Quiz 2 - Pain Flashcards
(151 cards)
1
Q
Define pain
A
an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage
2
Q
4 steps in the gate control theory of pain
A
- transduction
- transmission
- modulation
- perception
3
Q
Epidural opioids act on which part of the pain pathway?
A
modulation
4
Q
Non-steroidals act on which part of the pain pathway?
A
transduction
5
Q
LAs act on which part of the pain pathway?
A
transduction and transmission
6
Q
Systemic opioids act on which part of the pain pathway?
A
perception (cerebral cortex and thalamus)
7
Q
2 natural opioids
A
morphine and codeine
8
Q
2 semi-synthetic opioids
A
oxycodone and hydromorphone
9
Q
2 synthetic opioids
A
meperidine and fentanyl
10
Q
List the phenanthrenes
A
- codeine
- morphine
- oxycodone
- hydromorphone
- hydrocodone
- oxymorphone
11
Q
What effect does activation of codeine have on receptor binding?
A
activation to morphine increases receptor binding potency by 300-7000x
12
Q
3 phenanthrene antagonists
notable difference in structure?
A
- nalorphine
- naloxone
- naltrexone
(large nonpolar fxnl group on the N)
13
Q
2 phenylpiperazines
A
meperidine and fentanyl
14
Q
(ionized/nonionized) drugs are less likely to get into the CNS
A
ionized
15
Q
Describe the spread of fentanyl along the spinal canal and why?
A
minimal spread because fentanyl is very lipophilic - it quickly crosses the BBB and leaves the epidural space
16
Q
Describe the spread of morphine along the spinal canal and why?
A
significant spread because morphine is very hydrophilic - it does not get into the CSF as quickly –> longer DOA
17
Q
Precursors to endogenous opioids
A
- proenkephalin –> enkephalin
- proopiomelanocortin –> endorphin
- prodynorphin –> dynorphin
18
Q
Describe the pharmacology of exogenous opioids:
A
they mimic the actions of endorphins by binding to opioid receptors, resulting in activation of a pain modulating system - inhibits release of NT responsible for pain
- work primarily centrally
- NO ceiling effect
- YES specific antagonist
19
Q
What type of receptors are opioid receptors? Describe the effects:
A
- G-protein-coupled receptors
- Ginhibitory; decrease cAMP –> decrease Ca2+ –> decreased release of pain NT
20
Q
3 opioid receptor types and their activity
A
1) mu: supraspinal analgesia, euphoria, resp depression, bradycardia, physical dependence
2) delta: modulate mu receptor activity
3) kappa: analgesia with little to no resp depression
21
Q
Action of opioid agonist:
A
affinity and efficacy at mu receptor
22
Q
Action of opioid partial agonist:
A
partial activation of mu receptor w/ or w/o kappa activity
23
Q
Action of opioid agonist/antagonist:
A
agonist at kappa receptor and antagonist at mu receptor
24
Q
Action of opioid antagonist:
A
affinity without efficacy at any opioid receptor
25
Advantages of opioid partial agonists and agonist/antag:
- good if pt is hyperreactive to opioids
- used for partial reversal
- better SE profile
26
Disadvantages of opioid partial agonists and agonist/antag.:
- not very effective d/t ceiling effect
- opioid SE
- reversal is problematic if pure agonist also given
27
MOA of Tramadol:
weakly binds to mu receptor and inhibits reuptake of serotonin and NE
28
Advantages & disadvantages of Tramadol:
Advantages:
- new alternative to pain therapy
- not a controlled substance
Disadvantages:
- expensive
- no more effective than Tylenol + Codeine
- sz reported
29
MOA of Tapentadol:
weakly binds to mu receptor and inhibits reuptake of serotonin and NE (same as Tramadol)
30
Advantages & disadvantages of Tapentadol:
Advantages:
- new alternative to pain therapy
- improved SE over opioids
Disadvantages:
- Class II controlled substance
- expensive
- less effective than other opioids
31
Advantages & disadvantages of Codeine/Hydrocodone/Oxycodone:
Advantages:
- good 1st line agent if NSAIDS ineffective
- good for breakthrough pain
Disadvantages:
- SE
- PO Codeine = nauseating
- monitor Tylenol intake
32
Advantages & disadvantages of Morphine:
Advantages:
- good analgesia
- good maintenance for acute and long-term pain
- + effect on preload post-MI
- staff familiarity
Disadvantages:
- long onset
- SE
- morphine-6 glucoronide metabolite accumulation (esp renal)
33
Methadone used to treat what type of pain?
severe & opioid withdrawal
34
Advantages & disadvantages of Methadone:
Advantages:
- good analgesic
- long half-life for chronic pain
- d-isomer has NMDA antagonist effect that lowers tolerance
Disadvantages:
- accumulates
- opioid SE
- difficult to manage long-term
35
Advantages & disadvantages of Meperidine:
Advantages:
- OK for morphine allergic pts
- less effect on biliary spasm
- efficacious for chills
Disadvantages:
- long onset
- accumulation of nor-meperidine metabolite (esp renal)
- SE
36
Advantages & disadvantages of Fentanyl:
Advantages:
- rapid onset
- OK for morphine allergic pts
- effective analgesic
Disadvantages:
- SE
- chest wall rigidity
- fast on/off d/t redistribution
37
5 most important opioid SE
1) resp depression
2) decreased GI motility
3) biliary tract spasm
4) histamine release
5) N/V
38
Opioid-associated histamine release has a particularly strong effect on what patient population?
hypovolemic
39
List the 6 emesis receptors that affect the CTZ:
- histamine
- muscarinic
- 5HT3 (serotonin)
- opioid
- CN VIII (vestibulocochlear)
- dopamine
40
Opioids directly stimulate which CN? Why is this relevant?
CN VIII - also concurrently stimulates the CTZ
41
Which opioid SE do patients NOT develop a tolerance to?
- miosis
- constipation
- convulsions
- antagonist actions
42
Which opioid SE do patients develop a moderate tolerance to?
bradycardia
43
Which opioid SE do patients often develop a tolerance to?
- analgesia
- euphoria/dysphoria
- mental clouding
- sedation
- resp depression
- antidiuresis
- N/V
- cough suppression
44
MOA of Naloxone
competitive inhibitor of mu, kappa, and delta receptors
45
Onset/duration of Naloxone:
- onset 1-2 min
- duration 30-90 min
46
Dose and frequency of Naloxone:
0.05-0.1 mg IV repeated every 2-3 min
titrate up depending on clinical response and desired effect (OD - big dose fast, decreased RR - small dose)
47
SE of Naloxone administration:
- sudden and complete antagonism may cause severe HTN
- ventricular arrhythmias
- acute pulm edema d/t huge sympathetic outflow
48
Sedative-hypnotics + opioid interactions:
- increased CNS depression
- resp depression
49
Antipsychotic tranquilizers + opioid interactions:
- sedation
- resp depression
- CV effects
50
MAOIs + opioid interactions:
- hyperpyrexic coma
- HTN
- serotonin syndrome w/ phenylpiperidines (esp Meperidine)
51
Recommended agents for neuropathic pain:
TCAs (Imipramine, Doxepin, Duloxetine), Trazodone, Fluoxetine
52
Negative SE of TCAs and non-TCAs for neuropathic pain:
anticholinergic SE, sedation
53
Most NSAIDS are (acids/bases)?
acids
54
MOA of NSAIDS:
produce analgesia through inhibition of the enzyme cyclooxygenase, resulting in a decreased synthesis and release of prostaglandin
55
NSAIDS work (centrally/peripherally)
peripherally
56
Do NSAIDS have a ceiling effect?
yes
57
What effect does inhibition of prostaglandins have on the nerve cell?
decreased sensitization of nociceptors
58
List the alogenic mediators:
- K+
- serotonin
- bradykinin
- histamine
- prostaglandins
- leukotrienes
- substance P
59
Prostacyclin is associated with which 2 effects?
- vasodilation
- decreased PLT stickiness
60
Thromboxane A2 is associated with which 2 effects?
- vasoconstriction
- increased PLT stickiness
61
3 types of eicosanoids:
- prostaglandins
- thromboxanes
- leukotrienes
62
What are eicosanoids?
oxygenation products of polyunsaturated long chain fatty acids
(LARGE molecules)
63
Advantages & disadvantages of NSAIDS:
Advantages:
- reduce inflammation
- lower CNS effects
- no physical dependence
- able to combine with opioid tx
Disadvantages:
- hematological effects
- renal
- hepatic
64
4 effects of Aspirin:
- anti-inflammatory
- analgesic
- antipyretic
- antiplatelet
65
The antiplatelet effect of Aspirin is (reversible/irreversible)
irreversible
PLT have no nucleus and cannot make anything new when affected; must be regenerated
66
Inflammation is more associated with (osteoarthritis/rheumatoid arthritis)
RA
67
Compare the pathogenesis of osteoarthritis and RA:
osteoarthritis = biomechanical and leads to the loss of cartilage matrix
RA = autoimmune and leads to joint destruction
68
SE of NSAIDS
- GI disturbances
- renal dysfxn
- inhibition of PLT aggregation
- hypersensitivity
- inhibits uterine motility
- CNS effects
69
What effect can long-term NSAID use have on the renal system?
renal papillary necrosis
- renal toxicity in pts that rely on renal prostaglandins for maintenance of renal perfusion
(COX-2 selective and non-selective)
70
Describe how use of NSAIDS and ACE inhibitors affects GFR:
- NSAIDs inhibit prostaglandins that typically would dilate the afferent arteriole
- ACE inhibitors prevent production of angiotensin II what would typically constrict the efferent arteriole
- together these drugs decrease GFR by decreasing pressure through the glomerulus and decreasing renal filtration
*BIG problem in hypovolemic patient*
71
Which patients are at greatest risk for adverse effects of NSAIDs?
- impaired renal fxn
- HF
- impaired hepatic fxn
- taking diuretics and ACE inhibitors
- elderly
72
Equation for GFR:
(140-age) (weight in kg) / 72 x serum creat
*0.85 for women
73
Where is COX-1 located in the body?
everywhere (housekeeping enzyme)
- found in the GI tract where it produces prostaglandins
- also found in kidneys and PLT
74
Where is COX-2 located in the body?
sites of inflammation
75
COX enzymes are derived from what substance?
arachidonic acid
76
Why was the Rofecoxib drug trial stopped?
twice the increased risk of MI and stroke
77
MOA of Acetaminophen:
thought to be similar to NSAIDs but more central effect; no effect on inflammation OR PLTs
78
Disadvantage of Acetaminophen:
potentially fatal hepatic necrosis (no more than 4g/day) -- most recommendations are now less than 3.25g
79
How is Acetaminophen metabolized?
- sulfination conjugation
- glucoronidation conjugation
- CYP3A4 & CYP2E1
80
What happens to Acetaminophen that is metabolized via CYP3A4/CYP2E1 enzymes?
becomes NAPQI
- glutathione conjugation
OR
- reaction with proteins that causes toxicity
81
What accounts for half of all cases of acute liver poisoning?
acetaminophen poisoning
82
Describe the sequence of events leading to Acetaminophen toxicity:
- CYP metabolism to a reactive metabolite (NAPQI)
- glutathione depletion
- metabolite binds to proteins
- changes in mitochondrial permeability leading to oxidative stress, loss of mitochondrial membrane potential, and loss of ability of ability to synthesize ATP
83
Dosage adjustment of Acetaminophen for severe renal impairment:
increase dosing interval to Q8h
84
Dosage adjustment of Acetaminophen for moderate renal impairment:
- increase dosing interval to Q6h for adults
- normal or age-based dose for peds
85
Is IV Tylenol more effective?
no - equivalent plasma concentration is reached, IV just works faster
86
Effects of NSAIDs + Tylenol:
greater analgesia without significant increase in adverse effects associated with opioid-containing combos
87
MOA of Methotrexate:
immunosuppressive cancer chemotherapeutic
88
MOA of Hydroxycholoroquine:
antimalarial agent that suppresses T lymphocytes and leukocytes
89
MOA of gold for antirheumatism:
decrease bone and articular destruction
90
MOA of Penicillamine:
interferes with DNA synthesis and suppresses the immune system
91
MOA of Sulfasalazine:
metabolized to 5-ASA (mechanism for UC) - may work on B cell fxn
92
5 meds to treat gout:
- colchicine
- indomethacin
- allopurinol
- probenecid
- sulfinpyrazone
93
How is allopurinol used to treat gout?
- xanthine oxidase inhibition that prevents more gout
94
Presence of a charge (H+) on local anesthetics makes the molecule more (hydrophilic/lipophilic)
hydrophilic
95
Amide LAs are metabolized ___
by enzymes (CYP450) in the liver
96
Ester LAs are metabolized ___
by ester hydrolysis in the plasma
97
List some ester LAs
(one i in the names)
- Cocaine (medium)
- Procaine (short)
- Tetracaine (long)
- Benzocaine (surface use only)
98
List some amide LAs
(2 i in the names)
- Lidocaine (medium)
- Mepivacaine (medium)
- Bupivacaine (long)
- Prilocaine (medium)
- Ropivacaine (long)
99
3 physiochemical properties that affect absorption of LAs
pKa
pH
lipid solubility
100
3 physiologic conditions of the site of injection that affect absorption of LAs
pH
CO2 levels
temperature
101
In LAs, the + charged quaternary amine is (ionized/unionized) and the uncharged tertiary amine is (ionized/unionized)
quaternary = ionized
tertiary = unionized
102
For LAs to cross the epineurium, they must be _____.
For LAs to bind and block the Na+ channel, they must be _____.
unionized
ionized
103
A drug with a low % unionized and a (low/high pKa) will have a (shorter/longer) onset
high pKa and longer onset d/t a smaller amount of the drug is able to cross the membrane
104
A drug with a high % unionized and a (low/high pKa) will have a (shorter/longer) onset
low (close to physiologic pH) pKa and shorter onset d/t a larger amount of the drug is able to cross the membrane
105
Describe what happens when sodium bicarbonate is added to a LA
- raises pH of the solution
- increases amount of unionized LA
- faster diffusion of agent across the membrane
- faster onset of nerve blockade
106
Local anesthetics work on which parts of the pain pathway?
transduction & transmission
107
MOA of LAs:
block voltage-gated Na+ channels and decrease the ability to generate an AP
108
4 factors that contribute to a LA nerve blockade
1) myelination
2) fiber placement
3) fiber size
4) blood flow to the area
109
Describe how blood flow affects a nerve blockade
Areas with high blood flow will have increased diffusion and less of the LA staying at the site of action to block the Na+ channels
110
What impact does the refractory period of neuronal axon depolarization have on the impulse?
blocks another depolarization in that direction, forcing the impulse to only travel in one direction
111
MOA of TTX (tetrodotoxin)
- selective blockade of Na+ channel from the outside
- blocks the AP of nerve and skeletal muscle leading to respiratory paralysis
- made by bacteria in the puffer fish
- no reversal agent
112
Describe a frequency dependent block
Nerves firing at greater frequency have channels which open at a higher rate and will block faster d/t the agent entering the channel more quickly
113
(Smaller/Larger) fibers block more quickly
smaller
114
(Myelinated/Unmyelinated) fibers block more quickly
unmyelinated (C fibers)
115
2 types of nerve fibers associated with pain
A-delta and C fibers
116
LA can only block myelinated nerves at ____ and _(#)_ are required for a differential nerve block to be effective
nodes of Ranvier
3 are required
117
4 physical characteristics that affect a differential nerve block
1) placement
2) size
3) diameter
4) internodal distance
118
(Small/Large) nerve fibers promote faster conduction
Large
small=slow conduction
119
Describe how temperature affects frequency of neuron firing
frequency increases as T increases
120
Sensations are blocked in the following order:
- pain
- cold
- warmth
- touch
- deep pressure
- motor
121
Sensation is recovered in the following order:
- motor
- deep pressure
- touch
- warmth
- cold
- pain
122
Type of LA and profile of Procaine:
Used for:
- type: ester
- profile: slow onset, short duration, low tox
- use: local infiltration & spinal
123
Type of LA and profile of Chloroprocaine:
Used for:
- type: ester
- profile: very fast onset, short duration, very low tox
- use: local infiltration, nerve block, epidural
124
Type of LA and profile of Tetracaine:
Used for:
- type: ester
- profile: slow onset, long duration, moderate tox
- use: spinal
125
Type of LA and profile of Lidocaine:
Used for:
- type: amide
- profile: fast onset, moderate duration, moderate tox
- use: all types of regional
126
Type of LA and profile of Bupivacaine:
Used for:
- type: amide
- profile: slow onset, very long duration, high tox
- use: most types of local and regional
127
Type of LA and profile of Etidocaine:
Used for:
- type: amide
- profile: fast onset, very long duration, moderate tox
- use: nerve blocks, epidural
128
Type of LA and profile of Ropivacaine:
Used for:
- type: amide
- profile: slow onset, very long duration, moderate tox
- use: similar to Bupivacaine; most types of local and regional; less cardiac toxicity
129
4 major factors involved in distribution of LA:
1) site of administration - vascularity, fat content
2) vasoactivity
3) tissue binding - Vd, plasma protein binding
4) patient conditions - age, dz state, pregnancy
130
A 1% solution of any drug contains...
1 g of drug per 100mL of solution
131
A 1% lidocaine solution contains ___ mg/mL
10 mg/mL
132
A 1 mg ampoule of 1:1000 epinephrine soln contains ___ mg/mL
1 mg/mL
133
A 1:100,000 soln of epi contains ___ mg/mL
10 mcg/mL
134
A 1:200,000 soln of epi contains ____/mL
5 mcg/mL
135
Epi should not be added to LA that are administered to which body parts?
end organs (fingers, toes, penis, nose, ears)
136
Max safe dose of Epi =
4 mcg/kg
137
What s/s are you watching for when injecting large volumes of LA?
tachycardia
138
Recommended dose of sodium bicarb:
1 mL of 8.4% sodium bicarb per 10 mL of LA
139
There is little advantage in adding sodium bicarb to which LAs?
Bupivacaine or Ropivacaine
140
First clinical sign of Lidocaine toxicity:
circumoral and tongue numbness
THEN
tinnitus, lightheadedness
141
Allergic reactions to LA are most commonly to...
esters (PABA metabolite)
or a preservative
142
Which LA solutions should never be given spinally, epidurally, or via Bier block?
those with preservatives = acts as a neurotoxin
143
An NSAID that is least likely to cause a GI bleed is _______
selective COX-2 inhibitor (....coxib)
144
Describe the cardiovascular toxicity hypothesis:
NSAID-related hyperthrombotic state is d/t decreased prostacyclin and no effect on thromboxane
145
MAOIs + which drug class is associated with serotonin-reuptake and can cause serotonin syndrome?
phenylpiperidine opioids (esp Meperidine)
146
Parecoxib has a ceiling effect at what dose?
20mg (per the graph, it demonstrates a less significant effect at the next highest dose)
147
List some NSAIDS
*what is one important thing to know about dosing?*
- Ibuprofen
- Indomethacin
- Naproxen
- Diclofenac
*ceiling effect*
148
Common SE of Fentanyl
chest wall rigidity
149
Which opioid has the greatest effec ton SVR? Why?
Morphine d/t the histamine release
150
Fentanyl + Midazolam interact when it comes to hypoxemia/apnea. Describe this relationship.
synergistic effect
1+1=3
151
Drug that is most likely to be associated with Stevens-Johnson syndrome:
Valdecoxib - a sulfonamide
