(FE) Drugs for Gout and Osteoarthritis Flashcards
What drugs are used to treat acute gout attacks?
1) NSAIDS
- Non-selective COX inhibitors (Naproxen, Indometacin)
- COX-2 inhibitors (CELECOXIB, ETORICOXIB)
2) Corticosteroids (PREDNISOLONE)
3) Leucocyte mobility inhibitors (COCHICINE)
What drugs are used to treat hyperuricemia / prevent gouty arthritis?
1) Uric acid synthesis inhibitors / Xanthase oxidase inhibitors (ALLOPURINOL, Febuxostat)
2) Uricosuric agents (PROBENECID)
Note: Never use at the start of acute attacks
- Crystal gradient will be too much -> ^ movement of crystal into the joint
What is the MOA of NSAIDs in treating gout?
1) Inhibit production of prostaglandins (reduces inflammation)
2) Inhibits urate crystal phagocytosis
Indometacin, Naproxen (non-selective), CELECOXIB , ETORICOXIB (COX-2)
What are the contraindications for NSAIDs in treating gout?
- Use of low-dose aspirin or salicylates
What is the MOA of leucocyte mobility inhibitors in treating gout?
1) Binds to tubulin to prevent polymerization into microtubules
2) Inhibits leucocyte migration and phagocytosis
3) Inhibits leukotriene B and phagocyte production
4) Relieves pain and inflammation from gouty attack within 24 - 36 hours
COLCHICINE
What are the side effects of colchicine/leucocyte mobility inhibitors?
- Diarrhea, N&V, abdominal pain
- Muscle weakness
- Unusual bleeding
- Pale lips
- Change in urine amount
What are the indications for uric acid synthesis inhibitors / XOI?
- Debilitating gout attacks
- Chronic erosive arthritis
- Urate nephrolithiasis (kidney stones)
ALLOPURINOL (1st-line), Febuxostat (2nd-line)
What are the adverse effects of XOI / Allopurinol?
- Skin rash
- N&V, diarrhea, stomach
- Fever
- Sore throat
- Dark urine
- Jaundice
- Allopurinol hypersensitivity reaction (AHS)
- Severe cutaneous adverse reaction (SCAR)
~ Common in HLA-B 58:01 genotype
~ Higher risk in px with renal impairment (w/ creatinine clearance of <60ml/min)
What is the MOA of uricosuric agents?
- Prevents gout attacks
- Inhibits uric acid re-absorption from kidneys
- Increases uric acid excretion
PROBENECID
What are the indications for uricosuric agents?
- When allopurinol is contraindicated for tophaceous gout
- Increasingly frequent gouty attacks
- Only start 2-3 weeks after attacks start
What are the precautions and side effects of uricosuric agents?
- Requires frequent hydration to prevent formation of renal stones
- Requires sodium citrate to keep pH of body >6.0
- N&V
- Painful urination
- Lower back pain
- Allergic reactions, rash
What drugs can be used to treat osteoarthritis?
1) Analgesics
- PARACETAMOL
- NSAIDs (Diclofenac, celecoxib)
2) Anti-inflammatory
- Corticosteroids (Prednisolone)
3) Symptomatic slow-acting drugs
- Intra-articular (HYALURONIC ACID)
~ Helps in shock absorption, traumatic energy dissipation, protective coating of cartilage, lubrication, reduces pain & stiffness
What drugs can be used to treat rheumatoid arthritis?
1) NSAIDS
~ For short-term relief of joint pain and stiffness
2) CORTICOSTEROIDS
~ For anti-inflammatory therapy
3) Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDS)
- METHOTREXATE
4) Targeted Synthetic DMARDS (tsDMARDS)
- TOFACITINIB
5) Biologic DMARDS (bMARDS)
- INFLIXIMAB
What is the difference between csDMARDs, tDMARDs and bDMARDs?
1) csDMARD
- Traditional first-line treatments for RA
- Used in combination with other DMARDs
2) tsDMARD
- Target specific molecules in the inflammatory process
~ eg Janus kinases (JAK) inhibitors
- Typically used in px w/ inadequate response to csDMARDs
3) bDMARD
- Derived from living organisms, such as proteins, antibodies, or cytokines
- For px with moderate - severe RA who have not responded adequately to csDMARDs or tDMARDs
What is the MOA of csDMARDs?
- Increases adenosine levels (reduces inflammatory effects of cells and cytokines - major effect)
- Anti-proliferative effects on T cells and inhibition of macrophage functions
- Decrease in pro-inflammatory cytokines, adhesion molecules, chemotaxis and phagocytosis
METHOTREXATE (1st line) FEVER
What are the side effects of csDMARDs?
- N&V
- Mouth & GI ulcers
- Hair thinning
- Leukopenia
- Hepatic fibrosis
- Pneumonitis
Note: Giving folic/folinic acid 12-24 hrs after Methotrexate decreases toxicity
How does folinic acid help to treat methotrexate toxicity?
- Usually, dihydrofolate reductase is involved in the conversion of N5/N10-Methylene-FH4 into purines which make up DNA
~ Since methroxate inhibits enzyme action, DNA cannot be formed properly in toxicity - However, folinic acid is rapidly converted to N5, N10-MethyleneFH4, without the need of dihydrofolate reductase
~ Since enzyme activity is
bypassed, it is more efficient at rescuing
methotrexate toxicity
What are the MOA of the less common csDMARDs?
1) Sulfasalazine
- Decreases IgA and IgM rheumatoid factors
- Suppresses T and B cells and macrophages-
- Decrease in inflammatory cytokines (e.g., IL-1E, TNF and IL-6)
2) Leflunomide
- Inhibits T cell proliferation and B cell autoantibody production
- Inhibits NF-NB activation pro-inflammatory pathway
- Warning:
~ Very long half-life (detectable even years after last dosing)
~ Colestyramine (bile salt binding resin) wash-out (e.g., before pregnancy)
3) Chloroquine and Hydroxychloroquine
- Effective anti-inflammatory agents in RA (least potent DMARD)
- Reduced MHC Class II expression and antigen-presentation
- Reduced TNF and IL-1, and cartilage resorption
What are the side effects of the less common csDMARDs?
1) Sulfasalazine
- N&V
- Headache
- Rash
- Hemolytic anemia , neutropenia
- Reversible infertility in men
2) Leflunomide
- Diarrhoea
- Alopecia
- Increased liver enzymes
- Weight gain
- Teratogenic
3) Hydroxychloroquine
- N&V
- Stomach pain
- Dizziness
- Hair loss
- Ocular toxicity
What is the MOA of tsDMARDs?
- Combined with methotrexate for moderate - severe RA
- Janus-Kinase (JAK) pathway inhibitor
~ Blocks cytokine production by blocking JAK activation of gene transcription
TOFACITINIB
What are the side effects of tsMARDS?
- Cytopenia including neutrophils, lymphocytes,
platelets and natural killer cells - Anaemia (affects JAK2 activitation by erythropoietin)
- Immunosuppression
Note: Do not combine with biological DMARDs
What are the types of bDMARDS?
1) TNF blockers (INFLIXIMAB)
- Refer to screenshot
2) IL-1 blockers (ANAKINRA)
- Differs from the sequence of the protein by one
methionine
3) IL-6 blockers (TOCILIZUMAB)
- For px who do not respond well to sDMARD
- Used in combination with other Methatroxine
What are the side effects and contraindications for bDMARDS?
- Respiratory and skin infection
- Increased risk of lymphoma, optic
neuritis, exacerbation of multiple sclerosis, leukopenia, aplastic anemia - Contraindicated in live vaccines and hep B
- Need to screen for active TB
