💊370.3: Pain Flashcards
What are examples of endogenous opioids?
- Enkephalins
- Endorphins
- Dynorphins
What are the 3 types of opioid receptors?
Mu»_space; kappa»_space; delta
Analgesics don’t bind to delta, only endogenous opioids
What are important effects of activations of mu receptors?
- Analgesia
- Resp depression
- Sedation
- Sedation
- Euphoria
- Physical dependence
- Decreased GI motility
What are important effects of activations of Kappa receptors?
- Analgesia
- Sedation
- Decreased GI motility
What are prototypes of pure opioid agonists?
Morphine (strong)
Codeine (moderate to strong)
What is a prototype of opioid agonist-antagonists (partial agonists)?
Pentazocine (Talwin)
What is a prototype of a pure opioid antagonist?
Naloxone (Narcan)
What is the mechanism of action of morphine?
- Binds to CNS receptors, peripheral nerve terminals, and cells in GI tract
- Occupied opioid receptors = blocked pain impulses
What are the 2 major metabolites of morphine?
M6G = active, contributes to analgesia
M3G = no analgesia, but causes side effects
How is morphine cleared from the body?
Cleared through kidneys
Can cause renal and hepatic impairment
What is the most serious side effect of morphine and what is the mechanism of action?
Respiratory Depression.
Due to decreased sensitivity to CO2 in the Respiratory Center of the medulla
What opioid side effects have a tolerance?
- Respiratory depression
- Sedation
- Urinary retention
- Nausea
What opioid side effects DO NOT have a tolerance?
- Constipation
- Orthostatic hypotension
- Cough suppression
What is rescue therapy for respiratory depression due to opioid use?
- Naloxone
2. Ventilator if needed
What is the management for sedation due to opioid use?
- Reduce/skip dose
- CNS stimulant (methylphenidate)
- Pts should avoid hazardous activities
What are management strategies for opioid-induced constipation?
- Be proactive!!
- Physical activity, increase fluids and fibre
- Stimulant/osmotic laxatives, enemas
- Methylnaltrexone (last resort)
STOOL SOFTENERS NO EFRECT
What is the mechanism of action for Methadone?
Blocks NMDA receptors and re-uptake of Serotonin and NE. Binds to mu and delta opioid receptors.
What are the opioid prodrugs and what do they convert to?
Codeine ➡️ morphine
Hydrocodone ➡️ hydromorphone
By CYP450
Oxycodone
Natural opioid with analgesic actions equivalent to codeine.
High abuse potential.
Codeine
Natural opioid used for mild to moderate pain, cough suppression, and diarrhea.
Converted to morphine in the liver.
What is a safety teaching note for oxycodone?
Swallow tablets and whole. Do not break, crush, or chew.
Can form a gelatinous substance in throat ➡️ choking hazard
Hydrocodone
Semi-synthetic opioid, similar analgesic to codeine.
PRODRUG converts to HYDROmorphone.
Aka Vicodin
What is a prototype of a partial opioid agonist?
Pentazocine (Talwin)
Agonist at kappa receptors, antagonist at mu receptors.
Opioid tolerance
Reduction in drug effect over time due to drug exposure. Increased doses needed to obtain same response.
Physical dependence
State in which abstinence Syndrome will occur with abrupt dose reduction or discontinuation, or administration an opioid antagonist.
What are the symptoms of Abstinence Syndrome?
- Yawning
- Rhinorrhea
- Diaphoresis
- Violent sneezing
- Weakness
- N/v
- Diarrhea + abdominal cramps
- Bone and muscle pain
- Muscle spasms
- Kicking movements
How long does abstinence Syndrome last if left untreated?
7 to 10 days
What is the classic triad of clinical symptoms for opioid overdose?
- Respiratory depression
- Coma
- Pinpoint pupils
What is the treatment for opioid overdose?
- Ventilatory support
2. Opioid antagonist (ex. Naloxone)
What are patient risk factors for opioid overdose?
- Elderly
- Renal/hepatic impairment
- Sleep disorders
- Using CNS depressants
- Cognitive impairment
- COPD
What are provider risk factors for opioid overdoses?
- Incomplete assessment
- Rapid titration
- Failure to monitor
- Inadequate pt education
Naloxone (Narcan)
Structural analog of morphine, competitive antagonist at opioid mu and kappa receptors.
IV, IM, SC, or intranasal (not PO d/t large first pass effect)
Onset: 1 min IV, 2-5 for others
What are types of centrally-Acting analgesic actions?
- Tramados
- NSAIDs and COX2-inhibitors
- Acetaminophen
- Alpha2-adrenergic agonists
- Anticonvulsants
- Antidepressants (TCAs)
- Local anesthetics
- General anesthetics
Tramadol
- Works via opioid and non-opioid mechanisms.
- Weak agonist at mu receptors.
- Blocks reuptake of inhibitory NTs (serotonin and NE).
Similar effect to codeine, but minimal resp depression.
What are side effects of Tramadol?
- Sedation, HA, dry mouth
- Seizure
- Less nausea, constipation, diarrhea vs opioids
- Only partially reversed by naloxone
Avoid with drugs that increase serotonin levels due to seizure risk and Serotonin Syndrome
How is Tramadol excreted?
Renally
What are the most common adjuvant agents?
- Anticonvulsants
2. Antidepressants
What are the various mechanisms of action for anticonvulsants for pain relief?
- Block sodium channels which suppress abnormal discharge in pain nerves (carbamazepine, lanotrigine, topiramate)
- Increase GABA transmission (valproic acid, topiramate, gabapentin)
- Inhibit calcium influx and release excitatory NTs (pregabalin)
What are indications for anticonvulsants for pain relief?
- Adjuvants for pre- and post-operative pain (with opioids)
2. Neuropathic pain
What are common adverse reactions to Gabapentin and Pregabalin?
- Somnolence (sleepy)
- Dizziness
- Fatigue
- Ataxia
- HA
What are common side effects for Carbamazepine?
- Visual disturbances
- Ataxia
- Vertigo
- HA
- Mental clouding
- Leukopenia, anemia, thrombocytopenia (in cancer patients)
- Nausea, dry mouth, rash
What is the mechanism of action for Tricyclics Antidepressants (TCAs) for adjuvant pain relief?
Blocks serotonin and NE reuptake and enhances descending analgesic system
Neuropathic pain:
- Diabetic neuropathy
- Post-herpetic neuralgia
- Cancer pain
- Low back pain
What is a prototype of TCAs?
Amitriptyline (Eladio)
What are indications for opioid rotation?
- Unmanageable side effects
- Poor analgesia despite dose titration
- Alternate admin route needed
- Change in clinical status requires different pharmacokinetics (ex. Renal/hepatic dysfunction)
- Cost or availability
- Drug interactions
What is the general conversion suggestions when switching opioids?
If previous dose was:
HIGH ➡️ 50% or less of previous opioid
MODERATE OR LOW ➡️ 60-75% of previous opioid
How are equianalgesic doses compared?
Always compared to morphine
What should a nurse do if pre-administration Respiratory rate is 12 or less?
Hold dose and notify prescriber
What are analgesics that decrease pain responses in the brain?
- Opioids
- Alpha2-Agonists
- Centrally Acting analgesics
- NSAIDs
What are analgesics that act in the spinothalamic tract ascending input of pain?
- Local anesthetics
- Opioids
- Alpha2-agonists
- NMDA antagonists
Ex. Bupivacaine, ropivacaine, hydromorphone, ketamine
What are analgesics that act on the peripheral nocioreceptors?
- Local anesthetics
- NSAIDs
- COX2-inhibitors
- Ice
Ex. Lidocaine patch, ropivacaine nerve block
What are the regulations for opioid administration?
- Require WRITTEN prescription
- Repeats not allows unless specify interval
- Prescribed by licensed MD and NP
What are the consequences of pain in Cardiac patients?
- Prolonged activation of SNS
- Increased HR, BP, and PVR
- Increased oxygen consumption
- Worsened ischemia
What are the consequences of pain and GI function?
- Increased SNS
- Inhibition of GI secretion and motility
- Delays gastric emptying
- Paralytic ileus = absence of something physical
What are the consequences of pain and respiratory function?
- Pt limits movement and thoracic muscles
- ⬇️ Retention of sputum and secretions and Vital lung capacity
- Atelectasis and pneumonia
- Reduced alveolar ventilation
- Hypoxia
- Cardiac complications, delayed wound healing, disorientation and confusion
What are the consequences of pain on fluid balance?
- Release of hormones and enzymes (ie. ADH, angiotensin 2, Aldosterone)
- Retention of sodium and water
- Fluid moves to intracellular spaces
- Fluid overload, ⬆️ cardiac workload, hypertension
What are the consequences of pain on DVT?
- Reflex muscle spasms at tissue damage site
- Impaired muscle function and muscle fatigue
- Immobility
- Venous stasis, ⬆️ blood coagulation
- ⬆️ risk of DVT
What are the effect of pain on nausea and vomiting?
- CNS stimulation
- GI disturbance
- Release of NT 5HT3
- Activation of vomit centre in medulla
What systems are necessary for pain?
- Afferent pathways (PNS)
- Interpretive centres
- Efferent pathways (CNS to spinal cord)
What is necessary in order to interpret pain?
- Intact spinal cord
- Brain
- Peripheral nerves
What information is conveyed through the posterior/dorsal spinal root?
Somatosensory
What information is conveyed through the anterior/ventral spinal root?
Motor
Nociceptors
Free/unspecialized nerve endings.
Found in skin, muscle, connective tissues, circulatory system, abdominal, pelvic, and thoracic viscera.
What are the 4 mechanisms of pain pathways?
- Transduction
- Transmission
- Perception
- Modulation
What is the mechanism of pain transduction?
- Nocireceptors activates, threshold converted
- NT released (Substance P, neurokinin)
- Inflammatory response (Prostaglandins, histamines) decreases threshold for AP
- Action potential modulated by Na, Ca, and K
What is the mechanism of pain transduction inflammatory response?
Phospholipase ➡️ phospholipids ➡️ arachnidonic acid ➡️ BLOCK with Corticosteroids
Cyclioxygenase ➡️ archidonic acid ➡️ Prostaglandins ➡️ BLOCK with NSAIDs
The transmission of pain occurs in 3 segments:
- Nociceptor fibres ➡️ spinal cord (DERMATOMES)
- Spinal cord ➡️ brain stem + Thalamus (Dorsal Horn processing)
- Connections between Thalamus and cerebral cortex
Which spinal nerve does NOT have a dermatome?
C1
A-delta fibres
FAST
Mediate sharp, transient, prickling pain.
High threshold mechanoreceptors or thermoreceptors.
C-fibres
SLOW
Mediate slow and visceral pain.
Peripheral terminals respond to thermal and chemical stimuli.
“Aching pain”
What are the brain areas involved in the perception of pain?
- RETICULAR System = autonomic, responds pain as protective
- SOMATOSENSORY Cortex = localized and characterizes pain
- LIMBIC System = emotional and behavioural response to pain
What is the mechanism of the modulation of pain?
Descending Modulatory pain pathways (DMPP) modify and suppress pain impulses via inhibitory NTs (endogenous opioids, GABA, serotonin, NE).
Inhibit transmission of noxious stimuli thus producing analgesia.
Nocioceptive pain
- Caused by direct stimulation of peripheral nocireceptors.
- Somatic and visceral pain.
- Well-localized
- Burning, sharp, stinging, aching.
Somatic pain
- Superficial = well-localized
2. Deep = aching, more diffuse (muscle, bone, joints)
Visceral pain
Sharp of aching, diffuse, poorly localized.
Tumour, obstruction, involved with internal organs.
What is the mechanism of referred pain?
Sensory impulses both conducted through common nerve pathway.
Both merge into same pathway on spinothalamic tract, thus can’t differentiate.
What is a possible cause of chronic pain?
Dysregulation of nociception and pain modulation.
Leads to physiological adaptation.
Allodynia
Stimulus that does not normally produce pain
Ie. hypersensization
Does persistent chronic pain produce a physiological response similar to that of acute pain?
NO.
Chronic = behavioural
Acute = SNS
Which opioid has a toxic metabolite?
Normeperidine (Demerol)