44 terms

Opioids*

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Primary locations of opioid action (2)
Raise pain threshold at spinal cord (via action of ascending pain pathways); Modulate or alter pain perception in brain (via descending inhibitory pathways); also increase release of endogenous opioids
Endogenous opioids (3)
Enkaphalins; Beta-endorphins; dynorphins
Subtypes of opioid receptors (3) - which is most important in analgesia?
μ (mu) - most important in analgesia; κ (kappa); δ (delta)
All opioid receptors are ________.
G-protein coupled
Stimulation of opioid receptors results in inhibition of the conversion of ____ to _____ by ______
ATP; cAMP; Adenylyl cyclase
Postysnaptic ionic mechanism of action of opioids
hyperpolarization via potassium efflux
Preysnaptic ionic mechanism of action of opioids
inhibits release of substance P and other neurotransmitters (e.g., glutamate) via voltage-gated calcium channel closing
Strong opioid agonists (10)
Morphine; methadone; fentanyl; hydromorphone; oxymorphone; meperidine; oxycodone; sufentanil; alfentanil; remifentanil
Clinical applications of strong opioid agonists
Severe pain • adjunct in anesthesia (fentanyl, morphine) • pulmonary edema (morphine only) • rehabilitation programs (methadone only)
Unique points about meperidine (4)
Anticholinergic effects; Use with SSRIs increases risk of serotonin syndrome; not for chonic pain management; effects not fully reversed by naloxone
Which opioids are metabolized via CYP3A4 (2)
Oxycodone; fentanyl;
Which opioids are metabolized via CYP2D6? (3)
Oxycodone; codeine, hydrocodone
Moderate opioid agonists (2)
Codeine; hydrocodone
The toxicity of which opioids is highly dependent on genetic variation of metabolism? (2)
Codeine; hydrocodone
Parital mu agonist and kappa antagonist (1)
Buprenorphine
Kappa agonist and mu antagonist (3)
Nalbuphine, butrophanol; pentazocine
Hydrocodone active/inactive? Active metabolite?
Hydrocone is active and is converted to hydromorphone (active) via CYP2D6
Codeine active/inactive? Active metabolite?
Codein is a prodrug metabolized to morphine via 2D6
Opioids and related agents used as antitussives (i.e., cough suppressants)
Hydrocodone; codeine; dextromethorphan (OTC)
Side effects of dextromethorphan at supratherapeutic doses
"Large doses can cause hallucinations, confusion, excitation, nystagmus, seizures, coma, and decreased breathing"
Antidiarrheal opioids (2)
Diphenoxylate (w atropine); loperamide (OTC)
When should antidiarreal opioid NOT be used?
diarrhea due to Shigella, Salmonella, toxigenic Escherichia coli, campylobacter jejuni, or Clostridium difficle
Why is diphenoxylate combined with atropine
Deter abuse - atropine can cause unpleasant anticholinergic effects
Opioid antagonists (5)
Naloxone; naltrexone; nalmefene; methylnatrexone; naloxegol
Which opioid antagonist is primarily used for opioid overdose?
Naloxone - may need to be repeated due to short half life (~1-2 h)
Which opioid antagonist is used in rehabilitation programs and can block heroin effects fro upt to 48 h?
Naltrexone
Which opioid antagonists have poor entry into CNS and can be used to treat severe opioid-induced constipation without precipitating abstience sydrome? (2)
Methylnatrexone; naloxegol
Other analgesics used in moderate pain (2)
Tapentadol; tramadol
Tapentadol MOA
Moderate μ agonist, strong NET (norepinephrine reuptake transporter) inhibitor
Tramadol MOA
Mixed effects: weak μ agonist, moderate SERT (serotonin reuptake transporter) inhibitor, weak NET (norepinephrine reuptake transporter) inhibitor
Acute effects of opioid agonists (~10)
"Analgesia | Sedation | Euphoria; Respiratory depression - inhibit respiratory center in the medulla; Antitussive action - mechanism unknown (different receptors?); Nausea/vomiting - activate chemoreceptor trigger zone in medulla oblongata; Constipation - decrease peristalsis = delayed GI transit time; Miosis; Smooth muscle* (SM) - contract biliary SM, ↑ ureteral, bladder, & anal sphincter tone, ↓ uterine tone (may prolong labor) ; Flushing, pruritus - ↑ histamine release (esp. morphine); hypotension"
Opioids - Chronic effects (~2)
Tolerance and dependence
Tolerance does not develop to what acute effects of opioids? (2)
Miosis; constipation
Describe opioid cross-tolerance
Some cross-tolerance, but not complete. "Opioid rotation" may help maintain analgesia. When switching, choose lower than equipotent dose, initially.
Withdrawal symptoms usually begin ~__ hours after the last dose and peak at ___-___ hours
8; 36-48
Symptoms of opioid withdrawal, with time-frame
Up to 8 hours: anxiety; drug craving | 8-24 hours: anxiety, insomnia, GI upset, Rhinorrhea, Mydriasis, Diaphoresis | Up to 3 days: Tachycardia; nausea/vomiting; hypertension; diarrhea; fever; chills; tremors; seizures; muscle spasms
General contraindications to opioid agonists and agonist-antagonist
"Hypersensitivity ; Acute or severe bronchial asthma (e.g., status asthmatics); Severe respiratory depression; GI obstruction or paralytic ileus (Inability of the intestine to contract normally and move waste out of the body); Head injury - Opioids can increase intracranial pressure, thereby exacerbating injury"
Which drugs can worsen opioid withdrawal symptoms?
Opioid antagonists and agonist-antagonists
Opioid agonists and agonists-antagonists precautions
"Exaggerated response may occur in adrenal insufficiency or hypothyroidism; Avoid strong opioids in opioid naïve or non-tolerant patients; Caution in history of drug abuse or addiction; Renal dysfunction; Hepatic dysfunction; Elderly"
Opioid agonists and agonists-antagonists major drug interactions
"Other CNS depressants = additive effects (ethanol, benzodiazepines, barbiturates, muscle relaxers, anesthetics, tricyclic antidepressants, and antihistamines); Applicable combination products - ensure patient knows it contains acetaminophen; Tramadol and meperidine - increased risk of serotonin syndrome with(in): selective serotonin reuptake inhibitors (SSRIs) (fluoxetine, sertraline, paroxetine, escitalopram, citalopram) 14 days of monoamine oxidase inhibitors (MAO-Is) (selegiline, phenelzine)"
Opioid overdose triad of symptoms
"pupillary constriction (i.e., miosis); comatose state (i.e., deep unconsciousness); respiratory depression"
Opioid overdose treatment
"Ventilator support (bag-valve mask) and Naloxone - admin IV"
Opioids used in maintenance rehabilitation programs (~3)
Methdane; buprenorphine (w or without naloxone or naltrexone); naltrexone
Main uses of mixed opioid agonists-antagonists
Moderate pain; thought to have lower addiction potential; Buprenorphine aslo used in some maintenance rehabilitation programs