8.1- Opioids Flashcards
Define nociception
non-conscious neural traffic in response to potential trauma
Define pain
An unpleasant sensory and emotional experience associated with actual or potential tissue damage
Define nociceptive pain
pain caused by an inflammatory or non-inflammatory response to an overt or potentially tissue- damaging physical stimulus
Define neuropathic pain
pain caused by a lesion or disease of the somatosensory nervous system ( ie to the actual neurone itself )
Name 5 types of analgesia
- Paracetamol
- NSAIDs
- Opioids
- Adjuvants
- Placebo
What would you give as step 1 on the WHO analgesia ladder? ie MILD PAIN
give a NON-OPIOID +/- adjuvant
What would you give on step 2 on the WHO analgesia ladder? ie MODERATE PAIN
-give a WEAK OPIOID
+/- non opioid
+/- adjuvant
What would you give on step 3 on the WHO analgesia ladder? ie SEVERE PAIN
give a STRONG OPIOID
+/- non opined
+/- adjuvant
Give 3 examples of a non-opioid
ibuprofen
other NSAID
Paracetamol
aspirin
Give 3 examples of WEAK OPIOIDS
codeine
tramadol
low-dose morphine
Give 4 examples of STRONG OPIOIDS
morphine fentanyl oxycodone hydromorphone buprenorphine
What are some adjuvants for pain?
antidepressants anticonvulsants antispasmodic muscle relaxant bisphosphonate corticosteroid
What are the primary sensory afferent neurones of pain?
Adelta or C fibres
Between which 2 neurones does pain transmission occur?
between primary afferent sensory neurone and secondary relay neurone ie synapse of substance P
Where do the primary and secondary neurones synapse?
SUBSTANTIA GELATINOSA in the dorsal horn of the spinal cord
Where does inhibition of this pain transmission come from?
1) Inhibitory interneurones linked to Adelta and Abeta fibres, inhibiting synapse between primary and secondary neurones
2) inhibitory descending pathways from higher centres of the brain
Where are descending analgesia producing pathways located in the brain?
Periaqueductal Grey Matter ( PAG) in the midbrain
projects to Dorsal horn of spinal cord
Describe the central modulation of pain
- PAG sends signals to RVM and carried down medial pathways to serotonergic and Noradrenergic neurones
- Serotoneric and noradrenergic neurones are stimulated and release Serotonin and NA into spinal cord
- –> activate inhibitory interneurones which
- -> release ENDOGENOUS OPIOIDS binding to opioid receptors–> inhibit substance P release to secondary neurones going up ascending pathways
DEFINE:
A) Opiate
B) Opioid
a) Opiate: any agent derived from opium. ( alkaloid mixture from poppy seeds)
b) OPIOID: substances ( exogenous or endogenous ) with morphine-like properties
- act primarily in the SPINAL CORD and brain to inhibit transmission of pain
How do opioid work?
bind to specific opioid receptors in the CNS to mimic the endogenous peptide neurotransmitters
what are the endogenous opioids released by the inhibitory interneurone?
Enkephalins
B-endorphins
Dynorphins
Name:
2 natural opioids
3 semisynthetic opioids
3 synthetic opioids
NATURAL: morphine, codeine
SEMIsynthetic: hydrocodone, hydromorphone, oxycodone, oxymorphone, Buprenorphine
SYNTHETIC: fentanyl, tramadol, methadone
Describe the opioid receptors
- G protein coupled receptors
- Coupled to Gi; inhibitory G-protein subtype
- located pre AND post synaptically
Name the 4 types of opioid receptors
μ mu opioid receptor- most important
δ delta opioid receptor
K kappa opioid receptor
ORL1 ( Opioid receptor like 1 (NOP)
Describe opioid action PRE-SYNAPTIC
Gαβγi → Gαi + Gβγi
• Gβγi inhibits voltage operated Ca2+ channels (VOCC)
• Reduced Ca2+ → less neurotransmitter release of substance P going to ascending pathways
Describe opioid action POST-SYNAPTIC
Gαβγi → Gαi + Gβγi
• Gβγi opens K+ channels
• K+ efflux→ hyperpolarises the cells and makes them less excitable
Give an example of:
a) An opioid agonist
b) A partial opioid agonist
c) An opioid antagonist
a) MORPHINE
b) BUPRENORPHINE
c) NALOXONE
Give 3 uses of an opioid antagonist
- treats opioid toxicity
- reverses respiratory depression
- treatment for opioid dependence
Which opioid antagonist is commonly used?
NALOXONE
always prescribe with morphine to save time in an emergency
half life of 1-1.5 hrs
Give some routes of morphine admin
IV PO IM SC nebulized rectal epidural
Which route is the most preferred
IV
- gives the most rapid response
- AVOIDS hepatic first pass metabolism
- often used for severe pain w intrathecal route
- patient controls the level of analgesia directly (PCA)
Describe the oral pharmacokinetics of morphine
-well absorbed from gut
-undergoes EXTENSIVE first pass metabolism w a 25% oral bioavailability
normally its half life is 2 hours
What are the two metabolites of morphine (orally)?
morphine-6-glucoronide
morphine-3-glucoronide
What is the danger of morphine given orally and what condition is it avoided in?
morphine normally has a half life of 2 hrs, BUT one of its metabolites, Morphine-6-glucoronide is pharmacologically equivalent to morphine and has a half life of 4-5 hours
this EXTENDS the period of effective analgesia
Avoided in hepatic and renal failure as they can impair morphine excretion and increase half lives up to 50 hrs–> can cause morphine toxicity and terminal organ failure
What would you give methadone for and why?
suitable for treating chronic pain rather than post-op pain
-has a half life of 24 hours
What is the special case of codeine pharmacokinetics?
Codeine has to be metabolised to morphine by CYP2D6 in order to become pharmacologically active
BUT CYP2D6 polymorphisms (genetic) are present in some Caucasian populations therefore they cannot effectively convert codeine to morphine
therefore no analgesia achieved in these populations
Name 4 desirable pharmacological effects of morphine?
- Effective analgesia: At spinal and supraspinal level
- Sedation & Euphoria: By effect on midbrain dopaminergic, serotoninergic and noradrenergic nuclei
- Effect on bowel movements: Decrease in motility, increase smooth muscle tone
- Depression of cough reflex: Codeine and morphine have antitussive properties
Give a clinical use for each drug:
a) Morphine
b) Diamorphine
c) Methadone
d) Tramadol
e) Tapendatol
a) analgesic in terminal illness ( ADR is diarrhoea)
b) analgesic in terminal illness ( unlicensed epidural analgesic)
c) maintenance in dependence
d) analgesic ( 5-HT and NA effects)
e) Analgesic ( specific mu agonist, NA reuptake inhibitor
What opioid is given in labour as analgesia?
PETHIDINE
given IM
for convulsions
as a norpethidine metabolite
Name some undesirable side effects of opioids? (10)
Respiratory depression Nausea, vomiting Smooth muscle spasm Hallucinations Pruritis Bradycardia Hypotension Miosis Drowsiness Dysphoria ( if no pain, morphine can cause restlessness, unhappiness and agitation
Why would you get dependence and tolerance on opioid drugs?
down regulation of opioid receptors or decreased production of endogenous opioids
body becomes more tolerant to drug therefore increased dose needed for desired effect
How should prescriptions for controlled drugs be written?
- INDELIBLE
- signed by PRESCRIBER
- DATED
- contain PRESCRIBER’S ADDRESS
What points should a prescription of a controlled drug ALWAYS state?
• the name and address of the patient
• the form (and where appropriate the strength) of the preparation;
• for liquids, the total volume in millilitres (in both words and figures) to be supplied;
• for dosage units, the number (in both words and figures) to be supplied;
• in any other case, the total quantity (in both words and figures) to be
supplied;
• the dose
