Lecture 8 - Opioids Flashcards Preview

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Flashcards in Lecture 8 - Opioids Deck (165)
1

Describe the analgesic pain ladder:
Step 1 - Mild

*non-narcotics*
1st choice = ASA
Alternatives = acetaminophen or NSAID

2

Describe the analgesic pain ladder:
Step 2 - Mild to Moderate

*non-narcotics + weak narcotics*
1st choice = ASA + codeien
Alternatives = codeine or Acetaminophen + codeine

3

Describe the analgesic pain ladder:
Step 3 - Moderate to Severe

*moderate strength narcotics*
1st choice = codeine or morphine
Alternatives = oxycodone, levorphanol, anileridine, oxymorphone

4

Describe the analgesic pain ladder:
Step 4 - Severe

*strong narcotics*
1st choice = morphine
Alternatives = methadone, hydromorphone

5

List 3 endogenous opioids

-endorphines
-enkaphalins
-dynorphins

6

Describe endorphins

-from pituitary and hypothalamus
-polypeptides
-from poropiomelanocortin and prodynorphin
-potent analgesics

7

Describe enkephalins

-from proenkephalin and prodynorphin
-pentapeptide ligands
-involved in modulated pain response

8

Describe dynorphins

-from proenkephalin B
-polypeptides
-physiological role not yet understood

9

Are opioids direct neurotransmitters?

No - they just make the neuron more likely to fire - but are not directly neurotransmitters

10

Describe the 3 Mechanisms of action?

1 - hyper polarization of nerves by opening K+/Ca2+ channels in 1st (receptor to medulla) and 2nd order neurons (medulla to thalamus)

2 - inhibition of ascending pathways in the CNS

3 - excitation of descending adrenergic and seratonergic pathways

11

What can opioids be used for?

-pain control
-sedation and anxiolysis
-can be used before anesthesia

12

What is the #1 cause of opioid death?

depression of respiration

13

List the 7 pharmacological effects of opioids

1 - inhibition of pain and pain perception
2 - sedation and anxiolysis
-drowsiness and lethargy
-cognitive impairment
-relaxation inhibition of pain
3 - depression of respiration (main cause of death from opioid overdose)
4 - cough suppression (opioids suppress the cough centre in the brain)
5 - reduction of intestinal motility (codeine used to treat diarrhea)
6 - pupillary constriction (KEY SYMPTOM OF OVERDOSE)
7 - nausea and vomiting (first stimulated, then inhibited)

14

_____ are used for pain, diarrhea, coughing, panic breathing (COPD)

opioids

15

What 3 things do we dose opioids by ?

by the mouth
by the clock
by the ladder

16

Briefly explain the WHO pain ladder (slide 8)

0-3: mild pain
-acetaminophen
-NSAIDs
-maybe caffeine

4-6: moderate pain
-codeine (mild opioid)

7-10: severe pain
-morphine (strong opioid)

17

If you are increasing to a stronger or different pain med, do you discontinue the original medication?

no
never
not in a million years

**never stop the lower pain control!
-pain meds work by different mechanisms so you always want to keep the pain controlled and don't want to take away any form of pain management

18

By the mouth:
-Oral dosing is ___ effective than IV

less

*because of first pass metabolism

19

Describe 3 points of by the mouth

1 - oral dosing has longer term effect requiring less frequent doses
2 - oral dosing avoids the highs and thus is less addictive
3 - oral dosing is safer in terms of overdose

20

Describe 3 points of by the clock

1 - uses less drug. It takes more drug to bring pain down than it does to maintain a person pain-free (maintain dosing)
2 - avoids the euphoria associated with release of pain, so less addictive potential
3 - avoids the development of chronic pain syndrome (from pain pathway rewirling)

21

What is the #1 problem with dosing by the clock?

Pt does not want to comply because they do not feel pain and do not want to become addicted

*have to explain to pt that by dosing by the clock, you are actually reducing risk of addiction

22

Describe points of by the ladder

1 - it assures that the safest and least potent drug required for any specific case is used
2 - avoids addictive potential because opioids (and strong opioids) are not used until required

23

_____ - weakest commonly used opioid and has the least addiction risk

codeine

24

codeine has ___% of potency of morphine

10

25

Potency of codeine is so ___, it is has it's own special step on the pain ladder (possibly now shared with tramadol)

low

26

What is codeine used for?

pain
diarrhea
coughing
inhibit breathing

27

_____ = unique weak opioid agonist

tramadol

28

What is the main downside to tramadol?

expensive

29

Unlike other opioids, tramadol has two complementary mechanisms: describe them

1 - like other opioids, activates the micro-opioid receptor

2 - weak inhibitor of norepinephrine and serotonin reuptake

30

Tramadol has ____ potential for addiction and shows greater pain control

less

31

Oral dose of morphine has relatively ___ availability

poor (approx 20-30%)

32

onset of oral morphine?

15-60 mins

33

duration of action of oral morphine?

3-6 hours

34

IV morphine is ____ as potent as oral morphine

twice

35

duration of action for IV morphine?

almost immediate to 2 hours (high population variability)

36

Is oxycodone more potent than morphine?

yes up to 2X more potent

37

Oral bioavailability of oxycodone?

80% (remember that morphine has 20-30% oral bioavailability)

38

Oxycodone has a slightly ____ half-life than morphine

greater

39

You give oxycodone at ___ the dose of morphine for the equivalent effect

half

40

slow release form of oxycodone = ?

OxyContin

41

Oxycodone + tylenol = ?

Percocet

42

Oral hydromorphone onset = ?

15-30 mins

43

IV hydromorphone duration of action ?

3-4 hours

44

Peak effect of hydromorphone = ?

30-60 mins

45

Is hydromorphone stronger than morphine = ?

yes - 5X as potent

46

Where is hydromorphone used?

surgical settings for moderate to severe pain (cancer, bone trauma, burns, etc.)

47

Fentanyl is highly ______

lipophilic

48

Fentanyl is very _____

potent

49

Fentanyl comes as what dosage forms?

transdermal (patch)
sublingual
intravenous (rarely)

50

Fentanyl has ___ times the analgesic potency of morphine

80

51

Fentanyl has ___ times the analgesic potency of hydromorphone

10

52

latency of sublingual fentanyl?

7-12 mins

53

duration of sublingual fentanyl?

1-2 hours

54

What is sublingual fentanyl used for?

acute but temporary pain (fast onset, short duration) such as debriding wounds and breakthrough pain in palliative care

55

latency of transdermal fentanyl ?

12-17 hours

56

duration of transdermal fentanyl ?

72-96 hours

57

What is transdermal pain used for?

used in more severe pain (cancer, palliative care)

58

Sufentanyl is __x more potent than fentanyl

10

59

Naltrexone is an oral opioid ____

INHIBITOR

60

Naltrexone is a ??

reverse agonist (kind of considered an antagonist)

61

latency of naltrexone ?

15-30 mins

62

duration of naltrexone ?

24-72 hours

63

peak of naltrexone ?

6-12 hours

64

How does naltrexone work?

reverses the psychotomimetic effects of opiate agonists, reverses hypotension and cardiovascular instability

65

naltrexone is not highly effective in treating ??

opioid addiction

*mainly due to compliance*

66

naltrexone is effective to some extent in treating ??

alcohol addiction

67

Naloxone (Narcan) is a ?

potent opioid antagonist

68

Naloxone (Narcan) has a strucure almost identical to ?

oxymorphone

69

Naloxone (Narcan) very quickly blocks ?

opioid binding

70

When is Naloxone (Narcan) used?

in emergency situations such as respiratory depression in clinical situations or heroin overdose

71

Naloxone (Narcan) has a ____ half life

short

72

Naloxone (Narcan) blocks all major effects of _____

opioids (including pain control)

73

Describe methadone's half life

very long but variable
-up to 5 days
-but effective for only 6-12 hours

74

Is methadone more potent than morphine?

yes - at least 10X more potent

75

Although methadone is less addictive, it is a greater risk for ?

accidental overdose

76

Can any pharmacist dispense methadone?

not everyone - it requires special training and licensure

77

What is methadone primarily used for?

narcotic maintenance
-so like weening addicts off of narcotics/opioids

78

Dosing schedule is based on ??

time, not pain!
by the clock!

79

What is the rule for switching opioids?

30% rule

if you switch to a new opioid - you calculate the dose that would be equivalent and then use 30% less

80

Why do you use the 30% rule?

because for some unknown reason when you start a new drug, it can be more effective than when you have continued use of a drug

*this is done to prevent overdose

81

Why would you ever rotate opioids?

to improve analgesia

82

When would you discontinue therapy?

-when there is intolerable or unacceptable side-effects (myoclonus-neurotoxic effect, respiratory depression, level of conscience) with little or no evidence of analgesia

-high doses of opioids without analgesia

-there is evidence of addiction

-there is no evidence of any effort to increase function in the face of reasonable analgesia

83

Define tolerance

reduced potency of analgesic effects of opioids following repeated administration

84

What is the negative consequence with tolerance?

increased doses are necessary to produce pain relief - this increases risk of dependence and addiction

85

Define physical dependence

normal response to chronic opioid administration

86

List signs of dependence that would be evident with opioid withdrawl

yawning
sweating
tremor
fever
increased HR
insomnia
muscle/abdominal cramps
dilated pupils

87

How do you avoid dependence?

decrease dose by 20-30% per day

88

_____ = psychological dependece

addiction

89

Define addiction

a pattern of drug use characterized by a ... craving for opioids ... manifest .. [by] compulsive drug-seeking behaviour leading to .. overwhelming involvement in use and procurement of the drugs

90

List 3 ways to deal with tolerance

-prevent dose escalation
-use a medication holiday following slow withdrawal
-plan for this at the beginning of treatment

91

List some other effects of opioids on the body

-causes vomiting by stimulating the chemoreceptor trigger zone in the brainstem - then depresses vomiting
-pinpoint pupils - no tolerance
-vasodilation - flushing of skin and decrease in blood pressure
-methadone causes sweating
-constipation
-decreases sex hormones in males and females - decreases libido and fertility

92

Pain works by 3 different pathways: describe them

1 - descending inhibitory pathways (NE, seretonin, enkephalins)
-TCAs
-SSRIs
-SNRIs
-alpha adrenergic agents
-opioids
-tramadol

2 - peripheral sensitization (Na+)

3 - central sensitization
(Ca2+, NMDA)

93

What works on pain in the descending inhibitory pathways?

NE and S are pain mediators - inhibit pain signals from reaching the higher levels of brain

-part of the modulatory system in the spinal cord and brain

94

Drug classes that work on the descending inhibitory pathways for pain?

1 - antidepressants
-TCAs
-SSRIs
-SNRIs

2 - alpha 2 adrenergic agonists

3-opioids (esp tramadol)

95

How do TCAs work on descending inhibitory pathways?

-increases serotonin and/or NE in the synapse by inhibiting reuptake
-takes 1-3 weeks for pain control so used for chronic pain
-may have anticholinergic effects (dry mouth, dry eyes, etc.)
-more effective for conditions like diabetic neuropathy than other anti-depressants

96

Examples of TCAs

nortriptyline
amitryptyline

97

What is the 1st line treatment for neuropathic pain?

nortriptyline

98

How do SSRIs work on descending inhibitory pathways?

-specific inhibitor of Serotonin reuptake

99

Side effects of SSRIs

-suicide
-impaired platelet aggregation
-CNS depression
-QT prolongation
-serotonin syndrome
-SIADH/hyponatremia
-sexual dysfunction

100

examples of SSRIs

paroxetine (paxil)
fluoxetine (prozac)
sertraline (zoloft)

101

How do SNRIs work on descending inhibitory pathways?

-serotonin and norepinephrine reuptake inhibitors
-also weakly inhibits dopamine reuptake

102

side effects of SNRIs??

-suicide
-impaired platelet aggregation
-CNS depression
-hypercholesterolemia
-hypertension
-serotonin syndrome
-sexual dysfunction
-SIADH/ hyponatremia
-QT prolongation

103

example of SNRI

venlafaxine

104

What is venlafaxine used for?

neuropathic pain
DM neuropathy

105

onset of venlafaxine ?

1-2 weeks
max 6

106

common adverse effects of venlafaxine?

nausea
dizziness
drowsiness

107

How do alpha 2 adrenergic agonists work on descending inhibitory pathways?

-stimulate alpha-adrenoreceptors in brainstem - activating inhibitory neuron thus reducing sympathetic outflow of CNS
-prevents pain signal transmission

108

examples of alpha adrenergic agonists?

-clonidine (Catapres)
-tizanidine (Zanaflex)

109

What is clonidine used for?

neuropathic pain that is not responding to other treatment

110

Unlabeled uses of clonidine?

-heroin or nicotine withdrawal
-dysmenorrhea
-menopausal vasomotor symptoms
-migraine prophylaxis

111

routes available for clonidine?

epidural infusion
oral
transdermal

112

side effects of clonidine

bradycardia

CNS and respiratory depression

hypotension

113

Tizanidine is used to treat?

-tension type headache
-back pain
-neuropathic pain
-myosfascial pains

114

Is tizaidine better than clonidine?

Yes
-less side effects
-less likely to cause hypotension
-better tolerated than clonidine

115

Peripheral sensitization - caused by?

sodium channels on nerves

-neuropathic pain triggered by spontaneous peripheral nerve activity mediated by sodium channels

116

Causes of pain through peripheral sensitization ?

-local tissue injury
-ischemia
etc

releasing inflammatory factors thereby increasing Na channels leading to excitability of the nerve

117

Medication classes which dampen the peripheral sensitization include?

-carbamazepine
-TCAs
-Topiramate
-Lidocaine

118

How does carbamazepine (Tegretol) work on peripheral sensitization?

-anticonvulsant
-limits influx of Na+ ions across the cell membrane
-trigeminal or glossopharyngeal neuralgia and neuropathic pain

119

How does Topiramate (Topamax) work on peripheral sensitization?

-anticonvulsant
-limits influx of sodium ions across the cell membrane, antagonizes glutamate receptors

120

Adverse effects of Topiramate?

-dizziness
-ataxia
-somnolence (strong desire for sleep)
-psychomotor slowing
-parasthesia
-weight loss

121

What do you need to monitor for topiramate?

electrolytes
kidney function

122

How does lidocaine work on peripheral sensitization?

-topical application reduces discharge of small afferent nerve fibres by blocking voltage gated Na channels (decreases membrane permeability)

123

Lidocaine comes as?

gel
transdermal patch

124

What is lidocaine used for?

post-herpetic neuralgia or
peripheral neuropathic or other aetiologies

125

Side effects of lidocaine?

arrythmias
seizures
coma
respiratory depression or death

with patch:
-application site erythema
-swelling
-burning
-discomfort

126

Describe central sensitization-1?

calcium channels

-occurs in the dorsal horn of the spinal cord
-release of excitatory neurotransmitters (incl. glutamate and substance P)
-increased calcium transport causes spontaneous impulses (APs) - pain message sent to brain

127

What types of medication decrease Ca channel activity?

GBP - gabapentin
PreGab - pregabalin

128

Describe central sensitization-2?

NMDA receptor

-occurs in the dorsal horn of the spinal cord
-release of excitatory neurotransmitters (including glutamate and substance P)

129

What medications work on central sensitization 2 ?

medications that are NMDA antagonists (decrease nerve impulse)

-ketamine
-dextromethorphan
-methadone

130

How does Ketamine (Kelatar) work on central sensitization?

NMDA receptor antagonist

-decreases central sensitization and modulation by lowering the threshold for nerve transduction and reduces the effects of substance P
-also targets the opioid receptor, Na and K channels to reduce pain (dissociative agent)

131

common adverse rxn of ketamine ?

local skin rxns

132

Describe how dextromethorphan (Robitussin) works on central sensitization ?

low affinity uncompetitive NMDA antagonist - high doses needed (45-400 mg/day)

-also binds opioid receptors
-short half life (2-4 hours)

133

side effects of dextromethorphan (Robitussin)

serotonin syndrome (if in combination with other antidepressants)

-rash
-nausea/vomiting
-drowsiness/sedation
-constipation/diarrhea
-confusion
-nervousness
-closed eye hallucinations

134

Describe how methadone works on central sensitization

-mu and delta opioid agonist
-also blocks NMDA receptor
-inhibits reuptake of NE

-crossing BBB rapidly
-lipophilic so distributes in muscle and fat
-high bioavailability

135

side effects of methadone?

-CNS & respiratory depression
-QT prolongation
-constipation
-nausea and vomiting
-dizziness and disorientation

136

What is gout?

caused by accumulation of uric acid crystals in joints

137

What is gout associated with?

ingesting red meat, cheese, wine (large intakes of purines)

138

gout a.k.a. ?

rich man's disease

139

Uric acid production pathway

purine nucleotides (dietary and cellular)

inosinic acid

hypoxanthine
(xanthine oxidase)
xanthine
(xanthine oxidase)
uric acid

140

Drug therapy of gout?

-cholchicine
-allopurinol
-probenecid
-NSAIDs (indomethacin)

141

Describe colchicine

-weak anti-inflammatory agent
-not analgesic or antipyretic
-impairs PMN motility and chemotaxis and thus inflammatory response to urate crystals
-dose to toxicity - nausea, vomiting, diarrhea, abdominal cramping, may cause death
-no effect on plasma or urinary uric acid
-may be considered for low dose continuous prophylactic therapy

*decreases motility of immune cells
*doesn't affect underlying disease
*just reduces inflammation

142

Describe allopurinol

-xanthine oxidase inhibitor
-reduces urate formation
-active metabolite (oxypurinol/alloxanthine)
-risk of hypoxanthine stones

143

What is allopurinol used for?

-for prophylaxis when acute gouty attacks happen frequently

144

Caution with alloupurinol?

fluid intake
acute attack of gout

145

adverse events with allopurinol

allergic rxns
bone marrow
suppression
liver toxicity
renal toxicity

146

Describe NSAIDs (indomethacin)

-most common type of drug given for all kinds of arthritis
-drug of choice for gouty arthritis
-less toxic than colchicine with short term use
-not uricosuric
-affords symptomatic relief
-GI side effects with indomethacin

147

How do NSAIDs (indomethacin) work?

decreases inflammation

helps with uric acid formation a little bit

148

How does Probenecid work?

-uricosuric: inhibits reabsorption of uric acid (decreases amount of uric acid in the blood)
-half-life dose dependent
-highly protein bound
-inhibits excretion of other acidic drugs
-caution: renal urate stones (fluid intake)

149

Define: local anesthetic

-an agent that interrupts pain impulses in a specific region of the body without a loss of patient consciousness
-normally, the process is completely reversible - the agent doe snot produce any residual effect on the nerve fibre

150

end in "caine" = ?

sodium channel blocker
-decrease nerve sensitization
-decrease pain

151

Where are local anesthetics used?

to render a specific portion of the body insensitive to pain

152

How do local anesthetics work?

interfere with nerve impulse transmission to specific areas of the body

153

Do you lose consciousness with local anesthetics?

noooooope

154

Describe topical anesthetics

-applied directly to skin or mucous membranes
-creams, solutions, ointments, gels, ophthalmic drops, lozenges, suppositories

155

Describe parenteral anesthetics

injected into the CNS by various spinal injection techniques

156

Describe surface anesthesia

-this type of anesthesia is accomplished by the application of a local anesthetic to skin or mucous membranes

-surface anesthesia is used to relieve itching, burning, and surface pain (ex minor sunburns)

157

Describe nerve block anesthesia

-local anesthetic is injected around a nerve that leads to the operative site

-usually more concentrated forms of local anesthetic solutions are used for this type of anesthesia

158

Describe peridural anesthesia

this type of anesthesia is accomplished by injecting a local anesthetic into the peridural space (one of the coverings of the spinal cord)

159

Describe spinal anesthesia

the local anesthetic is injected into the subarachnoid space of the spinal cord

160

List the 5 types of local anesthesia

-epidural
-infiltration
-nerve block
-spinal
-topical

161

Describe the drug effects of local anesthesia

-first, autonomic activity is lost
-then pain and other sensory functions are lost
-motor activity is the last to be lost
-as local agents wear off, they do so in reverse order (motor, sensory, then autonomic activity are restored)

162

Indications of local anesthetics ?

-surfical, dental, and diagnostic procedures
-treatment of certain types of pain:
-infiltration anesthesia
-nerve bock anesthesia

163

Indication for infiltration anesthesia

-minor surgical and dental procedures
-injection of the anesthetic solution intradermally, subcutaneously, or submucosally across the path of nerves supplying the target area
-may be given in a circular pattern around the operative area

164

Indication for nerve block anesthesia

-surgical, dental and diagnostic procedures
-also used for therapeutic management of pain
-the anesthetic agent is injected directly into or around the nerve trunks or nerve ganglia that supply the area to be numbed

165

adverse side effects of local anesthetics ?

-usually limited

adverse effects result if:
-inadvertent intravascular injection occurs
-excessive dose or rate of injection is given
-slow metabolic breakdown
-injection into a highly vascular tissue