Opioids and Analgesics Flashcards
physiologic pain
Defensive role. Acute in nature (labor, surgery, trauma). Easy management.
pathologic pain
No known benefit. Chronic and spontaneous. Low pain threshold to both noxious and innocuous stimuli. Associated with nerve damage (trauma, amputation, diabetes mellitus, HIV and VZV. Difficult to treat.
ascending pain transmissionpathway
From primary afferent nociceptors to dorsal horn cells.
descending pathway. Pain response.
Inhibitory regulation. Starts in Frontal Cortex, Amygdala, and Cingulate Cortex. Synapses PAG, RVM, then Dorsal Horn Cells.
desscending pathway receptors/transmitters
5HT, norepinephrine, glycine, GABA, and opioids.
Opioid Mu receptor
stabilize neuronal membrane by enhancing K+ conductance, and inhibiting voltage gated Ca++ channels. 1 - dependence, analgesia. 2 - euphoria, respiratory depression,
Opioid K receptor
Inhibitory.
Opioid D receptor
Inhibitory.
physical dependence
diaphoresis, insomnia, restlessness, abdominal cramps, N/V/D
psychological dependence
mediated by the ventral sriatum. Interactions between opioids and dopaminergic system in Nucleus Accumbens.
tolerance
Mediated by NMDA signaling (Glutamate). Normally cosmetic. Rotation therapy.
euphoria
Mediated by Mu. Does not occur with Codeine or Pentazocine. Improves life quality and compliance.
sedation
More so in the elderly. Greater in Phenanthrene derivatives than synthetic agents. Drowsiness, mental clouding, no amnesia.
antitussance
No correlation with analgesia or respiratory depression. Most potent with Codeine or Pholcodine. Dextromethorphan is preferred.
2 opioid receptor antagonists
Naloxone, Naltrexone
3 partial and mixed agonists
Butorphanol, Buprenorphine, Nalbuphine
7 synthetic opioids
Methadone, Meperidine, Fentanyl, Sufentanyl, Alfentanil, Ramifentanil, Diphenoxylate
5 naturally occuring opioids
Codeine, Morphine, and derivatives (hydromorphone, hydrocodone, oxycodone). Most widely used fo pain control (epidural, trauma, surgery)
Morphine
Naturally occuring. Hepatic metabolism - M3G to M6G (analgesic).
Hydromorphone
Widely used more potent Morphine derivative.
Codeine
antitussant, no euphoria, naturally occuring. Useful for mild to moderate pain. Hepatic deamination to Morphine by CYP2D6. Genetic alteration of CYP 2D6 and 3A4 voids analgesic effect.
Oxycodone
effective mild analogue of codiene.
Hydrocodone
effective mild analogue of codiene.
Pholcodine
potent antitussant
Dextromethorphan
Preferred to Codeine and Pholcodine bc - Low adverse effects, neuroprotective, useful in neuropathic pain.
Pentazocine
no associated euphoria
Methadone
Long plasma T1/2 - lipophilic and plasma protein binding. Chronic pain and terminally ill cancer patients. High risk of respiratory depression and QT prolongation - torsades de pointes.
Meperidine
poor oral bioavailability. Metabolites cause seizures. Similar efficacy to Morphine, but less potent. Causes mydriasis (contrast to other opioids)
Fentanyl
short acting, 100x more potent than morphine, highly lipophilic. Available in transdermal patch for slow delivery. Sufentanil, Alfentanil, and Ramifentanil.
Butorphanol
K agonist, Mu partial agonist yields analgesia with a milder euphoria. Opioid addiction Tx, and maintenance in balance anesthesia, labor pain.
Buprenorphine
K antagonist, Mu partial agonist. Moderate-severe long-term chronic pain management.
Nalbuphine
K agonist, Mu antagonist. High psychological dysphoria. Moderate-severe pain, pre and post-op, obstetrical analgesia.
Naloxone
Competetive antagonist ant Mu and K. Shorter T1/2 than Morphine. Parenteral administration. Opioid antidote whether known or suspected.
Naltrexone
Opioid antagonist. Oral admin. Outpatient settings. Tx - dependence, relapse, following detox, and prophylaxis. Alcohol withdrawal.
opioid respiratory depression
decrease sensitivity of chemosensitive neurons to PCO2. occurs at therapeutic doses. Most common cause of death in acute poisoning.
GI Disturbances
epigastric distress and biliary colic (confused with angina). Increse pyloric sphincter tone, enhance and decrease frequency of peristalsis - constipation.
miosis
diagnostic tool. Mu and K mediated. Involves edinger westphal nucleus.
N/V
involving area postrema
Hypotension and Bradycardia
impaired sympathetic response - orthostatic hypotension (morphine). Rapid IV admin of large dose causes non-specific mast cell degranulation. Synthetics and short-acting opioids generally do not evoke histamine release.
NSAIDs and Acetominophen
decrease prostaglandin synthesis and therefore pain sensation.
Antidepressants
Amitriptyline, Nortriptyline, and Imipramine - Tx of chronic pain that in not responsive to opioids. Venlafaxine and Duloxetine - used for neuropathic pain.
NMDA receptor antagonists
Ketamine and Dexamethorphan - chronic pain syndrome and post-op pain. Ketamine - acute severe pain, strong psychomimetic effects.
Adrenergic agonists
Clonidine - acute and chronic pain state. As well as withdrawal.
Gabapentin
synthetic GABA analog - inhibits voltage-gated Ca channels. Chronic pain and post-op pain state. Erratic oral bioavailability - has to be monitored.
Pregabalin
GABA analog - inhibits voltage gated Ca2+ channels in the CNS. Faster onset, more potent, and predictable bioavailability than Gabapentin. Neuropathic pain, fibromyalgia, spinal chord injury.
Lamotrigine
Na+ channel blocker. Tx - neuropathic pain, trigeminal neuralgia. Skin reaction - steven/johnsons.
Carbamazepine
Na+ channel blocker. Tx - trigeminal neuralgia. May cause Hypotension.
