Opioid Analgesics

Front 1

Opioid Drugs
1. Agonists
2. Partial Agonists
3. Mixed Agonists/Antagonists
4. Antagonist

Back 1

1. morphine, hydromorphone, oxymorphine, codeine, oxycodone, hydrocodone, dihydrocodeine, methadone, meperidine, fentanyl, sufentanil, alfentanil, remifentanil
2. buprenorphine
3. pentazocine, nalbuphine, butorphanol
4. naloxone, nalmefene

Front 2

Actions of Opiod Receptors
1. mu 1
2. mu 2
3. delta
4. kappa

Back 2

1. supraspinal analgesia
2. respiratory depression, CV and GI effects, spinal nalgesia, miosis, dependence
3. spinal and supraspinal analgesia
4. spinal analgesia, sedation, dysphoric effects, some miosis and resp depression

Front 3

MOA of Opioid Analgesics

Back 3

1. bind opioid receptors (mu, delta, kappa) which are coupled to G proteins
2. causes conformational change and protein activation
3. inhibits adenyl cyclase

Front 4

Which opioid receptors do they act on?
1. pure opioids (morphine)
2. mixed or partial agonists (pentazocine, butorphanol, buprenorphine)
3. nalbuphine, nalorphine
4. nalaxone

Back 4

1. agonists at mu and kappa
2. partial agonists at mu, agonists at kappa
3. antagonists at mu, agonists at kappa
4. antagonist at all receptors (more potent at mu)

Front 5

Central Actions of Opiod Analgesics

Back 5

1. analgesia: no ceiling effect
2. sedation
3. respiratory depression: cause of death
4. cough suppression: codeine, dextromethorphan
5. miosis: pinpoint pupils, no tolerance, due to parasymp
6. N/V: stimulates CTZ, more common in ambulatory pts
7. seizures: merpiperidine generates convlusive metabolites (normeperidine), propoxyphene
8. endocrine: dec LH, FSH, ACTH, inc prolactin

Front 6

Peripheral Actions of Opiod Analgesics

Back 6

1. cardiac: vasodilation, decrease preload (pulm edema tx),orthostatic hypotension
2. GI: decreases emptying/motility in all segments (constipation), no tolerance
3. bladder: increases tone (inhibits voiding reflex)
4. uterus: prolong labor, post oxytocics
5. skin: flushing, itching (histamine release)

Front 7

Morphine

Back 7

pure opioid, gold standard, can give IV, SQ, PO, rectal, hepatic metabolism via glucuronic acid conjugation

Front 8

Heroin

Back 8

pure opioid, rapid high, heroine>MAM>morphine (morphine prodrug)

Front 9

Codeine

Back 9

pure opioid, antitussive, combined with acetominophen (Tylenol 3), 10% metabolized to morphine via CYP2D6

Front 10

Meperidine

Back 10

pure opioid, anti-muscarinic axn, short acting, active metabolite (normeperidine) may cause seizures

Front 11

Levorphanol

Back 11

pure opioid, long half life, oral, risk of accumulation so titrate carefully

Front 12

Methadone

Back 12

pure opioid, long half life, maintenance programs, NMDA antagonist activity (neuropathic pain)

Front 13

Oxycodone

Back 13

pure opioid, oral, combined with acetominophine (Tylox)

Front 14

Propoxyphene

Back 14

pure opioid, for mild pain not responsive to aspirin, combined with acetominophin (Darvocet)

Front 15

Fentanyl

Back 15

pure opioid, 60-80X mroe potent than morphine, can get as patch, lollipops, good for chronic pain, similar to sufentanil but sufentanil is 5-10x more potent, can be used for anesthesia

Front 16

Pentazocine, Butorphanol

Back 16

mixed action opioid, CV effects (elevated aortic pressure, inc cardiac work- don't give for MI pain), respiratory depression ceiling present, abused with amphetamines, may have psychomimetic effects at high doses (weird thoughts, hallucinations, etc), available as nasal spray for migraines (butorphanol)

Front 17

Nalbuphine

Back 17

mixed action opioid, not as many CV effects (ok for MI pain), used a lot for post-surgical pain, respiratory ceiling effect

Front 18

Buprenorphine

Back 18

partial agonist opioid, 25-50 more potent than morphine, acts similarly to morphine but can actually displace morphine from the mu receptor (antagonist action), slower onset and longer duration of action compared to morphine

Front 19

Tramadol
1. relation to opioids
2. MOA
3. derived metabolite
4. SE, dosing
5. ceiling effect
6. addiction
7. effects

Back 19

1. chemically unrelated to opioids
2. binds mu, inhibits 5HT and NE uptake
3. M1: more potent analgesic and more potent in bindign receptors
4. seizures, adjust dose for poor kidney function
5. ceiling effect present
6. not scheduled narcotic, but is proving to be addictive
7. less respiratory depression, minimal cardiac effects

Front 20

Potency and Availability of Opioids
1. oral administration
2. Ceiling Effect

Back 20

1. poor systemic absorption or high first pass (high oral/parenteral potency ration)
2. Absent in pure opioids (can keep increasing dose to see increasing analgesia), present in mixed action agents

Front 21

General Side Effects of Opioids

Back 21

-mood changes
-somnolence
-CTZ stimulation (N/V)
-respiratory depression (don't respond to inc CO2 levels)
-constipation
-inc sphincter tone (urinary retention, biliary spasm)
-histamine release (pruritis)
-seizures (esp meperidine, propoxyphene)
-hypotension
-tolerance (none for GI or miosis)
-dependence (withdrawal w/ abrupt discontinuation: tremor, anxiety, tachy, BP, etc)

Front 22

Opioid Poisoning
1. triad
2. specific antidote

Back 22

1. miosis (pinpoint pupils), respiratory depression, sedation
2. Naloxone: competitive opioid antagonist, IV only, may have to repeat since it's DOA is shorter than most opioid agonists

Front 23

Opioid Drug Interactions

Back 23

-CNS depressants, antipsychotics, antidepressants, antihistamines
-antidiarrheals (inc risk of constipation)
-anticholinergics (inc constipation, urinary retention)
-antihypertensives (hypotension)
-metoclopramide (GI effects are antagonized by opioids)
-MAO inhibitors