Pharmacology Flashcards
Drugs which treat chronic inflammations such as rheumatoid arthritis target this cytokine
TNF-alpha (tumor necrosis factor-alpha)
What are DMARDS and what are they used for?
Disease-Modifying Anti-Rhemuatic Drugs; slow down progression of rheumatoid arthritis
What is the goal of therapy for Rheumatoid Arthritis?
remission
Are NSAIDs disease modifying for RA?
No; used for pain and inflammation
What are the 2 branches of DMARDs?
1) Biologic DMARDs 2) Conventional DMARDs
What is the main side effect of using corticosteroids to treat RA?
Cushing’s Syndrome (and growth retardation in children)
What are the 3 goals of therapy with DMARDs?
1) preventing/controlling joint damage 2) preventing loss of function 3) decreasing pain
What is the stem for naming monoclonal antibodies?
-mab
What is the biggest concern with using monoclonal antibodies?
Allergic reaction to mouse protein
What do fusion proteins target during treatment?
TNF-alpha
How do fusion proteins work in drugs?
Fuse the receptor to the Fc portion of IgG and picks off the TNF-alpha to serve as a decoy receptor (adds stability and leads to longer action time)
Which action is blocked by fusion proteins?
CD80/86 on APC blocked from binding to CD28 on T-cell
What is the stem for the name of kinase inhibitors?
-nib
What is a commercially available kinase inhibitor used to treat RA?
Xeljanz (tofacitinib citrate) oral JAK inhibitor
What is the stem for the name of fusion proteins?
-cept
What are the most significant side effects of biologica DMARDs
1) increased risk of tuberculosis 2) fungal infections
What are 2 conventional oral DMARDs?
1) Methotrexate (MTX) 2) Leflunomide
How is folic acid important to the administration of methotrexate?
MTX antagonist to folic acid, but low dose of MTX does not have same MOA as folic acid. Give with folic acid supplement so the folic acid does not affect the MOA of MTX i.e., folic acid fights the side effects of MTX
What is the active intracellular form of folic acid?
tetrahydrofolate
What is the role of Dihydrofolate Reductase?
modifies folate we ingest to its active form
What is the role of methotrexate in relation to intracellular folate?
MTX inhibits DHFR, preventing formation of tetrahydrolate and ultimately inhibiting DNA/RNA synthesis
How does methotrexate affect adenosine?
Promotes the release of adenosine, an endogenous anti-inflammatory mediator
How does methotrexate affect AICAR?
Inhibits AICAR transformylase and leads to increase in AICAR which ultimately leads to increase in adenosine
What are the main adverse reactions to methotrexate?
1) GI intolerance 2) Bone marrow suppression 3) liver cirrhosis
What is leflunomide?
Prodrug which rapidly converts to its active metabolite A77 1726; **suppresses pyrimidine synthesis which cannot be made by T-cells otherwise!
When A77 1726 (teriflunomide) is isolated, what is it’s MOA?
non-competitive inhibitor of DHODH (dihydroorotate dehydrogenase)
What is the drug elimination procedure for leflunomide?
1) administer cholestyramine 2) verify plasma levels are below 0.02 mg/L
How is septic arthritis treated?
1) adequate drainage of purulent joint fluid 2) appropriate antimicrobial therapy
Which 4 drugs are used to treat septic arthritis?
1) daptomycin 2) linezolid 3) clindomycin 4) ceftaroline
What is bacteremia used for and what is its treatment course?
endocarditis; 2-6 weeks (long)
What is special about the structure of cephalosporins?
beta-lactam antibiotics which inhibit cell wall synthesis
Which drug(s) are used for inhibition of protein metabolism?
1) clindomycin 2) linezoid (tedizolid)
Which drug(s) alter cell membrane permeability?
daptomycin
What is the spectrum coverage of cephalosporins?
broad spectrum
What is ceftaroline used to treat?
1) MRSA, CA-MRSA 2) S. epidermidis
What is ceftriaxone used for?
1) N. gonorrhea 2) N. meningitidis
What is cefepime used for?
P. aeruginosa
What is ceftazidime used for?
P. aeruginosa
What is cefoxitin used for?
1) B. fragilis 2) B. thetaiotaomicron
What is cefazolin used for?
MSSA **Not MRSA**
Which drug do you have to worry about a reaction with the MTT side chain leading to cleeding and alcohol reactions?
cefotetan
When can a cephalosporin still be given due to an allergic reaction to penicillin?
Hives; immediate hypersensitivity
Which cepahlosporin has best activity against MSSA?
cefazolin (1st generation)
Which cephalosporin is used in treating menegitis, Lyme disease, and Gonorrhea?
ceftriaxone
Which cephalosporin has Pseudomonas aeruginosa activity?
ceftazidime, cefepime
Which cephalosporin has anaerobic Bacteroides fragilis activity?
cefoxitin
Which cephalosporin has MRSA activity?
ceftaroline
What are the stem names for cephalosporins?
-cef -ceph
What is the MOA for daptomycin?
binds to bacterial membranes and causes rapid depolarization, resulting in inhibition of protein/DNA/RNA synthesis; causes rapid cell death
What is the antibacterial spectrum of daptomycin?
gram + only
Is daptomycin effective for lung infections?
No; lipid tail binds to cerfactin in the lung
When administering daptomycin what should be monitored?
CPK levels; creatine phosphokinase
When administering daptomycin what should be avoided?
Statins (HMG-CoA Reductase Inhibitors)
What is the MOA of linezolid?
inhibits bacterial protein synthesis by binding to bacterial ribosome
What is the MOA of tedizolid?
same as linezolid; inhibits bacterial protein synthesis by binding to bacterial ribosome
What is the antibacterial spectrum for linezolid?
Gram +
What is Serotonin Syndrome?
drug interaction where 2 drugs hit the CNS in separate places and lead to toxic levels of serotonin in the body; i.e., linezolid + antidepressentants (SSRI)
Mechanistically, what causes Serotonin Syndrome?
inhibition of monoamine oxidase which normally inhibits NE inactivation; ultimately leads to increase of serotonin
What is another name for serotonin?
5-Hydroxytriptamine (5-HT)
What is an SSRI?
Selective Serotonin Reuptake Inhibitor; i.e., prozac; blocks serotonin from being taken back into presynaptic terminal and allows it to bind to serotonin receptor on postsynaptic terminal
What is the MOA of clindamycin?
inhibits protein synthesis by binding to ribosome
What is the anibacterial spectrum of clindamycin?
Gram +, Gram - anaerobes
Which infection is commonly treated with clindamycin?
necrotizing fasciitis
What is an adverse drug reaction to clindomycin?
diarrhea which may lead to C. difficile colitis
Is clindamycin a good drug for MRSA and MSSA infections?
No; 70-80% sensitivity to drug
Is clindamycin a good drug to treat B. frag or B. thetaiotaomicron?
No; use metronidazole instead
What are the 3 stages in which gout is managed?
1) treating acute attack 2) provide prophylasix to prevent acute flares (while lowering uric acid levels) 3) lowering excess stores of urate to prevent flares of gouty arthritis and to prevent tissue deposition of urate crsytals
Which drugs can be used to lower uric acid levels in chronic gout?
1) allopurinol (Xanthine Oxidase inhibitor) 2) febuxostat (Xantine Oxidase inhibitor) 3) probenecid (uricosuric) 4) pegloticase (uricase)
Which drugs are used to treat acute gout?
1) NSAIDs 2) Colchicine 3) Glucocorticoids (corticosteroid)
When comorbidities limit the use of NSAIDs or colchicine to treat acute gout, what is used instead?
intra-articular steroid injection
What is the MOA of colchicine?
inhibits or halts cell division by interferring with microtubules
Acute gout flare is the most common adverse event of which treatment?
initiation of serum urate-lowering therapy
What is the role of uricase in the treatment of gout?
converts uric acid to highly soluble allatonin and allows for its excretion
What is Tumor Lysis Syndrome?
elevation of plasma uric acid after cancer treatment and it is treated by Elitek (uricase)
