Komiskey Opioid Analgesics

Question 1

Meperidine

Answer 1

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

Question 2

Diphenoxylate

Answer 2

Meperidine congeners
Treatment of diarrhea-constipation
High doses = typical opioid

Question 3

Loperamide

Answer 3

Meperidine congeners
Anti diarrheal
Slows gastric motility, decreased GI secretion
Poor BBB penetration

Question 4

Oxymorphone

Answer 4

10x more potent than morphine 
Pain relief = 2-6 hrs 
No vomit or histamine 
Less depressant on respiratory 
Anticholinergic given to prevent bradycardia

Question 5

Fentanyl

Answer 5

75-200 more potent
Duration=45-60 minutes
Bardyarrhythmias, respirator distress more than morphine
Mu agonists

Question 6

Sufentanil

Answer 6

Like fentanyl

500-1000 times more potent

Question 7

Alfentanil and remifentanil

Answer 7

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

Question 8

Piperidines

Answer 8

Alfentanil and remifentanil

Used for short, painful procedures

Question 9

Pharmacokinetics of opiates

Answer 9

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

Question 10

Morphine

Answer 10

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

Question 11

Acute morphine poisoning

Answer 11

Coma, miosis, cyanosis 
Asphyxia
Biliary spasms, GI smooth muscle spasm 
Pulmonary edema 
Muscle twitches, peripheral vasodilation, hypotension and shock 
Respiratory failure- 2-4 hrs

Question 12

Intrabuccal fentanyl

Answer 12

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

Question 13

Oxycodone

Answer 13

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

Question 14

Codeine

Answer 14

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

Question 15

Tramadol

Answer 15

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

Question 16

Hydrocodone

Answer 16

Synthetic similar to codeine and more potent

Highest prescribed drug in USA, highly abused

Question 17

Pentazocine

Answer 17

Opioid receptor mixed agonist/antagonist
1/3 potent as morphine
K agonist and delta partial
Oral: shorter duration and faster onset than morphine

Question 18

Buprenorphine

Answer 18

Potent long acting phenanthrene derivative
M partial agonist, mu and delta antagonist
High affinity and stays at receptor longer

Question 19

Naloxene hydrochloride

Answer 19

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

Question 20

Naltrexone

Answer 20

Pure antagonist

Longer duration of action than naloxone

Question 21

Methylnaltrexone

Answer 21

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

Question 22

Buprenorphine pharmacology

Answer 22

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

Question 23

Methadone

Answer 23

Full opiate agonist on mu receptor
Inhibit adenylate cyclase
Increase K channel, decrease Ca channel
Inhibit serotonin reuptake, non competitive antagonist NMDA receptor

Question 24

Opiate dependence

Answer 24

Methadone
Buprenorphine
Naltrexone