Everything Ever Flashcards
<p>What is indomethicin used for?</p>
<p>Like naproxen, NSAID
| Long-term relief of symptoms in RA and other musculoskeletal disorders</p>
<p>Why are COX-2 inhibitors being used more than NSAIDs?</p>
<p>Cox-2 inhibitors decrease the incidence of gastric and duodenal ulcers by 50% as compared with traditional NSAIDs
Provide therapeutic relief until a DMARD takes effect.</p>
<p>What is sulfasalazine used for?</p>
<p>Oldest DMARD
Fast-acting (1 month)
Mechanism not understood, may inhibit IL-1 and TNF-alpha release
Adverse effects - nausea, rashes, headaches, neutropenia</p>
<p>What is one advantage of using antimalarials to treat rheumatic disorders?</p>
<p>Less efficacious than other DMARDs but also less toxic</p>
<p>What is the gold-standard DMARD therapy?</p>
<p>Methotrexate</p>
<p>Why is cyclosporine A not used more often as a DMARD?</p>
<p>Toxic</p>
<p>What is leflunomide?</p>
<p>Similar effects to sulfasalazine and methotrexate
DMARD
Newest
prevents de novo pyrimidine synthesis
Side effects are diarrhea, alopecia and hepatotoxicity</p>
<p>What is the mechanism of action of prednisone?</p>
<p>Glucocorticoids in general:
inhibit phospholipase A2 activity --> inhibits release of arachadonic acid from cell membranes --> inhibits formation of prostaglandins
Glucocorticoids also inhibit production of numerous cytokines which prevent induction of COX-2. </p>
<p>What are the long term effects of glucocorticoid use?</p>
<p>Hyperglycemia
Osteoporosis
Poor wound healing
Though usually benefits outweigh complications
Use glucocorticoids to induce remission while slower-acting DMARD takes effect</p>
<p>What are examples of antimalarials in use as DMARDs?</p>
<p>Chloroquine (can cause irreversible retinal damage if used long term)
Hydroxychloroquine (better tolerated) for RA, lupus
Overall, less efficacious than other DMARDs
Act by inhibiting chemotaxis</p>
<p>What is the most commonly used DMARD (is also immunosuppressive)?</p>
<p>Methotrexate
Folate analog
Inhibits reaction catalyzed by dihydrofolate reductase that is essential for DNA synthesis
Also used as anticancer agent
Major complication is hepatotoxicity
At low doses (for rheumatic diseases) --> inhibition of aminoimidazolecarbomide transformylase and thymidylate synthetase with secondary effects on polymorphonuclear chemotaxis --> AMP then accumulates and is converted to adenosine, which inhibits inflammation</p>
<p>What are the TNF-alpha antagonists?</p>
<p>Etanercept Infliximab Adalimumab Golimumab Certolizumab</p>
<p>How does Etanercept (Enbrel) work?</p>
<p>TNF-alpha antagonist --> less inflammation systemically
Binds to TNF and prevents its binding to receptors
example of an antagonist that binds a receptor but does not activate it
SubQ 2x/wk</p>
<p>What is Infliximab (Remicade)?</p>
<p>TNF-alpha antagonist --> less inflammation systemically
Monoclonal antibody (chimeric mouse-human)
TNF-alpha antagonist
Effective within 1 week of injection
Antigenic</p>
<p>Why is Adalimumab favored over etanercept?</p>
<p>TNF-alpha antagonist --> less inflammation systemically
More convenient dosing regimen (2x/monthly)
Fully human anti-tnf-alpha mab
Not antigenic</p>
<p>How does Golimumab work?</p>
<p>TNF-alpha antagonist --> less inflammation systemically
Once monthly dosing
human mab, binds to both membrane bound and soluble tnf-alpha
Opportunistic pathogen infection risk is increased (ie TB) **which is generally true of all TNF-alpha blockers</p>
<p>How is Certolizumab different from other TNF-alpha antagonists?</p>
<p>TNF-alpha antagonist --> less inflammation systemically
| It's a humanized Fab fragment congugated to polyethylene glycol to delay metabolism and elimination</p>
<p>What is Anakinra?</p>
<p>Cytokine antagonist (IL-1)
Soluble human IL-1 receptor antagonist
Short half life necessitates frequent daily treatment in high doses</p>
<p>What IL-6 receptor antagonist has had serious issues with opportunistic infections?</p>
<p>Tocilizumab
| Approved as "Actemra"</p>
<p>What is the MOA of Abatacept?</p>
<p>Inhibits T-cell activation and induces T-cell apoptosis
Name brand: Orencia
approved for RA refractory to TNF-alpha inhibitors
Side effects - headaches, infections</p>
<p>What is Rituximab?</p>
<p>Anti-CD20 mAb that reduces circulating B cells
considered a "costimulation modulator"
approved for RA refractory to TNF-alpha inhibitors</p>
<p>What signaling pathway inhibitor is used for RA treatment?</p>
<p>Tofacitinib
inhibitor is JAK kinase 1 and 3
inhibits production of inflammatory mediators</p>
<p>RA is characterized by chronic inflammation of the synovial membrane and infiltration by blood-derived cells, for example....</p>
<p>CD4+ T-cells, which produce inflammatory cytokines</p>
<p>T/F: TNF-alpha and IL-1 play a central role in RA.</p>
<p>True
IL-6 also plays a role in pro-inflammatory plathways.</p>
What is the rheumatoid pannus?
Synovial membrane --> inflammatory tissue (the pannus) which destroys surrounding cartilage and bone Pannus: type A and B synoviocytes and plasma cells
Uric acid, which accumulates and crystallizes in the joints in gout, is the major end product of what metabolic process?
Purine metabolism (catablolism) | hypoxanthine --> xanthine --> uric acid (xanthine oxidase used to catalyze both steps)
Normal serum uric acid concentration is:
40-50 mg/L | Uric acid precipitates at > 100 mg/L
Name some causes of hyperuricemia:
Alcohol use (beer) Obesity (high fructose corn syrup) Renal disease (less excretion) Diabetes HTN Drugs is thiazide diuretics, aspirin, diuretics, levodopa, pyrazinimide, cytotoxic drugs, cyclosporine Cancers - diseases associated with rapid production and destruction of cells ie Hodgkins disease
What is podagra?
Gouty arthritis attack of metatarsaophalangeal joint of the big toe Tophi (deposits of urate)
What is the MOA of colchicine?
Inhibits spindle formation --> neutrophils can't travel --> lowers inflammatory response **Low therapeutic index means than the diff between therapeutic dose and toxicity is small Side effects: nausea, diarrhea, vomiting...long term can cause peripheral neuropathy, neutropenia
What are the commonly used NSAIDs for gout?
Naproxen indomethicin sulindac celecoxib (selective COX-2 inhibitors)
Uricosuric agents act by:
Increasing the rate of excretion of uric acid Normally, only 10% of uric acid is excreted Uricosuric acids compete with uric acid in the renal tubule to prevent reabsorption Example: Probenecid (developed as an adjunct to penicillin to increase its effectiveness) --can also have the effect of increasing urate crystal mobilization
What is the MOA of Allopurinol?
Inhibits xanthine oxidase competitively AFTER being metabolized to its active form (alloxanthine) by xanthine oxidase itself Used much more often than probenecid Maculopapular rash in 2% of patients
What is the other xanthine oxidase antagonist besides allopurinol?
Febuxostate New Non-purine, non-competitive antagonist of xanthine oxidase Cardiovascular safety still under investigation
T/F: Developing gout without hyperuricemia is possible.
True
Why are pubic lice called crabs?
Their body shape is longer than body and head lice. Presence of pubic lice warrants screening for all STIs
How do you stain for treponema?
Darkfield, no gram staining in the "poorly staining bacteria" category cannot be cultured they are too small to be seen by standard light microscopy
What is the result of immune evasion with treponema?
Low virulence but persisting symptoms that worsen over time Humans raise mostly useless antibodies against the infection T pallidum enters lymphatics ans bloodstream immediately and does not need to build up numbers for symptoms to begin
What is the infection caused by treponema palladum?
Syphilis, transmitted sexually and congenitally
What is the Argyll-Robertson pupil?
The prostitute will accomodate but not react... | tertiary (neuro) syphilis
What are the stages of syphilis?
1. primary chancre, 2. secondary body-wide rashes, condylomata lata (Reddish-brown papular lesions on the penis or anogenital area) and patchy alopecia, 3. latent period - 2/3 patients progress only to here 4. tertiary gummas, neurosyphilis, cardiac involvement - 1/3 of patients progress to tertiary syphilis
Neurosyphilis may includes what sequelae?
meningitis, tabes dorsalis (damage to spinal cord → impaired sensation, wide-based gait), general paresis, check for Argyll-Robertson pupil
Why is congenital syphilis dangerous?
kills 50% fetus/newborn, survivors are infected, bone deformities, interstitial keratitis, progress rapidly to symptoms of secondary&tertiary syphilis if untreated
Why are body lice (pediculus humanus) dangerous?
Can transmit typhus and relapsing fever, trench fever
What is the relationship between syphilis and HIV?
Ulcerations of syphilis facilitate HIV infection | HIV immunosuppression accelerates syphilis course, and reduces efficacy of treatment
What is the treatment for syphilis?
Penicillin G IV (same for yaws and pinta which are also treponema)
How do you test for syphilis?
Syphilis serology for reagin (VDRL, RPR) is best test for disease-in-progress and for efficacy of treatment; confirm exposure with tests for treponeme-specific antibodies; histo of lesions shows infiltrate rich in plasma cells
What kind of organism is Neisseria gonorrhea?
Gram (-) diplococci oxidase + catalase +
How does gonorrhea present in males, females and neonates?
Males - urethritis Females - asymptomatic or cervicitis or PID Neonates - purulent conjunctivitis - can treat with prophylactic eye ointment
T/F: Gonorrheal infection is a marker for sexual abuse in children.
True
What are virulence factors for gonorrhea?
IgA protease - clears IgA from mucosal surfaces to facilitate colonization Pili LOS (less immunogenic than LPS) - local inflammation Opa - opacity-associated proteins enhance binding
Arthritis/dermatitis can be signs of what disseminated infection?
N. gonorrhea | Other complications are DGI, meningitis, endocarditis
What is the best way to test for gonorrhea?
Nucleic acid amplification tests (NAAT) - same for chlamydia gram stain (-) organism is delicate culture on Thayer-Martin (chocolate agar)
What are important similarities between N. meningitides and N. gonorrhea?
Culture on Thayer-Martin Septic arthritis as a complication IgA protease as a virulence factor
What are the treatment options for gonorrhea?
Ceftriaxone | Cefotaxime
What are the treatment options for C. trachomatis?
Doxycyline (or azithromycin) unless pregnant, then use erythromycin these drugs must penetrate cell membrane bc chlamydia is intracellular
What is the known virulence factor for chlamydia that is involved in inclusion body formation?
T3SS Reticulate bodies form intracellular inclusions that are visible on microscopy; within the inclusions they multiply by binary fission, forming new reticulate bodies and later new elementary bodies.
What are the symptoms of chlamydia in women?
May be asymptomatic Easily induced endocervical bleeding Mucopurulent endocervical discharge Intermenstrual bleeding Dysuria Abdominal pain can cause PID ``` ``` Men: can be asymptomatic reservoirs Urethral discharge Urinary frequency and/or urgency Dysuria Scrotal pain/tenderness Perineal fullness
```What causes reactive arthritis?
Defined as Conjunctivitis + Urethritis + Arthritis | From chlamydia infection - aka Reiter's syndrome
What is lymphogranuloma venereum?
Painless ulcer leads to swollen lymph nodes (buboes) caused by chlamydia bacterium (diff serovar than genital)
What is blinding trachoma?
Leading cause of preventable blindness worldwide | Serovar of chlamydia
