MSK Flashcards
Teriparatide
Recombinant PTH analog. increase osteoblastic activity when administered in pulsatile (low dose bolus) fashion.
CLINI CAL USE
Osteoporosis. Causes increased bone growth compared to antiresorptive therapies (eg, bisphosphonates).
AD VERSE EFFECTS INcreases risk of osteosarcoma (avoid use in patients with Paget disease of the bone or unexplained elevation of alkaline phosphatase). Avoid in patients who have had prior cancers or radiation
therapy. Transient hypercalcemia.
Alendronate, ibandronate, risedronate, zoledronate
-dronates
Bisphosphonates:
Pyrophosphate analogs; bind hydroxyapatite in bone, inhibiting osteoclast activity.
CLINI CAL USE Osteoporosis (1st line), hypercalcemia (1st line), Paget disease of bone, metastatic bone disease, osteogenesis
imperfecta.
AD VERSE EFFECTS Esophagitis (if taken orally, patients are advised to take with water and remain upright for 30
minutes), osteonecrosis of jaw, atypical femoral stress fractures.
CI: in significant renal insufficiency
Bone: estrogen
Increase OPG secretion, decreases MCSF and RANK, to induce apoptosis of osteoblasts.
Tamoxifen
Raloxifene
(SERMS)
Tamoxifen- Antagonist at breast; agonist at bone, uterus; increase risk of thromboembolic events and endometrial
cancer. Used to treat and prevent recurrence of ER/PR ⊕ breast cancer.
Raloxifene Antagonist at breast, uterus; agonist at bone; increase risk of thromboembolic events but no increased risk
of endometrial cancer (vs tamoxifen); used primarily to treat osteoporosis.
Denosumab
Tx: for osteoporosis
denosumab
(monoclonal antibody against RANKL
Tx for secondary hyperparathyroidism
Vitamin D analogues
– Calcitriol, paracalcitol, doxercalciferol
Directly decreases PTH secretion because they are or act like 1,25 (OH)2 D
– Indicated for chronic kidney disease
– Concerns about inducing hypercalcemia or increasing
ectopic calcification
• “Calcimimetics” – Cinacalcet positive, allosteric activator of calciumsensing receptor (CaSR) – Directly decreases PTH secretion – Contraindications: Hypocalcemia – Dose adjustments with hepatic failure
• Phosphate binders -reduce phosphate
absorption in gut
Aspirin
MECHANISM: NSAID that irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) by covalent acetylation
> decreased synthesis of TXA2 and prostaglandins. Increased bleeding time. No effect on PT, PTT. Effect lasts
until new platelets are produced.
CLINICAL USE Low dose (< 300 mg/day): Blocks platelet aggregation. Intermediate dose (300–2400 mg/day): antipyretic and analgesic. High dose (2400–4000 mg/day): anti-inflammatory.
ADVERSE EFFECTS Gastric ulceration, tinnitus (CN VIII). Chronic use can lead to acute renal failure, interstitial
nephritis, GI bleeding. Risk of Reye syndrome in children treated with aspirin for viral infection.
Toxic doses cause respiratory alkalosis early, but transitions to mixed metabolic acidosis-respiratory
alkalosis.
Celecoxib
Reversibly and selectively inhibits the cyclooxygenase (COX) isoform 2 (“Selecoxib”), which is
found in inflammatory cells and vascular endothelium and mediates inflammation and pain;
spares COX-1, which helps maintain gastric mucosa. Thus, does not have the corrosive effects
of other NSAIDs on the GI lining. Spares platelet function as TXA2 production is dependent on
COX-1.
CLINICAL USE Rheumatoid arthritis, osteoarthritis.
ADVERSE EFFECTS Increase risk of thrombosis. Sulfa allergy.
Acetaminophen
MECHANISM Reversibly inhibits cyclooxygenase, mostly in CNS. Inactivated peripherally.
CLINICAL USE Antipyretic, analgesic, but not anti-inflammatory. Used instead of aspirin to avoid Reye syndrome
in children with viral infection.
ADVERSE EFFECTS Overdose produces hepatic necrosis; acetaminophen metabolite (NAPQI) depletes glutathione and
forms toxic tissue byproducts in liver. N-acetylcysteine is antidote—regenerates glutathione.
naproxen ketorolac, diclofenac, meloxicam, piroxicam
Reversibly inhibit cyclooxygenase (both COX-1 and COX-2). Block prostaglandin synthesis.
CLINICAL USE Antipyretic, analgesic, anti-inflammatory. Indomethacin is used to close a PDA.
ADVERSE EFFECTS Interstitial nephritis, gastric ulcer (prostaglandins protect gastric mucosa), renal ischemia (prostaglandins vasodilate afferent arteriole), aplastic anemia.
Leflunomide
MECHANISM Reversibly inhibits dihydroorotate dehydrogenase, preventing pyrimidine synthesis. Suppresses
T-cell proliferation.
CLINICAL USE Rheumatoid arthritis, psoriatic arthritis.
ADVERSE EFFECTS Diarrhea, hypertension, hepatotoxicity, teratogenicity
Infliximab,
adalimumab,
certolizumab,
golimumab
Anti-TNF-α monoclonal antibody.
Tx: Inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriasis
Etanercept
Etanercept Fusion protein (receptor for TNF-α + IgG1 Fc), produced by recombinant DNA.
Etanercept intercepts TNF.
Rheumatoid arthritis, psoriasis, ankylosing
spondylitis
Rituximab
Monoclonal antibody against CD20, which is found on most B-cell neoplasms.
CLINICAL USE Non-Hodgkin lymphoma, CLL, ITP, rheumatoid arthritis.
ADVERSE EFFECTS Increases risk of progressive multifocal leukoencephalopathy.
methotrexate
Folic acid analog that
competetively inhibits
dihydrofolate reductase
Decrease dTMP and decreases DNA synthesis
Tx: Cancers: leukemias
(ALL), lymphomas,
choriocarcinoma, sarcomas.
Non-neoplastic: ectopic pregnancy, medical abortion (with misoprostol), rheumatoid arthritis, psoriasis, IBD, vasculitis
ADVERSE: Hepatotoxicity. Mucositis (eg, mouth ulcers). Pulmonary fibrosis.. Myelosuppression, which is reversible with leucovorin “rescue.”
