Peripherally-Acting Analgesics and Corticosteroids Flashcards

1
Q

What are the effects of NSIADs?

A

Have central & peripheral effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the principle action of NSAIDs?

A

blockade of prostaglandin production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What does the NSAIDs inhibit?

A

the activity of cyclooxygenase enzymes (COX-1 and COX-2) that are required for the production of prostaglandins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the primary MOAC of NSAIDs?

A

inhibiting the biosynthesis of prostaglandins by preventing the substrate arachidonic acid from binding to the COX enzyme active site

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is arachidonic acid?

A

present in cellular tissues and is released when the cellular membranes are disrupted by injury or disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is prostaglandins?

A

localized hormones that are responsible for inflammatory activity (vasodilation, erythema, edema, fever) and nociceptor sensitization

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

NSAIDS can be classified by ______ selectivity

A

COX

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the two COX forms?

A

cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is COX1?

A

catalyzes production of prostaglandins that maintain physiologic functions: – maintain normal renal function, mucosal protection in GI tract, proaggregatory thromboxane A2 in platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is COX2?

A

expression induced by inflammatory mediators in tissues, role in mediation of pain, inflammation, & fever; some anticoagulation activity, modulation of cell proliferation and pain sensitization

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is COX-1 activity?

A
  • Hemostasis

- gastric mucosa protection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is COX-1 inhibition benefits?

A
  • possible reduced neuro inflammation targets at microglia

- cardio-protective anti coagulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is COX1- inhibition risks?

A
  • can cause bleeding

- increased risk of gastric irritation & ulcers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What can COX-2 activity?

A
  • inflammatory response
  • fever
  • pain sensation
  • anticoagulation
  • modulation of cell proliferation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What can COX-2 inhibition benefits?

A
  • reduced inflammation
  • reduced fever
  • reduced pain sensation
  • possible reduction in cancer progression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What CO2 inhibition risks??

A

Increase risk of thrombotic activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What properties of NSAIDS?

A

Antipyretic, anti-inflammatory and analgesic properties

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the characteristics of NSAIDs?

A

Weakly acidic, highly protein bound, lipophilic, low volume of distribution, and only the unbound portion is effective

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the pKa of NSAIDs? What formed does it exist?

A
  • NSAIDs are weak acids with pKa values typically lower than 5
  • Exists mostly in the ionized form at physiologic pH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the protein bind of NSAIDs?

A

> 90% bound to albumin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What can occur from hypoalbuminemia with NSAIDs?

A

hypoalbuminemia & displacement by other drugs that are albumin bound can result in greater unbound NSAID & increased risk for toxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the elimination of NSAIDs?

A

Elimination via hepatic oxidation and conjugation (less than 10% eliminated via renal activity)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What some principles of NSAIDs?

A
  • Decreased activation and sensitization of peripheral nociceptors
  • Attenuation of the inflammatory response
  • Absence of dependence or addiction potential
  • Synergistic effects with opioids
  • Preemptive analgesic effects
  • Absence of respiratory depression
  • Minimal N&V compared to opioids
  • Long duration of action
  • No effects on cognition
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is true about NSAIDs and hypersensitivity?

A
  • Hypersensitivity reactions more common in individuals w/nasal polyps or asthma
  • allergic reactions – bronchoconstriction, rhinitis, urticaria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What is the platelet effects of NSAIDs?
Platelet inhibition/dysfunction, increased intraoperative bleeding
26
What is the gi effects of NSAIDs?
ulcers, perforation, GI bleeds
27
What is the CV effects of NSAIDS?
increased risk of MI, heart failure, and HTN
28
What is the NSAIDs drug of choice for pt with cardiovascular complications?
Naproxen
29
What is the renal effects of NSAIDS?
changes in the excretion of sodium, changes in tubular function, potential for interstitial nephritis, and reversible renal failure – should be avoided in patients with renal failure
30
What is the liver effects of NSAIDS?
liver failure and increased hepatic transaminase level reported with some NSAIDs
31
What is the pulmonary effects of NSAIDS?
due to inhibition of prostaglandin synthesis in local tissues
32
Who is at increased risk for anaphylaxis for NSAIDs?
Patients with allergic rhinitis, nasal polyposis, asthma
33
What are some drug interactions of NSAIDs?
- Increased bleeding risk for patients taking other antiplatelet agents - NSAIDs decrease lithium clearance and increase serum lithium concentrations - Conflicting data regarding interactions between NSAIDs and ACE inhibitors - Concurrent administration of digoxin can decrease renal clearance of of digoxin, increase plasma dig levels, and potentiates dig toxicity
34
What is the route for acetaminophen?
po, rectal, IV
35
What does acetaminophen lack?
- Lacks significant anti-inflammatory properties | - Inhibits COX activity in the CNS rather than in the periphery
36
IV Acetaminophen: Analgesic and antipyretic for adults and children __________
> 2 years of age
37
IV Acetaminophen: Significant __________ sparing effect
opioid
38
What is true regarding the effects of IV Acetaminophen?
Does not exhibit significant GI and CV effects associated with NSAIDs
39
What is the onset, duration and peak effect of IV Acetaminophen?
10 minutes; peak effect 1 hour; duration of action 4-6 hours
40
What is the dosing of acetaminophen > 13 years old?
1000 mg infused over 15 minutes
41
What is the dosing of acetaminophen 2-13 years old | ?
15 mg/kg
42
When is hepatotoxicity a concern with IV acetaminophen?
Side effects rare but hepatotoxicity a concern with > 4000 mg/day
43
What drug class is Acetylsalicylic Acid (Aspirin)?
Nonselective COX inhibitor
44
What is the MOA of Acetylsalicylic Acid (Aspirin)?
- Causes irreversible inhibition of COX enzymes (inhibition lasts approx. 7 days until new protein is produced) - Prevents production of prostaglandins
45
What are the properties of Acetylsalicylic Acid (Aspirin)?
Excellent long-term antipyretic and anti-inflammatory properties
46
What can be prolonged with Acetylsalicylic Acid (Aspirin)?
Significant impact on platelet aggregation that may be prolonged
47
What is ketorolac?
Nonselective NSAID
48
What is the characteristics of ketorolac?
Low incidence of nausea/vomiting and lack of respiratory depression
49
What is the dosing of ketorolac?
30-60 mg IM/max IV dose = 30mg
50
What is the onset and duration of action of ketorolac?
Onset 30 minutes; duration of action 4-6 hours
51
When should ketorolac be used?
atopic or asthmatic patients, the elderly, patients with renal or GI dysfunction or bleeding disorders
52
What negative effects of ketorolac can be seen (2)?
-Bone healing is delayed (Blocks the mesenchymal stem cells chondrogenic differentiation) -Bleeding may also be an issue in intracranial surgery
53
What are the properties of Ibuprofen (Caldolor)?
Analgesic and antipyretic, Clinical effects similar to ketorolac
54
What is the dose of Ibuprofen (Caldolor)?
400-800 mg IV over 30 minutes
55
What is the onset and duration of Ibuprofen (Caldolor)?
Onset 30 minutes; duration 4-6 hours
56
What are the contraindications of | Ibuprofen (Caldolor)?
Contraindications and precautions similar to ketorolac
57
What is the derivative of Ibuprofen (Caldolor)?
Proprionic acid derivative
58
What is the only COX2 selective inhibitor on the market?
Celecoxib (Celebrex)
59
What is the dose of Celecoxib (Celebrex)?
loading dose = 400 mg followed by 200 mg q 12 hours
60
What are the positive effects of Celecoxib (Celebrex)?
COX2 inhibitors have reduced incidence of GI ulceration and do not inhibit platelet function
61
What can Celecoxib (Celebrex) cause?
fluid retention and hypertension
62
When should Celecoxib (Celebrex) not be prescribed?
Should not be prescribed to patients with known history of CAD or cerebrovascular disease
63
What can cause increase incidence of side effects with Celecoxib (Celebrex)?
Be wary of ketorolac at end of case of patient received full celebrex dose preoperatively (increased incidence of side effects)
64
How do Celecoxib (Celebrex) (COX2 inhibitors) differ from nonspecific NSAIDs?
Highly lipophilic, neutral, non-acidic molecules with limited solubility in aqueous media
65
What are the effects of Corticosteroids (Glucocorticoids)?
have analgesic, anti-inflammatory, and antiemetic effect
66
When is Corticosteroids (Glucocorticoids) used?
Used in multimodal analgesia protocols to minimize opioid doses: dexamethasone at doses > 0.1 g/kg decreases acute postop pain & reduces opioid use esp. when administered preoperatively
67
What causes the anti-inflammatory and analgesic effects of Corticosteroids (Glucocorticoids)?
inhibition of phospholipase A2 enzyme necessary for inflammatory chain reaction along both the lipoxygenase and COX enzyme pathways
68
What does Corticosteroids (Glucocorticoids) inhibit?
- Inhibits prostaglandin synthesis | - Also results in decrease in inflammatory cytokines
69
What are side effects of Corticosteroids (Glucocorticoids)?
adrenal suppression, osteonecrosis, increased blood glucose, and impaired wound healing
70
What is the primary corticosteroid?
hydrocortisone – standard against which synthetic corticosteroids are judged
71
What is the MOA of Corticosteroids (Glucocorticoids)?
- Attach to cytoplasmic receptors to enhance or suppress changes in the transcription of DNA & synthesis of proteins - Inhibit secretion of cytokines
72
What is Glucocorticoids?
widely distributed; evoke anti-inflammatory response (glucocorticoid effect)
73
What is a Mineralocorticoid?
present in distal renal tubules, colon, salivary glands, hippocampus; evokes distal renal tubular reabsorption of sodium in exchange for potassium ions (mineralocorticoid effect)
74
Why are Glucocorticoids important during surgery?
critical for the maintenance of homeostasis during severe stress & mounting an appropriate stress response
75
______physiologic steroid concentrations prepare the individual for responding to stress
Low
76
_______ concentrations exert anti-inflammatory & immunosuppressive effects
Higher
77
What is cortisol?
is released from the adrenal glands in an episodic manner, is linked to sleep-wake cycle
78
What is max and min concentrations of cortisol?
maximal plasma concentrations of cortisol occur just before awakening & lowest levels 8-10 hours late
79
What changes does stress-induce have on cortisol?
Stress-induced changes in plasma concentrations of cortisol occur (in addition to baseline release of cortisol)
80
What controls cortisol synthesis?
governed by adrenocorticotropic hormone (ACTH) which is controlled by: hypothalamic hormones, corticotropin-releasing hormone, & arginine vasopressin
81
What are endogenous corticosteroids?
cortisol, cortisone, coricosterone, desoxycortisosterone, aldosterone
82
What are synthetic corticosteroids?
prednisolone, prednisone, methylprednisolone, betamethasone, dexamethasone, triamcinolone
83
Review Clinical uses.
Slide 86-87
84
What are the side effects of corticosteroids?
- Suppression of the HPA (hypothalamic-pituitary-adrenal) axis - Electrolyte and metabolic changes - Osteoporosis - Peptic ulcer disease - Skeletal muscle myopathy - Inhibition of normal growth - Increased susceptibility to bacterial or fungal infection
85
Who should receive corticosteroid supplementation?
Patients taking > 20mg/day of prednisone or its equivalent for > 3 weeks have a suppressed HPA axis
86
Patients taking < 5mg/day of prednisone or its equivalent can be considered ___________ HPA axis
considered not to have suppression of the HPA axis
87
Patients taking 5-20mg/day of prednisone or its equivalent for > 3 weeks __________ have suppression of the HPA axis
may or may not
88
For patients with ________ (pts taking > 20mg/day of prednisone for > 3 weeks), glucocorticoid supplementation should consider the stress of surgery
Suppressed HPA axis
89
What is the recommended minor surgical stress for corticosteroid supplementation?
(i.e., inguinal hernia repair) – hydrocortisone 25mg IV or methylprednisolone 5mg IV is sufficient
90
What is the recommended moderate surgical stress for corticosteroid supplementation?
(i.e., non-laparoscopic cholecystectomy, colon resection, total hip replacement) – hydrocortisone 50-75mg/day IV for 1-2 days
91
What is the recommended majoe surgical stress for corticosteroid supplementation?
(i.e., pancreatoduodenectomy, esophagectomy, cardiopulmonary bypass) – hydrocortisone 100-150mg/day IV for 2-3 days