Pain Management Flashcards
Enkephalins
Endogenous pentapeptides derived from pro-enkephalin
Two families: (Met) enkephalin and (Leu) enkephalin
Rapidly broken down by peptidases, so act only at a short distance (synapse)
Endorphins
Derived from proopiomelanocortin (POMC)
B-endorphin - 31 amino acid peptide; less susceptibility to degradation by proteases allows it to act more systemically as both a neuropeptide and a neurohormone
Dynorphins
Derived from prodynorphin
Dynorphin A is K-opioid receptor selective
Where do opioid receptors function in the brain?
PAG (descending pain) Medulla nuclei (respiratory depression) Spinal cord dorsal horn (ascending pain) Limbic regions (affective response to pain) Reinforcement regions (addiction/abuse) Gut (constipation)
Indications for clinical use of opiates
Relief of moderate to severe pain associated with:
Malignancy
Post-operative pain
Obstetrical anesthesia
Patient-controlled analgesia
Alleviation of pain and myocardial load in MI
Alleviation of dyspnea associated with cardiac dysfunction
What is the mechanism of respiratory depression in opiate use?
Decreased sensitivity to CO2 levels in brain stem respiratory centers
Increased blood CO2 levels leads to cerebral vasodilation, which can exacerbate head injury via elevation of ICP
Contraindications to opioid use
Compromised respiratory function (asthma, emphysema, severe obesity) Suspected head injury Hypotension / Shock Histamine release Hypothyroidism Impaired hepatic function
Use of opiates in cough
Provide symptomatic relief from cough at lower doses than necessary for analgesia and respiratory depression
Codeine
Dextromethorphan - non analgesic opiate
Which opiate use effects do not demonstrate tolerance?
Pupillary Constriction (Miosis)
Use of opiates in GI
Anti-diarrheal / induction of constipation following GI surgery
Loperimide (Imodium) and diphenoxylate act locally in GI tract and are not absorbed into bloodstream; Schedule IV (low abuse potential)
Histamine-mediated side effects of opiates
Itching
Urticaria (hives)
Local vasodilation
Headache
Exacerbation of asthma symptoms
Peripheral vasodilation with decreased blood pressure
Cardiovascular effects of opioid drugs
Decreased cardiac work load
Orthostatic hypotension via inhibition of baroreceptor reflex
Therapeutic uses: MI (analgesia and decreased cardiac load)
Therapeutic use of opioids in pulmonary edema
Useful in pulmonary edema associated with cardiac dysfunction
Alleviation of dyspnea
Opioids - DDIs
Barbituates - synergistic CNS depression
Antipsychotics - synergistic respiratory depression
MAOI Inhibitors and TCADs - increased respiratory depression; risk of CNS excitation, delirium, seizures
Opioids - Pharmacokinetics
Absorption: Oral, but efficacy is increased if given parenterally due to first-pass hepatic metabolism
Rapidity of onset (and abuse potential) is highly correlated with lipid solubility
Metabolism: morphine is conjugated with glucuronide in the liver; morphine-6-glucuronide is a potent metabolite
Excretion via urine
Tramadol - Mechanism
Acts at mu receptors but also blocks monoamine reuptake; potentiates descending analgesic pathway
Demerol
Used to treat severe, short term pain
Faster onset/offset than morphine with decreased biliary spasm, constipation, tolerance
Not antitussive
Toxic metabolites cause CNS excitation; limits use to short-term
Buprenorphine - Mechanism
Partial mu agonist; can cause analgesia but precipitates withdrawal in opiate dependent patients
Pentazocine & Butorphanol
K agonist, mu antagonist
Used for spinal analgesia with less respiratory depression
Precipitates withdrawal in patients dependent on mu agonists
Naloxone vs. Naltrexone
Competitive antagonists of mu receptors
Naloxone is short acting and not orally active; Naltrexone is longer acting and orally active
Codeine metabolism
Codeine is an agonist at mu opioid receptors; additionally, 10% of the dose is metabolized to morphine by CYP2D6
10% of Caucasians are deficient in this enzymatic pathway and may experience diminished analgesia with codeine
Delta opioid receptors
Endogenous agonists - Met/Leu enkephalins, B-endorphins; produce analgesia without respiratory depression
No exogenous agonists available
Kappa opioid receptors
Endogenous agonists - Dynorphins
Exogenous agonists - Pentazocine
Produce spinal analgesia with reduced respiratory depression
Opioid withdrawal
Characterized by:
Dilated pupils Insomnia / restlessness Rhinorrhea Sweating Diarrhea Nausea Cramps Chills
Clonidine (a2-adrenergic agonist) treats withdrawal symptoms
Neuropathic Pain
Pain that persists and has become disengaged from noxious stimuli or the healing process; often a result of nervous system damage or pathology
Often presents with paresthesias, hyperalgesia, allodnia; ex: postherpetic neuralgia, diabetic neuropathy
Nociceptive Pain
“Normal” pain resulting from active of nociceptive nerve fibers; may be somatic or visceral
Acute Pain Management Guidelines
Mild Pain (1-3): NSAID +/- adjuvant
Moderate Pain (4-6): slow titration of short acting opioids + NSAID +/- adjuvant
Severe Pain (7-10): rapid titration of short acting opioid + NSAID +/- adjuvants
How do NSAIDs affect post-op opioid requirements?
Reduction by 20-40%
Acetaminophen
Inhibits COX-2 in the CNS to block central sensitization only; no peripheral anti-inflammatory action
Major dose-limiting side effect is hepatotoxicity; daily dose should not exceed 3.25-4g/day
Multimodal pain management - drug classes
Opioids NSAIDs / Acetaminophen Local anesthetics a-2 adrenergic agonists (Clonidine) NMDA receptor antagonists (Ketamine)
Role of a-2 adrenergic agonists in pain management
i.e. Clonidine
Act on post-synaptic receptors on dorsal horn neurons to decrease ascending pain transmission
May decrease opioid requirements; administered via epidural infusion in cases of severe, intractable pain as adjunct to neuraxial opioids
Side effects: Hypotension, bradycardia, sedation, rebound hypertension
Role of NMDA receptor antagonists in pain management
i.e. Ketamine
Blocks glutamate binding at NMDA receptors in ascending pain pathway; reduces development of tolerance to long-term opioid use
