Week 5 (Quiz 3) (Anti-inflammatory) Flashcards
1
Q
NSAIDS block
A
COX-1 and COX-2
2
Q
NSAIDS desired effects come from:
A
COX-2
3
Q
NSAIDS SE come from:
A
COX-1
4
Q
Salicylates example
A
Aspirin
5
Q
Salicylates mechanism
A
selectively acetylates serine residue in COX active site (irreversible) - more COX-1 selective therefore higher doses are needed to have COX-2 inhibition
6
Q
4 A’s (Uses of salicylates)
A
- low doses: Anti-platelet (TIAs, stroke, MI prophylaxis)
- intermediate doses: Analgesic; Anti-pyretic (medium to
low grade fevers) - high doses: Anti-inflammatory (arthritis, joint swelling)
7
Q
Propionic acid examples
A
Ibuprofen, Naproxen
8
Q
Mechanism of propionic acids
A
competitively, reversibly binds COX active site
9
Q
Use of propionic acids
A
anti-inflammatory, analgesic, antipyretic
10
Q
SE of propionic acids
A
- less GI distress and ulcers than ASA
- acute renal insufficiency and chronic interstitial
nephritis (↑ vascular tone) - allergic reactions (rash, urticaria, bronchoconstriction)
11
Q
COX-2 selective inhibitor examples
A
Celecoxib, rovecoxib
12
Q
Mechanism of COX-2 selective inhibitors
A
drug is too large to bind COX-1 active site –> competitively binds COX-2 active site
13
Q
Use of COX-2 selective inhibitors
A
osteoarthritis, RA, familial adenomatous polyposis, dysmenorrhea, acute pain
14
Q
Goal of COX-2 selective inhibitors
A
to decrease the GI and vascular side effects common
with other NSAIDs
15
Q
SE of COX-2 selective inhibitors
A
- Increase risk in CV events
- renal damage
- allergic reactions
16
Q
Indomethacin mechanism
A
↓ movement of granulocytes into affected area
17
Q
Indomethacin use
A
close a patent ductus arteriosus; acute gout
18
Q
PGI2 effects
A
Decreased vascular tone, platelet aggregation and acid secretion
19
Q
PGE2 effects
A
Decreased vascular tone
Increased gastric mucous production, pain sensation, and body temp
20
Q
TXA2 effects
A
Increased vascular tone and platelet aggregation
21
Q
Acetaminophen examples
A
APAP, Tylenol
22
Q
Mechanism of acetaminophen
A
(most recent theory) conjugates with arachidonic acid in CNS (enzymes that do this are only in CNS) –> metabolite binds COX-1 and COX-2 to inhibit them
23
Q
Use of acetaminophen
A
analgesic, antipyretic; pain/fever control in children with viral infections and adults with bleeding/GI risks; weak anti- inflammatory action
24
Q
SE of acetaminophen
A
- almost none at therapeutic doses;
- allergic reactions (rash, urticaria, bronchoconstriction)
- highly hepatotoxic w/ overdose
25
When can acetaminophen be toxic?
When glutathione is used up
26
Synthetic prostanoids examples
Misoprostol
27
Mechanism of synthetic prostanoids
Synthetic PGE1 analog, enhances normal PGE1 effects
Decreased acid production
28
Synthetic prostanoids use
- prevention of NSAID-induced peptic ulcers
- maintenance of patent ductus arteriosus (PDA)
- induces labor
29
SE of synthetic prostanoids
abortifacient (NEVER give to pregnant pts); diarrhea
30
Early response in asthma
bronchoconstriction
31
Late response in asthma
bronchial hyperreactivity, inflammation, mucous plugging, smooth muscle hypertrophy
32
Presentation of asthma
coughing, episodic wheezing, dyspnea, chest tightness (esp. at night/early morning)
33
Pathophys of asthma
antigen binds preformed IgE on mast cells --> degranulation of leukotrienes, prostaglandins, histamine --> inflammation and bronchoconstriction
34
What are the two first line bronchodilators?
Short acting B2 agonists, long acting B2 agonists
35
What are the members of the first line short acting B2 agonists?
albuterol, terbutaline
36
What is the action of the short acting B2 agonists?
bronchodilation
37
What is the use for short acting B2 agonists?
inhaled for acute attacks of mild asthma
38
What are the SE of short acting B2 agonists?
tachycardia, hyperglycemia, hypokalemia, hypomagnesemia
39
What are the members of the first line long acting B2 agonists?
salmeterol, formoterol
40
What is the acton of long acting B2 agonists?
bronchodilation
41
What is the use for long acting B2 agonists?
adjunctive therapy with corticosteroids - long-term management
42
What are the SE for long acting B2 agonists?
tachycardia, hyperglycemia, hypokalemia, hypomagnesemia
43
What are the members of the first line inflammation inhibitors?
Corticosteroids, glucocorticoids
44
What are the 2 dangerous side effects of salicylates?
- GI bleeding
| - Reye's syndrome
45
Members of corticosteroids/glucocorticoids
beclamethasone, fluticasone, prednisone
46
Actions of corticosteriods and glucocorticoids
inhibit inflammatory cascade
47
Use of corticosteriods and glucocorticoids
long-term management by reducing inflammatory response
48
SE of corticosteriods and glucocorticoids
few if inhaler used properly
49
Inflammation inhibitors combination therapy
Salmeterol + fluticasone
50
Action of salmeterol + fluticasone
inhibits inflammatory cascade and bronchodilates
51
Use of salmeterol + fluticasone
long-term management
52
Two second line brochoconstriction blockers/bronchodilators
Ipratropium and montekulast
53
Ipratropium mechanism
muscarinic receptor antagonist, blocks vagally mediated bronchoconstriction
54
Ipratropium use
asthma, COPD - esp. in pts unable to tolerate β2 agonists
55
Ipratropium SE
few if inhaled
56
Montekulast mechanism
binds cysteinyl leukotriene receptor (CysLT1) - blocks action of leukotriene D4 (prevents bronchoconstriction)
57
Montekulast use
prophylactic treatment of chronic asthma/seasonal allergies (> 12 y/o)
58
Montekulast SE
Churg-Strauss syndrome (autoimmune vasculitis); elevated liver function tests; HA
59
Cromolyn mechanism
prevents degranulation of mast cells
60
Cromolyn use
asthma prophylaxis ONLY
61
Cromolyn SE
few
62
Zileuton mechanism
inhibits 5-lipoxygenase --> ↓ leukotriene synthesis
63
Zileuton use
chronic asthma prophylaxis
64
Zileuton SE
elevated liver function tests
65
RA is characterized by what two things?
1) lymphocytic infiltration of synovial joints
| 2) granulomatous extra-articular nodules
66
Presentation of RA
morning stiffness that resolves throughout day; symmetric joint involvement; systemic symptoms
67
Pathophys of RA
autoimmune; positive rheumatoid factor (anti-IgG antibodies) --> ---> promotes release of IL-1, IL-6, TNF-α + activates T- cells --> activates B-cells to release autoantibodies + synovial inflammation and destructive changes (metalloproteases, osteoclasts)
68
Disease-modifying Anti-rheumatic Drugs (DMARDs) members
Methotrexate
Leflunomide
Sulfasalazine
Hydroxychloroquinone
69
Biologic Therapies
Anti-TNA-alpha antibodies
| Entanercept
70
Methotrexate mechanism low dose
inhibition of lymphocyte proliferation (blocks
| purine synthesis)
71
Methotrexate use
immunosuppressant for RA, psoriasis, Crohn's, etc.; for cancer at high doses
72
Methotrexate SE
mucosal ulceration, nausea, cytopenia, liver cirrhosis, pneumonia-like illness
73
Methotrexate mechanism high dose
folate antagonist
74
Leflunomide mechanism
block pyrimidine synthesis; acts on dihydroorotate dehydrogenase to inhibit autoimmune lymphocyte proliferation
75
Leflunomide use
alternative to MTX
76
Leflunomide SE
hepatotoxic, myelotoxic, HTN
77
Steroids mechanism
binds nuclear receptors in cell cytoplasm -->
changes protein levels in cells; possibly indirect inhibition of phospholipase A2 and reduced expression of COX-2 in immune cells; ↓ both prostanoids and leukotrienes
78
Steroids use
RA, allergic disorders (asthma etc.); acceleration of lung maturation in premature infants; cancer chemotherapy (trigger apoptosis and appetite)
79
Steroids - 2 major SE
Osteoporosis and iatrogenic Cushing's syndrome
80
Sulfasalazine (SSZ) mechanism
anti-inflammatory; antimicrobial
81
Sulfasalazine (SSZ) use
anti-inflammatory; antimicrobial
82
Sulfasalazine (SSZ) SE
leukopenia, hepatotoxic, hypersensitivity rxns
83
Hydroxychloroquinone mechanism
interferes with antigen processing; inhibits phospholipase A2
84
Hydroxychloroquinone use
malaria (primary); in combination with MTX/SSZ for autoimmune disorders
85
Hydroxychloroquinone SE
retinopathy
86
Anti-TNF-α Antibodies members
Infliximab, adalimumab
87
Anti-TNF-α Antibodies mechanism
binds/neutralizes TNF-α preventing downstream signaling and destructive symptoms
88
Anti-TNF-α Antibodies use
IV for autoimmune disorders; in combination with MTX (otherwise body develops antibodies to drug)
89
Anti-TNF-α Antibodies SE
Infusion rxns; increased risk of infection
90
Etanercept mechanism
genetically engineered fusion protein - binds TNF-α to prevent downstream signaling and destructive symptoms
91
Etanercept use
subQ for autoimmune disorders alone or in combination with MTX
92
Etanercept SE
local inflammation @ injection site; increased risk of infection
93
Presentation of gout
sudden onset of pain in first MTP; erythematous, swollen, exquisitely tender joint
94
Drug risk factor for gout
Thiazide diuretics
95
Why do you not treat gout with aspirin?
competes with uric acid for secretion via proximal kidney tubule
96
Three acute gout therapy drugs
Indomethacin
NSAIDS
Glucocorticoids
97
Three prophylactic/chronic gout treatments
Allopurinol
Colchicine
Probenecid
98
Allopurinol mechanism
purine analog --> competitive inhibition of uric acid synthesis; less likely to form crystals
99
Allopurinol use
chronic primary gout; secondary hyperuricemia (tumor lysis)
100
Allopurinol SE
hypersensitivity rxns; otherwise few side effects
101
Colchicine mechanism
plant alkaloid; depolymerizes MT by binding tubulin --> ↓ granulocyte ability to migrate to affected site
102
Colchicine use
gout prophylaxis
103
Colchicine SE
- acute: nausea, vomiting, abd pain, diarrhea
- chronic: myopathy, neutropenia, aplastic anemia,
alopecia
104
Probenecid/Sulfinpyrazone mechanism
weak organic acid; inhibits urate-anion exchanger (mediates uric acid reabsorption in proximal tubule) to promote clearance of uric acid
105
Probenecid/Sulfinpyrazone use
chronic hyperuricemia
106
Probenecid/Sulfinpyrazone SE
- S: GI distress
| - P: drug-drug interactions
