Pain medications

Question 1

Definition of pain

Answer 1

unpleasant sensory and emotional experience associated with actual/potential tissue damage

Question 2

Analgesia

Answer 2

absence of pain in response to stimulation which would normally be painful

Question 3

Narcotics

Answer 3

drugs that produce sleep

Question 4

Opiates

Answer 4

drugs derived from opium

Question 5

Opioids

Answer 5

drugs that bind to opioid receptors

Question 6

Mu1 receptor

Answer 6

Morphine
supraspinal analgesia
High density in the brain

Question 7

Mu2 receptor

Answer 7

morphine
respiratory depression
high density in respiratory centre of the brainstem

Question 8

Delta receptors

Answer 8

Enkephalins
spinal analgesia
high density in spinal cord - use for epidural

Question 9

Kappa receptor

Answer 9

Dynorphin A
spinal analgesia
sedation

Question 10

NOP (ORL1) receptors

Answer 10

non-opioid
opioid-receptor-like
Nociceptin/orphanin FQ binds
action not fully understood

Question 11

Opioid receptor structures

Answer 11

7 transmembrane segments (G-protein)
K+ and Ca2+ channels
opioid binding --> conformational change
K+ channel opens --> hyperpolarization
Ca channel closes in presynaptic membranes --> block conductance

Question 12

Opioid sites of action

Answer 12

brain
brainstem
spinal cord
primary afferent neurons
medullary respiratory centre –> could lead to death
medullary chemoceptor zone –> activation triggers vomiting
Gut

Question 13

opioid action in GI

Answer 13

slows down contractile frequency
paralyzes gut
constipation

Question 14

Opioid MOA

Answer 14

Postsynaptic: hyperpolarization by opening of K+ channels (inhibitory)
Presynaptic: reduction of excitatory transmitter release (glutamate, peptides, tachykinin) by closing of calcium channels (inhibitory)

Activation of inhibitory enkephalin interneurons in dorsal horn of spinal cord
Activation of inhibitory descending pathways: endogenous analgesic mechanism (built in opioids)

Question 15

Endogenous opioid peptide examples

Answer 15

beta-endorphin
Leu-enkephalin, met-enkephalin
Dynorphin

Question 16

Endogenous opioid peptide characteristics

Answer 16

Mimic most effects of morphine
Antagonized by naloxene
Produce tolerance and physical dependence
Participate in endogenous control mechanisms
Modulate nociceptive transmission
May be responsible for placebo effect

Question 17

Phenanthrene examples

Answer 17

Morphine
Hydromorphone
Diacetylmorphine (heroin)
Codeine
Oxycodone
Nalbuphine
Naloxone

Question 18

Phenylheptylamine example

Answer 18

Methadone

Question 19

Benzomorphan example

Answer 19

Pentazocine

Question 20

Phenylpiperidine examples

Answer 20

Fentanyl
Sufentanil
Ramifentanil
Meperidine

Question 21

Morphinians examples

Answer 21

Levorphanol

Question 22

Pure opioid agonists

Answer 22

Morphine
fentanyl
Codeine
Hydromorphone
Oxycodone
Meperidine
Methadone

Question 23

Opioid agonist-antagonists

Answer 23

Nalbuphine

Pentazocine

Question 24

Opioid partial agonists

Answer 24

Buprenorphine

Question 25

Dosing of opioids

Answer 25

Most drugs used clinically are pure agonists Different oral bioavailability Codeine 12x less potent than morphine parenterally Fentanyl 100x more potent than morphine parenterally Agonist-antagonist decrease respiratory depression (agonist at kappa, antagonist at mu)

Question 26

Absorption of opioids

Answer 26

Most absorbed readily

Question 27

Absorption of morphine

Answer 27

increased hepatic first-pass, decreased oral bioavailability (25%)

Question 28

Absorption of codeine

Answer 28

increased oral bioavailability (60%)

Question 29

Absorption of heroin

Answer 29

increased lipid solubility --> BBB penetration

Question 30

Metabolism of morphine

Answer 30

hepatically converted to morphine-6-glucuronide (active) and morphine-3-glucuronide (excitatory and toxic at higher concentrations, myoclonic seizures)

Question 31

Metabolism of meperidine

Answer 31

hepatic conversion to normeperidine (excitatory and toxic)

Question 32

Heroine/Codeine metabolism

Answer 32

converted to morphine

Question 33

Remifentanil metabolism

Answer 33

rapidly hydrolyzed by nonspecific esterases | useful for continuous, easily adjustable iv infusion

Question 34

Morphine excretion

Answer 34

90% as glucuronides (urine), 10% unchanged (bile, feces)

Question 35

Central effects of morphine

Answer 35

``` analgesia hyperalgesia (at high doses) cough suppression euphoria (also dysphoria) sedation respiratory depression Nausea and vomiting Pruritis Miosis Truncal rigidity Convulsions ```

Question 36

Peripheral effects of morphine

Answer 36

constipation urinary retention constriction of sphincter of Oddi (increased biliary colic) Histamine release (direct mast cell degranulation; particularly morphine) bradycardia (no other significant direct effects on the heart) hypotension due to v/d

Question 37

Indications of morphine

Answer 37

analgesia for acute pain (mod to severe), cancer pain, anesthesia Cough suppression - codeine, dextromethorphan Antidiarrheal: loperamide, diphenoxylate Acute pulmonary edema: iv morphine for pulmonary vasodilation

Question 38

Opioid tolerance

Answer 38

Begins with first opioid dose no tolerance to miosis or constipation cross-tolerance among opioids

Question 39

Opioid dependence

Answer 39

Occurrence of withdrawal symptoms (physical) | and/or craving (psychological)

Question 40

Opioid addiction

Answer 40

dependence accompanied by abuse and drug-seeking behaviour | All opioids carry abuse potential

Question 41

Naloxene/naltrexone MOA

Answer 41

antagonists at mu/delta/kappa receptors almost no effects when given in the absence of agonists rapid reversal of agonist effects no tolerance potential to precipitate withdrawal symptoms in dependent patients

Question 42

Opioid OD presentation

Answer 42

clinical triad: coma miosis respiratory depression

Question 43

Opioid OD tx

Answer 43

general measures - ABCs, 100% O2 | Specific: naloxene iv

Question 44

CI and cautions of opioids

Answer 44

Respiratory disease (COPD, OSA) Drug interactions: meperidine+ MAOi --> hyperpyrexic coma Opioids + sedatives/ethanol --> high CNS depression Pregnancy - physical dependence of fetus Use of pure agonists with agonist-antagonists: less analgesia, withdrawal