Rheumatology, NSAIDs, Acetaminophen Flashcards
Rapidly converted to mycophenolic acid which inhibits inosine monophosphate dehydrogenase (an enzyme in the de novo pathway of guanosine triphosphate synthesis GTP)
Supresses both B and T lymphocyte activation
Mycophenolate mofetil
Ind: SLE, Transplants
Mycophenolate toxicity
GI
Myelosupression (neutropenia)
Alkylating agents
Cyclophosphamide
Cisplatin
Antimetabolites
5-FU
Methotrexate
Gemcitabine
6-mercaptopurine
Antitumor antibiotics
Bleomycin
Doxorubicin
Mitomycin
Natural product
Etoposide
Paclitaxel
Vincristine
Alklyating agents form reactive molecular species that alkylate
nucleophilic groups on DNA bases particulary N-7 position of guanine
Nitrogen mustard alkylating agent that alkylates nucleophilic groups ob DNA bases particularly the N-7 position of guanine
Cross-linking of bases, abnormal base pairing, and DNA strand breakage
Used in SLE, leukemia, non-Hodgkin’s, breast, ovarian cancer and neuroblastoma
Cyclophosphamide
Breakdown product of cyclophosphamide by CYP450
Needed for antitumor activity
Acrolein
Cyclophosphamide toxicity
GI distress
Myelosupression
Alopecia
Hemorrhagic cystitis
Cardiac dysfunction
Pulmo toxicity
SIADH
Adverse effect of cyclophosphamide from acrolein formation
Decreased by vigorous hydration and by use of mercaptoethane sulfonate (MESNA)
Hemorrhagic cystitis
First ever targeted biological treatment for SLE
Fully humanized IgG1 gamma monoclonal antibody against soluble B lymphocyte stimulator
Belimumab
Enter the cell and bind to cytosolic receptors that transport it into the nucleus
This complex alters genes expression by binding to GRE (response elements) and tissue specific responses are made possible by protein regulators
Glucocorticoids
Glucocorticoid organ and tissue effect on metabolism
Stimulates gluconeogenesis Blood glucose rise Muscle protein catabolism Increased insulin secretion Lipolysis and lipogenesis stimulation with fat deposition
Glucocorticoid catabolic effect
Muscle protein catabolism
Lymphoid tissue connective tissue fat and skin wasting
Osteoporosis
Glucocorticoid immunosupressive effect
Inhibit cell mediated immunologic functions especially those dependent on lymphocytes
Glucocorticoid anti-inflammatory effect
Supressant on inflammatory process
Increase neutrophil
Decrease lymphocyte, eosinophil, basophil, monocyte
Inhibition of leukocyte migration
Induced synthesis of inhibitor of phospholipase A2
Decreased mRNA for COX2
Decreased IL-2 and IL-3
Decreased platelet activating factor
Other glucocorticoid effects
Normal renal excretion of water
CNS behavioral change
Stimulate gastric acid secretion
Decreased resistance to ulcer formation
DMARDs that interfere with activity of T lymphocytes
Immunosupressant used for rheumatoid arthritis
DMARDs
Hydroxychloroquine
Chloroquine
DMARD toxicity
Retinal toxicity Rash GI distress Myopathy Neuropathy
Inhibitot of dihydroorotate dehydrogenase an enzyme involved in de novo pyrimidine synthesis
Used in RA
Leflunomide
Cytotoxic to rapidly dividing immune cells due to inhibition of dihydrofolate reductase
Anticancer, rheumatoid disorders
Methotrexate
Methotrexate toxicity
Nausea Mucosal ulcera Hematoxicity Hepatotoxicity Teratogenecity
Inhibition of microtubule assembly decreases macrophage migration and phagocytosis
Chronic and acute gout
Familial Mediterranean Fever
Colchicine
Colchicine toxicity
Diarrhea
Severe liver and kidney damage in overdose
Aminosalicylate
Contains 5-aminosalicylic acid (5-ASA generic Mesalamine) used as topical therapy for IBD and RA
Inhibiting synthesis of prostaglandin and inflammatory leukotrienes, and interfering with the production of inflammatory cytokines
5 ASA + sulfapyridine
Sulfasalazine
Sulfasalazine adverse effect
Sulfonamide toxicity due to absorption of sulfapyridine moiety
Cytotoxic drug
Prodrug of anticancer drug mercaptopurine, which interferes with purine nucleic acid metabolism used for rheumatic diseases and organ transplantation
Azathioprine
Acetylation of COX-1 and COX-2 results in decreased prostaglandin synthesis
Irreversible COX inhibition
Analgesia
Antipyretic
Anti-inflammatory
Anti-thrombotic
Prevents colon cancer
Aspirin
Salicylate
Reversible inhibition of COX-1 and COX-2 results in decreased prostaglandin synthesis
Analgesia
Antipyretic
Anti-inflammatory
Closure of Patent Ductus Arteriosus
Interferes with aspirin’s antithrombotic action
Ibuprofen
Nonselective NSAIDs
Selective, reversible inhibition of COX-2 results in decreased prostaglandin synthesis
Analgesia
Antipyretic
Anti-inflammatory
Hepatic metabolism
Less risk of GI toxicity
Greater risk of thrombosis
Celecoxib
COX-2
Mechanism unknown
Weak COX inhibitor
Analgesia
Antipyretic
NOT ANTI-INFLAMMATORY
Hepatic conjugation
Hepatotoxicity in overdose more likely in chronic alcohol consumltion which induces CYP450
Acetaminophen
Inhibition of renal reuptake of uric acid
Chronic gout, prolongation of antimicrobial drug action
Exacerbation of acute gout
Inhibits renal tubular secretion of weak acids such as methotrexate
Probenecid
Sulfinpyrazone
Active metabolite irreversibly inhibits xanthine oxidase and lowers production of uric acid
Chronic gout, adjunct to cancer chemotherapy
Activated by xanthine oxidase
Allopurinol
Reversible inhibitor of xanthine oxidase
Febuxostat
Biologic agents that inhibit the action of tumor necrosis factor - alpha
Decreases formation of interleukins and adhesion molecules involved in leukocyte activation
Used in RA, IBD, Ankylosing spondylitis,
Infliximab
Adalimumab
Etanercept
Recombinant human interleukin-1 receptor antagonist
Anakinra
