narcotic analgesics

Question 1

effects/side effects

Answer 1

• mood alteration; reward
• neuroendrocine
• miosis (no tolerance developed)
• convulsions (lowered seizure threshold)
• depressed respiration
• antitussive
• nausea/emesis (no tolerance developed)
• constipation
• urinary retention
• vasodilation and urticaria

Question 2

absorption, metabolism, excretion

Answer 2

• rapid GI absoprtion
• conjugation with glucuronic acid in liver
• excreted by kidney
• ** kidney or liver damage can result in toxic levels

Question 3

Time to Cmax for po, SC/IM, IV

Time to steady state

Answer 3

• po= 1 hour
• SC/IM = 30 mins
• IV = 6 mins
• SS= 24 hrs

** IV reaches Cmax first then drops off 1st, SC/IM is 2nd then po/pr

Question 4

Morphine

Answer 4

• 2 major metabolites – morphine-6-glucuronide is the active one
• M-3-glucuronide has litter receptor affinity

Question 5

codeine

Answer 5

• analgesia is from conversion to morphine (only 10% is demethylated to morphine)
• conversion via CYP2D6 (10% of caucasians can’t convert and experience SE w/o analgesia)
• antitussive action

Question 6

tramadol

Answer 6

• synthetic codeine analog, weak mu agonist
• demethylated metabolite is more potent
• part of analgesia from inhibition of NE and 5HT reuptake
• less effective for severe pain
• less constipating

Question 7

Fentanyl

Answer 7

• very potent, very long t1/2
• more lipid soluble than morphine –> stores in subQ fate –> delayed effect and toxicity
• wait 7 days betweeen dose changes
• transdermal patch

Question 8

methadone

Answer 8

• long duration of action
• 90% bound to plasma protein –> accumulation in tissues
• tx: chronic pain and Heroin users
• adjust dose every 4-7 days

Question 9

oxycodone

Answer 9

• very effective, very potent oral analgesic
• oxycontin = long-acting form

Question 10

Meperidine

Answer 10

• metabolite toxicity (normeperidine) so not in use anymore
• analogs used for diarrhea

Question 11

Naloxone

Answer 11

• opioid antagonist
• tx opioid toxicity

Question 12

Naltrexone

Answer 12

• opioid antagonist
• tx alcoholism

Question 13

max dose of acetaminophen

Answer 13

3000 mg/24 hrs

Question 14

routine oral dosing for immediate-release preps

Answer 14

every 4 hours

Question 15

routine oral dosing for extended-release preps

Answer 15

every 12 hours

dont crush or chew tablets

Question 16

breakthrough dosing

Answer 16

• use immediate-release opioids
• dose = 10% of total 24 hr dose
• offer after CMax reached ( every hr for po, every 30 min for SC/IM and every 10-15 mins for IV)

Question 17

equianalgesic dosing

Answer 17

• converting between routes of administration or converting between opioids
• significant 1st pass metabolism for po/or so oral doses are usual 2-3 times higher than parenteral doses
• if cross-tolerance (usually incomplete): start with 50-75% of of the calculated equianalgesic dose when switching formulations
• for methadone and fentanyl start much lower (10%)

Question 18

summary slides

Answer 18

• mechanism of action via GPCRs
• extended release preps improve adherence and analgesia
• no ceiling for analgesia- usually limited by SE (NSAIDs do have a ceiling)
• tolerance occurs with all SE but constipation (and miosis) –> always start stool softner and stimulant laxative with opioids
• caustion with long acting formulations fentanyl and methadone