Komiskey Opioid Analgesics Flashcards
Meperidine
MOA: activation of mu receptors -1/3 potency of morphine
CNS, PNS of bowels
Post anesthetic shivering, adverse effects like morphine
Normeperidine-CNS excitation
Absorption: 50% 1st pass, BBB crosses more readily
Diphenoxylate
Meperidine congeners
Treatment of diarrhea-constipation
High doses = typical opioid
Loperamide
Meperidine congeners
Anti diarrheal
Slows gastric motility, decreased GI secretion
Poor BBB penetration
Oxymorphone
10x more potent than morphine Pain relief = 2-6 hrs No vomit or histamine Less depressant on respiratory Anticholinergic given to prevent bradycardia
Fentanyl
75-200 more potent
Duration=45-60 minutes
Bardyarrhythmias, respirator distress more than morphine
Mu agonists
Sufentanil
Like fentanyl
500-1000 times more potent
Alfentanil and remifentanil
Remi= equipotent with fentanyl/ metabolized by esterase 20 mins 1/2
Alfentanil= 20-30 less / liver metabolized 1-2hr 1/2 life
1 min onset
Piperidines
Alfentanil and remifentanil
Used for short, painful procedures
Pharmacokinetics of opiates
Absorption: most opiates are rapidly absorbed in GI tract
High first pass metabolism
Highly lipophilic = transdermal
Distribution: binds plasma proteins at various levels
Rapidly leave blood to concentrate other tissues
Excretion= kidney
Morphine
Metabolism: glucuronide metabolism
Morphine-6-glucuronide=active metabolite 2x potency
1st pass is significant
1/2 life= 2hrs / pain suppression is 4-7 hrs
Elimination: metabolized and renal
Acute morphine poisoning
Coma, miosis, cyanosis Asphyxia Biliary spasms, GI smooth muscle spasm Pulmonary edema Muscle twitches, peripheral vasodilation, hypotension and shock Respiratory failure- 2-4 hrs
Intrabuccal fentanyl
Oralet- administer fentanyl painlessly to kids and adults undergoing procedure
Actiq- cancer pts w/ breakthrough pain
15-20 mins, lasts 1-2 hrs
Patches used for chronic pain: duration 72 hrs
Oxycodone
Pure oxycodone inside matrix with controlled release
Abusers crush tablet and destroy matrix -attractive to addicts
Metabolized to oxymorphone, then noroxymorphine, then noroxycodone
8-12 hrs
Codeine
10% of codeine converted to morphine Less resp, dependence, and euphoria Moderate pain and antitussive Hugh oral efficacy, slow dev of tolerance Max analgesia= 12-15% morphine
Tramadol
Codeine analog MOA: NE and 5HT reuptake blockade Weak mu agonist, racemic mixture 68% bioavailability oral vs parenteral N/V, dizzy, sedation and HA, seizures Metabolism: liver o methylation - metabolite more potent 1/2 life 6 hours, 7 1/2 for metabolite Elimination- renal
Hydrocodone
Synthetic similar to codeine and more potent
Highest prescribed drug in USA, highly abused
Pentazocine
Opioid receptor mixed agonist/antagonist
1/3 potent as morphine
K agonist and delta partial
Oral: shorter duration and faster onset than morphine
Buprenorphine
Potent long acting phenanthrene derivative
M partial agonist, mu and delta antagonist
High affinity and stays at receptor longer
Naloxene hydrochloride
Opioid antagonist
Reverses effect of opioid (including analgesia)
Does not produce respiratory or cardiovascular depression
Give to addicts
Almost pure antagonist
Reverses coma and resp distress w/n 30 secs but short duration of action
Naltrexone
Pure antagonist
Longer duration of action than naloxone
Methylnaltrexone
For opioid induced constipation Pts with advanced illness Contraindications: - mechanical bowel obstruction -stop if opioids are discontinued - dizziness - concomitant with SSRI, lithium, carbamazepine or valproic acid - caution with severe renal failure
Buprenorphine pharmacology
Partial agonist, tight binding mu Ceiling effect on respiratory depression Less physical dependence Blocks withdrawal in mildly dependent/ precipitates in moderate to severe 20-50 times potency of morphine
Methadone
Full opiate agonist on mu receptor
Inhibit adenylate cyclase
Increase K channel, decrease Ca channel
Inhibit serotonin reuptake, non competitive antagonist NMDA receptor
Opiate dependence
Methadone
Buprenorphine
Naltrexone
