Exam 2: NSAIDs and Opioids Flashcards
(105 cards)
1
Q
Receptor most responsible for transmission of pain signals:
A
TRPV1
2
Q
Function of B2 receptor:
A
Enhances TRPV1 activity
3
Q
Function of prostanoid receptor:
A
Aids in depolarization of pain fiber via enhancement of voltage-gated Na+ channel
4
Q
Function of opioid, cannabinoid, and norepi receptors:
A
Hyperpolarization of pain fibers via ↑ K+ retention
5
Q
B2 receptors activated by:
A
Bradykinin
6
Q
Laminae of Αδ fibers:
A
I, II, III, V
7
Q
Laminae of C fibers:
A
I, II
8
Q
Laminae of substantia gelatinosa:
A
II, III
9
Q
Substantia gelatinosa is important because:
A
Richly populated with opioid peptides, receptors
Inhibitory interneurons
10
Q
Area of the brain that descends neurons into substantia gelatinosa:
A
Nucleus raphe magnus
11
Q
Opioid action in the brain:
A
Pre- and postsynaptically activate descending inhibitory pathways
12
Q
Opioid action in the SC:
A
Directly on the dorsal horn
13
Q
Opioid action in the periphery:
A
Peripheral terminals of nociceptive neurons
14
Q
Opioid effect on pain perception:
A
Changes tolerance of pain without necessarily changing ability to perceive pain
15
Q
Opioid effect on physiological response to pain:
A
Reduces neuroendocrine response:
SNS activation
Cortisol
Norepi release
16
Q
Opioid use in anesthesia:
A
Attenuate SNS response to stimuli
Adjunct to IAs
Can be sole anesthetic (cardiac/trauma)
Periop/postop pain mgmt
17
Q
Unique characteristics of opioids vs. other analgesics:
A
No max dose or ceiling effect
Tolerance develops with chronic use
Produces analgesia without loss of touch/proprioception/consciousness
18
Q
Ex. of naturally occuring opioids:
A
Morphine, codeine
19
Q
Ex. of semisynthetic analogs of morphine:
A
Heroin, dihydromorphone
20
Q
Classifications of opioids:
A
Full agonist
Partial agonist
Mixed agonist/antagonist
Antagonist
21
Q
MoA (presynaptic) of opioids:
A
Inhibits release of excitatory NTs (ACh, dopamine, norepi, substance P)
22
Q
MoA (postsynaptic) of opioids:
A
Directly decreases neurotransmission
↑ K+ conductance: hyperpolarization
↓ Ca2+ channel activity: ↓ NT release
Modulation of phospholipase C
↓ cAMP
23
Q
Opioid receptors:
A
Mu
Kappa
Delta
24
Q
Mu-1 receptor locations:
A
Supraspinal*
Spinal
Peripheral
25
Effects of mu-1 receptor activation:
```
Euphoria
Miosis
Bradycardia (good in adults, not in peds)
Urinary retention
Hypothermia
```
26
Effects of mu-2 receptor activation:
Hypoventilation
Physical dependence
Constipation
27
Mu-2 receptor locations:
Spinal*
| Some supraspinal
28
Kappa receptor locations:
Supraspinal*
Spinal*
Peripheral
29
Effects of kappa receptor activation:
Dysphoria
Sedation
Miosis
Diuresis
30
Drugs that work on kappa receptors:
Dynorphins
| Opioid agonist-antagonists
31
Delta receptor locations:
Peripheral*
Supraspinal
Spinal
32
Effects of delta receptor activation:
Hypoventilation
Constipation
Urinary retention
33
Drugs that work on delta receptors:
Enkephalins
34
Two mutations to 6q24-q25 that can affect response to opioids:
```
Nucleotide 118 (10-20%)
Nucleotide 17 (1-10%)
```
35
CYP450 mutation that alters metabolism of some opioids:
CYP2D6
| Unpredictable PK and t1/2 of codeine, oxycodone, hydrocodone, and methadone
36
Drug least likely to be impacted by genetic variability:
Fentanyl
37
Ultra-rapid metabolizers at increased risk of:
PONV
| and other side effects
38
CV effects of opioids:
Minimal impairment when used alone
Dose dependent bradycardia (vagal stimulation, direct SA/AV node depression)
Vasodilation/↓SVR (impairment of SNS tone, leading to ↓CO, ↓BP esp. with hypovolemia)
39
CV effects of morphine and meperidine:
Dose dependent histamine release
Bronchospasm
↓SVR, ↓BP
40
Exception to bradycardia effect of opioids:
Meperidine; causes tachycardia with direct myocardial depression
41
CNS effects of opioids:
```
Analgesia
Euphoria
Drowsiness
Miosis
Nausea
No amnesia
Decrease ICP and CBF - only if no hypoventilation though
```
42
Renal, GI, liver effects of opioids:
↑ tone of ureter and detrusor tone leads to urgency without ability to void
↓ catecholamine and cortisol release
Sphincter of Oddi spasm, ↑ biliary pressure
GI smooth muscle spasm
Constipation
N/V
43
How can opioids cause angina-mimicking pain?
Sphincter of Oddi/gallbladder spasms
44
Means by which opioids cause N/V:
↓ gastric emptying
| Stimulation of CTZ on floor of 4th ventricle
45
Describe pruritis from opioids:
Unknown cause, likely histamine release
| Primarily on face, esp. nose
46
Skeletal muscle effects of opioids:
Rigidity in chest, abdomen, jaw, extremities (esp. large, rapid doses)
Difficult/impossible ventilation, ↑ airway pressure
Glottic rigidity/closure
47
Opioids particularly prone to causing rigidity:
Fentanyl
Sufentanil
Hydromorphone
48
Ventilatory effects of opioids:
Dose dependent respiratory depression (small doses: ↑ Vt, ↓ RR with overall ↓ MV; large doses: ↓ Vt and RR)
↓ chest wall compliance
Cough suppression
Constriction of laryngeal/pharyngeal muscles
↓ response to hypercarbia, hypoxia
Morphine/meperidine: histamine-related bronchospasm
49
Opioid-induced changes in ventilatory response curve:
Reduced slope and shifted to right
50
Indications for PO morphine:
Severe acute pain: IM/IV
| Chronic/cancer pain: PO
51
PK of PO morphine:
Considerable first pass effect
Et1/2: 3-4 hrs
Active metabolite
52
Indications for PO codeine:
Mild pain
| Cough (lower dose)
53
PK of PO codeine:
Et1/2: 3hrs
| Prodrug; 10% converted by CYP2D6 to active form, morphine
54
Racial groups prone to missing CYP2D6:
Caucasian (10%)
| Asian (30%)
55
Indications for PO hydrocodone:
Chronic pain
| Post-op pain relief
56
Formulation of PO hydrocodone:
Always combined with APAP, ASA, ibuprofen, or antihistamine
57
Indications for PO oxycodone:
Moderate to severe pain
Chronic pain
Post-op pain
58
Formulation of PO oxycodone:
Alone
Sustained-release
Combined with APAP or ASA
59
Patient population for which oxycodone and methadone are safer:
Renal - no active metabolites
60
Indications for PO methadone:
Chronic pain syndrome
| Opioid addiction
61
PK of PO methadone:
Et1/2: 8-59 or 13-100 hrs
| No active metabolites
62
Dosing schedule for methadone:
QD for addiction
| BID/TID for pain
63
Order of events when tolerance develops to opioids:
↓ adverse effects
↓ duration of analgesia
↓ effectiveness of each dose
64
When switching from one opioid to another:
Start with half or less of equianalgesic dose
65
Side effect of opioids that pts do not develop tolerance to:
Constipation
66
Breakthrough pain dose for opioids:
10-15% of total daily dose in immediate release form
67
Receptors that provide neuraxial analgesia from opioids:
Mu receptors in substantia gelatinosa
68
Cephalad movement of opioid in CSF limited by:
Lipid solubility
Fentanyl (highly lipid soluble) limited in migration
Morphine (less lipid soluble) will remain in CSF and migrate to cephalic region
69
Epidural vs. spinal opioid dose:
Epidural is 5-10x higher dose
70
Indications for non-opioid analgesics:
Mild to moderate pain
71
Ceiling effect dose of ASA and APAP:
650-1300mg
72
MoA of acetaminophen:
Central anti-prostaglandin effect
Blockade of NMDA receptor in CNS
Blockade of substance P in spinal cord
Weak anti-inflammatory behavior; no peripheral activity
73
Dosage of acetaminophen:
PO: 325-650mg q4-6hr
IV: 1gm over 15 min infusion q4-6hr
74
PK of acetaminophen:
Conjugated/hydroxylated to inactive metabolites
| Very little excreted unchanged by kidneys
75
Overdose of acetaminophen:
Serious or fatal hepatic injury when glutathione overwhelmed by acetaminophen
↑ risk of toxicity in ETOH, isoniazid use
Tx with acetylcysteine to sub for glutathione
76
Renal toxicity from acetaminophen:
Metabolites accumulate in renal papillae and cause renal cell necrosis
Relatively low risk
77
Three pathways of arachadonic acid metabolism:
Cyclooxygenase
Lipoxygenase
Epoxygenase
78
Cyclooxygenase metabolism of arachadonic acid leads to formation of:
Prostaglandins
Prostacylcin
Thromboxanes
79
Lipoxygenase metabolism of arachadonic acid leads to formation of:
Leukotrienes
| Lipoxins
80
COX-1 prostaglandins serve in:
Gastric protection
Hemostasis
Renal function
81
COX-2 prostaglandins serve in:
Pain
Inflammation
Fever
82
Indications for aspirin:
Mild to moderate pain
Fever
MI/stroke prevention
83
Duration of action of aspirin:
Life of platelet; 8-10 days
Irreversible!
84
System side effects of aspirin:
```
Prolonged bleeding but no renal disease
Can ↑ LFTs (reversible)
Can potentiate asthma
GI bleeding/PUD
CNS stimulation
```
85
Dosage of aspirin:
Analgesic: 325-650mg
| Anti-inflammatory: 1000mg (3-5g/day)
86
PK of aspirin:
Hepatic clearance
Active metabolite
Et1/2: 15-20 min for ASA, 2-3 hrs for salicylic acid
87
S/s of ASA overdose:
Metabolic acidosis
| Tinnitis
88
Efficacy of NSAIDs:
More effective than ASA/APAP
Equal or greater than usual doses of opioid+APAP
Anti-inflammatory
89
MoA of NSAIDs:
Blocks conversion of arachidonic acid to prostaglandins --> analgesic, anti-inflammatory, antipyretic
90
PK of NSAIDs:
```
Weak acids, well absorbed
Highly protein bound (>95%)
Small Vd
Extensively metabolized
Excreted in urine
Et1/2 varies: < 6 to > 12 hrs
```
91
Side effects of NSAIDs:
Asthma/anaphyalctoid rxns
Plt inhibition (reversible)
Hepatic injury, aseptic meningitis (rare)
92
Pregnancy and NSAIDs:
Avoid in third trimester d/t premature closure of DA
93
COX inhibition in the peri-op period can cause:
Renal injury
Gastric ulcers
Bleeding
Impaired bone healing
94
GI adverse effects of NSAIDs:
```
Dyspepsia
GI bleeding
PUD
↑ acid production
↓ mucus production, gastric blood flow
Irritation due to trapping in mucosal cells
```
95
Risk factors for GI effects with NSAIDs:
```
High dose
Long-term use
Hx of ulcer/GIB
ETOH
Elderly
*Corticosteroids
```
96
Low-risk NSAIDs:
Low-dose ibuprofen, naproxen
Etodolac
Sulindac
Celecoxib
97
High-risk NSAIDs:
```
Tolmetin
Piroxicam
Aspirin
Indomethacin
Ketorolac
```
98
Renal side effects of NSAIDs:
↓ synthesis of renal vasodilator PGE2
↓ renal blood flow --> fluid/Na+ retention --> renal failure/hypertension (this is only in susceptible populations)
99
Drug interactions with NSAIDs:
Displaces other protein-bound drugs (warfarin, phenytoin, sulfonamides, digoxin)
↓ effect of diuretics, β blockers, ACEIs
↑ lithium levels
Probencid ↑ levels of NSAIDs
100
Only IV NSAID in US:
Ketorolac
101
PK of ketorolac:
```
Onset 10 min (IV)
Et1/2: 5 hrs
Duration: 6-8 hrs
99% protein-bound
Conjugated in liver
```
102
Dosing of ketorolac:
30mg IV q6hr
Daily max 120mg
1/2 dose for elderly
103
Only selective NSAID:
Celecoxib
104
Dosing of celecoxib:
< 200mg/day
105
Adjuvant analgesics:
Antidepressants/anticonvulsants for neuropathic pain
Hydroxyzine for cancer and post-op pain (plus ↓ PONV)
Corticosteroids for inflammatory disease of tumor infiltration of nerves
Topical analgesics
