Exam 1 Flashcards
(115 cards)
1
Q
Acetaminophen
A
Tylenol Starting dose: 325-500mg PO TId Max: 3g/day max dose decreased in those with kidney or liver dysfunction or alcohol-use disorders scheduled dosing works better takes 1-2 weeks to work
2
Q
Aspirin
A
Bayer, Ecotrin, Bufferin
starting dose: 325mg TID
Max: 2600(pain)-3600*mg/day(inflammation)
3
Q
diclofenac
A
Voltaren XR
SD: 100mg QD
Max: 200mg/day
4
Q
Etodolac
A
Lodine
SD: 300mg BID
Max: 800-1000mg/day
5
Q
Ibuprofen
A
Motrin, Advil SD:200mg PO TID Max: 3200mg/day OTC & RX do not give in immediate fracture-repair period
6
Q
indomethacin
A
indocin
SD: 25mg PO BID or 75mg PO QD
max: 150mg/day
7
Q
Meloxicam
A
Mobic
- 5mg PO QD
max: 15mg/day
8
Q
Naproxen
A
Naprosyn- 250 mg PO BID
Anaprox, Aleve, Neprelan- 220mg PO BID
Max: 1500mg/day
OTC & RX; may be safest NSAID w/ CV risk factors
9
Q
Oxaprozin
A
Daypro
SD: 600mg PO QD
Max: 1200mg/day
10
Q
Piroxicam
A
Feldene
SD: 10mg PO QD
Max: 20mg/day
11
Q
Celecoxib
A
celebrex
SD: 100mg/day
Max: 200mg/day
COX-2 selectivity is lost w/ concomitant ASA
12
Q
osteochonral junction is composed of
A
subchondral bone and cartilage
13
Q
In OA, Initial
A
thickening of articular cartilage followed by fibrillation, degradation and erosion
14
Q
osteophytes
A
new bone formation at joint margins in OA
15
Q
with disease progression in OA, there is
A
vascular invasion & calcifaction of nearby articular cartilage-> decreased thickness of cartilage, bone remodeling & enhanced cartilage deterioration
16
Q
primary enzymes responsible for the degradation of cartilage are:
A
the matrix metalloproteinases (MMPs)- MMP-13 specificty for collagen type II.
in OA, these are over expressed and inhibitors get overwhelmed
17
Q
What secretes MMPs?
A
synovial cells and chondrocytes
18
Q
Inhibitors of MMPs:
A
Alpha-2-macroglobulin and TIMPs
19
Q
OA symptoms
A
Localized, deep, aching pain; pain on motion and joint stiffness < 30min
20
Q
Heberden’s nodes
A
bony enlargements of DIP (ends of fingers)
21
Q
Bouchard’s Nodes
A
bony enlargements of PIP (middle of fingers) 10X more common in women
22
Q
Crepitus
A
cracking noise caused by bones rubbing each other
23
Q
Labs in OA are
A
generally normal
ESR may be slightly elevated
24
Q
X-ray in OA will show
A
narrowing of joint space, appearance of marginal osteophytes, subchondral bone sclerosis or cyst formation->eventually joint deformity
25
COX-1
present in many cells and responsible for housekeeping functions- increase gastric mucus, release of PGE2 to control release of gastric acid, motility, control renal blood flow, produce TXA2 in plateleys
26
COX-2
inducible at sites of injury or damage. Also present naturally in CNS, kidney and bone
27
first line treatment for OA
APAP
| - primarily CNS MOA (COX-2)
28
APAP does NOT
produce GI irritation
affect bleeding or excretion of uric acid
respiratory or CV effects
29
APAP COX MOA
scavenges & eliminates peroxide tone
| periheral COX protected by excess peroxides produced at sites of inflammation- overcome APAP
30
Critical radical needed to produce COX activity is generated by abstracting an electron from
tyrosine 385
31
APAP 3 MOA hypothesis
1. inhibition of COX
2. central serotonergic mechanism
3. endocannabinoid pathway
32
____ & ____ block activity of APAP
5-HT3 antagonists & antagonists of cannabinoid BC-1
33
Main elimination of APAP
via glucuronide & sulfate conjugation pathways- but can become overwhelmed in high concentrations
34
too much APAP forces it through:
P450-CYP3#4 and CYP2E1 to NAPQI
35
NAPQI is elimiated
by conjugation to GSH and excreted in urine
36
in APAP overdose, GSH:
becoe depleted & NAPQI reacts with critical molecules of the cell
37
hepatotoxicity of APAP dose
10-15g
38
Death from liver damage of APAP dose
>20g
39
treatment of APAP overdose
N-Acetyl-L-cysteine- GSH precursor; best if given w/in 10 hours
40
Aspirin chemical name
acetyl salicylic acid; developed by Felix Hoffman
41
Aspirin is a _____ inhibitor
irreversible COX-1; acetylates Ser530
42
NSAIDs block:
prostaglandin biosynthesis
43
Positive effects of NSAIDs by inhibition of _____
COX-2 (CV problems)
44
Adverse effects of NSAIDs by inhibition of ____
COX-1 (GI problems)
45
COX-1 vs COX-2
Iso 434 and 523 are substituted for valines in COX-2
46
COX-2 selective inhibitors tend to be
larger V shaped molecules
47
in pregnancy, COX inhibitors:
can block induction of labor
48
treatment of GI symptoms with NSAIDs
add PPIs or Misoprostol
49
Altered blood coagulation- COX-1 inhibitors block:
platelet function-> bleeding
| Platelets cannot make more COX-1 bc they do not have a nucleus
50
Renal function- NSAIDs:
reduce renal blood flow and GFR-> water and salt retention-> inc. BP in pts with renal insufficiencies
little effect in healthy pts
51
NSAIDs w/ short half lives
<5 hours
| aspirin, diclofenac, indomethacin, ibuprofen
52
NSAIDs with long half lives
>10 hours
| naproxen, piroxicam, celecoxib, refecoxib
53
primary route of elimination of NSAIDs
hepatic metabolism
54
Salicylate clearance from the body follows:
nonlinear PK
55
watch for NSAID drug interactions with:
lithium, warfarin, oral hypoglycemics, high dose MTX, antihypertensives (ACE-I, Beta-blockers, diuretics)
56
Capsaicin (Zostrix) MOA
Depletes substance P- involved in pain transmission
57
Nutritional supplements for OA
Glucosamine & chondroitin- little benefit
58
Intra-articular corticosteroids in OA
inhibit PG synthesis
Triamcinolone & methylprednisolon most used
can induce osteoporosis
useful in pts w/ effusions, local inflammation
injected intro joint after aseptic aspiration
never into infected joint
mono or combo therapt
59
Intra-articular hyaluronic acid (HA) in OA
```
HA- shock absorber & lube in cartilage
mild anti-inflammatory
3-4 injections/yr
knee & hip
not really recommended
```
60
Opioids in OA
LAST RESORT!
Tramadol
low dose, sustained release- oxycodone, morphine, fentanyl
61
Tramadol MOA
dual mechanism- mu-receptor
R enantiomer- simulates release of serotonin
S enantiomer- blocks reuptake of NE
62
Goals of therapy in OA
Alleviate pain and stiffness
maintain or improve function
maintain or improve QOL
avoid side effects of therapy
63
Topical agents in OA
can be used 1st line- small joints
64
Capsaicin OA
3-5x/day
no PRN dosing
smaller joints
65
Bio-Freeze OA
Menthol 3.5%/Camphor 0.2%
| up to 4X/day
66
topical NSAIDs
diclofenac 1% topical gel (Voltaren)
Deiclofenac 1.3% patch (Flector)
caution in >75 yo
67
Oral NSAIDs in OA
2nd line
PRN or scheduled
takes 2-3 weeks to see benefit
68
bisphosphonates in OA
Alendronate (Fosamax)- knee
Risedonate (Actonel)- decrease joint space narrowing; decrease need for joint replacement surgery
may be useful in pts with osteoporosis too
69
RA MOA hypothesis
1. low affinity MHC receptors- no negative selection of T cells
2. citrullinated proteins- shared epitope HLA-DR molecules bind with higher affinity
70
presense of ___ & ___ in RA synovium
PAD and citrullinated epitopes
71
citrullination
arginine to citrulline by PAD - autoimmune response to it
| change in charge
72
RA has been linked to genetic polymorphisms in
PTPN22 & STAT4
73
RA potential triggers
smoking- in ACPA+ pts
| viruses, bacteria, stress/trauma
74
Series of events in RA
Initiating event- APC & T cells
Autoimmune response
Inflammation
autoantibodies
75
Autoantibodies in RA are called
rhematoid factors- produced by B cells
| form complexes in serum, synovial fluid & membranes-> inflammation & destruction
76
initial changes in RA
Microvascular damage & inflammation of synovial space
77
Sjögren's syndrome
a systemic autoimmune disease in which immune cells attack and destroy the exocrine glands that produce tears and saliva
78
extra-articular involvement in RA
Rheumatic nodules, vasculitis, ocular manifestations, cardiac involvement, splenomegaly & neutropenia
79
Felty's syndrome
splenomegaly & neutropenia
80
Lab findings in RA
Anemia, Thrombocytosis, erythrocyte sedimentation rate, rheumatoid factors antinuclear antibodies (ANA), anticyclic citrullinated peptides antibodies (anti- CCP & ACPA), turbid synovial fluid
81
radiologic evaluation in RA
soft tissue swelling, joint space narrowing, osteoporosis near joint, erosions
82
RA vs OA swelling of the joint
RA- feels soft and spongy
| OA- bony and hard
83
Non-biologic DMARDs
small, synthetic molecues
| MTX, hydroxychloroquine, sulfasalazine & leflunomide
84
Biologic DMARDs
proteins
anti-TNF: infliximab, adalimumab, etanercept, Golimumab, certolizumab
Non-TNF: Abatacept, Rituximab, Anakinra
85
MTX
```
folic acid antagonist
acts against rapidly proliferating cells
polyglutamated MTX is a high affinity inhibitor for DHFR
inhibits formation of DNA & RNA
20-30mg/week
```
86
MTX adenosine MOA
MTX inhibits AICAR transformylase-> accumulation of AICAR-> inhbits AMP and adenosine deaminase-> increased extracellular adenosine-> anti-inflammatory
87
MTX polyamine MOA
MTX blaocks THF-> reduces polyamine formation-> decrease local toxicity
88
First line treatment in RA
MTX
2-3 week onset
can lead to bone marrow suppression & liver/renal insufficiencies
avoid in prego
89
administration of ____ can reduce/prevent some adverse effects
folic acid
90
leflunomide
converted to A77-1726->inhibits dihydroortate DH
critical for formation of pyrimidines
no bone marrow suppression
do not use in prego for MEN & women or liver diease
100mg po qdX3days then 20mg PO QD
91
hydroxychloroquine
```
concentrates as cationic base in acidic lysosomes & raises their pH->impedes their function
2-6 months for onset
one of the least toxic DMARDs
ocular toxicity!!- need yearly eye exams
200-400mg PO QD
```
92
Sulfasalazine (Azulfidine)
```
cleaved by bacteria in the gut
sulfapyridine is the active compound
inhibits AICAR transformylase & increases adenosine-> decreased inflammation
onset 2 months
hyemolytic anemia in pts w/ G6PD deficiency
interacts w/ warfarin
Stevens-Johnson syndrome
avoid use w/ antibiotics
titrated to 1g PO BID
```
93
gold salts
inhibit maturation & function of macrophages & T cells
6 month onset
reversible renal toxicity/ lots of toxicities
suppression of blood cell production
94
Azathioprine
prodrug converted into 6-MP
95
D-Penicillamine
metal chelating agent
| reduces reactive aldehydes which bind to collagen preventing it from cross-linking and facilitating its degradation
96
minocycline
attenuates TNF-alpha production, downregulating pro-inflammatory cytokine production
100mg PO BID
chelation w/ bones & teeth
97
biologic DMARDs cannot be given
orally!
98
TNF-alpha antagonists
```
all prego category B
screen for TB
risk of HF
infliximab- mouse/IV
adalimumab- human/SQ
golimumab- human/SQ; once/month
etanercept-binds 2 molecules of TNF-alpha/SQ; 50mg/week
certolizumab pegol- not a full antibody; no Fc region
```
99
IL-1 receptor antagonist
Anakinra
not glycosylated
4-6 hr half life
prego catecory B
100
Anti IL-6
Tocilizumab- mouse
binds to both soluble and membrane receptors
require an effector molecule-GP130
101
Abatacept
costimulation blocker
CTLA-4
binds to CD80/86 & inhibites CD28 interaction
102
rituximab
B cell depletion
mouse
binds to B cell CD20
60 hr half life
103
glucocorticoids are secreted by
Zone F
104
mineralocorticoids are secreted by
Zone G
105
cortisol inhbits
immune system
106
keto group on glucocorticoids
makes it inactive!
| i.e. prednisone
107
11 beta-hydroxysteroid DH
type 1: reduces keto-> hydroxyl; activation
| Type 2: oxidizes back to keto & shuts down glucocorticoid
108
transrepression of steroids
repress gene transcription of pro-inflammatory modulators of the host immune system
109
transactivation of steroids
increase release of anti-inflammatory factors
110
glucocorticoids are ____ bound to plasma proteins
largely
111
adverse effects of glucocorticoids
```
infection
hyperglycemia
osteoporosis
fluid & electrolyte changes
cataracts
adrenal insufficiency
```
112
features of poor prognosis in RA
```
functional limitations
extra-articular disease
positive rheumatoid factor
positive anti-CCP antibodies
bony erosions by radiography
add biologic DMARD
```
113
Goals of therapy in RA
achieve full remission or low disease activity
alleviate pain
maintain QOL
maintain function essential for ADLs & work
slow rate of joint damage
avoid or minimize adverse effects & toxicities of therapies
114
full remission is defined as absence of:
```
symptoms of active, inflammatory joint pain
morning stiffness
fatigue
synovitis on joint exam
progression of radiographic damage
elevated ESR & CRP
```
115
tofacitinib
targeted DMARD
need to be screened for TB & hepatitis
BBwarning- serious infection & malignancy
DO NOT USE w/ BIOLOGIC
