Opiod agonists and antagonists Flashcards
MOA of opioid analagesics
agonists at opiod receptors, inhibitory signalling
blocks pain transmission and response
raises pain threshold
anti-anxiety effect
Receptor subtypes activated by morphine
mu, kappa, delta
pharmacokinetics of morphine
Rapid acting, 5-15 min
Maximum effect within 60-90 min
half-life 2.5-3 hrs
lasts 4-5 hrs
Standard dose of morphine
10 mg i.m. s.c. , 7 mg for elderly/ children
Metabolism of morphine
High level of first pass metabolism
Glucuronic acid conjugation
renal clearance of metabolites, caution with impared liver or renal function
Mechanism of respiratory failure in morphine OD
decreased sensitivity to plasma CO2
hypoxic response still intact
tolerance develops with analgesia tolerance
“First dose effect of morphine”
nausea and vomiting
GI effects of morphine
constipation, little or no tolerance, major problem with chronic use. Naltrexone.
Minor side effects of morphine
Miosis
Euphoria, tranquility
Pruritis
Mild CV, orthostatic hypotension
Therapeutic use of morphine
moderate to severe pain
primarily in acute pain
chronic pain use is discouraged except in terminal disease
Other: sickle cell crisis, end stage lung cancer and other terminal pain (and COPD)
Additional side effects and precautions of morphine (5)
biliary colic, increase urinary tract pressure allergic reactions dysphoria, excitement neonates and aged more sensitive dependence
Drug interactions with morphine (2)
CNS depressants
Ethanol and long release preps
Limitations and contraindications or morphine (3)
decreased respiratory reserves
head injuries
pregnancy
Advantages of codeine
more orally reliable
effective cough suppressant
Disadvantages of codeine
more constipation
Therapeutic use of codeine
mild to moderate pain
Advantages of methadone
very reliable orally
long half life
full agonist- same effect as morphine
Disadvantages of methadone
may prolong Q-T interval
metabolized by CYP 3A4
Also abused like morphine
Advantages of fentanyl
full agonist like morphine
potent, short acting
can be used transdermally for chronic pain
lozenge/film/tablet for breakthrough pain
less effect on cardiovascular system
Disadvantages of fentanyl
more likely to produce muscle rigidity of chest and abdominal muscles
Hydrocodone highlights
similar to codeine, #1 prescription, major abuse problem
Oxycodone highlights
more potent than codeine, abuse of timed release formulation
Therapeutic use of loperamide
anti-diarrheal agents, full opiod agonists, but do not cross membranes readily
Dextromethorphan highlights
chemically similar to opioids, effective cough suppressant, no analgesia, abuse increasing
Meperidine highlights
excitatory, at high doses with chronic use due to long lasting metabolite, less effect on GI tract. Can be used IV for infusion related rigors and chills
Advantages of mixed agonist-antagonist, partial agonists
ceiling in both respiratory depression and pain analgesia
Disadvantages of partial agonists
most have kappa receptor side effects, dysphoria
Pentazocine compared to morphine
limited analgesia, resp depression
more reliable orally
antagonist properties in dependence
Therapeutic use of pentazocine
analgesia in moderate to severe pain, not used chronically due to dysphoria
Buprenorphine summary
partial agonist at mu receptors- similar effects as morphine
antagonist at kappa receptors- no dysphoria
may prolong Q-T interval
Therapeutic use of buprenorphine
moderate to severe pain
to treat opiod dependence
MOA of tramadol
weak mu agonist, inhibits NE and 5HT
Therapeutic use of tramadol
can produce dependence, seizures, serotonin syndrome seen. suicide risk, drug interactions. No advantage clinically
Naloxone MOA
blocks opiate receptors
Therapeutic use of naloxone
used for overdose/high dose treatment
precipitate withdrawal in opiate dependence
Diagnosis of opioid overdose
respiratory depression
miosis
coma
Opiod overdose treatment
- support respiration
- prevent absorbance if taken orally
- naloxone IV repeatedly at short intervals
