Drugs to Treat Inflammation/Arthritis/Gout

Question 1

Describe the differences between conventional and biological DMARDS as drugs.

Answer 1

DMARDs are drugs aimed at slowing or preventing disease progression by suppressing autoimmune activity, remission possible with RA

Conventional – small molecule, slow onset over 1-6 months, all need close monitor for toxicity, hydroxychloroquine

(1) MET,: inhibit AICAR
 SZS: T/B cell proliferation suppression
 HCQ: MHC II APC loading (no myelosuppresion)
(2) LEF: inhibits T cell proliferation

Biological – recombinant DNA technology, large cost, large size, target TNF-A/IL-1/IL-6, more targeted for RA, if conventional do not work, older patients have more AEs, can cause infection

 TNF -a: Etanercept, adalimumab (MC RESISTANCE TO MET)
 IL-1: Anakinra
 IL-6: tocilizumab and sarilumab
 MAB: Rituximab
 Tcell activation: Abatacept

Combination therapy uses conventional and biological

Question 2

Identify three ways drugs are used to reduce plasma uric acid.

Answer 2

1 treat gout flares
2 lower urate
3 anti-inflammatory prophylaxis

Question 3

5. Know the expected physiological effects of the main drug classes used to treat gout.

Answer 3

Urate lowering therapy – block xanthine to uric acid or break down uric acid to allantoin

o Allopurinol: reduces uric acid level
o Febuxostat: hyperuricemia
o Probenecid: Inhibits active transport at urate from proximal tube
o Cholecine: suppres neutrophils, acute attaches, G1 arrest
o Pegloticase: severe
o Anakina: Suppress Immune system, inhibit urate crystal induced inflammation

Acute Gout flare treatment – NSAID, corticosteroids, Cholechine inhibit IL-1

Question 4

Know the clinical factors affecting drug management of gout.

Answer 4

Lifestyle/diet modification should be done but ineffective

Flares – corticosteroids, NSAIDs, colchicine, whatever patient likes bests

Anti-IL-1 for severe cases, cannot discontinue ULT during flares

Question 5

Know some examples of cellular and molecular actions that account for the therapeutic actions of DMARDs.

Answer 5

Cellular and Molecular – NSAIDS COX1/2, glucocorticoids anti-inflammatory

Question 6

Describe the key factors involved in acute and chronic inflammation and known druggable targets in those processes.

Answer 6

Acute inflammation
● Injury → vasodilation → cell recruitment → chemotaxis -> phagocytosis → resolution
● Redness, heat, swelling, pain

Chronic Inflammation
● Acute → Sustained low level tissue response to an ongoing stimulation

Question 7

Describe the development of RA and the known druggable targets in that process

Answer 7

● Chronic inflammatory and immune disease
● Drug approaches
○ SYmptomatic treatment: NSAIDS and GC
○ Drugs aimed at slowing or preventative progression by suppressing autoimmune activity (DMARDs)

Question 8

NSAIDS

Answer 8

o NSAIDS: Block COX,
 Anagelsa: reduce pain signals in DRG
 Antipyretic – PGE2 via COX 2
 Anti-platlet – Cox 1
 Consideration: Symptomatic relif
 ADE: Dyspepsia (GI ulcers), Low renal, CVD
 Acetaminophen
* Analgestic antipyetic action
* MOI: COX 1 and COX 2
* Effects: Liver

Question 9

GC

Answer 9

 Affecting signaling pathways, reduce leukocytes, macrophages, vasoconstrict
 Rapid and strong w/RA along with DMARDS
 SE: DOSE RELATED: diabetes, cushing syndrome, Oposorosis