Lecture 8 - Opioids Flashcards
1
Q
Describe the analgesic pain ladder:
Step 1 - Mild
A
non-narcotics
1st choice = ASA
Alternatives = acetaminophen or NSAID
2
Q
Describe the analgesic pain ladder:
Step 2 - Mild to Moderate
A
non-narcotics + weak narcotics
1st choice = ASA + codeien
Alternatives = codeine or Acetaminophen + codeine
3
Q
Describe the analgesic pain ladder:
Step 3 - Moderate to Severe
A
moderate strength narcotics
1st choice = codeine or morphine
Alternatives = oxycodone, levorphanol, anileridine, oxymorphone
4
Q
Describe the analgesic pain ladder:
Step 4 - Severe
A
strong narcotics
1st choice = morphine
Alternatives = methadone, hydromorphone
5
Q
List 3 endogenous opioids
A
- endorphines
- enkaphalins
- dynorphins
6
Q
Describe endorphins
A
- from pituitary and hypothalamus
- polypeptides
- from poropiomelanocortin and prodynorphin
- potent analgesics
7
Q
Describe enkephalins
A
- from proenkephalin and prodynorphin
- pentapeptide ligands
- involved in modulated pain response
8
Q
Describe dynorphins
A
- from proenkephalin B
- polypeptides
- physiological role not yet understood
9
Q
Are opioids direct neurotransmitters?
A
No - they just make the neuron more likely to fire - but are not directly neurotransmitters
10
Q
Describe the 3 Mechanisms of action?
A
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
Q
What can opioids be used for?
A
- pain control
- sedation and anxiolysis
- can be used before anesthesia
12
Q
What is the #1 cause of opioid death?
A
depression of respiration
13
Q
List the 7 pharmacological effects of opioids
A
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
Q
_____ are used for pain, diarrhea, coughing, panic breathing (COPD)
A
opioids
15
Q
What 3 things do we dose opioids by ?
A
by the mouth
by the clock
by the ladder
16
Q
Briefly explain the WHO pain ladder (slide 8)
A
0-3: mild pain
- acetaminophen
- NSAIDs
- maybe caffeine
4-6: moderate pain
-codeine (mild opioid)
7-10: severe pain
-morphine (strong opioid)
17
Q
If you are increasing to a stronger or different pain med, do you discontinue the original medication?
A
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
Q
By the mouth:
-Oral dosing is ___ effective than IV
A
less
*because of first pass metabolism
19
Q
Describe 3 points of by the mouth
A
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
Q
Describe 3 points of by the clock
A
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
Q
What is the #1 problem with dosing by the clock?
A
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
Q
Describe points of by the ladder
A
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
Q
_____ - weakest commonly used opioid and has the least addiction risk
A
codeine
24
Q
codeine has ___% of potency of morphine
A
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
