Narcotics Flashcards
How is analgesic different from anesthetics
Analgesics - relief from pain
Anesthetics - eliminates all sensation including pain
What determines choice of analgesia
Type of pain eg neuropathic pain responds better to TCAs/AEDs, migraine responds better to triptans and NSAIDs
Severity of pain
Response to other analgesics
What are the endogenous opioid receptors
Mu, kappa, delta
What are endogenous opioid peptides
endorphin, enkephalins, dysnorphins
Types of opioid analgesics
Full agonist, partial agonist and antagonists
Central and peripheral location of receptors do what?
Modulates pain
Inhibit respiration
Slows GIT transit
Modulate NT and hormonal release
Psychomimetic effects
Describe the absorption and distribution of opioids
Good absorption SQ, IM and oral
High interpatient variability in first pass effect
Rapidly distributed to highly-perfused organs (brain, kidney, liver, lungs)
Accumulates in fatty tissues
Morphine metabolized to what compounds?
M3G - neuroexcitatory (GABA/glycinergic)
M6G - more potent analgesic
Route of elimination of morphine, and effects when impaired
Excreted by kidney
Renal failure may lead to M3G-induced seizures
M6G - enhanced opioid effects
Explain metabolism of codeine
Metabolized to active compounds by P450 CYP2D6 - demethylation to morphine
Genetic polymorphism linked to variation in analgesic response
MOA of opioids
Binds to GPCR that:
1) closes voltage-gated calcium channel on presynaptic terminals, reduces NT release:
- glutamate
- ach
- NE
- seotonin
- substance P
2) open potassium channel - K efflux = hyperpolarised and inhibit post-synaptic neurons and nerve activity
Opioids act on multiple synapses, transmitters and receptors, such as in
Inflamed/damaged peipheral tissue
spinal dorsal horn where pain fibers are
Descending inhibitory neurons (periaqueductal grey, rostral ventral medulla)
Release of endogenous ligands
Define tolerance
Gradual loss of effectiveness with frequently repeated doses of opioid analgesics
To reporduce original response, larger dose must be given
Mechanism of development of tolerance
Concepts:
1) upregulation of secondary messenger system (CAMP)
2) Failure of receptor recycling - normally activation leads to endocytosis followed by resensitisation and recycling of receptor to cell surface
3) Receptor uncoupling: dysfunction of structural interactions between mu receptor, G proteins, 2nd messenger system and target ion channel
CNS effects of opioids
analgesia
euphoria
sedation without amnesia
respiratory depression
cough suppression
NV
miosis
temperature dysregulation
trunchal rigidity
no effects on cerebral blood flow and ICP UNLESS resp depression = increase PCo2
Effects of opioids of CVS
Bradycardia (except meperidine - antimuscarinic actions = tachy)
Hypotension
Effects of opioid on GIT
constipation due to actions on enteric and CNS - reduced motility, increased tone
biliary colic
Effects of opioid on urinary system and kidneys
Urinary retention due to:
increased sphincter and detrusor tone
decreased awareness of bladder stimuli
Renal dysfunction from decreased renal blood flow
Other effects of opioids
Release of ADH, prolactin, somatotrophin
Pruritus
Modulation of immune system
Opioids are part of management plan for what type of pain on the WHO ladder
Moderate to severe pain
Common errors in analgesic prescription
Failure to assess pain severity
Failure to match severity to appropriate level of therapy
Failure to monitor effectiveness and modify plans if response inadequate/excessive
Failure to distinguish between acute and chronic pains - rolerance and physical dependence
Clinical uses of opioids
Analgesia
Adjuvant analgesia added to less-than-satisfactory opioid regime
Anesthetic
What type of pain does opioid works best on
Opioid works best on severe constant pain (sharp intermittent less effectively controlled)
Pain a/w cancer requires continuous use of potent opioids. How to administer?
Fixed interval administration rather than PRN use
Slow release form - longer and more stable level of analgesia
Transdermal patches if GI function prevents oral use
Buccal and nasal prep can be effective
Use of opioids in obstetric labour results in
neonatal respiratory depression
Safer alternative is meperidine
Types of adjuvant analgesiics
Multipurpose (antidepressants, corticosteroids, alpha2 adfrenergic, neuroleptics)
Neuroleptic pain (AEDs, LA, NMDA antagonists)
Bone pain (calcitonin, bisphosphonates, radiopharm)
MSK (muscle relaxants)
Painr from bowel obstrction (octreotide, anticholinergics)
Clinical use of opioid as anesthetic
preop - premed as sedative, anxiolytic, analgesic
intraop - adjuncts to other anesthetic agents
high dose used as primary component of anesthetic regime
regional analgesia by administration into epidural or subarachnoid space to act on spinal cord dorsal horn superficial neurons
epidural has less SE (resp depression, pruritus, NV)
GOOD for post op pain control
When does tolerance manifest
2-3 weeks of frequent exposure to ordinary therapeutic doses
Develops mores readily in more potent opioids, when large doses given at short intervals
Degree of tolerance depends on
1) Opioid - more common in mu
Cross tolerance may be partial or incomplete agonists
2) Effects:
- marked tolerance to analgesic, sedative, respi depressant, antidiuretic, emetic and hypotensive effects
tolerance does NOT develop to miotic, convulsant and constipating actions
How is tolerance managed
Opioid rotation - change to another opioid
Use of adjuvant non-opioid to allow recoupling of opioid receptors
- ketamine shown to reduce post-op pain and opioid requirement in tolerant patients
Symptoms of physical dependence
rhinorrhea
lacrimation
yawning
hyperthermia
piloerection
hypervenetilation
mydriasis
muscular aches
vomiting
diarrhea
anxiety
hostility
Time of onset, intensity and duration of symptoms of physical dependence related to
DRUG and half life
morphine/heroin withdrawal starts 6-10h, peaks 36-48h, ends aft 5 days
methadone - less severe but last up to 2 wks
Psychological dependence such as?
euphoria, sedation, pleasurable sensation promote compulsive use
How to minimize risk of tolerance
- establish therapeutic goals before starting opioid
- limit dosage at lowest effective level (no early refills, no multiple prescrtibers)
- consider alternative eanalgesics
- frequently re-evaluate need for opioids
Contraindications of opioids
1) Combining full agonist (morphine) with partial agonist (pentzocine) = reduce analgesia and induce withdrawal
2) HI - resp depression = cerebral vasodilation = raised ICP
3) Pregnant women - fetus develops dependent, early postpartum w/drawal
4) Avoid/reduce dose in hepatic/renal dysfx
5) Avoid combination with sedative-hypnotics (resp depression)
antipsychotics (sedation, CV effects)
MAOi (hyperpyrexic coma)
Contraindications of opioids
1) Combining full agonist (morphine) with partial agonist (pentzocine) = reduce analgesia and induce withdrawal
2) HI - resp depression = cerebral vasodilation = raised ICP
3) Pregnant women - fetus develops dependent, early postpartum w/drawal
