inhibits folate utilization; used as part of tx for toxoplasmosis
What is the moa of trimethoprim?
inhibits folate utilization
What is the drug of choice for a UTI in an non hospitalized patient?
Trimethoprim-sulfamethoxazole (TMP-SMX)
What type of anemia may be caused by anti-folate drugs (e.g. pyrimethamine, sulfa-drugs, dapsone)?
Megaloblastic anemia
What inhibitor of DNA synthesis is used to treat acute lymphoblastic leukemia (ALL)? What is its mechanism of action?
6-Mercaptopurine; Acts as a purine analog
What inhibitor of DNA synthesis is used to treat non-lymphocytic leukemias? What is its mechanism of action?
Cytarabine; Acts as a pyrimidine antagonist, inhibiting the reduction of CDP to dCDP; so it's terminated DNA chain elongation
What is the moa of fluorouracil (5-FU)?
inhibits thymidine synthesis; used for slow growing solid tumors (like breast, colorectal, gastric tumors)
memorize
What class of drug is contraindicated in children < 16 years of age because of the risk of joint cartilage injury? What is the most suffix shared among the drugs of this class? Fluoroquinolones; -floxacin
What enzyme is inhibited by fluoroquinolones? What is this enzymes function? DNA gyrase; Relieves strain while double-strand DNA is being unwound by helicase
Are fluoroquinolones active against gram negative organisms, gram positive organisms, or both? Both
4 drug regimen - vincristine, prednisone, an anthracycline, cyclophosphamide or L-asparaginase
MOA of prednisone in the treatment of ALL
Prednisone is a steroid that induces lymphocytopenia
MOA of vincristine in treatment of ALL?
Binds to tubulin and blocks it from forming microtubules. Mitosis is therefore inhibited. This is classified as a mitosis inhibitor
SE of vincristine?
Peripheral neuropathy, phlebitis (vein inflammation), alopecia, and multiple GI problems
POMP stands for
prednisone, oncovin (vincristine), methotrexate, purinethol. Treatment for Treatment for non mature B cell ALL
L-asparaginase MOA
causes asparagine to convert to aspartic acid so it deprives neoplastic cells of any formally available asparagine
L-asparaginase SE
severe hypersensitivities
Anthracyclines MOA
inhibits RNA/DNA synthesis via nucleic acid intercalation
Anthracyclines SE
cardiotoxic, mutagenic
Ara-C MOA
aka cytarabine; potent inhibitor of tumor cell DNA polymerase
Methotrexate MOA
inhibits dihydrofolate reductase, inhibiting the use of folate and therefore the synthesis of DNA.
Purinethol
another term for 6-MP.
Purinethol (6-MP) side effects?
stomatitis, bone marrow suppression, alopecia, nausea, vomiting and renal and hepatic damage
ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) is used to treat what?
Hodgkin's lymphoma
MOA of bleomycin and adriamycin?
Destroy DNA by creating radical oxygen species
Dacarbazine MOA
alkylating agent, killing neoplastic cells by adding an alkyl group to their DNA. Highly emetogenic and potent bone marrow suppressor
Mechlorethamine
alkylating agent, alkylating guanines in DNA so that they cross-link in pairs or are removed.
mechlorethamine SE
severe nausea and vomiting, extreme bone marrow suppression, herpes zoster, extensive blisters
Procarbazine
inhibits both DNA and RNA synthesis. bone marrow suppression, disulfiram reactions and neurotoxicity (drowsiness that progresses to hallucinations and paresthesias)
What enzyme is used to make arachidonic acid from phospholipids in plasma membrane?
phospholipase A2
What inhibits phospholipase A2?
corticosteroids
What increases phospholipase A2?
bradykinin and/or angiotensin II
What enzyme is used to make PGG2 from arachidonic acid?
cyclooxygenase
What is PGG2 converted to?
PGH2 --> PGI2, PGF2, thromboxane A2, PGE2
What does PGE2 do?
mediates pain by sensitizing nerve endings to other pain mediators such as bradykinin, histamine, and other mediators of inflam process
What happens when the ant hypothalamic thermoregulatory center set point is elevated?
fever
What does PGI2 (prostacyclin) do?
inhibits gastric secretions
What does PGE2 and PGF2 do?
stimulate production of protective mucus in stomach and SI
Aspirin MOA
acetylates cyclooxygenase IRREVERSIBLY
Why is aspirin contraindicated in gout?
it competes with uric acid at the renal transporters resulting in inc levels of uric acid
why is acetaminophen not truly an NSAID?
it inhibits COX but only acts in the CNS so it still reduces fever and perception of pain
DOC for closing PDA?
indomethacin
what are COX 2 inhibitors?
selectively inhibits cyclooxygenase 2 - responsible for catalyzing formation of prostaglandins in inflammatory or injurious conditions
NSAID risks
all NSAIDS (except acetaminophen) increase risk of miscarriage at conception. May exacerbate HTN and heart failure. Chronic use may promote serious GI disorders, may increase bleeding risk
Chapter 20 Specialized Drugs for Inflammatory Disorders
Question
Answer
What are DMARDS?
disease modifying antirheumatic drugs; used for chronic inflammatory conditions; includes nonbiologic agents and biologics
What agent, although not first line because of its severe side effects, is considered to be the most effective for the treatment of rapidly progressive rheumatoid arthritis?
Gold
MOA of gold
prevents further damage by suppressing macrophages and other phagocytes, depressing their lysosomal enzyme activity.
What is the antidote for gold toxicity?
Dimercaprol
What specialized drug for inflammatory disorders is associated with chrysiasis (grey-blue discoloration of skin)?
Gold
What is the only drug known to reduce rheumatoid factor? What is its function in modern medicine?
D-penicillamine; Chelation
What drug can treat copper toxicity?
D-penicillamine
What is the mechanism of action of methotrexate?
Inhibits dihydrofolate reductase
What enzyme is inhibited by steroids?
Phospholipase A2, preventing arachidonic acid production and ultimately preventing prostaglandin production
What cytokine is inhibited by drugs like thalidomide, pentoxifylline, infliximab, and etanercept?
Tumor necrosis factor (TNF)
What two conditions must be met before a woman can be started on thalidomide?
(1) Negative pregnancy test (2) Started on oral contraceptives
What can thalidomide be used for?
multiple myeloma and inflammatory complications of leprosy
What are the monoclonal antibodies of infliximab and adalimumab directed against?
Tumor necrosis factor (TNF)
What anti-tumor necrosis factor agent may worsen heart failure and thus must be monitored closely in that patient population?
Adalimumab
MOA of etanercept
recombinant TNF receptor that binds up TNF in the bloodstream
MOA of golimumab
monoclonal ab against TNF causing a decrease in TNF levels in serum
What metabolic disorder is marked by increased amounts of uric acid in the blood?
gout
What is the drug of choice for acute episodes of gout?
Colchicine
Where does urate eventually precipitate to?
joints and kidney
Acute attacks of gout are often d/t
high alcohol consumption, high purine diet, kidney disease
Chronic gout may be d/t
kidney disease, malignancy
What is the mechanism of action of colchicine?
Binds tubulin inhibiting the synthesis and release of leukotrienes
What is the drug of choice for chronic gout?
allopurinol
What is the mechanism of action of allopurinol?
Inhibits xanthine oxidase
What are the SE of allopurinol?
hypersensitivity reactions - mostly skin rashes that occur only after months to years of chronic use
What drug, known to compete for renal transporters, worsens gout, but, at high doses will improve gout?
Probenecid
What is the MOA of probenecid?
uricosuric agent; blocks tubular reabsorption of uric acid to cause greater uric acid excretion
What inherited condition is due to a deficiency in hypoxanthine-guanine phosphoribosyltransferase (HGPRT) resulting in excess uric acid and self-mutilation? What is its pattern of inheritance?
Lesch-Nyhan syndrome; X-linked recessive
Although NSAIDs are acceptable for gout, what NSAID should never be used? Why should it not be used in patients with gout?
Aspirin; Competes with uric acid at the renal transporters
What is the first drug given to a patient with an acute gout attack?
NSAIDs (except aspirin)
What are the six primary drugs/drug classes that compete for renal transporters?
rename
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