Narcotic (opioid) Anaesthetics

Question 1

What does Phenanthrenes include?

Answer 1

Morphine (10%) - strong
Codeine (0.5%) - weak
Thebaine (0.2%)

Question 2

What are Endogenous opioid peptides?

Answer 2

Naturally exists in our brain

3 major families:
* Β-endorphin (30 aa)
* Enkephalins (5)
* Dynorphins (18-20)

Previously collectively called endorphins, now called opioid peptides

Question 3

What is the psychophysiology of pain?

Answer 3

Brain has modulatory circuits to regulate the perception of pain.

Attitude, mood, and physical exercise can influence the perception of pain

Question 4

How does brain modulate pain?

Answer 4

Pain pathway: Aδ / C fibre primary afferent neurone → spinothalamic tract → thalamus → efferent neurone from brain, which reduce pain amplitude by reducing depolarisation, reducing pain perception.

Question 5

Opioid analgesia affect Endogenous mec to…

Answer 5

1. Inhibit propagation of pain signals
2. Alter the emotional perception of pain (doesn’t sense the pain in heightened emotions)
3. Elevate pain threshold

Question 6

3 sites of opioid receptors regulating pain?

Answer 6

1. peripheral nociceptive terminals (peripheral analgesia)
2. spine (spinal analgesia)
3. brain (supraspinal analgesia)

Question 7

Functional effects of opioid receptor regulation?

Answer 7

µ receptor is responsible for most effects + most side effects
-All supraspinal analgesia (brain) is mediated by µ

All dysphoria is mediated by k

Onset of effect is slow as opioid receptors are GPCR, need time for cell signalling involving 2nd messenger to happen.

Question 8

3 Major Opioid Receptor types

Answer 8

μ (Mu)
δ (Delta)
κ (Kappa)
All are GPCR

Question 9

Dose-dependent tissue expression

Answer 9

Nociceptive terminals > Spine > Brainstem > “Emotional brain” > Oculomotor > GIT > Respiratory nuclei

Question 10

Dose-dependent effects of opioids from good to bad

Answer 10

reduced gut motility > euphoria > pupil constriction > constipation > dysphoria > severe sedation > respiratory depression

Question 11

What are some individual differences of dosing opioids?

Answer 11

Elderly patients usually require a lower dose to achieve effective pain relief than younger patients.

Neuropathic pain usually requires higher opioid doses than nociceptive pain.

Lower doses are usually required for continuous maintenance of pain relief than administration in response to recurrence of pain

Question 12

What are the principles of Dosing Opioid Analgesics

Answer 12

Opioid analgesics should be started at a low dose and carefully titrated until an adequate level, or until persistent and unacceptable side effects warrant a re-evaluation of therapy.

[stop] Failure of at least partial analgesia with incremental dosing in the opioid-naive patient may indicate that the pain syndrome is unresponsive to opioid therapy

[increase] Px with chronic pain, opioids do not exert an appreciable analgesic effect until a threshold dose has been achieved.

Question 13

Clinical uses of opioid agonists for Analgesia?

Answer 13

Analgesia: Morphine, Codeine, pethidine

Question 14

Clinical uses of opioid agonists for Anaesthetic adjuvant?

Answer 14

Fentanyl

Question 15

Clinical uses of opioid agonists for Cough suppressant?

Answer 15

Codeine

Question 16

Clinical uses of opioid agonists for Anti-diarrhoeal?

Answer 16

Diphenoxylate

Question 17

Name a long-acting opioid analgesic (T 1/2 > 24h)

Answer 17

Methadone

Question 18

Name a short-acting anaesthetic adjuvant

Answer 18

Fentanyl

Question 19

Name the strong opioid agonists

Answer 19

Morphine
Methadone
Fentanyl
Pethidine

Question 20

What are the features of Pethidine?

Answer 20

Strong μ agonist (weaker δ and κ agonist), high analgesic effect + high addiction

Shorter duration of action than morphine (especially in
neonate therefore used in labour).

N-demethylated in the liver to norpethidine
(hallucinogenic and convulsant effects at high dose)

Restlessness rather than sedation

Antimuscarinic (i.e. parasympatholytic): dry mouth, pupil dilation, smooth muscle relax

Question 21

What are the features of Codiene?

Answer 21

Weak μ and δ agonist (not a κ agonist), Low max analgesic efficacy, Moderate liability for addiction

~10 % demethylated to morphine***

~10 % of population show reduced analgesic effect due to
lack of demethylating enzyme.

Question 22

What are the features of Tramadol?

Answer 22

Weak μ agonist
Weak inhibitor of 5-HT (serotonin) and noradrenaline re-uptake.

Question 23

How does respiratory depression occur?

Answer 23

Action in nucleus tractus solitarius and nucleus ambiguus (brainstem regulation of breathing).

reduce responses to COS

suppresses voluntary breathing

Question 24

What are common adverse effects of opioids?

Answer 24

Nausea, due to actions on chemoreceptor trigger zone

Drowsiness/Sedation, caution against operating machinery

Constipation, due to reduced GIT motility

Miosis, action in oculomotor nucleus. Yet mydriasis can occur from hypoxia

Urinary retention

Postural hypotension, bradycardia

Immunosuppressant with chronic use

Morphine cause Histamine release, caution in asthmatics

Question 25

What is tolerance?

Answer 25

less effective after prolonged use,
need to increase dose

Question 26

What is addiction?

Answer 26

Psychological craving, loss of control over use

Question 27

What is physical dependence?

Answer 27

Physiological dependence such as physical withdrawal symptoms

Question 28

What are the opioid antagonists?

Answer 28

Naloxone
- Strong μ antagonism; also δ and κ antagonism.

Naltrexone
- long acting

Nalmefene
- long acting

Question 29

Rank the opioids from weakest to strongest

Answer 29

Codeine < Tramadol (also NA) < Morphine < Fetanyl