Opioids Flashcards
What is nociception ?
Non- conscious neural traffic due to trauma due to trauma or potential trauma to tissue
What is pain?
complex unpleasant awareness of sensation modified by variable experiences , context, etc.
how is pain generated ?
Via Spinothalmic tract:
- Nociceptors stimulated
- Release of sub P and glutamate
- afferent nerves stimulated
- fibres decussate
- AP ascends and synapse in thalamus
- project to Post central gyrus
what modulates pain peripherally ?
Substantia gelantinosa- dorsal horn
what modulates pain centrally ?
peri adueductal grey
what do A(delta) and c fibres ?
send stimulatory signals up from nociceptors the spinothalmic tract
inhibit the Substantia gelantinosa
how does rubbing your knee help reduce pain ?
stimulate AlphaBeta fibres which stimulates substantia geletanosa to modulate the pain from A(delta) and C nerves to reduce signals of pain
how do when modulate pain centrally ?
Cortex usually inhibits peri aqueductal Grey matter . During pain , thalamus and cortex send stimulatory signals to PAGM which inhibits spinal cord to reduce pain signals via 5-HT and endogenous opioids
Name the endogenous opioids
Enkephalins
Dynorphins
B endorphins
what are the 3 Opioid receptors ?
Mop = mu DOP= delta KOP= kappa
outline how opioid receptors work
Hyperpolarisation and decrease of substance P
what does Mop receptors modulate ?
analgesia , depression , euphoria , dependence , respiratory sedation
Whta do Dop receptors modulate ?
analgesia, inhibit dopamine, modulate Mop
what do Kop receptors modulate ?
analgesia , duiresis , dysphoria
what is the order of WHO analgesic ladder ?
Simple analgesia
weak opioid = codeine
strong Opioid
what should you use for neuropathic pain e.g diabetic neuropathy ?
Anticonvulsants
tricyclics
SSRIs, NARI
what other indications can you use opioids ? what receptor is the main one affected ?
cough , diarrhoea and palliation
Mop
what is the absorption of morphine ? bioavailibilty ?
PO, IV, IM , SC, PR
Gut absorption erratic-
40%
what is the distribution of morphine ?
elimination ?
rapidly enters all tissues including foetal
struggles to enter BBB
Renally
what is the metabolism of morphine ?
what molecules
significant first pass effect
combines with glucuronic acid –> M6G (Analesgic) and M3G (Neuro stimulatory and irritabilty )
what is the MOA of morphine and what is its actions ?
Strong affinity to Mop and less so Dop and Kop
Analgesia and Euphoria
what are Respiratory side effects of morphine and how do they occur ?
resp depression
medullar resp centre less responsive to CO2
what are GI side effects of morphine and how do they occur ?
Emesis - stimulate chemoreceptor trigger zone decrease motility and increase sphincter tone = constipation , nausea
what other side effects are seen in morphine ?
Miosis
Histamine- be careful in asthmatics
what is the Absorption of fentanyl ?
IV, Epidural, Intrathecal , Nasal
80-100% bioavail
What is the distribution if fentanyl like ?
highly lipophilic , highly protein bound and CNS crossing high
What is the metabolism and Elimination like in fentanyl ?
Met = CYP3A4
Renally excreted
What are features of fentanyl compared to morphine ?
100x more potent
high affinity for Mop
less histamine , sedation and constipation
what are side effects of Fentanyl ?
resp depression
Constipation
vomiting
what enzyme metabolises Codeine ? what inhibits said enzyme ?
CYP2D6
Fluoxetine , SSRIs
how is codeine eliminated ?
glucoronidation and renal exertion
what is codeine metabolised to ?
Codein to morphine via CYP2D6
what are the actions of codiene?
Cough depressant
Mild/mod analgesia
what are side effects of morphine ?
Constipation
resp depression - esp in children , dont give under 12
what is the pharmokinetics of Buprenorphine ? ADME
A- Transdermal
D- Very lipophilic
M- Via CYP3A4
E- Biliary system so safe in renal impairment
what are features of Buprenorphine compared to morphine ?
Very high affinity to Mop = low Kd, not displaced
long action duration
low Emax as it is partial agonist
Antagonist at Kop
what are indications for buprenorphine ?
Moderate to sever pain
polypharmacy patients
Opioid addiction
what are side effects of Buprenorphine ?
Resp depression
Low Bp
Nausea
dizziness
what is the absorption of Naloxone ?
IV, IM , IN, PO
Low oral bioavail (First pass)
rapid onset of action
What is the D, M and E of Naloxone ?
D= rapid due to lipophilicity
M and E= renally excreted, within 30-60 Mins
what are features of Naxolone ?
affinity MOP>DOP>KOP
Greater affinity than morphine , less than Buprenorphine
What must you be aware of naxolone in acute setting ?
short acting so give long infused dose to avoid secondary OD
How does opioid tolerance build ?
Up regulation of opioid receptors when using opioids leads to more Mop receptors = increased mount of opioid for cellular response
how can stopping an opioid lead to withdrawls ?
endogenous opioids cannot initiate a cellular response
what is given to opioid addicts during withdrawl and how does it work ?
Methadone is given to stop withdrawal effects leading without much of a high . weaning of slowly to allow Mop receptors to down-regulate
what patients should you be considerate of when prescribing opioids ?
Manual labourers/Drivers • Elderly • Bedbound • Asthmatics • Biliary tract obstruction • Respiratory Diseases • Renal impairment • Pregnancy
what are contraindications of opioids?
Hepatic failure
acute respiratory distress
comatose
Head injuries , raised ICP = M3G causes irritability
what should you in do palliative prescribing for opioids ?
ignore special considerations
laxatives
if in pain and SOB
