Opioids Flashcards
What is pain
• Nociception- “non conscious neural traffic due to trauma or potential
trauma to tissue.”- reflex eg withdrawing from sharp
• Pain- “complex, unpleasant awareness of sensation modified by experience, expectation, immediate context and culture”. - SEnsation associated with pain - not neccesaruly tissue damage
What is pain
Serotonin, prostaglandins, released
- Nociceptors stimulated
- Release of Substance P and Glutamate
- Afferent nerve stimulated
- Fibres decussate
- Action potential ascends
- Synapse in thalamus
- Project to Post central gyrus
What are a delta and C fibres
Afferent nerves - ap up towards dorsal
hoen
A delta - sharp. C fibres- dull????? A delta
myelinated - fast coducting
Reach threshold to stimulate c fibres. To
myelinated. Slower. Dull throbbing pain
Enter lamina 1 - 5, synapse on 2o -
decussate - synapses before projecting to
somatosensory cortex
How can we modulate pain?
- Have modulators in peripheral system and in central system
- Peripherally:
- Substantia Gelatinosa
- Centrally:
- Peri aqueductal grey
Bilateral. Tissue damage > afferent fibres -> AP ->lamina 1-5 -> spinothalamic tract -> thalamus - > a delta and c send out inhibitory signals to SG -> inhibits modulation Rubbing it better - a beta fibres - stimulate SG - inhibition o the lamina - decrease the pain signals going to thalamus
Periaqueductal grey matter - midbrain - pain modulation - inhibition by cortex normally. When
we get a pain response - thalamus can act on periaquiductal grey matter. - can then inhibitor send signals to spinal cord -
5ht - endogenous opioids (rewtahc)
Reduce pain
What are endogenous opioid receptors
GPCRs, ss
Act on central and peripheral receptors - mu delta
kappa. Gpcrs. Hyperpolarise cell - decrease
substance p release - decrease nociceptor
stimulations. But in other tissues - so other effects
such as resp depression,
What are diffferent strengths of analgesia ?
Simple - paracetamol, nsaids
Weak opioids - codeine
Strone opioid - morphine, fentanyl
also neuropathic
- anticonvulsants
- tricyclics
- serotonin/NA reuptake inhibitors
Acute situation - a&e - can jump to end step. Strong options work best for acute severe api, making/non main chronic. But not best for everything Arthritics tho responds to nsaids. Neuropathic pain work better with antidepressants - tricyclics, antiemileptics
What are the general principles of opioids
Acute situation - a&e - can jump to end step. Strong options work best for acute severe api, making/non main chronic. But not best for everything Arthritics tho responds to nsaids. Neuropathic pain work better with antidepressants - tricyclics, antiemileptics
Describe the pk of morphine
Commonly sused - good effect, can be given multiple different ways. Child or patient without good venous cation - can take it in syrup form. Gut absorption is variable. Iv or sc better if fast acting needed,. Cab b=enter placenta/fetus - baby an have effect - resp depression, withdrawal
- Absorption • PO, IV, IM, SC, PR
- Gut absorption erratic
- Significant first pass effect- 40% oral bioavailability
- Distribution • Rapidly enters all tissues including foetal
- Struggles to cross blood- brain barrier
• Metabolism • Morphine + glucuronic acid Æ M6G +M3G
M63 has analgesics efect. M3g
neuroexciattior and irritable efect - can
easily assthru bbb
• Elimination
- Renally
Cautious of ckd and Aki
What are the actions of morphine
- Strong affinity to μ receptors, minimal for κ and δ.
- Complete activation of μ.
- Actions:
- Analgesia
- Euphoria
What are the side effects of morphine
- Side Effects: • Respiratory Depression- medullary resp centre less responsive to CO2
- Emesis- stimulate chemoreceptor trigger zone
- GI tract- decreasing motility, increase sphincter tone
- Cardiovascular
- Miosis
- Histamine release- caution in asthmatics
Doesn’t do anything to tell brain smth Reduces response to co2 in resp centres. Reduce responsiveness but do not notice o2 increasing - wont increase breathing to react to that CTZ - nausea - exacerbated by decreased mobility and increased sphincter tone
Morpheme - cautions in asthmatic -
mast cell degranualiton - histamines -
can case asthma attach
Describe the PK of fentanyl
Press the button - gives a dose -
generally iv, can give epidural. High level
of cns crossing. Gets into tissues - rly good pain relief response. Less excreted
than morphine - to as safe for patients
with renal issue
- Absorption • IV, Epidural, Intrathecal, Nasal
- 80-100% bioavailability
- Distribution • Highly lipophilic, highly protein bound
- High level of CNS crossing
• Metabolism • Hepatic via CYP3A4
- Elimination • Half life 6 minutes
- Renally excreted
What are the actions of fentanyl
• Compared to morphine: • 100x potency • Higher affinity for μ receptor • Less histamine release, sedation and constipation • Actions: • Analgesia • Anaesthetic Much more potent. More of a pain rele f response.
What are the side effects of fentanyl
- Side Effects: • Respiratory Depression
- Constipation
- Vomiting
Describe the PK of codeine
- Absorption
- PO, SC administration
- Metabolism
- Codeine ÆMorphine via CYP2D6
- CYP2D6 inhibited by Fluoxetine
- Variable expression
- Elimination
- Glucoronidation of morphine and renal excretion
Important to know bc given out a lout, say to get hold off, low dose otc, highest street value. An melt it dow and make into morphine. CYP2D6 very important - converts codeine to morphine. More of
the enzyme, more morphine, more
toxicity and side effects. Less for enzyme,
less broken dow, less morphine, less effects of codeine varies - depends on the amount of the enzyme
What are the actions and side effects of codeine
• Compared to morphine • Approx 1/10th potency • Actions: • Mild- moderate analgesia • Cough depressant • Side Effects: • Constipation • Respiratory Depression- worse in children Children have massive adenoids Make rd write in children
