Lecture 13 (+14) - opioids Flashcards
Use of opioids when pain - advantages and disadvantages
Advantages - risk prevention - support healing? Disadvantages - catabolic state - loss of appetite - respiratory depression, circulation (anesthesia) - delayed wound healing
Pharmacological effects of opioids
- analgesia (!)
- nociception, Ø nerve fiber (act on site on injury, prevent nerves from working)
- sedation
- euphoria (dysphoria)
- cough relief
- antidiarrheal
What are the 3 stages of reaction?
- peripheral (+)
- spinal (! +++)
- supraspinal (++)
Effects on μ-opioid receptor (MOR)
- specific, strong analgesic effect (best sc)
- slight sedation (Ø cat)
- brainstem –> inhibiting impulses of the respiratory centers (pCO2 sensitivity down) –> respiratory depression (most imp side effect)
- -> doxapram IV to stimulate
- antitussive
- brainstem vasomotor center –> bradycardia
- -> atropine to stimulate
- inhibition of plexus myentericus –> obstipation –> vomiting
- medulla oblongata CTZ –> emesis
Effect on κ-opioid receptor (KOR)
- slight analgesic effect (sc)
- slight sedation
- dysphoria (cat)
Effect on δ-opioid receptor (DOR)
- analgesia (sc)
- most important in the eye (cornea)
–> only if damaged (1% morphine eye
drops)
Definition of full agonist + example of drug
- binds to and activates receptor and produces a maximum effect
- morphine, fentanyl, methadone on μ-opioid receptor
Definition of partial antagonist + example of drug
- binds to receptor but only have a moderate effect
- buprenophine (used if morphine/fentanyl overdose, higher affinity to receptor) on μ-opioid receptor
Definition of full antagonist + example of drug
- binds to receptor but have no effect
- naloxone (dont like) on both major receptors
Pharmacokinetics of opioids
- absorption
- distribution
- metabolism
- absorption: good excellent
- per os: first pass metabolism (heroin,
morphine, buprenorphine) - fentanyl: very lipophilic, skin (transdermal
patch)
- per os: first pass metabolism (heroin,
- distribution: max effect: 15-45 min morphine
(iv (15), im (30), sc (45))
2-3 min fentanyl
45 min buprenorphine (peak when 45) - metabolism: frequent activation (liver):
morphine –> morphine-glucuronide
(Fe, active metabolite)
tramadol –> O-desmethyltramadol (Fe)
remifentanyl: plasma esterases (very safe)
Side effect of opioids?
- respiratory depression
full agonist >> partial agonist
buprenorphine: "ceiling effect" (very safe)
- emesis: CTZ
- bradycardia --> but! CV risk patients
- obstipation
inhibition of plexus myentericus
decreased pancreas secretion
- histamine release
morphine >> fentanyl
iv: carefully! (infusion, ACP
- hyperthermia
- dysphoria (cats)
ACP, BDZMorphine
-intermediate duration of action (2-6 h)
- sedation, respiratory depression, bradycardia, emesis
- IV slowly!, IM 100% bioavailability
- 0.1-0.8 mg/kg IM –> at least 4 h postop. analgesia
TI = 460
Fentanyl
- short duration of action (15-30 min)
- sedation, respiration depression, bradycardia
- IV bolus or infusion pump
- transdermal patch (ca: 24 h, fe: 12h)
- other: sufentanyl, remifentanyl (safe but expensive)
Tramadol
- weak full agonist (not as strong as morph/fenta)
- intermediate duration of action (4-6 h) delayed release tablets
- rare side effects
- oral dose: ca 4-10, fe 2-4 mg/kg
- approx. 65 and 90% absorption po
- analgetic + dry cough relief
Buprenorphine
- long duration of action, appears slowly
- moderate analgesia (“ceiling effect”)
- very slight sedation
- respiratory depression: “ceiling effect”
- P.O. first pass effect
- partial agonist –> pronounced receptor binding –> decreases analgetic effect of full agonoists –> postoperative usage
- -> soft tissue surgery: anytime
- -> pancreatitis
