[2.2] Pain Medicines and Drugs used in Joint Disorders Part 2 (DMARDS onwards)

DMARDS is short for what

Disease-Modifying Antirheumatic Drugs (DMARDS)

DMARDS is also called ?

SAARDs or Slow-Acting Antirheumatic Drugs

DMARDS are the only drugs that can alter the course of this affliction and in rare instances it may provide a cure

Rheumatoid Arthritis

Used in conjunction with what to modify the immunologic response

NSAIDs

6 Classifications of Conventional DMARDS

Immunosuppressants, Antimalarials, Gold Preparations, Penicillamine, Steroids, and Sulfasazine

What are the drugs under immunosuppressants

Methotrexate, Azathioprine, Cyclophosphamide, Cyclosporine

What are the drugs under Antimalarials

Chloroquine, Hydroxychloroquine

What are the drugs under Gold preparations

Gold sodium thiomalate, Aurothioglucose, Auranofin

What are the drugs under Steroids

Prednisone, Dexamethasone, Beclomethasone

Methotrexate MOA, Uses, and Drug interactions

MOA: Inhibits AICAR transformylase hinders → adenosine and guanine metabolism

Uses: First-line DMARD

Drug Interactions: Aspirin and other NSAIDs decrease the rate of MTX excretion Most significant/serious interactions with: NSAIDs and PPIs

Cyclosporine MOA, Source, and Side Effects

MOA: Inhibits IL-2 transcription

Source: Isolated from the fungus Tylopocladium inflatum in 1971

Side Effects: Nephrotoxic, ↓ Glomerular filtration rate & Renal plasma flow

Azathioprine MOA, CI, and Side Effects

MOA: Converted to 6-mercaptopurine ribose phosphate inhibits purine synthesis

CI: Hepatitis B/C (risk of infection) Lung fibrosis/emphysema (CXR needed)

S/E: Nephrotoxic, Neurotoxic

Cyclophosphamide MOA and Side Effects

MOA: Liver activation: DNA cannot copy → itself properly, Cell Cycle arrest: the drug stops the cells from growing & dividing at any stage of their life, and Immune Suppression: cycle reduces the body's autoimmune attack on the joints.

S/E: Alopecia, GI distress, Bone marrow depression, Hemorrhagic cystitis

Antimalarials MOA, Drugs, and Side Effects

MOA: Stabilize lysosomal membranes & trap free radicals, thus slowing the progression of erosive bone lesions

Drugs: Chlorquine, Hydroxychloroquine

S/E: Cinchonism (tinnitus, decreased hearing, GI manifestations)

Gold Preparations MOA, Drugs, and Adverse Effects

MOA: Taken up / sequestered in macrophages and phagocytes within the inflamed synovium and inhibits phagocyte maturation and function, and reduces migration and phagocytic activity of macrophages in inflammatory exudates, as well as lysosomal enzyme activity

Drugs: Gold Sodium thiomalate, Aurothioglucose, and Auranofin

Adverse Effects: Cutaneous reactions (Vasodilation, Nitroid reactions, Exfoliative dermatitis, Lesions of mucous membrane)

Gold Sodium thiomalate Gold Content and Route

50%, IM

Aurothioglucose Gold Content and Route

50%, IM

Auranofin Gold Content and Route

2%, PO

Penicillamine MOA, Onset, and Side Effects

MOA: Analogue of the amino acid cysteine, slows bone destruction by an unknown mechanism, inhibits T-cell function and proliferation, and lowers IgM rheumatoid factor in the blood

Onset: 2-3 months to show initial clinical benefits

Side Effects: Highly toxic, Teratogenic, Dermatologic problems, Nephritis, Aplastic anemia

Steroids MOA, Uses,and Drugs

MOA: Upregulates Lipocortin stops phospholipase A2 from producing arachidonic acid and downstream inflammatory prostaglandins and leukotrienes

Use: Given by direct Intrasynovial injection for the management of acute, progressive, erosive RA

Drugs: Prednisone (5-10 mg/day PO), Dexamethasone, Beclomethasone

Sulfasalazine MOA and Side Effects

MOA: Prevents progression of joint damage, as effective as penicillamine but less toxic

Side Effects: Rashes, GI disturbances

Biological DMARDS Anti-TNF MOA and Side Effects

Neutralizes TNF-alpha→ binds soluble/membrane bound TNF-alpha →prevents activation of TNFR1→ & TNFR2 (cell surface receptors) halts → downstream inflammatory cascades ↓ Joint tissue destruction and slows progression of RA

Side Effects: Infection risks (URTI, Bacterial pneumonia, Reactivation of TB, UTI, Fungal infections), Injection site reactions, Infusion reactions (Chills, Fever, SOB, Itchy lips), N/V, Headache, Upset stomache, Fatigue

Biological DMARDS Drugs

Monoclonal Antibodies (-mab): Infliximab, Adalimumab, Golimumab, Certolizumab pegol

Receptor Fusion Protein: Etanercept

Most common form of arthritis and is caused by the breakdown of protective joint cartilage over time

Osteoarthritis

Osteoarthritis Symptoms

Joint pain during/after movement, Stiffness, especially in the morning or after rest, Swelling/tenderness around the joint, Decreased flexibility and range of motion, Crepitus during movement

Osteoarthritis Risk Factors

Wear and tear, Joint injuries, Weight, Genetics, Sex: Women > Men

Drugs Used for OA

Pain Relievers, NSAIDs, Corticosteroid injections, Duloxetine

Pain Relievers does what for OA?

Acetaminophen helps with mild-to-moderate pain

Does not reduce swelling

NSAIDs does what for OA?

Non-steroidal anti-inflammatory drugs (e.g., Ibuprofen & Diclofenac gels) reduce pain and local inflammation with fewer systemic risks when applied to the skin

Corticosteroid injections does what for OA?

Short-term pain relief during severe flare-ups

Intra-articular steroids

Duloxetine does what for OA?

Antidepressant

Sometimes recommended for chronic knee pain

SYSADOA stands for?

Symptomatic Slow-Acting Drugs in OA

Glucosamine sulfate MOA, Onset, and Side Effects

MOA: Stimulates cartilage building blocks, blocks inflammatory pathways involved in joint destruction

Onset: 4-8 weeks of consistent daily use

S/E: Upset stomach, Heartburn, Diarrhea, N/V, Indigestion

Glucosamine sulfate is supposed to be taken alongside

Food

A standard dose of 1,500 mg/day crystalline glucosamine sulfate helps

Reduce joint pain and improve function in mild-to-moderate knee OA

Sodium Hyaluronate/ Hyaluronic Acid MOA, Onset, and Side Effects

MOA: Restores joint lubrication, Reduce inflammation, Protects cartilage

Onset: Lubrication → Immediate, Pain relief/Improved mobility → 1-3 weeks and is a part of a multi-injection course (often given weekly for 3 to 5 weeks)

S/E: Hypersensitivity, Shock, Injection-site pain

Soybean + Avocado Oil (unsaponifiables) MOA, Onset, and Side Effects

MOA: Reduces joint inflammation, Prevents cartilage breakdown, Stimulates repair of joint tissue

Onset: 2-3 months of daily use to notice a meaningful reduction in pain and a decrease in reliance on NSAIDs

S/E: Infrequent lipid-scented regurgitation → Avoided by taking with meals

Gouty Arthritis (GA) is more common in

More common in men than women

Gouty Arthritis (GA)

Presence of needle-shaped uric acid crystals in synovial fluid

↑ Uric acid levels

Colchine MOA, Use, and Side Effects

MOA: Inhibits PMN leukocyte migration to the inflammatory area

Use: Effective treatment and prophylactic agent for acute gout attacks

S/E: Diarrhea - major untoward effec, Myopathy, Agranulocytosis, Aplastic anemia, Alopecia

Colchine source and fatal dose

Source: Plant alkaloid from Calchicum autumnale

Fatal dose: 8 mg in 24 hours

Allopurinol MOA and Use

MOA: Purine analog

Use: Chronic gouty arthritis

Side Effects:

Allopurinol Side Effects and what is DRESS syndrome

Allopurinol is generally well tolerated but Hypersensitivity reactions (eg., cutaneous) can occur.

Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) - most common untoward reaction

During initial therapy with allopurinol these may occur more frequently

Acute gout attacks may occur more frequently during initial therapy with allopurinol → Colchicine prophylaxis may be given simultaneously

Alloxanthine (Oxypurinol) - the primary metabolite of allopurinol also inhibits

xanthine oxidase

Uricosuric Agents MOA

Lowers serum levels of uric acid by inhibiting the proximal tubular reabsorption of uric acid

Drugs under Uricosuric Agents

Probenecid, Sulfinpyrazone

Probenecid Use, Drug interactions, and Side Effects

Use: Chronic gout pain

Drug Interactions: Increases serum levels of penicillin. Action blocked by aspirin

Side Effects: GI disturbances , Skin rash, and Drug fever

Probenecid should not be given for this

Should not be given for acute attack

Probenecid does not exhibit this property

No analgesic activity

Sulfinpyrazone Use

Chronic gout

Sulfinpyrazone should not be given for this

Should not be given for acute attack

Sulfinpyrazone should be taken with

Taken with meals

Drugs under NSAIDs

Indomethacin, Phenlybutazone, Aspirin & other salicylates