Immunosuppressants & DMARDs Flashcards
3 classifications of immunosuppressants? & e.g.
1) IL-2 inhibitor
CYCLOSPORINE & TACROLIMUS
2) Cytokine gene inhibitor
PREDNISONE & PREDNISOLONE
3) T-cell blockers
E.g. bDMARDS (anti-cytokines)
INFLIXIMAB & ETANERCEPTImmunosuppressants:
1) Do what?
2) Two principle applications?
3) Two major toxicities?
1) Inhibit immune responses
2) Organ rejection / Autoimmune disorders
3) ^Risk of infection / ^Risk of cancer
Immunosuppressants are used to? (3)
1) Treat autoimmune disease
[RA, Lupus, Myasthenia Gravis]
Suppress:
2) Transplant rejection: Organ & Tissues
3) Graft v Host disease: Bone marrow transplant
1) Most important immunosuppressive agent in transplantation?
2) By selectively inhibiting which lymphocyte?
1) CLYCLOSPORINE
Key drug for TRANSPLANT REJECTION
2) IL-2
Cyclosporine: Drug interaction? Food?
- CYP3A4 inhibitors ^ cyclosporine levels
E.g. Diltiazem, ketoconazole, ERYTHROMYCIN
Food: GRAPEFRUIT JUICE:
^ cyclosporine 50-200%
Therefore hard to control concentration; can lead to toxicity.
1) Compare Tacrolimus (FK506) to Cyclosporine.
MOA, potency, effectiveness, toxicity.
2) Tacrolimus (FK506) therapeutic use?
3) Used in conjunction with?
1) Similar MOA/ ^ potent/ ^ effective/ ^toxic
(more pts discontinue)
2) ORGAN REJECTION (Prophylaxis- prevent)
(liver, kidney, heart)
3) Glucocorticoids
Glucocorticoids:
1) What do they inhibit in early phase inflammation?
2) What do they INHIBIT in late phase inflammation?
(Adverse & Therapeutic)
1) Initial redness, heat, pain, & swelling
2) Adverse: Wound healing & repair
Therapeutic: Proliferative (Productive) reactions in chronic inflammation
(i.e. one leading to the production of new connective tissue fibres)
Glucocorticoids:
Pharmacological effects? (3)
- ANTI-INFLAMMATORY
- Immunosuppressant: ˅ lymphocytes
- Effects metabolism & electrolytes:
**^BSL glucose, ^Na+
¥K+ ¥potassium
¥ Protein synthesis –> growth retardation; Weight gain
Glucocorticoids:
1) What do they inhibit in early phase inflammation?
2) What do they INHIBIT in late phase inflammation?
(Adverse & Therapeutic)
3) Pharmacological effects?
1) Initial redness, heat, pain, & swelling
2) Adverse: Wound healing & repair
Therapeutic: Proliferative (Productive) reactions in chronic inflammation
(production of new connective tissue fibres)
3) ANTI-INFLAMMATORY
Immunosuppressant: ˅ lymphocytes
Besides Anti-inflammatory AND Immunosuppressive uses (I.e. RA & Prevention of Graft vs Host disease), what are other uses of Glucocorticoids? (3)
Asthma
Topically: inflammation: skin, eyes, nose, ear (e.g. Eczema, conjunctivitis, rhinitis)
Hypersensitivity: Severe Allergic Reactions
Corticosteroids: Route of administration & e.g. (4)
Corticosteroids:
*ORAL: Prednisone / Prednisolone
(Prednisone inactive, rapidly metabolised to active Prednisolone by liver)
*IV: Dexamethasone / Methylprednisolone
*INTRA-ARTICULAR (in joint cavity): Methylprednisolone/ Betamethasone/Triamcinolone
*INHALATION (asthma): Beclomethasone / Budesonide / Fluticasone
Corticosteroids: immunosuppressant MOA?
T CELLS:
˅ T-helper cell activation
˅ Proliferation (rapid reproduction) of T cells
Main cytokines involved in immunosuppressive action? (4)
IL-1, IL-2
TNF-a (alpha)
IFN-y (gamma)
Corticosteroids: Adverse effects? (2)
Iatrogenic Cushing’s Syndrome (++cortisol)
(Adverse effects of treatment from doctor)
- Immunosuppression: Risk of infections
- Osteoporosis: Bone density loss
Also: weight gain, moon face, psych disturbances, poor wound healing, sodium retention, hypertension
Glucocorticoids: Adverse effects: Osteoporosis?
Bone loss time? Effects on other rheumatological diseases e.g. Ankylosing spondylitis?
Strategies to minimise bone density loss if >1 month glucocorticoids?
Osteoporosis: Bone Density Loss
Rapid loss
Exacerbate osteoporosis, I.e. further bone loss
Weight bearing exercise, Calcium, Vitamin D, Biophosphonate (drugs that prevent bone mass loss)
Glucocorticoids: Besides Osteoporosis, what are 3 other adverse effects & their treatment?
- Atherosclerosis: Reduce other risk factors I.e. smoking, heart pressure
- Hyperglycaemia (^BSL): Oral hypoglycaemic drugs, Insulin
- Infections
1 in 3 with RA –> severely disabled.
What joint changes occur? (3)
- Inflammation
- Proliferation of the synovium (synovial membrane –> bone-forming cartilage)
- Erosion of bone & cartilage
Which 2 cytokines play a major role in pathogenesis (development of disease) of RA?
IL-1 & TNF-a
Anti rheumatoid Drugs: 3 most commonly used drugs?
NSAIDs
DMARDs
Steroids
What are DMARDs? Types?
Disease-Modifying AntiRheumatic Drugs: Nonbiological DMARDs & (Biological bDMARDs aka Anti-cytokines)
- Reduce joint destruction &
- Retard (slow) disease progression
DMARDs: How long for therapeutic effects? Toxicity?
Therapeutic benefits develop SLOWLY (3-4 months initial effects; 6 months good effects)
More toxic: Close monitoring required
DMARDs: Drug of first choice in RA? MOA?
METHOTREXATE:
Folic acid antagonist
Inhibits DIHYDROFOLATE REDUCTASE
Methotrexate: Fast/slow action? Dose? Toxicity?
Faster action than other DMARDs
SINGLE WEEKLY DOSE PO 7.5mg Max 20mg
10-15% suffer dose-limiting toxicity
50% pts stop DMARDs <2yrs (Too Toxic)
Methotrexate can cause? (3) Contraindicated in? Drug interactions?
- Blood dyscrasias (some fatal) abnormal levels of blood components
- Liver cirrhosis
- Birth defects (Teratogenic)
Contraindicated: RENAL IMPAIRMENT
Interactions: Folate synthesis inhibitors (Trimethoprim & Triamterene)
