Pharm Exam 2 Flashcards
1
Q
How long can bone remodeling take?
A
3-4 months
2
Q
What reabsorbs (removes) bone?
A
osteoclasts
3
Q
What forms (synthesizes) bone?
A
osteoblasts
4
Q
What do osteoblasts secrete?
A
alkaline phosphatase (ALP)
5
Q
When is secretion of alkaline phosphatase increased?
A
In bone growth (children & adolescents)
6
Q
What causes the loss of bone mass after 30?
A
Reabsorption > Formation
7
Q
Name of vitamin D2?
A
Ergocalciferol
8
Q
Name of Vitamin D3?
A
Cholecalciferol
9
Q
“Vitamin D”
A
D2 & D3 (both act similarly)
10
Q
Where is vitamin D converted into 25-hydroxyvitamin D?
A
Liver
11
Q
Where is 25-hydroxyvitamin D converted to 1-25 dihydroxyvit D (calitriol;D3)
A
Kidneys
12
Q
What is the result of:
Low serum Ca 2+ and
Increases in PTH
A
Increased bone resorption AND Increased Ca2+ resorption from the gut
13
Q
What is the precursor condition of osteoporosis?
A
osteopenia
14
Q
What is the bone density of osteopenia?
A
1 to <2.5 SD below average bone mass
15
Q
What is the bone density of osteoporosis?
A
> or = to 2.5 SD below average bone mass
16
Q
What are the 3 categories of osteoporosis?
A
Post menopausal
Age-related
Secondary: medications
17
Q
What causes postmenopausal osteoporosis?
A
Decreased estrogen (E2), Increased bone resorption WITHOUT increased formation
18
Q
What are the 2 cytokines that are stimulated and released by decreases in estrogen?
A
IL-1
TNF-alpha
19
Q
What does IL-1 do?
A
potent inducer of resorption
20
Q
What does TNF-alpha do?
A
induces osteoclast maturation
21
Q
When does peak bone density occur?
A
2nd- 4th decades
22
Q
Why are females more likely to have fractures compared to men with age related osteoporosis?
A
females have smaller mass and therefore a smaller loss results in fracture
23
Q
What are the causes of age related osteoporosis? (6)
A
- Decreased osteoblast function
- Decreased Ca2+ and Vitamin D intake and absorption
- Decreased sex hormone levels
- Increased mechanical bone stress
- Decreased physical activity
- Decreased sun exposure (Decreased formation of DHVitD)
24
Q
What is secondary osteoporosis associated with in men?
A
risk factors
25
What are the drug-induced medications of secondary osteoporosis?
Steroids, heparin, thyroid hormone replacement & anticonvulsants are most common
Prednisone >7.5mg/d (decreased bone formation; increased bone resorption)
Heparin greater than 15K-30K units/day for > 3-6 months :MOA unknown
T3 & T4 increase osteoclast activity
anticonvulsants increase vitamin D metabolism (osteomalacia & OP)
26
Osteoporosis Risk Factors (5)
```
Lifestyle
Diet
Chronic Illness
Medications
Fall-related conditions ( meds: anxiolytics & benzodiazepines)
```
27
Dietary changes for Osteoporosis therapy? (3)
Increase Ca2+ to 1200-1500mg/d
Increase Vet D to 200-600 units/daily
Dairy products; oily fishies; fortified milk; 15-20 mins sun 2-3x/week
28
What are the nonpharmacologic therapies for osteoporosis? (3)
Dietary changes
social habit changes
exercise
29
Why should calcium supplements be taken with meals?
best absorbed in acid pH
30
What type of calcium is pH independent?
calcium citrate (24% Ca, $$$)
31
Why is calcium citrate beneficial in elderly?
elderly may have decreased gastric acid output
32
What is a common SE of calcium supplements for osteoporosis?
constipation
33
Calcium cannot be taken within 1-2 hours of : (5)
```
iron
tetracycline
quinolones
bisphosphonates
phenytoin
```
34
What is first line therapy for osteoporosis in men and women?
Bisphosphonates
35
How do bisphosphonates work?
they are absorbed to the bone later becoming permanent
| inhibit action of osteoclasts
36
How are bisphosohonates taken?
take with water and don't lie down for half an hour
37
What are a SE of oral bisphosphonates?
esophagitis may occur
| Osteonecrosis of bone!!! (esp jaw)
38
What are bisphosphonate medications? (6)
```
alendronate (fosamax)
Etidronate (Didronel)
Ibanronate (Boniva)
Pamidronate (Aredia)
Risedronate (actonel)
zoledronic acid (Reclast)
```
39
How is alendronate (fosamax) taken for OP prevention and treatment?
prevention: 5mg daily/ 35mg weekly
| TreatmentL 10mg daily/ 70 mg weekly
40
What is etidronate (didronel) used for?
Paget's disease
41
What is the indication for pamdronate (aredia)?
hypercalcemia of malignancy
42
What is a monoclonal antibodies (MAb) for osteoporosis?
denosumab (prolia)
43
What is the method of action of denosumab (prolia)?
inhibition of osteoclast formation, function & survival
| NOT FIRST LINE
44
What is denosumab (prolia) different compared to bisphosphonates?
unlike bisphosphonates, effects of osteoclasts are reversible
45
What medication is a recombinant human parathyroid hormone PTH for osteoporosis?
Teriparatide (forteto)
46
Why is teriparatide (forteo) only reserved for pts with very high risk of fracture?
$$$$$
47
What is a common SE of teriparatide (forteo)?
orthostatic hypotension may occur early in therapy
48
What is the blackbox warning associated with teriparatide (forteo)?
induces osteosarcoma in animals (no cases reported in humans)
49
What is the line of therapy for osteoporosis AFTER bisphosphonates, denosumab or terparatide?
selective estrogen receptor modulators (SERMs)
50
What is the MOA of SERMs?
estrogen- like activity on bone
51
What are the types of selective estrogen receptors modulators (SERMS)? (2)
Raloxifene (Evista)
| Bazedoxifene (Duavee)
52
What SERM is used in combination with conjugated estrogen and only for shoe term use?
Bazedoxifene (Duavee)
53
What medication for OP opposes action fo PTH?
calcitonin
54
What medication decreases osteoclast activity and resorption but is not as effective as other OP meds?
calcitonin
55
What medication is reserved for acute fractures or chronic osteoporosis pain?
calcitonin
56
What medications should be given with calcitonin?
concurrent Ca 2+ and Vit D should be given
57
Pharmacologic doses decrease bone resorption and are less effective than bisphosphonates?
calcitonin
58
What is the more potent type of calcitonin compared to mammalian?
salmon calcitonin
59
What form is calcitonin given?
nasal spray
60
Osteonecrosis or aseptic necrosis is associated with what?
steroid therapy
61
When will you see the greatest bone loss with steroid therapy?
1st 6-12 months of therapy
62
What does of prednisone is usually required for steroid induced osteoporosis (SIO)?
>7.5mg/ daily
| therefore important to use lower dose for shortest duration
63
What are the 3 main types of arthritic conditions?
1. osteoarthritis: "wear and tear"; obesity
2. Rheumatoid Arthritis: autoimmune
3. Gouty Arthritis: elevated uric acid
64
What is the most common of the joint diseases that affects nearly 50% of adults over 65 years of age?
Osteoarthritis
65
What joint disease affects mainly all the weight bearing joints and hands?
osteoarthritis
66
What type of joint disease is often unilateral and early in the disease the pain decreases with rest; however morning stiffness usually lasts less than 30 mins
osteoarthritis
67
How many people in the US are affected by OA?
15.8 million
68
What are the risk factors of OA?
obesity
| repetitive use injury
69
What are the categories of OA?
Primary (idiopathic): no known cause
Secondary: known abnormalities or trauma
Erosive: reflects changes to underlying bone
70
What are the treatment options for OA?
diet
physical & occupational therapy
surgery
71
What are the diet treatments for OA?
weight reduction
glucosamine supplements
chondrotin sulfate
Neither are PDA approved!
72
What are the physical and occupational therapy treatments for OA?
heat treatments, exercise- reduce pain, decrease stiffness
| caution against heat >30 mins (burns)
73
What is OA drug therapy target at?
pain relief
74
What is the oral analgesic of choice for OA?
acetaminophen
75
What is the second choice oral agents for OA?
NSAIDs
76
What medicine for OA is better for significant inflammation?
NSAIDs
77
What other two medications besides NSAIDs and Acetaminophen may help with OA?
```
topical analgesics (Cepsaicin)
COX-2 inhibitors
```
78
What medication is a COX-2 Inhibitor?
Celecoxin (Celebrex) 100-200mg BID or 200mg QD
79
What is chronic inflammation of synovial lining with proliferation = pannus
Rheaumatoid arthritis
80
What does pannus do to the joint?
erodes cartilage and bone surface
81
RA causes erosions that ultimately destroy the joint resulting in what?
immobility
82
What joints are usually affected with RA?
small joints of hands
wrists
feet
83
How long does morning stiffness usually last with RA?
>30 minutes or ALL DAY
84
What are the non-pharmacologic therapies for RA? (5)
```
rest
occupational therapy
physical therapy
use of assistive devices
weight reduction
```
85
What are the recent changes in approach to therapy for RA? (4)
1. early diagnosis and treatment
2. combination of DMARDs
3. agents that target cytokines (anti tif alpha & interleukin-1 receptor antagonists)
4. recognizing coexisting illnesses (infection, OP, cardiovascular dz)
86
What are the 2 classifications for 'length of disease' for RA?
early : less than 6 months
| established: greater than 6 months
87
What is the 'extent of disease activity' for RA?
low
moderate
high
88
what is the 'presence of poor prognostic factors' for RA?
functional limitation
extra-articular disease (nodes, RA vasculitis)
Positive Rheumatoid factor
bony erosions by X-ray
89
What are the pharmacologic agents for RA?
NSAIDs
Corticosteroids
DEMARDS
90
When are NSAIDs especially helpful with RA?
early disease to provide pain relief pending diagnosis. they DO NOT slow progression of the disease
91
What are potent suppressors of inflammatory response that decrease the progression of RA on X-ray?
corticosteroids (CS)
92
Over 1/2 patients will receive what LOW dose of CS therapy?
less than or equal to 10mg prednisone daily
93
What high dose CS therapy is used for RA?
greater than 10mg- 60mg daily of prednisone
| used less than 3 months followed by a taper over 7-10 days
94
What is a predictable side effects of corticosteroids for RA?
adrenal cortex suppression
95
What are common csDMARDS(Conventional synthetic Disease modifying anti rheumatic drugs) medications?
methotrexate (MTX)
Leflunomide (LEF)
Hydroxychloroquine (HCQ)
Sulfasalazine(SSZ)
96
What is the csMARD of choice for RA that is most often selected for initial therapy?
methotrexate (MTX)
97
What is the RA low dose for methotrexate?
less than 30mg weekly; start at 7.5mg weekly and increase by 5mg a week
98
What is the standard of care for RA patients without contraindications?
methotrexate
99
Methotrexate oral absorption is variable therefore if poor PO response what do you do?
try IV / Sub Q
100
What mediation can be taken with methotrexate on skip days to minimize toxicity?
folic acid 1-3mg/daily
101
What pregnancy category is methotrexate?
Category X
102
What mediation used with methotrexate is potentially complimentary (additive toxicity)?
leflunomide (LEF)
103
What csMARD has a long half life of 15-18 days and can take 2 years for complete elimination?
leflunomide (LEF)
104
Since leflunomide is a category X what is important in females?
females need reliable birth control during use and verify non detectable blood level prior to pregnancy
105
What is a rare complication of leflunomide?
hepatic necrosis (0.02-0.04%)
106
What is the least potent but best tolerated csDMARD and commonly combined with methotrexate?
hydroxychloroquine (HCG)
107
What was the first DMARD that was developed specifically for RA and is most commonly used in combination therapy?
sulfasalazine (SSZ)
108
What are the dual therapy combinations of csDMARDS for RA? (4)
MTX + SSZ
MTX + HCQ
SSZ + HCG
combos with LEF
109
What is the triple therapy csDMARD combination for RA?
MTX + SSZ + HCQ
110
What is the anti- TNFbiologic for RA?
Infliximab (Remicade)
111
What is the non TNF RA biologic?
Tofacitinib (Xeljanz)
112
What was the first biologic agent available for RA?
Infliximab (Remicade)
113
What medication is chimeric (human/mouse) monoclonal antibody?
Infliximab (Remicade)
114
What mediations may reactivate latent TB and other infections.
Infliximab (Remicade) & Tofacitinib (Xeljanz)
115
What testing should be done prior to starting Infliximab (Remicade) & Tofacitinib (Xeljanz)?
TB skin test & CXR
116
What medications may minimize anaphylactoid reactions of Infliximab (Remicade)?
antihistamines
APAP
steroids
117
In feb 2016 the FDA approved the first BIOSIMILAR product in the US, which is a "generic" of what medication for RA?
Infliximab (Remicade)
118
What is the only FDA approved oral non DMARD for RA?
Tofacitinib (Xeljanz)
119
What medications for RA has a MOA to inhibit janus kinase (JAK)
Tofacitinib (Xeljanz)
120
What is gout characterized by? (3)
Hyperuricemia (greater than 7mg/dL)
Recurrent attacks of gouty arthritis
Caused by precipitated monosodium rate crystals in joints (decreased pH)
121
Gout is the result of what 2 things?
uric acid overproduction (increase PRPP synthetase and decreased HGPRT enzyme)
uric acid under excretion (100% filtered, 90% reabsorbed)
122
What are the risk factors for gout?
```
obesity
male (10x)
increased age
alcohol intake
protein/purine rich diet
htn
```
123
IN gout what suggests increased synthesis?
greater than 1 g uric acid/ 24 hour urine
124
What are chronic uric acid deposits?
tophi
125
What are the gout treatments? (5)
```
patient education (diet)
analgesics for gout: NSAIDs
Mediations for acute attacks: colchicine high dose
Corticosteroids
Prevention of future attacks
```
126
What medication is given in gout for prevention of future attacks? (4)
colchicine (low dose)
Xanthine oxidase inhibitor (first line)
Uricoseuric agents (add on)
recombinant urate oxidase
127
When should NSAIDs be taken for Gout?
Around the clock-NOT PRN
128
What is a common analgesic agent for gout?
celecoxib (Celebrex)
129
What mediation is used for acute attacks (flares), max is 3 tabs in an hour, 75-95% of patients respond
colchicine
130
What percentage of people taking colchicine experience GI side effects(diarrhea) before relief of gout?
50-80%
131
How is colchicine prescribed prophylactic ?
0.6 mg QD or BID
| stop when symptom free for 1 year
132
When are corticosteroids used for gout?
reserved for patients with contraindications to NSAIDs or colchicine
133
How are the corticosteroids given for gout?
oral
IM
intraarticular injection
134
What is the adult doing for allopurinol with mild gout?
200-300mg po daily
135
What is the adult dose for moderate- severe gout for allopurinol?
400-600mg po daily
136
When do you increase the dose of allopurinol
increase over 3-4 weeks
137
When do you decrease dose of allopurinol?
with increased age or decreased renal function
138
What is an adverse effect of allopurinol?
agranulocytosis <1%
139
Why is allopurinol given with colchicine prophylaxis?
may predicate gout
140
what mediation has no advantage over allopurinol but is more expensive. May predicate gout with initial use
Febuxostat (Uloric)
141
what agents promote urinary UA elimination inhibiting UA resorption?
uricosuric agents for gout
142
What are the uricosuric agents? (2)
probenecid
| sulfinpyrazone
143
what is the first in new class-urate oxidase (uricase) enzymes?
pegloticase (krystexxa)
144
What medication is a pegylated recombinant (procine) enzyme?
pegloticase (krystexxa)
145
What medication may produce anaphylaxis (<7%) and is suggesting to premeditate with antihistamine AND steroids?
pegloticase (krystexxa)
146
What medication is used ONLY for severe gout refractory to or intolerant of approximately dosed oral ULT?
pegloticase (krystexxa)
