overdose

Question 31

What are the types of new endogenous opioid receptors

Answer 31

Opioid receptor like 1:

GPCR -vely coupled to AC

Question 32

What are the types of new endogenous opioid peptides

What do they bind to

Answer 32

Nociceptin - ORL1

Endomorphine 1
Endomorphine 2
Mu receptors with higher affinity + efficacy

Question 33

What are medico-legal implications of opioids

Answer 33

Some opiates are Controlled drugs
Schedule 5: diamorphine, morphine, pethidine
Schedule 2: codeine

There are prescribing requirements

Question 34

What are prescribing requirements of opioids

Answer 34

Must write down: 
Dose
If preparations - form + strength
If liquids - volume, dosing units
In words and figures