Lecture 8 - Opioids & Pain Control Flashcards
What is the mechanism of action for opioids?
- Hyperpolarization of nerves by opening K and Ca channels in 1st and 2nd order neurons
- Inhibition of ascending pathways in CNS
- Excitation of descending adrenergic and serotonergic pathways
- Decrease emotional connectivity to pain
Which processes of pain do opioids decrease?
Transmission and maybe transduction
What are the pharmacological effects of opioids?
- Inhibition of pain and pain perception
- Sedation and anxiolysis (before surgery)
- Depression of respiration
- Cough suppression
- Decrease in intestinal motility
- Pupillary constriction and nausea and vomiting
Why are opioids given as anxiolytics?
To decrease the amount of anesthetic needed
What is the main cause of death from opioid overdose?
Respiration depression
Which opioid is used to treat diarrhea?
Codeine
What is a key symptom of opioid overdose?
Pupil constriction
Can a px be on both acetaminophen and morphine?
Yes b/c they work via different mechanisms
___ dosing is less effective than IV
Oral
Why should opioids be given by the mouth?
- Oral dosing has longer term effect requiring less frequent doses
- Oral dosing avoids the “highs” and thus is less addictive
- Oral dosing is safer in terms of overdose
Why should opioids be given by the clock?
- Uses less drug
- Avoids euphoria associated w/ release of pain, so less addictive potential
- Avoids development of chronic pain syndromes
- Do not reward px w/ opioids for having pain
Why should opioids be given by the ladder?
- Assures safest and least potent drug is used
- Avoids addictive potential b/c opioids aren’t used until required
What is the weakest commonly used opioid?
Codeine
What is codeine used for?
- Pain
- Diarrhea
- Coughing
- Inhibit breathing
What is special about tramadol?
Has 2 complementary mechanisms
- Activates u-opioid receptor (like other opioids)
- Weak inhibitor of NE and serotonin reuptake
IV morphine is ____ as potent as oral
Twice as potent
Is morphine considered a strong opioid?
No
What is the potency of oxycodone compared to morphine?
Oxycodone has equal or slightly higher potency
A 10 mg dose of morphine is equivalent to how much oxycodone?
5 mg
What is the slow-release form of oxycodone?
OxyContin
What is percocet?
Oxycodone and tylenol
What is the danger w/ oxycodone?
Repression of breathing
Hydromorphone is ___ times more potent as morphine
5
When is hydromorphone used?
Surgical settings for moderate to severe pain (cancer, bone trauma, burns)
Fentanyl is ___ times more potent as morphine
80
What is sublingual fentanyl used for?
Acute but temporary pain (ex: debriding wounds)
What is transdermal fentanyl used for?
More severe pain (cancer, palliative)
Sufentanyl is ___ times more potent than fentanyl
About 10
What is the most common opioid given intravenously?
Morphine
What is naltrexone?
Oral opioid inhibitor
What is the function of naltrexone and what is it effective at?
- Reverse psychomimetic effects of opiate agonists, reverses hypotension and CV instability
- Effective in treating alcohol addiction, but not opioid addiction
What is naloxone?
- Potent opioid antagonist
- Blocks all major effects of opioids including pain control
When is naloxone used?
Emergency situations (respiratory depression in clinical situation of heroin overdose)
Methadone is ___ times more potent than morphine
At least 10 (highly variable per px)
What is methadone used for?
Addiction medicine and palliative care where px has developed resistance or toxicity to other opioids
Why does methadone work?
Only a partial agonist, so a high enough dose of methadone reverses opioid effects
What should be considered when prescribing opioids?
- Titrate dose based on response and side effects until max. analgesia and function are attained w/ tolerable side effects
- If possible, switch short acting opioid to a long-acting opioid at equianalgesic dose b/c long-acting opioids decrease peaks and valleys of pain control
What should be noted when switching from one opioid to another?
The new opioid seems to be about 50-70% more effective than it should be b/c body is responding differently, so initial dose should be 50-70% less
When should opioid therapy be discontinued?
- Intolerable or unacceptable side effects w/ little to no analgesia
- High doses w/o analgesia
- Evidence of addiction
- No evidence of px trying to increase function in the face of reasonable analgesi
What is tolerance?
Decrease potency of analgesic effects of opioids following repeated administration
Is tolerance common in px w/ cancer pain?
No
What type of opioids should be given to px in a great deal of pain?
Slow release
What is physical dependence?
Normal response to chronic opioid administration
What is addiction?
Psychological dependence (craving)
What are common symptoms of opioid withdrawal?
- Yawning
- Sweating
- Tremor
- Fever
- Increased heart rate
- Insomnia
- Muscle/abdominal cramps
- Dilated pupils
How can you deal w/ tolerance?
- Avoid increasing dose
- Take a medication holiday following slow withdrawal to allow opioid receptors to go back up
What is central sensitization?
Decreased brain sensitivity to pain
Which NTs are pain mediators?
NE and serotonin
What do tricyclic antidepressants do for pain?
Increase serotonin and/or NE in synapse by inhibiting reuptake
What type of pain are TCAs used for and why?
Chronic pain b/c takes 1-3 weeks for pain control
Which type of antidepressants are most effective for diabetic neuropathy?
TCAs
Will TCAs given for pain have any effect on depression?
No b/c a low dose
Can SSRIs be given for pain in a px already on a high dose of antidepressants for depression?
No
Which 2 TCAs are given for pain?
Nortriptyline and amitriptyline
Which 3 SSRIs are given for pain?
Paroxetine, fluoxtine, and sertraline
What are SNRIs?
- Serotonin and NE reuptake inhibitors
- Potent inhibitor of neuronal serotonin and NE reuptake and weak dopamine reuptake
Are TCAs or SNRIs more effective for pain?
TCAs
What are the 2 SNRIs used for pain and which types of pain is each used for?
- Venlafaxine - neuropathic pain
- Duloxetine - diabetic neuropathy, fibromyalgia
What do alpha 2 adrenergic agonists do to decrease pain?
- Stimulates alpha-adrenoreceptors in brainstem causing activation of inhibitory neurons thus decreasing symp outflow
- Prevent pain signal transmission
What are the 2 alpha 2 adrenergic agonists used for pain and which types of pain is each used for?
- Clonidine - neuropathic pain that is not responding to other tx (last line of tx in this class)
- Tizanidine - tension-type headache, back pain, neuropathic pain (better tolerated than clonidine b/c less likely to cause hypotension)
What are the medication classes that help w/ peripheral sensitization?
- Carbamazepine
- TCAs
- Topiramate
- Lidocaine
What is carbamazepine?
- Anticonvulsant
- Limits influx of Na across cell membrane
- *Inhibits firing of a nerve b/c decreases influx of sodium ions
What is topiramate?
- Anticonvulsant
- Limits influex of Na across cell membrane and antagonizes glutamate receptors
What are common adverse reactions of topiramate?
Dizziness, ataxia, psychomotor slowing
What does topical application of lidocaine do for pain?
Decreases discharge of small afferent nerve fibres by blocking voltage-gated Na channels
What effect does increased Ca transport have on pain?
Causes spontaneous action potentials, sending a pain message to the brain
What are some medications that decrease Ca channel activity?
- Gabapentin and pregabalin
- First choice for neuropathic pain; pregabalin is 1st line therapy
What are some medications that are NMDA antagonists?
- Ketamine
- Dextromethorphan
- Methadone
What does ketamine do?
- Decreases central sensitization and modulation by decreasing the threshold for nerve transduction and decreases effects of substance P
- Targets opioid receptors and Na and K channels to decrease pain
What is a common adverse reaction w/ ketamine?
Local skin reaction
Can ketamine stack w/ opioids?
Yes
When is ketamine generally used?
Surgery
What is dextromethoprhan?
Low affinity uncompetitive NMDA antagonist
What is methadone?
Mu and delta opioid agonist but also blocks NMDA receptor and inhibits NE reuptake
1 mg of methadone = __ mg of morphine
10
Does methadone have active metabolites?
No, so less incidence of side effects
What causes gout?
Accumulation of uric acid crystals in joints
What can gout cause?
Gouty arthritis
Which joint is gout most common in?
Joint of big toe
What is uric acid produced from and which enzyme catalyzes this process?
- Xanthine
- Xanthine oxidase
What are some medications used to treat gout?
- Colchicine
- Allopurinol
- Probenecid
- NSAIDs
What is colchicine?
Weak anti-inflammatory
Colchicine should be dosed to _____
Toxicity
What is allopurinol?
Xanthine oxidase inhibitor
What is the drug of choice for gouty arthritis?
Indomethacin
What is probenecid?
A uricosuric (inhibits reabsorption of uric acid)
What is local anesthetic?
- *Sodium channel blocker
- Agent that interrupts pain impulses in a specific region of the body w/o loss of px consciousnesss
Do local anesthetics produce any side effects?
No b/c only used in a specific area (only need to be concerned if enters bloodstream and reaches the brain)
What is surface anesthesia?
Accomplished by application of a local anesthetic to skin or mucous membranes
What is surface anesthesia used for?
To relieve itching, burning, and surface pain
What is a nerve block?
Local anesthetic is injected around a nerve that leads to the operative site
A nerve block is exactly like ____
Lidocaine
What is peridural anesthesia?
Injection of a local anesthetic into peridural space
What is the peridural space?
One of the coverings of spinal cord
What is spinal anesthesia?
Local anesthetic injected into subarachnoid space of spinal cord
What are the effects of local anesthetics?
- First, autonomic activity is lost
- Then, pain and other sensory functions are lost
- Motor activity is last to be lost
- As local agents wear off, they do so in reverse order
What are local anesthetics used for?
- Surgical, dental, and diagnostic procedures
- Treatment of certain types of pain
What is infiltration anesthesia used for?
Minor surgical and dental procedures
What is infiltration anesthesia?
Injection of anesthesia intradermally, subcutaneously, or submucosally across path of nerves supplying target area
What are nerve blocks used for?
- Surgical, dental, and diagnostic procedures
- Therapeutic management of pain
When will adverse effects result from a local anesthetic?
- Inadvertent intravascular injection
- Excessive dose or rate of injection
- Slow metabolic breakdown
- Injection into highly vascular tissue
How can you determine a local anesthetic based on name?
All end in “aine”
