Exam 2: NSAIDs and Opioids Flashcards Preview

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Flashcards in Exam 2: NSAIDs and Opioids Deck (105):
1

Receptor most responsible for transmission of pain signals:

TRPV1

2

Function of B2 receptor:

Enhances TRPV1 activity

3

Function of prostanoid receptor:

Aids in depolarization of pain fiber via enhancement of voltage-gated Na+ channel

4

Function of opioid, cannabinoid, and norepi receptors:

Hyperpolarization of pain fibers via ↑ K+ retention

5

B2 receptors activated by:

Bradykinin

6

Laminae of Αδ fibers:

I, II, III, V

7

Laminae of C fibers:

I, II

8

Laminae of substantia gelatinosa:

II, III

9

Substantia gelatinosa is important because:

Richly populated with opioid peptides, receptors

Inhibitory interneurons

10

Area of the brain that descends neurons into substantia gelatinosa:

Nucleus raphe magnus

11

Opioid action in the brain:

Pre- and postsynaptically activate descending inhibitory pathways

12

Opioid action in the SC:

Directly on the dorsal horn

13

Opioid action in the periphery:

Peripheral terminals of nociceptive neurons

14

Opioid effect on pain perception:

Changes tolerance of pain without necessarily changing ability to perceive pain

15

Opioid effect on physiological response to pain:

Reduces neuroendocrine response:
SNS activation
Cortisol
Norepi release

16

Opioid use in anesthesia:

Attenuate SNS response to stimuli
Adjunct to IAs
Can be sole anesthetic (cardiac/trauma)
Periop/postop pain mgmt

17

Unique characteristics of opioids vs. other analgesics:

No max dose or ceiling effect
Tolerance develops with chronic use
Produces analgesia without loss of touch/proprioception/consciousness

18

Ex. of naturally occuring opioids:

Morphine, codeine

19

Ex. of semisynthetic analogs of morphine:

Heroin, dihydromorphone

20

Classifications of opioids:

Full agonist
Partial agonist
Mixed agonist/antagonist
Antagonist

21

MoA (presynaptic) of opioids:

Inhibits release of excitatory NTs (ACh, dopamine, norepi, substance P)

22

MoA (postsynaptic) of opioids:

Directly decreases neurotransmission

↑ K+ conductance: hyperpolarization
↓ Ca2+ channel activity: ↓ NT release
Modulation of phospholipase C
↓ cAMP

23

Opioid receptors:

Mu
Kappa
Delta

24

Mu-1 receptor locations:

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