Msk Flashcards
(178 cards)
1
Q
Indications for NSAIDS
A
Osteoarthritis
Bursitis
Gout flare
Ankylosis spondylitis
Dysmenorrhea, HA
2
Q
Same COX1 and 2
A
Same substrate-AA
Same products-PG
Same role in inflammation
Same physiological role in renal function
3
Q
COX 1 only
A
Constitutive
In alll tissues alt he time
Prominent role in responding to physiological stimuli
Contributes to response to any pathological stimuli that release AA
4
Q
How does COX1 work
A
Inflammation stimulates AA release
COX1 converts AA into PGE2
PGE2 causes symptoms
Constitutive: COX1 PGE2-erythema edema pain
5
Q
COX2 only
A
Induced in some tissues some times
Physiological role in kidney complications and complements COX1
Prominent role in response to any pathological stimuli that release AA
6
Q
How COX2 work
A
Inflammation induces COX2 expression
Cox2 also converts AA into PGE2
COX2 derived PGE2 amplifies symptoms
Induced COX2 increase PGE2 and worsen erythema, edema, pain
7
Q
Asprin MOA
A
Inhibits COX1 and 2 cant cause beneficial effects
IRREVERSIBLE
Platelets cant make new COS
8
Q
Bad effects asprin
A
Gastric ulceration, bleeding and renal impairment
9
Q
Indication asprin
A
Anti-inflammatory doses higher than analgesic or antipyretic
RA
Chronic inflammatory conditions
Analgesic
10
Q
Minimize risk asprin
A
Test for eliminate h pylori
Give PPI
11
Q
When take asprin for primary prevention
A
Reduce risk of first MI in men is first ischemic stroke in women
12
Q
Non asprin nsaids that antagonize the antiplatelet actions of asprin
A
Ibuprofen, naproxen antagonize the antiplatelet actions of asprin
13
Q
Increased risk of bleeding from asprin when take what
A
Warfain, heparin or other
14
Q
When see renal function issue with asprin
A
Advanced age, preexisting renal dysfunction, hypovolemia, HTN, hepatic cirrhosis, heart failure
15
Q
Asprin induced asthma
A
PG and LT balance toward LT
16
Q
BAD risk asprin
A
Papillary necrosis
Reye syndrome
Reduce spontaneous uterine contractions , indue premature closure of ductus arteriosus, and intensify uterine bleeding in labor and delivery
Asprin poisoning in kids lethal
Hypersensitivity reactions
17
Q
Difference from asprin and non asprin nsaids
A
Others are reversible
Increase risk MI and stroke
Use lowest effective dose for shortest time
18
Q
Coxibs second generation NSAIDS
A
Celecoxib-blocks COX2
Suppresses inflammation, pain, and fever
Less gastric ulceration
Does not inhibite platelet aggregation, so does not pose risk of bleeding and increase risk MI and stroke
19
Q
NSAIDs
A
Asprin Celecoxib Diclofenac Ibuprofen Indomethacin Ketorolac Naproxen
20
Q
Cardiovascular AHA on nsaids
A
All , espicially COX2 avoided if cardiovascular risk factors and used only with sufficient pain relief is not achieved with their therapies and the benefit outweighs the increased cardiovascular risk
-use naproxen if have to
21
Q
Contraindications NSAIDS
A
CKD
Ulcer
Heart failrue or uncontrollable HTN
NSAID allergy
Ongoing anticoagulant
22
Q
Acetaminophen
A
Suppresses pain and fever BUT NOT inflammation
Lacks antiinflammatory actions
No GI ulcers
No platelet aggregation
No renal impairement
23
Q
Bad acetaminophen
A
Hepatic necrosis from acetaminophen overdose when glutathione is depleted
Treated withacetylcysteine
Inhibits metabolism of warfarin and increase risk of bleeding
24
Q
Tricyclic antidepressants
A
Independent analgesic effects can relieve depressive symtpoms
Usually amitryptyline
25
SNRI
Venlafaxine, duloxetine
Beneficial with concurrent depression
Weaker evidence for effectiveness of pain relief as TCA
26
Pregabalin
GABA analog bind alpha2 delta subunit of voltage gated calcium channels
27
What pregabalin used for
```
Neuropathic pain
Diabetic neuropathy
Postherpetic neuralgia
Partial seizures
Fibromyalgia
```
28
Gabapentin moa
Bind alpha2delta subunit of voltage gated ca channels
29
Indications gabapentin
Anti seizure
Post hepatic neuralgia, diabetic neuropathy, prophylaxis for migraine, fibromyalgia, restless leg
30
Tramadol
Weak mu agonist but works by blocking NE and 5-HT reuptake
-naloxone only partially blocks
Activates monoaminergic spinal inhibiton of pain
Used by millions for moderate to moderately severe pain
31
Side effects tramadol
Sedation, dizziness, HA, dry mouth constipation
32
Ketamine
NDMA antagonist used for maintain anesthesia
Common side effects include psychological reactions
33
Dexmedetomidine
Alpha 2 adrenergic agonist for analgesia and sedation
34
Clonidine
Alpha2 adrenergic agonist
| for HTN and relief of severe pain
35
MOA centrally acting muscle relaxants
Unclear, relieve muscle spasm for low back pain
36
Ziconotide
For chronic severe pain in whom intrathecal administration si warranted and when refractory to other treatments
37
Capsaicin
Heat red pepper TPRV1
38
Camphor
TRPV1 heat
39
Methanol
TRPM8 cold
40
Topical NSAIDS
Yup
41
Topical Na channel blockers
Ok
42
Acute vs chronic gout
A-precipitation of uric acid in tubules
Chronic-monosodium urate in medullary interstitium
43
IMP and GMP are dephosphorylated and ribose cleaved from the base to give )) and ))0
Hypoxanthine and guanine
44
Xanthine formation
From hypoxanthine by xanthine oxidase and from guanine deamidation
45
Xanthine is converted to what by what
Uric acid by xanthine oxidase
46
Preformed nucleotide from diet or breakdown of endogenous nuclei acids is salvaged by
APRT
| HGPRT
47
Lesch Nyhan
Defiency HGPRT
Intellectual defiency
Self utilization
Severe gout
48
Treat gout
Anti-inflammatories
Acute-intercritical period <2 years
Prophylactic
If recur-increase uric acid renal excretion ith uricosuric drugs and or reduce uric acid production with xanthine oxidase inhibitors and recombinant uricase
49
Treat acute gout
NSAIDS naproxen, indomethacin, celecoxib
Glucocorticoids-systemic/intra-articular
50
MOA coaching
Diffuse into cells to bind to tubules, blocks formation of microtubules
51
Effects coaching
Leads to inhibiton of leukocyte migration and phagocytosis
52
Clincial colchinen
If NSAIDS intolerance or contraindication
53
How colchicine given
Orally
| HL 30 hours
54
AE colchicine
Very common is gastrointestinal distress, diarrhea, vomiting, nausea
55
If underexcreted with good GFR no tophi or stones
Urate lowering therapy with allopurinol, febuxostat, or uricosuric agent
OtherwiseUrate lowering therapy with low allopurinol and otherwise allopurinol
56
If allopurinol not tolerated
Febuxostat
57
Last resort
Pegloticase
58
Allopurinol MOA
Competitive inhibitor of xanthine oxidase
59
Effects allopurinol
Hypoxanthine and xanthine are excreted
60
AEA allopurinol
Rash
Hypersensitivity Stevens johnson syndrome can be fatal
61
Febuxostat OMA
Inhibitor of xanthine oxidase
62
Effects febuxostat
Hypoxanthine and xanthine are excreted
63
Clincial febuxostat
Those who cant tolerate allopurinol
64
Pegloticase moa
Recombinant mammalian uricase
Methoxy polyethylene glycol
65
Effects pegloticase
Converts uric acid the far more soluble allantoin
66
Rasburicase
No PEGylated recombinant uricase for acute uric acid nephorpathy due to tumor lysis syndrome with high risk lymphoma or leukemia
67
Probenecid moa
Organic acid blocks urate reabsorption more than urate secretion
Low dose asprin promotes urate reabsorption
68
Effects probenecid
Increases the fractional excretion of urate
Decreases plasma urate concentration
69
Clincial probenecid
Underexreters with GFR>60 ml/min and no stone !!!!!
Hyperuricemia
Frequent attacks
Tophi
70
AE probenecid
Kidney stones
Gouty arthritis flare
Suffer containg drug may cause hypersensitivity
71
Acute gout
NSAIDS colchinie glucocorticoids
72
Prevent recurrent gout
Urate lowering
Diet, weight reduction
Allopurinol, febuxostat, probenecid, pegloticase
73
How treat RA
Stop inflammation
Relieve symptoms
Prevent joint and organ damage
74
RA non pharm
Exercise, PT, OT< nutrition, bone protection, CVD risk , vaccination
75
RA need pain relief addition
Acetaminophen
76
First drug of choice for RA
NSAIDS
Anti inflammation and pain relief-naproxen and celecoxib
-doesnt alter disease progression
77
Opioids with RA
No
78
MOA glucocorticoids
Complexing with NFKB and AP1 transcription factors is a major indirect mechanism for immunosuppression
Lipocorticin, and inhibitor or PLA2
79
Clincial glucocorticoids
Autoimmune disease like RA
Relieves pain and inflammation while waiting for DMARD effects
Treats flares
80
Pharmacokinetics glucocorticoids
Others for RA, can be give PO, IM or intra articularly
81
Prednisone
No effect until make to prednisolone in liver
82
Side effects of glucocorticoids
Psychosis depression impaired glucose tolerance, salt water retention, buffalo hump, osteoporosis
83
Abruptly stop glucocorticoids
Deadly
84
Use of glucocorticoids
In sicker patient with RA prednisone is frequently added for a short period while awaiting a clincial repsonse to a slower acting disease modifying drug
85
Chronic use of glucocorticoids
No
And keep <5 mg/day can generally be taken without significant adverse effects but no reduction in disease progression
86
MILD RA
<5 inflated joints
Increase erythrocyte sedimentation rate and CRP
No extra articular disease
No evidence of erosions
Low levels of measures of disease activity
Most lack poor prognostic features such as rheumatoid factor or antibodies to cyclic citrullinated peptides
87
Moderate RA
>5 inflamed joints
Increase ESR and CRP
Rheumatoid factor and or anticyclic citrullinated peptide antibodies
Evidence of inflammation
Minimal joint space narrowing and small peripheral erosions
88
Methotrexate MOA
Inhibitos of dihydrofolate reductase
Thymineless death
Undergoes polyglutamation to MTX whihc accumulates in cells over multiple weeks and also blocks thymidylate synthase and 5 aminoimidazole 4 carboxamide ribonucleotide transformylase
AICAR accumulation leads to adenosine efflux which binds to purinergic GPCR on cell surface to exert anti inflammatory effects
89
Effects MTX
Faster than all other DMARDS in 3-6 weeks
For 80%
90
Clincila MTX
Drug of first choice for RA due to its efficacy relative safety low cost and extensive use
Combination with other
Continued when patient is switched to biological DMARD
91
Pharmacokinetics MTX
Once per week oral or injection
92
AR MTX
Low doses
Well tolerated
Weekly folate supplements
Life threatening major toxicities
Higher doses include bone marrow suppression, hepatic fibrosis GI ulceration and pneumonitis
Fetal death and congenital abnormalities
93
Hydroxychloroquine
Liphilic weak base
Accumulates in lysosomes
94
Effects hydroxychloroquine
Higher pH of these lysosomal vesicles in antigen presenting cells limits the association of peptides with class II MHC molecules
Delayed onset 3-6 months
95
Clincial hydroxychloroquine
Antimalarial
Combined with TMX
Safe in pregnancy
96
Pharmacokinetics hydroxychloroquine
Half life of 23 days
Loading doses
97
Toxicities hydroxychloroquine
Retinal damage
Low dosages carry little risk
98
MOA sulfasalazine
Sulfapyridine active with RA unlike in IBD where 5-ASA
99
Clincial sulfasalazine
Alone or in combination with hydroxychloroquine and/or MTX in triple therapy
Seems ok in pregnancy less studies
100
AE sulfasalazine
Sulfa drug
GI side effects
101
MOA leflunomide
Inhibiton of a mitochondrial enzyme dihydroorate dehydrogenase to block the synthesis of pyramiding rUMP
102
Effects leflunomide
Inhibits T cell proliferation
103
Clincial leflunomide
Alternative nonbiological DMARD to MTX second choice due to cost
In combination with MTX , sulfasalazine or hydroxychloroquine
104
Pharmacokinetics leflunomide
16.5 days HL so loading doses needed
105
AE leflunomide
Common adverse effects
106
Biological DMARDS
Never be combined
But faster onset of action, high rate of response, more expensive, increased risk for severe adverse effects
107
TNF antagonist MOA
Work by neutralizing TNF
108
Effects TNF antagonist
Highly effective at reducing RA symptoms and disease progression
109
Clincial TNF antagonist
Moderate to severe RA after DMARDS have proven ineffective
In combination with TMX
110
AE TNF antagonist
All agents pose risk of developing serious infections
TB
Severe allergic reaction
111
Etanercept
Of two p75 TNF receptors bound to the Fc portion of IgG
Once of trice weekly via SQ injection
112
Infliximab
Chimeric mAb directed against TNF
IV infusion approximately every six weeks
113
Adalimumab
Recombinant fully human anti TNF mAb SQ every 2 weeks
Best selling in world
114
Rituximab MOA
B cell lineage
Surface expression of CD20
Beginning at the pre B cell state
CD20 lost as B cells differentiate into plasma
115
Effects rituximab
Plasma cell resistance
Ig levels in normal range, despite profound B cell lymphopenia that persists for months following a single course
Autoantibodies
Affected by B cell depletion
116
Clincial rituximab
With MTX for RA
Positive testing for Rheumatoid factor or anti cyclic citrullinated peptide greater likelihood of responsiveness
117
AE rituximab
Infusion related hypersensitivity reactions
118
Abatacept MOA
Prevents CD28 from binding to its counter receptor CD80/CD86
119
Clincal abatacept
Moderate ot severe RA
Used in combination with nonbiological DMARDS like MTX
120
AE abatacept
Generally well tolerated
Can increase the risk of serious infections
121
Tocilizumab MOA
Anti human il6 receptor antibody
Competes for both the membrane bound and soluble forms of humans il6 receptor
122
Effects tocilizumab
Blocking the binding of il6 to its receptor
Limits hepatic acute phase response and activation of T cells, B cells, macrophages and osteoclasts
123
Clincial tocilizumab
IL6 levels are abnormally high in autoimmune disease
Moderate to severe RA if other DMARDS and TNF a blockers have proven to be ineffective
Can be used with or without MTX
124
AE tocilizumab
Most common URI
Life threatening infections
125
Tofacitinib MOA
Inhibitor of enzyme janus kinase 3
126
Effects tofacitinib
Directly suppressed hte production of il17 and IFNy and ther proliferation of CD4 T cells
127
Clincial tofacitinib
Moderately to severely active RA
With or without NTX
128
Pharmacokinetics
Overpriced
129
AE tofacitinib
Serious and sometimes fatal infections
Opportunistic pathogens
Increased malignancies
130
MOA anakinra
Recombinant, non glycosylated version of IL1 receptos antagonist
131
Effects anakinra
Endogenous il1ra are low in RA
Blocks the proinflamamtory activity of naturally occurring il1
132
Clincial anakinra
Moderate to severe RA
Considered less efficacious
133
AE anakinra
Increased incidence of serious infections
Hypersensitivity reactions
134
Calcium salts
Oral for hypocalcemia, as dietary supplements in adolescents, elderly and postmenopausal women, but take too much and get hypercalcemia, GI disturbances, CNS, and renal dysfunction
Parenteral-given to rapidly increase calcium levels in patents with severe hypocalcemia
135
What are vitamin D
Ergocalciferol D2 and cholecalciferol D3
Shiitake mushrooms and oily fish
Not in lots of foods
Fortified!
136
MOA calcitonin-salmon
Similar in structure to human calcitonin but longer HL and potency
137
Effects calcitonin salmon
Decrease bone resorption by inhibiting osteoclasts
| Inhibits renal tubular resorption of calcium to increase calcium excretion
138
Use of calcitonin
Osteoporosis
Paget disease
Hypercalcemia
139
Pharmacokinetics calcitonin
Intranasal spray as parenteral for SC or IM administration
140
Toxicities calcitonin
Sade
Nasal dry
Injection site reactions
May develop neutralizing antibodies
141
Bisphosphonates MOA
Pyrophosphate analog
142
Effects bisphosphates
Incorporate into bone and inhibit resorption by decreasing both the number and activity of osteoclasts
143
Clincila use of bisphosphonates
Osteoporosis, paget, hypercalcemia of malignancy
144
Pharmacokinetics aldronate
PO
145
AE alendronate
Esophagitis, osteopetrosis of jaw, atypical femur fractures
146
Risedronate
PO
147
Ibandronate
PO IV
148
Tiludronate
PO
149
Zolendronic acid
IV
150
Zolendronic acid
IV -osteopetrosis of jaw after tooth extraction
Dose dependent kidney damage and rarely atrial fibrillation
151
SERMS
Raloxifene
Tamoxifen
152
Raloxifene MOA
SERM
153
Effects raloxifene
Blocks in breast and uterus
| Estrogen effect in bone
154
Raloxifene clincial
Due to its estrogen agonist effects on bone, prevent and treat postmenopausal osteoporosis
Antiestrogen effects in the breast, used to reduce the risk for estrogen dependent breast cancer
155
Pharmacokinetics raloxifene
Administrated orally
Extensive first pass
Excreted in feces
HL 28 hrs
156
AE raloxifene
DVT, pulmonary embolism, stroke
Discontinue at 72 hours before planned/prolonged immobilization
Pregnancy risk
Hot flashes
157
Tamoxifen
Not for osteoporosis
158
Teriparatide MOA
Truncated version of PTH from recombinant DNA
159
Effects teriparatide
Increases bone formation!
Osteoclasts and osteoblasts
Continuously-resorption
Pulsed-osteoblast predominant
160
Clincial teriparatide
Treatment of osteoporosis
161
Pharmacokinetics teriparatide
20mcg is injected once daily with 28 doses
162
Toxicities teriparatide
Nausea, HA, back pain leg cramps
Ca Mg uric acid rise but then back to normal
163
Denosumab moa
Monoclonal antibody that is a first in class RANKL inhibitor
164
Effects denosumab
Bind RANKL decreases formation of osteoclasts decrease bone resorption
165
Clincial denosumab
Osteoporosis, prevent skeletal related events in patients with bone metastases from solid tumros, should be taken with ca and VD
166
Pharmacokinetics denosumab
Injected every 6 months
For osteoporosis
Bone metastases SQ injected every 4 weeks
167
Toxicities denosumab
Back pain, msk pain, UTI, hypercholestermia
In bone metastases fatigue, hypophosphatemia, nausea
Delays fracture healing, increase risk new fracture and osteopetrosis of jaw
Severe infections
168
Osteoporosis in men treat
Terosterone replacement
Glucocorticoids, androgen deprivation therapy
Bisphosphonates , denosumab
169
Drugs for hypercalcemia
Furosemide, glucocorticoids, gallium nitrate, bisphosphnates, inorganic phosphates, edetate disodium
170
Cinacalcet moa
Calcimimetic drug
171
Effects cinacalcet
Binds to calcium sensing receptors on the parathyroid gland
Increase their sensitivity to extracellular calcium
Decrease PTH secretion
172
Clincial cinacalcet
Primary hyperparathyroidism
Secondary hyperparathyroidism due to CKD
173
Pharmacokinetics cinacalcet
Dosing is oral with food
30-40 hrs HL
174
AE cinacalcet
Nausea, vomiting, diarrhea
175
Joint mice
Osteoarthritis
176
OTC osteoarthritis
Glucosamine, chondroitin, DMSO, SAMe failed to prove benefit
Devil claw, stinging nettle, rose hips, avocado, soybean, lack reliable evidence of benefit and consistency in preparation
177
Pain treatment OA
Acetaminophen
NSAIDS
Topical NSAIDS or capsaicin
-topical is 1% diclofenec gel
Resistant to opioid, intraarticular hyaluronans
178
Osteomyelitis treatment
Based on pathogens
-clindamycin, rifampin, TMP SMX, fluoroquinolone
For 4-6 weeks
