Opioids

Question 1

What is the difference between pain and noniception?

Answer 1

Nociception- non-conscious neural traffic due to trauma and potential trauma to tissue (heat removal).

Pain- complex, unpleasant awareness of sensation modified by experience, expectation, immediate context and culture. Doesn’t need tissue damage, sensation is from the somatosensory cortex.

Question 2

What stimulates nociceptors?

Answer 2

Tissue damage - release serotonin, bradykinin and prostaglandin.

Question 3

How is pain stimulated?

Answer 3

Nociceptors stimulated, release substance P and glutamate.
Afferent nerve stimulated - in the dorsal horn (lamina 1-5), A delta fibres - myelinated sharp pain
C fibres - unmyelinated, dull ache.
Send action potentials via the spinothalamic tract.

Question 4

Pain can be modulated by what central and peripheral centres?

Answer 4

Peripheral- substantia gelatinosa

Central - peri-aqueductal grey

Question 5

How can pain be modulated peripheral?

Answer 5

Tissue damage stimulates A delta and C fibres which stimulate the thalamus and inhibit the substantia gelatinosa (allowing pain to reach the thalamus).

By “rubbing it better” the substantia gelatinosa is stimulated, inhibiting lamina 1-5 (which is stimulated by pain) and then reducing projections to the thalamus.

Question 6

How can pain be modulated centrally?

Answer 6

Stimulatory fibres to both the thalamus and cortex, stimulate the periaqueductal grey matter and cause inhibitory fibres to release serotonin and enkephalins to the dorsal horn.
These stimulate the endogenous opioids and prevent pain from being perceived.

Question 7

What type of receptor do endogenous opioids act at?

Answer 7

GPCR

Mu, delta and kappa

Question 8

What is the major effects of stimulating opioid receptors?

Answer 8

Decrease cAMP and cause hyperpolarisation, decreasing substance P release and increase dopamine release.

Question 9

Where are the 3 types of opioid receptors found and what are they stimulated by?

Answer 9

MOP- supraspinal/GIT, enkephalins and b-endorphins

DOP-wide distribution, enkephalins

KOP- spinal cord, brain, periphery- dynorphins

Question 10

What are the main principles of opioids as a class?

Answer 10

Exploit receptors either agonising or antagonising
Main therapeutic effect is via Mu receptors
Aim to modulate pain
Also indicted in cough, diarrhoea and palliation

Question 11

Give an example of a strong agonist

Answer 11

Morphine or fentanyl

Question 12

What is the action of morphine?

Answer 12

Strong affinity and complete activation of Mu receptors.
Minimal affinity for KOP and DOP.
Causes analgesia and euphoria

Question 13

What are the side effects of morphine?

Answer 13

Respiratory depression - medulla less responsive to Co2
Emesis- stimulate chemoreceptor zone
GIT- decrease motility and increase sphincter tone
Cardiovascular - hypotension and syncope
Miosis
Histamine release -itchy (caution in asthmatics)

Question 14

Why might fentanyl be used instead of morphine?

Answer 14

100 times more potent and higher affinity for Mu receptor.
Less histamine release, sedation and constipation.

Reduced side effects; respiratory depression, constipation and emesis.
Act as a analgesic and anaesthetic

Question 15

Name a moderate agonist and its mechanism of action

Answer 15

Codeine

1/10th potency of morphine, with a mild to moderate analgesic effect and cough depressant.

Question 16

What side effects must be considered in giving codeine and which patient groups should be prescribed something else?

Answer 16

Side effects: constipation and respiratory depression, worse in children.

Since codeine is metabolised by CYP2D6 into morphine, those who are on fluoxetine and other SSRIs may not experience analgesic effects due to inhibition of the enzyme by SSRIs.

Question 17

Name an opioid with a mixed effect and its main uses

Answer 17

Buprenophine

Moderate to severe pain and opioid addiction treatment.

Question 18

Compared to morphine, buprenorphine…

Answer 18

Has very high affinity for MOP receptor, with low Kd.
Long duration of action and not easily displaced.
Lower EMax as a partial agonist, lower efficacy.
Antagonist at KOP.

Question 19

What are the common side effects of buprenorphine?

Answer 19

Respiratory depression
Low BP
Nausea
Dizziness

Question 20

Name an opioid antagonist and its effectiveness in comparison to morphine.

Answer 20

Naloxone - used for overdoses
Greater affinity than morphine, but less than buprenorphine.
Affinity MOP>DOP>KOP

Question 21

What are the problems with giving naloxone?

Answer 21

Short half life and slow infusion

Question 22

How might a patient develop opioid tolerance?

Answer 22

Phosphorylation and uncoupling

CAMP production.

Question 23

What groups of patients should be under special considerations when prescribing opioids?

Answer 23

Manual labourer/driver 
Elderly 
Bed bound 
Asthmatics 
Biliary tract obstruction 
Respiratory disease 
Renal impairment 
Pregnancy

Question 24

What are the contraindications of opioids?

Answer 24

Hepatic failure 
Acute respiratory distress 
Comatose 
Head injuries 
Raised ICP