Narcotic (opioid) Anaesthetics Flashcards
What does Phenanthrenes include?
Morphine (10%) - strong
Codeine (0.5%) - weak
Thebaine (0.2%)
What are Endogenous opioid peptides?
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
What is the psychophysiology of pain?
Brain has modulatory circuits to regulate the perception of pain.
Attitude, mood, and physical exercise can influence the perception of pain
How does brain modulate pain?
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.
Opioid analgesia affect Endogenous mec to…
- Inhibit propagation of pain signals
- Alter the emotional perception of pain (doesn’t sense the pain in heightened emotions)
- Elevate pain threshold
3 sites of opioid receptors regulating pain?
- peripheral nociceptive terminals (peripheral analgesia)
- spine (spinal analgesia)
- brain (supraspinal analgesia)
Functional effects of opioid receptor regulation?
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.
3 Major Opioid Receptor types
μ (Mu)
δ (Delta)
κ (Kappa)
All are GPCR
Dose-dependent tissue expression
Nociceptive terminals > Spine > Brainstem > “Emotional brain” > Oculomotor > GIT > Respiratory nuclei
Dose-dependent effects of opioids from good to bad
reduced gut motility > euphoria > pupil constriction > constipation > dysphoria > severe sedation > respiratory depression
What are some individual differences of dosing opioids?
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
What are the principles of Dosing Opioid Analgesics
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.
Clinical uses of opioid agonists for Analgesia?
Analgesia: Morphine, Codeine, pethidine
Clinical uses of opioid agonists for Anaesthetic adjuvant?
Fentanyl
Clinical uses of opioid agonists for Cough suppressant?
Codeine
Clinical uses of opioid agonists for Anti-diarrhoeal?
Diphenoxylate
Name a long-acting opioid analgesic (T 1/2 > 24h)
Methadone
Name a short-acting anaesthetic adjuvant
Fentanyl
Name the strong opioid agonists
Morphine
Methadone
Fentanyl
Pethidine
What are the features of Pethidine?
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
What are the features of Codiene?
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.
What are the features of Tramadol?
Weak μ agonist
Weak inhibitor of 5-HT (serotonin) and noradrenaline re-uptake.
How does respiratory depression occur?
Action in nucleus tractus solitarius and nucleus ambiguus (brainstem regulation of breathing).
reduce responses to COS
suppresses voluntary breathing
What are common adverse effects of opioids?
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
What is tolerance?
less effective after prolonged use,
need to increase dose
What is addiction?
Psychological craving, loss of control over use
What is physical dependence?
Physiological dependence such as physical withdrawal symptoms
What are the opioid antagonists?
Naloxone
- Strong μ antagonism; also δ and κ antagonism.
Naltrexone
- long acting
Nalmefene
- long acting
Rank the opioids from weakest to strongest
Codeine < Tramadol (also NA) < Morphine < Fetanyl
