Narcotic analgesics Flashcards
Endogenous opioid peptides are
endorophins; its precursor has commonality with ACTH, MSH, b-LPH (ACTH could account for stress analgesia);
they will
1. inhibit responses to painful stimuli
2. Modulate GI, endocrine, autonomic function
3. Rewarding (addicting) propertiesr
Where can you find opioid receptors? What do agonists to opioid receptors do?
- Brain, spinal cord, and peripheral nerves
- Inhibit release of substance P and inhibit ascending transmission from dorsal horn; also activate pain control circuits descending from midbrain
Opioid receptors are ____, and they activate and inhibit which channels respectively?
GPCR; they activate receptor-operated K currents and suppress voltage-gated Ca currents!!!
Major opioid receptor subtype?
Mu, or MOR: most important for analgesia and the most prescribed opioids are selective for mu!!
What does tolerance entail?
Decreased effectiveness with repeated administration (could involve phosphorylation or receptor internalization in short term, other mech’s in long term)
Routes of administration of narcotic analgesics:
- Rapid GI absorption (sublingual, oral, rectal)
- also SC, IM, IV, epidural and intrathecal
- Orally: FIRST PASS METABOLISM BY LIVER;
conjugation with glucuronic acid in liver and excreted by kidney, so NEED both liver and kidney to be normal functioning
Which route of admin is quickest for opioids? What is the half-life at steady state and duration of effect of most immediate release formulations except methadone?
IV = 6 min; SC, IM = 30 min; PO = 1 hr;
half-life at SS for po, pr, SC, IM, IV = 3-4 hr;
SS after 4-5 .5 lives, or about ONE DAY; duration of effect is 3-5 hrs po/pr
Bolus effect is; solution?
swings in plasma concentration where one is drowsy .5-1 hr after ingestion and you have pain before the next dose given; move to EXTENDED release prep and continuous SC, IV infusion
For routine oral dosing of immediate-release preps,
dose every 4 hours and adjust the dose daily, especially for severe uncontrolled pain (codeine, hydrocodone, morphine, hydromorphone, oxycodone)
For extended-release preps and dosing
- we see IMPROVED COMPLIANCE, adherence
- Dose every 8, 12, or 24 hours; adjust dose every 2-4 days as the SS is reached; for METHADONE, dose every 4-7 days!! (long half life and risk of OD)
For breakthrough dosing use
immediate-release opioids (10% of 24 hr dose) which you offer after Cmax has been reached; do NOT use extended release opioids
Mixed agonists-antagonists include ____ and are
pentazocine, butorphanol, nalbuphine, dezocine; NOT RECOMMENDED (compete with agonists and can lead to withdrawal); there is NO analgesic ceiling effect but there is a ceiling based on SE's
______ can develop to most SE’s over time except
constipation and also the pinpoint pupils!!
Physical dependence is a; how to avoid?
process of neuroadaptation; reduce dose by 50% every 2-3 days, and ANTAGONISTS will cause abrupt withdrawal symptoms
In the case of pain poorly responsive to opoids
dose escalation could lead to adverse effects;
INSTEAD, try alternative route or rotate opioids;
you might even want to try a coanalgesic (antidepressant) or a nonpharmacologic approach
With equianalgesic dosing, what could be necessary? List some alternative routes of admin:
- Need to convert to alternative routes of delivery and convert between opioids while MAINTAINING ANALGESIA, which requires conversion of doses from po/pr to SC/IV/IM and vice versa;
enteral feeding tubes, transmucosal, rectal, transdermal, parenteral (SC, IM, IV, bolus vs. continuous), and then epidural vs. intrathecal
With changing opioids, what do you have to account for?
INCOMPLETE cross-tolerance (so start with 50-75% equianalgesic dose); if methadone and fentanyl, start with much lower, like 10%!!!
If a patient presents with delirium, what would this show? How could you minimize risk?
Confusion, bad dreams/hallucinations, restless and agitated, myoclonic jerks, depressed LOC, respiratory depression;
follow dosing guidelines and CHECK LIVER AND KIDNEY;
Sedation can start with
onset of opioids, but tolerance usually develops within several days; if persistent change opioid or route or even give PSYCHOSTIMS
LOC precedes
respiratory depression, but tolerance is rapid;
manage: maybe reduce opioid dose, but if unstable vital signs, O2 sat, CO2 retention, use NALOXONE!!
If urticaria or pruritis emerges:
due to mast cell destabilization by morphine, hydromorphone;
treat with long-acting, nonsedating anti-H1’s: loratidine and fexofenadine!!
Constipation is common to all opioids and should be treated with
stimulant laxative (e.g. senna) and combined with a stool softener (now senna PLUS docusate sodium); osmotic laxatives like milk of magnesia could work, but start the first two once you START THE OPIOID!!
What should we know about CNCP and opioids?
Widespread prescriptions for CNCP has resulted in increasing substance abuse;
could cause unintentional and intentional overdose, increased numbers of ER visits related to drug OD, and overtreatment of chronic pain
Morphine
Class: Opioid
Mech: Mu-opioid receptor agonist
Thera: Severe analgesia, mood alteration, antitussive, sedation
Important SE’s: Miosis, constipation, respiratory depression
Other SE’s: Dry mouth, nausea/vomiting, sedation, sweating; dreams, dysphoria, delerium, myoclonus, seizures, pruritis, urticaria, urinary incontinence
Misc: 2 major active metabolites: M6 (more potent/active), M3 (little affinity); intraspinal administration possible
Codeine
Class: Opioid
Mech: Mu-opioid receptor agonist (low receptor affinity); demethylated to form morphine (10% of oral ingestion, via CYP2D6)
Thera: Moderate analgesia, antitussive (found in many cough medicines)
SE’s same as morphine
Misc: 10% of Caucasians unable to convert codeine to morphine (can still experience side effects, though)
Tramadol (Ultram)
Class: Opioid
Mech: Mu opioid receptor agonist (weak); some NE/5HT uptake inhibition (leading to analgesia); synthetic codeine analog
Thera: Moderate (not severe) analgesia
SE’s same as mor
Misc: 1 metabolite: demethylated, more potent analgesic
Fentanyl (Duragesic)
Class: Opioid
Mech: Mu-opioid receptor agonist (strong); highly lipid-soluble
Thera: Severe analgesia after identification of dose level via other opiod (e.g., morphine)
SE’s: same as mor
Misc: IV, transdermal; do not change dose more than 1/week (long half-life); intraspinal administration possible; might not be effective with THIN patient
Methadone (Methadose)
Class: Opioid
Mech: Mu-opioid receptor agonist
Thera: Chronic, severe pain; treatment of heroin and opiod addicts
SE’s: same as mor
Misc: 90% bound to plasma protein, accumulates in tissues (thus, extended duration of action); do not change dose more than 1/week (long half-life)
Oxycodone
Class: Opioid Mech: Mu-opioid receptor agonist Thera: Moderate to severe analgesia SE's same as mor Misc: Oxycontin is extended release (seen widespread abuse and OD's)
Meperidine (Demerol)
Class: Opioid
Mech: Mu-opioid receptor agonist
Thera: Don’t use this (metabolite toxicity)
IMportant SE’s: Miosis, constipation, respiratory depression; mental status changes and seizures (normeperidine)
Misc: 1 metabolite: normeperidine
Naloxone (Narcan)
Class: Opioid antagonist
Mech: Competitive mu-, delta-, and kappa-opioid receptor antagonist
Thera: Acute opioid toxicity (depressed RR best predicts reponse)
Important SE’s: Can precipitate withdrawal (flu-like symptoms of nausea, vomiting, diarrhea; piloerection, yawning, irritability)
Misc: Continuous parenteral infusion, as lasts only 15-30 minutes (oral almost completely metabolized by liver); patient has normal mental status
Naltrexone (Revia)
Class: Opioid antagonist
Mech: Mu-opioid receptor antagonist
Thera: Alcoholism
Important SE’s: May produce a prolonged withdrawal state (nausea, vomiting, piloerection, yawning)
