Pharmacology Flashcards
1
Q
What are the first line treatments for osteporosis?
A
- bisphosphonates, Denosumab, SERMs (raloxifene), hormone-replacement therapy (HRT), and strontium ranelate
2
Q
Which drugs are anti-resportive in nature? Anabolic/bone-forming? Which have a dual action?
A
- anti-resorptive: bisphosphanates, Denosumab, HRT, raloxifene (SERM), Odanacatib
- bone-forming: teriparatide (synthetic PTH)
- dual action: strontium ranelate
3
Q
Bisphosphanates
A
- “-dronate” (etidronate, aldendronate, risedronate)
- anti-resportive drugs used to treat osteoporosis and paget disease
- MOA: the drug gets taken up in large amounts and is stored in bone; when osteoclasts come in contact with the drug, they undergo apoptosis
- etidronate (older form): resembles PPi and generates cytotoxic ATP
- aldendronate/risendronate (newer form): much more potent; contains nitrogen and interferes with protein trafficking
- side effects: esophageal irritation, dyspepsia, heartburn, nausea (these are swallowed), osteonecrosis of the jaw
4
Q
Zolderonic Acid
A
- an IV form of bisphosphanates
- avoid the side effects of the oral forms, but has its own side effects: flu-like symptoms and osteonecrosis of the jaw)
5
Q
Denosumab
A
- an anti-resorptive drug used to treat osteoporosis
- MOA: monoclonal antibody against RANKL; prevents osteoclast activation
- side effects: hives, difficulty breathing, swelling of the face and lips, osteonecrosis of the jaw
6
Q
Teriparatide
A
- synthetic PTH; a bone-forming drug used to treat osteoporosis
- MOA: PTH analog; in small, intermittent doses, it promotes osteoblast activity without activating osteoclasts
- side effects: if used too long, osteoclast activation will dominate; increased risk for osteosarcoma if used longer than 18 months
7
Q
Hormone Replacement Therapy (HRT)
A
- anti-resorptive drugs used to treat osteoporosis in post-menopausal women
- estrogen is re-introduced to the body, increasing it protective effects against bone loss
- side effects: increased risk for CAD, thromboembolism, and breast cancer
8
Q
Raloxifene (a SERM)
A
- SERM: selective estrogen receptor modulator; an anti-resorptive drug used to treat osteoporosis in women
- MOA: acts like estrogen, but for specific bone receptors only, thus avoiding the increased risk of breast cancer seen with HRT
- only works on the vertebrae
- side effects: venous thromboembolism and CAD
9
Q
Strontium Ranelate
A
- a drug used to treat osteoporosis
- MOA: stimulates osteoblast activity and induces osteoclast apoptosis
10
Q
Odanacatib
A
- an anti-resorptive drug used to treat osteoporosis
- MOA: inhibits cathepsin (the enzyme used by osteoclasts to degrade the organic component of bone matrix)
11
Q
” -dronate “
A
- bisphosphanate
12
Q
What treatments are available for rheumatoid arthritis?
A
- analgesics for pain
- NSAIDs for pain and stiffness and some anti-inflammation
- corticosteroids for anti-inflammation
- DMARDs and biological agents (TNF inhibitors) for anti-inflammation (these are the mainstay of treatment)
13
Q
NSAIDs
A
- reverse inhibition of cyclooxygenase (both COX-1 and COX-2) blocks prostaglandin synthesis to provide an analgesic and anti-inflammatory action
- used to provide relief in rheumatoid arthritis, gout, seronegative spondyloarthropathies, etc.
- often given with PPIs as prophylaxis for gastric ulcers
- (the NSAID Indomethacin is given to close PDA!)
14
Q
Aspirin
A
- irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) to block prostaglandin synthesis; a type of NSAID
- in small doses: decreased platelet aggregation
- in intermediate doses: anti-pyretic and analgesic
- in high doses: anti-inflammatory
15
Q
DMARDs
A
- disease modifying anti-rheumatic drugs
- the mainstay of treatment for rheumatoid arthritis
- Methotrexate, Sulfasalazine, hydroxychloroquine, Leflunomide
- alleviate inflammation to greatly improve joint function
16
Q
Methotrexate
A
- the most effective DMARD (used for RA and chron disease)
- MOA: an anti-metabolite that blocks dihydrofolate reductase to inhibit the production of thymidine (a pyrimidine) from folic acid, which is needed for DNA synthesis; an anti-folate (inhibits nucleotide synthesis)
- side effects: teratogenic, GIT issues
- patients often take supplemental folic acid to help reduce the GIT side effects
17
Q
Sulfasalazine
A
- a DMARD that works well for moderate rheumatoid arthritis
- side effects: Stevens-Johnson syndrome if allergic to sulfonamides
18
Q
Hydroxychloroquine
A
- a very mild DMARD used for mild disease
- MOA: binds to DNA to inhibit lymphocyte function
- originally developed for malaria
- is commonly used in conjunction with Methotrexate for synergistic effect
19
Q
Leflunomide
A
- a new DMARD, nearly as good as Methotrexate
- inhibits IL-2 production to provide anti-inflammatory action (interferes with nucleotide synthesis by inhibiting dihydroorotate dehydrogenase
20
Q
Corticosteroids
A
- a powerful immunosuppressant and anti-inflammatory
- inhibit phospholipase A2 (the pre-cursor of arachidonic acid) by inducing transcription of lipocortin (inhibits phospholipase A2)
- good for short term medication, but prolonged use has serious contraindications (osteoporosis, diabetes, cushings)
21
Q
Biological Agents
A
- “bDMARDS,” “bioDMARDS”
- these are TNF-alpha inhibitors used to treat rheumatoid arthritis, IBD, and spondyloarthropathy
- Etanercept: a decoy receptor for TNF (subcutaneous injection)
- Infliximab and Adalimumab: monoclonal Ab against TNF (IV)
- side-effects: infection, reactivation of latent TB
22
Q
Which combo therapies are used to treat patients with rheumatoid arthritis who are not responding to monotherapy with Methotrexate?
A
- try MTX + SSZ or HCQ
- then try MTX + SSZ + HCQ
- then try MTX + LEF
- then try MTX + CYC
- then try MTX + bDMARDS
- (MTX = methotrexate, SSZ = sulfasalazine, HCQ = hydroxychloroquine, LEF = leflunomide, CYC = cyclosporin, bDMARDS = biologics)
23
Q
Which drugs do we treat ankylosing spondylitis with?
A
- NSAIDs and biological agents (bDMARDs, TNF inhibitors)
- regular DMARDs do not work so well
24
Q
How do we treat an acute bout of gout?
A
- NSAIDs for pain and some anti-inflammation
- Colchicine for pain and anti-inflammation
- corticosteroids (aspirate the joint and inject intra-articular corticosteroids, can also be oral or intra-muscular)
- biologic agents have no significant effect
25
Q
Colchicine
A
- drug used for analgesic and anti-inflammatory actions for treating acute gout
- MOA: binds to and stabilizes tubulin to inhibit microtubule polymerization, thus impairing leukocyte chemotaxis and degranulation
26
Q
How do we treat chronic gout?
A
- goal is to lower the patient’s uric acid levels via ULT (urate lowering therapy) with drugs; weight loss; avoiding alcohol, red meats, seafood; etc.
- two types of ULT drugs: xanthine oxidase inhibitors (XOIs) and uricosuric drugs
- don’t give these patients aspirin, as aspirin inhibits renal excretion of uric acid (other NSAIDs are OK)
- (note that initiating ULT can actually trigger an initial flare up of the disease)
- (optimum serum uric acid is less than 360 umol/L [6 mg/dL] )
27
Q
XOIs
A
- xanthine oxidase inhibitors; part of ULT (urate lowering therapy) for treating chronic gout
- Allopurinol, Febuxostat
- MOA: inhibit conversion of hypoxanthine to xanthine AND of xanthine to uric acid (xanthine oxidase catalyzes both reactions)
28
Q
Allopurinol
A
- a xanthine oxidase inhibitor
- MOA: a purine analogue; a non-specific competitive inhibitor of xanthine oxidase
29
Q
Uricosuric Drugs
A
- drugs use in ULT (urate lowering therapy) for treating chronic gout
- Probenecid
- MOA: bind to urate anion exchanger-1 (URAT-1) of the kidneys to prevent uric acid reabsorption at the proximal renal tubule (increases uric acid excretion)
- side effect: uric acid nephrolithiasis (make sure patients stay well hydrated!)
30
Q
Probenecid
A
- a uricosuric drug
