RA Pathogenesis category Use class drug

reduce inflammation & Acetylsalicylic Acid

pain. Acts as a bridge NSAIDs Ibuprofen
COX-2-selective
drug for relief of
Symptomatic relief of Celecoxib
Treats acute pain & Prednisone
Symptoms: inflammation. more Glucocorticoid Cortisone
potent than NSAIDs, s Hydrocortisone
less desirable side Methylprednisolone
• Memory T-cell activation in Initial
effectstreatment to Synthetic Methotrexate (MTX)
response to peptides achieve Clinical (Conventional) Antimetabolite/
presented by antigen Remission & prevent Disease- antifolate
Leflunomide
presenting cells Modifying Anti-
• Occurs in genetically
irreversible damage
susceptible individuals Alters to joints. Rheumatic drugs Sulfasalazine
Hydroxychloroquin
• amplification of Progression same as above ^ and... Biologic e
inflammation, autoantibody (Disease- Slow-acting, so need aka DMARDs Anti-malarial
Disease- Etanercept
Organic compounds made by
modifying) living cells that modify Modifying Anti- Infliximab
biologic responses Rheumatic
• Antibody-antigen interactions drugs: Anakinra
• Cytokine-receptor interactions
• Cell signaling proteins, Sarilumab
aka bDMARDs
 mechanism line? Notes from guest lecture
First line drugs for
COX-1: more protective/constitutive esp symptomatic relief
of GI tract (gastric
(Arachidonic mucosa)
Acid so blocking can most commonly
pathway)
used steroid to tx RA
& lupus can add glucocorticoids
act through glucocorticoid
but withdraw ASAP/not
receptors can activate anti- no for long term use
inflammatory pathways and
↑ EC adenosine
inhibit & inhibit T-cell
pro-inflammatory first-line DMARD
activation, cytotoxic to moderate-to-severe
2nd line:
T/B-cell proliferation 1st line Methotrexate
proliferating lymphocytes RA to
alternative
↓ B-cell function → ↓ IgA & IgM 2nd line:
methotrexate if contraindicated →
mechanism
rheumatoid unclear: anti-
factor prod. initial3rd
tx ofline:
mild RA
inflammatory actions. Stabilize leflunomide or
anti-TNF: initial4th
tx line:
of mild RA sulfasalazine
lysosomes & decrease chemotaxis, for pts not
recombinant
anti-TNF: TNF receptor
responding to if still not working after
Chimeric monoclonal Antibody moderate
DMARDS to severe
IL-1 Receptor Antagonist three months:
IL-6 Receptor Inhibitor: RA not
for pts add bDMARD
Human monoclonal Antibody responding to MTX or

r
Sketchy pic
Gout Pathogenesis Use class drug
Indomethacin
Acute gout (and
Stop acute gouty NSAIDs NOTnaproxen)
low-dose
attacks & Provide Aspirin
Glucocorticoid Cortisone
control of pain and s Hydrocortisone
inflammation other Colchicine
Oxidase Allopurinol
inhibitors -
reduce Febuxostat
Prophylaxis
Probenecid
• Increase UA
excretion Uricosuric
• Prevent production drugs increase Sulfinpyrazon
of uric acid (esp in renal excretion e
context of renal stones,
of UA
tophi or renal failure)
sketchy drugs:
pegloticase &
Rasburicase
 mechanism indication
First-line treatment: Very notes from sketchy
Inhibit urate crystal
retention of uric acid = worsens effective for inflammation
phagocytosis all acute gout medications
withNOT
do acute gouty arthritis
gout
Intra-articular steroid Patients USE ASPIRIN
who cannot are also indicated in the
(but high does increases tolerate NSAIDs, or failed
injection: Beneficial in patient with just side effect treatment of pseudogout
microtubular polymerization → NSAID/colchicine therapy
Blocks
Decreased xanthine → uric acid by also
precipitate a gout attack if if given
XO also prevents UA kidney&
used in pericarditis w/out NSAIDs or colchicine,
Blocks xanthine → uric acid by – Used in
stones patientslysis
& tumor with
•XOcan cause SJ & DRESS syndrome allopurinol ineffectiveness also inhibit the breakdown of
Increase renal clearance
• More selective of uric
than allopurinol or poor tolerance purine analogs (e.g., 6-
acid by inhibiting PCT
Do NOT use if patient has
reabsorption (via inhibiting OAT Probenecid = sulfa drug, also
& URAT) renal impairment or is can decrease excretion of other
predisposed to urate drugs, increasing their serum
conc. like cidofovir
only for underexcretors of UA stones
can cause acute gouty attacks if given to
an overproducer
recombinant uricases that Pegloticase - refractory can cause anaphylaxis &
convert uric acid into water gout Hemolytic anemia in G6PD
soluble allantoin Rasburicase - tumor lysis deficiency
↓ UA renal secretion.
prevented
• Loop andwith aggressive
thiazide diuretics
IV fluids + either xanthine
oxidase inhibitors OR
 class drug • induces apoptosis mechanism
of immune cells
glucocorticoids Prednisone •expression
inhibit IL-2 production
Cyclosporine •3.Reduced neutrophilof
blocks activation chemotaxis
T cells
calcineurin inhibitors same mechanism as cyclosporine but binds to &
Tacrolimus
forms a complex
2. inhibits target ofwith
mTORFKBP(rapamycin)
(an immunophilin)
Sirolimus
Antiproliferative/ Azathioprine/6- 3. thio-IMP
5. Inhibits T→ cell activation & proliferation
6-thioguanine
antimetabolic agents MPMycophenolate 6. incorported into DNA →bcinhibits
3. inhibits DNA synthesis DNA
B/T cells = no salvage
mofetil surface of lymphocytes
pathway
Antithymocyte
Polyconal antibodies • Deplete
The CD80 & circulating lymphocytes
CD86 bind to CTLA-4 and cause negative
recombinant fusion Globulin (ATG) – ADCC are also the are the same molecules that bind
costimulation
Belatacept
proteins to CD28 and cause positive costimulation. Belatacept uses
Monoclonal Basiliximab Blocks binding of IL-2 → Inhibits downstream
antibodies C52 has an
cascade unknown
activation → mechanism but when
reduces T cell
Alemtuzumab Nonselective Kinase
bound by antibody →inhibitors
ADCC & of JAK‐STAT
Complement-
JAK inhibitors Tofacitnib signaling (JAK1 & JAK3) that disrupt B & T cell
differentiation

special side effects Drug

hyperglycemia Prednisone
Gingival hyperplasia Cyclosporine
Diabetes mellitus tacrolimus
• Nephrotoxicity Cyclosporine
• Neurotoxicity tacrolimus
Serum sickness ATG
PTLD Belatacept

Cyclosporine
affect T cells only
• Both B drugs tacrolimus
• Both calcineurin inhibitors Belatacept
• sirolimus
Basiliximab
affects immune cells prednisone
Mycophenolate
m.
Sirolimus
Azathioprine/6-
affect T AND B cells MP
• all the A drugs ATG
Alemtuzumab
Tofacitnib
 Use
autoimmune adverse effects
• Hyperglycemia
disorders
transplant •• Hypertension in renal & cardiac
Hyperlipidemia
– gold standard
rejection & transplant patients drug-drug
autoimmune

as a class...
autoimmune •• Hypertension
Hyperlipidemia interactions
disorders
transplant •– Alopecia
Hypertension As
▪ bcadegraded
class: by
– gold standard
rejection
transplant& – Hypertriglyceridemia
autoimmune
rejection & – Myelosuppression •
– autoimmune
gold standard •– drug interactions w Xanthine
GI upset myelosuppressuin
for maintenance •– Serum sickness
Myelosuppression • leukopenia
Transplant •anemia,
Anaphylaxis (rarely)
& diarrhea
Transplant • Leukopenia & thrombocytopenia
Generally, well tolerated, Slight
acute rejection •riskPosttransplant
of hypertension and

class
as a
prophylaxis, graft • Leukopenia leukopenia

...
rejection &
•gastrointestinal distress
thrombocytopenia
autoimmune
Autoimmune •• Hyperlipidemia
anemia
Disorders • Hypertension

Common side
Has side effect how to remember
effect only 3 w no
Sirolimus leukopenia
Azathioprine • Prednisone
Mycophenolate mofetil • Cyclosporine
Leukopenia Antithymocyte globulin • Tofacitinib
Basiliximab
Alemtuzumab
Belatacept
Mycophenolate mofetil
Basiliximab Torture my Bloody
GI upset
Belatacept Bowels
Tofacitinib
prednisone
Cyclosporine
& Hyperlipidemia
Sirolimus
Hypertension
Tofacitinib
Tacrolimus
hypertension only
Basiliximab
Azathioprine
except (Belatacept)
Antithymocyte globulin All of the "A" drugs
NO hypertension
Alemtuzumab (A=absent) +
or hyperlipidemia
Mycophenolate mofetil Mycophenolate
mofetil
Belatacept
Sirolimus
aka anti-
myleosuppressio Azathioprine/6-MP
metabolites +
n Mycophenolate mofetil Tofacitnib
Tofacitnib
Long-term therapy (everyone): hydroxychloroquine
Acute exacerbations (flare): glucocorticoids