Rapid - Musculoskeletal Flashcards Preview

M2 - Pharm Rapid > Rapid - Musculoskeletal > Flashcards

Flashcards in Rapid - Musculoskeletal Deck (53):
1

Calcium Salts

  • Use:
    • HypOcalcemia
    • Prevention/Rx Osteoporosis
  • S/E:
    • MI
    • Constipation
    • Decreased absorption of ciprofloxacin, phenytoin, levothyroxine and tetracyclines

2

Vitamin D

  • Increases bone formation
    • Increases calcibindin (Ca2+ carrier protein) synth
    • Increases Ca2+ and PO43- absorption from intestines, kidney, bone
  • Use: Osteoporosis

3

ergocalciferol

Vitamin D2

4

cholecalciferol

Vitamin D3

5

calcitriol

1,25-dihydroxyvitamin D3 (most active form)

6

calcifediol

25-hydroxycholecalciferol

7

Teriparatide

  • Recombinant human PTH
  • Use: Osteoporosis
    • Short-term: stim osteoBlasts > osteoclasts
    • Long-term: stim osteoClasts
  • S/E:
    • Increased risk osteosarcoma
    • Transient hypERcalcemia

8

Alendronate

  • Bisphosphonate
    • Pyrophosphate analog → binds hydroxyapatite in bone → inhibits osteoClast activity
    • Also promotes osteoClast apoptosis and decreases development/recruitment of osteoClast precursors
  • Use:
    • Osteoporosis
    • HypERcalcemia
    • Paget bone
    • Metastatic bone disease
    • Osteogenesis imperfecta
  • S/E:
    • Esophagitis
    • osteonecrosis of jaw
    • atypical stress fractures

9

Ibandronate

  • Bisphosphonate
    • Pyrophosphate analog → binds hydroxyapatite in bone → inhibits osteoClast activity
    • Also promotes osteoClast apoptosis and decreases development/recruitment of osteoClast precursors
  • Use:
    • Osteoporosis
    • HypERcalcemia
    • Paget bone
    • Metastatic bone disease
    • Osteogenesis imperfecta
  • S/E:
    • Esophagitis
    • osteonecrosis of jaw
    • atypical stress fractures

10

Risedronate

  • Bisphosphonate
    • Pyrophosphate analog → binds hydroxyapatite in bone → inhibits osteoClast activity
    • Also promotes osteoClast apoptosis and decreases development/recruitment of osteoClast precursors
  • Use:
    • Osteoporosis
    • HypERcalcemia
    • Paget bone
    • Metastatic bone disease
    • Osteogenesis imperfecta
  • S/E:
    • Esophagitis
    • osteonecrosis of jaw
    • atypical stress fractures 

11

Zoledronate

  • Bisphosphonate
    • Pyrophosphate analog → binds hydroxyapatite in bone → inhibits osteoClast activity
    • Also promotes osteoClast apoptosis and decreases development/recruitment of osteoClast precursors
  • Use:
    • Osteoporosis
    • HypERcalcemia
    • Paget bone
    • Metastatic bone disease
    • Osteogenesis imperfecta
  • S/E:
    • Esophagitis
    • osteonecrosis of jaw
    • atypical stress fractures 

12

Calcitonin

  • Keeps bone in
    • Inhibits osteoClast bone resorption
    • Promotes osteoBlast Ca2+ deposition
  • Use: HypERcalcemic states
    • Postmenopausal osteoporosis
    • Paget’s disease
  • Used only short-term--long-term fx unclear

13

Denosumab

  • Human IgG2 monoclonal antibody
    • Binds to and inactivates RANKL → RANK → NF-kB pathway inhibits gene exp req for osteoClast fcn
  • Use: Osteoporosis
  • S/E: Hypocalcemia may be worsened

14

Leflunomide

  • Reversibly inhibits dihydroorotate dehydrogenase → prevents pyrimidine synth
  • Suppresses T-cell prolif
  • Use:
    • Rheumatoid arthritis
    • Psoriatic arthritis
  • S/E:
    • Diarrhea
    • HTN
    • hepatotoxicity
    • teratogenicity

15

Acute Gout Rx

  • Pain is the major concern → use NSAIDs (indomethacin, naproxen, sulindac) and Colchicine
  • Avoid:
    • Allopurinol, febuxostat (can cause flares)
    • Aspirin / salicylates (dec urate excretion)
    • Diuretics (vol depletion increases urate levels in blood)

16

Chronic Gout Rx

Target: get blood uric acid below 4-5 mg/dl

  • Probenecid / rasburicase (in underexcretors)
  • Febuxostat (in overproducers)
  • Lesinurad (SURI)

17

Colchicine

  • Gouty inflammation suppressant
    • Binds / stabilizes tubulin → inhibits microtubule polymerization in neutrophils → impairs neutrophil chemotaxis / degranulation
  • Use: Gout, acute and prophylaxis
  • S/E:
    • Diarrhea / GI upset
    • Alopecia
    • Hematuria
    • BM suppression
    • Peripheral neuropathy

18

Probenecid

  • Inhibits PCT uric acid reabsorption
  • Use: Chronic Gout
  • S/E:
    • Can precipitate uric acid calculi
    • Prolonged duration of action of penicillins, cephalosporins

19

Allopurinol

  • Competitive xanthine oxidase inhibitor
    • Decreases conversion of hypoxanthine and xanthine → urate
  • Use:
    • Chronic Gout
    • Lymphoma / leukemia (prevent tumor lysis-assoc urate nephropathy)
    • Increases conc of azathioprine and 6-MP (metabolized by xanthine oxidase)
  • S/E: SJS

20

Febuxostat

  • Xanthine oxidase inhibitor
    • Decreases conversion of hypoxanthine and xanthine → urate
  • Use:
    • Chronic Gout
    • Increases conc of azathioprine and 6-MP (metabolized by xanthine oxidase)
  • S/E: SJS

21

Pegloticase

  • Recombinant uricase
    • Catalyzes metab of uric acid → allantoin (a more water-soluble product)
  • Use: Chronic Gout

22

Glucocorticoids

  • Oral, intra-articular, or parenteral.
  • Use: Acute Gout
  • See endocrine cards

23

TNF-α Inhibitor S/E

All TNF-α inhibitors predispose to infection, including reactivation of latent TB, since TNF is important in granuloma formation and stabilization.

24

Etanercept

  • TNF-α Inhibitor
    • Fusion protein (receptor for TNF-α + IgG1 Fc) → decoy receptor
  • Use:
    • Rheumatoid arthritis
    • psoriasis
    • ankylosing spondylitis 
  • S/E: Infxn

 

25

Infliximab

  • TNF-α Inhibitor
    • Anti-TNF-α monoclonal antibody
  • Use:
    • Inflammatory bowel disease
    • rheumatoid arthritis
    • ankylosing spondylitis
    • psoriasis
  • S/E: Infxn

26

Adalimumab

  • TNF-α Inhibitor
    • Anti-TNF-α monoclonal antibody
  • Use:
    • Inflammatory bowel disease
    • rheumatoid arthritis
    • ankylosing spondylitis
    • psoriasis 
  • S/E: Infxn

27

Rasburicase

  • Recombinant uricase
    • catalyzes metab of uric acid → allantoin (a more water-soluble product)
  • Use: Prevention and treatment of tumor lysis syndrome

28

Acetaminophen

  • COX Inhibitor
    • Reversibly inhibits COX, mostly in CNS. Inactivated peripherally.
  • Use: Antipyretic, analgesic, but NOT anti-inflammatory.
    • Used instead of aspirin to avoid Reye syndrome in children with viral infxn.
  • Overdose → hepatic necrosis
    • Metabolite (NAPQI) depletes glutathione, forms toxic tissue byproducts in liver
    • Antidote: N-acetylcysteine (regenerates glutathione)

29

Aspirin / Salicylic Acid

  • COX Inhibitor
    • Covalentely acetylates and irreversibly inhibits COX 1&2 → decreases TXA2 and PG synth
  • Use:
    • Low dose (
    • Intermed dose (300–2400 mg/day): antipyretic and analgesic.
    • High dose (2400–4000 mg/day): anti-inflammatory.
  • S/E:
    • Gastric ulceration
    • Tinnitus (CN VIII)
    • Chronic use: acute renal failure, interstitial nephritis, GI bleeding.
    • Risk of Reye syndrome in children w/viral infxn
  • OD: Respiratory aLKalosis early → transition to mixed metabolic aCidosis-respiratory aLKalosis.

30

Celecoxib

  • COX2 inhibitor
    • Reversibly inhibits COX2 in inflamm cells and vascular endothelium (mediates inflamm/pain) → no GI corrosion, no antiplatelet agg fx
  • Use:
    • Rheumatoid arthritis
    • osteoarthritis
  • S/E:
    • Increased risk thrombosis
    • Sulfa allergy

31

Ibuprofen

  • NSAID
    • Reversibly inhibits COX → blocks PG synth
  • Use:
    • Antipyretic
    • Analgesic
    • Anti-inflammatory 
  • S/E:
    • Interstitial nephritis
    • Gastric ulcer (PGs protect gastric mucosa)
    • Renal ischemia (PGs vasodilate afferent arteriole)

32

Naproxen

  • NSAID
    • Reversibly inhibits COX → blocks PG synth
  • Use:
    • Antipyretic
    • Analgesic
    • Anti-inflammatory 
  • S/E:
    • Interstitial nephritis
    • Gastric ulcer (PGs protect gastric mucosa)
    • Renal ischemia (PGs vasodilate afferent arteriole)

33

indomethacin

  • NSAID
    • Reversibly inhibits COX → blocks PG synth
  • Use:
    • Close PDA
    • Antipyretic
    • Analgesic
    • Anti-inflammatory  
  • S/E:
    • Interstitial nephritis
    • Gastric ulcer (PGs protect gastric mucosa)
    • Renal ischemia (PGs vasodilate afferent arteriole) 

34

ketorolac

  • NSAID
    • Reversibly inhibits COX → blocks PG synth
  • Use:
    • Antipyretic
    • Analgesic
    • Anti-inflammatory  
  • S/E:
    • Interstitial nephritis
    • Gastric ulcer (PGs protect gastric mucosa)
    • Renal ischemia (PGs vasodilate afferent arteriole) 

35

Sulindac

  • NSAID
    • Reversibly inhibits COX → blocks PG synth
  • Use:
    • Antipyretic
    • Analgesic
    • Anti-inflammatory  
  • S/E:
    • Interstitial nephritis
    • Gastric ulcer (PGs protect gastric mucosa)
    • Renal ischemia (PGs vasodilate afferent arteriole) 

36

diclofenac

  • NSAID
    • Reversibly inhibits COX → blocks PG synth
  • Use:
    • Antipyretic
    • Analgesic
    • Anti-inflammatory  
  • S/E:
    • Interstitial nephritis
    • Gastric ulcer (PGs protect gastric mucosa)
    • Renal ischemia (PGs vasodilate afferent arteriole) 

37

meloxicam

  • NSAID
    • Reversibly inhibits COX → blocks PG synth
  • Use:
    • Antipyretic
    • Analgesic
    • Anti-inflammatory  
  • S/E:
    • Interstitial nephritis
    • Gastric ulcer (PGs protect gastric mucosa)
    • Renal ischemia (PGs vasodilate afferent arteriole) 

38

piroxicam

  • NSAID
    • Reversibly inhibits COX → blocks PG synth
  • Use:
    • Antipyretic
    • Analgesic
    • Anti-inflammatory  
  • S/E:
    • Interstitial nephritis
    • Gastric ulcer (PGs protect gastric mucosa)
    • Renal ischemia (PGs vasodilate afferent arteriole) 

39

Arachidonic Acid Pathway

A image thumb
40

Purine Metabolism

A image thumb
41

NSAIDs

Reversibly inhibit COX → block PG synth

  • Ibuprofen
  • Naproxen
  • Indomethacin
  • Ketorolac
  • Sulindac
  • Diclofenac
  • Meloxicam
  • Piroxicam

Note: gastric ulceration; renal ischemia; interstitial nephritis

42

TNF-α Inhibitors

Anti-TNF-α monoclonal Ab

  • Adalimumab
  • Certolizumab
  • Infliximab

Note: Etanercept is a decoy receptor, NOT a mab

43

Bisphosphonates

Pyrophosphate analogs → bind hydroxyapatite in bone → inhibit osteoClast activity

Also promote osteoClast apoptosis and decrease development/recruitment of osteoClast precursors

  • Alendronate
  • Ibandronate
  • Risedronate
  • Zoledronate

Note: esophageal erosion; jaw osteonecrosis

44

Xanthine Oxidase Inhibitors

Decrease conversion of hypoxanthine / xanthine → urate

  • Allopurinol
  • Febuxostat

Note: increase conc of Azathioprine and 6-MP; do NOT use for acute gout

45

Recombinant Uricases

Catalyze metab of uric acid → allantoin (a more water-soluble product)

  • Pegloticase

46

Meds that can cause Osteoporotic Fractures

  • CYP450-inducing anticonvulsants
  • Aromatase inhibitors
  • Medroxyprogesterone
  • GnRH Agonists
  • Proton Pump Inhibitors
  • Glucocorticoids
  • Unfractionated Heparin
  • Thiazolidinediones

47

Low Ca2+ / Low PTH

1° HypOparathyroidism

48

Low Ca2+ / High PTH

2° hypERparathyroidism

49

High Ca2+ / Low PTH

PTH-Independent HypERcalcemia

50

High Ca2+ / High PTH

1° HypERparathyroidism

51

PTH Analog

Short-term: stim osteoBlasts > osteoclasts

Long-term: stim osteoClasts

  • Teriparatide

Note: osteosarcoma; transient hypERcalcemia

52

TNF-α Decoy Receptor

Fusion protein (TNF-α + IgG1 Fc)

  • Etanercept

Note: Infxn

53

COX-2 Inhibitors

Reversibly inhibit COX-2 in inflamm cells and vascular endothelium (mediates inflamm/pain) → no GI corrosion, no antiplatelet agg fx

  • Celecoxib

Note: Thrombosis; C/I in sulfa allergy