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
Describe the PK of buprenorphine
- Absorption
- Transdermal, Buccal, sublingual
• Distribution • Very lipophilic
- Metabolism
- Hepatic via CYP3A4
- Then glucoronidation before biliary excretion
- Elimination
- Biliary > Renal
- Safe in renal impairment
- Half life 37 hours
Chronic pain, palliative care. Transdermal application - long acting medication - patch last about a week - slowly release analgesia. Long half lif - Polypharmacy eg elderly patients - less syncopal effects. This wont make even more risk o falls
What are the actions of buprenorphine
- Compared to morphine:
- Very high affinity for μ receptor. Low Kd
- Long duration of action
- Not easily displaced
- Lower E(max) as partial agonist, lower efficacy
- Antagonist at κ receptors
- Actions: • Moderate to severe pain
- Opioid addiction treatment
The highest affinity. -will displace other opioids. Same prolonged
mechanism of actions. Once bound,partial agonist - analgesic affects but
less side effects - less resp d. Treatment for addiction. Switch normal one
for buprenoprihine. Will still have withdrawal side effects. Binds so well
to receptors - if worried abt overdose - cant give normal treatment,
displace . But Less likely to cause side effects at normal treatment dose
What are the side effects of buprenorphine
- Respiratory depression
- Low BP
- Nausea
- Dizziness
Describe teh PK of naloxone
• Absorption • IV, IM, Intranasal, PO
• Very low oral bioavailabilty as extensive first pass effect
Only 2% into circulatrion bc first pass. Readily bind to and
competitively inhibit
• Rapid onset of action
- Distribution
- Rapid distribution as very lipophilic
- Metabolism • Hepatic Ænaloxone-3- glucuronide
- Renally excreted
• Elimination • Duration of action 30-60mins
What are the actions and side effects of naloxone
- Compared to morphine:
- Affinity μ>δ>κ
- Greater affinity than morphine
- Affinity less than buprenorphine
- Action:
- Competitive antagonism of opioid
- Side Effects:
- Short half life
- Slow infusion
If youre giving it iv to someone taken overdose - neeed
togive slow infusion. If you giv bolus.-comp antagonise -
reverse teh high but morphine still circulating longer than
halo one - resp depression. Short slow infusion - comp
antagonise - reverse effects slowly but safely. - patient can
metabolism opioids while naloxon is still bound
How does opioid tolerance develop and why do withdrawal symptoms occur?
Act on receptors to get response. If you have cell and give
synthetic opitondd. - body begins to upregulate receptors
to get ore of a response by that ell. Need 50% bound to get response
Endogenous and synthetic.
More receptors. Dont get
cell response bc havent
bound enough of he
receptors. Need 50% but there are now more receptors
Need to increase dose of synthetic to get 50% bound - withdrawal side effects. This
patient has been on opioid for some time - receptors unregulated. Then stopped opioid -
wond hve enough endogenous opioid to get a response bc unregulated. To treat this, give
methadone, which has agonist activity - removes slide effects, but improve withdrawal effects. Doesn’t give as much
high. Slowly decrease receptors. Then come
off methane eventalt
What are the causes and effects of overdose
- μ receptor
- Variable effects of doses
- Respiratory Depression most common cause of death
- Can decrease effects- δagonists, 5HT4 agonists
- Naloxone infusion as treatment
Dependence, vomiting, constipation, hypotension and bradycardia, decreased sex drive, histamine release, miosis, drowsiness, resp drepression -> apnoea
What are special considerations when prescribing opioids
• Manual labourers/Drivers - Sedative effects - if operating machinery. - do
not give opioid
• Elderly - Larger effects for a given dose
• Bedbound
• Asthmatics - Do not wat to reduce drive to breathe further
• Biliary tract obstruction
• Respiratory Diseases
• Renal impairment
• Pregnancy - Baby can experience withrawal
What are the contraindications to opioids
• Hepatic failure
• Acute respiratory Distress
• Comatose
• Head injuries
• Raised ICP
Head injury - m3g morphine elimation -
crops bbb - irritant effect on brain. I head
injury has bbb isrutopin and inflammation -
opioid can make . Smth cross bbb, increased
inflammation
Describe palliatve prescribing
- Buprenorphine, diamorphine, fentanyl, morphine and oxycodone
- Difficult area of prescribing
- Tend to ignore special considerations - eg even if someone had renal impairment, still give adequat pain relief bc end of life
- Indications: Pain, Shortness of breath - reduce sensitivity to co2
- Manage side effects: nausea, constipation - dont want them to feel sick, eg 1 dose a day of laxatives
How are opiods controlled?q
- Controlled under Misuse of Drugs Legislation
- Aim to prevent • Misuse
- Illegal obtainment
- Harm being caused
• Benefit of medical use vs Risk of harm
Specific prescribing rules. Locked cupboard.
Anyone who wants to take one out - sign book
double check by someone esle.if unused. Binned
and recorded. Pharmacist check how much
delivered vs how much signed out. Only codein
and smthelse ora not comptrollers
What info should be written when an opioid is prescribed
• Must include:
• Date and prescribers address and Full name
• Patients address and name
• Form of the drug- tablets, syrup, capsules, patches, ampoules etc
• Units- mgs, mls etc
• Total volume- in words and figures
• Clearly defined dose
• E.g. New regime is 60mg BD Zomorph and 20mg Oramorph PRN
Take one 60mg Zomorph tablet, twice daily, supply fifty six (56) tablets.
