Exam 3: Autoimmune diseases Flashcards
What occurs during immune system dysfunction
Self-tolerance and Immune tolerance fail, activated T lymphocytes and antibodies attack the individual’s own cells.
- RESULTS:
- tissue damage and altered physiologic function
- causes release of a greater quantity of self antigen
- initiates adaptive immune response via activated T lymphocytes or antibodies
- ** THESE REACTIONS = AUTOIMMUNITY
What genes predispose to autoimmune disease
Major histocompatibility complex (MHC) genes
- Encode cytokines and are recognized by T lymphocytes for antigen processing
- many autoimmune diseases are linked to specific MHC alleles
List diseases classified as familial autoimmunity:
- Thyroid disease
- Systemic Lupus Erythematosus
- Rheumatoid arthritis
- Multiple sclerosis
- type 1 diabetes mellitus
Autoimmune diseases are often preceded by what? (See slides 13&14 to study more..
Infection
- triggers local immune response - produces immune attack against self-antigens * - Cytokines and other chemical messengers released locally from foreign antigens activate antigen-specific T lymphocytes and self-reactive T lymphocytes * - Antigens released from injured tissues that have been damaged due to infection may also initiate an autoimmune reaction
How do autoantibodies initiate disease and give example of each
- Alter/inhibit receptor function (no tissue damage)
* *Myasthenia graves = acetylcholine receptors are inhibited; neurotransmission fails, resulting in paralysis - Stimulate receptors that would normally be stimulated by a hormone
* *Hyperthyroidism = antibodies against the thyroid-stimulating receptor stimulate thyroid cells directly
Organ specific autoimmune disease is mediated by what cells?
Mediated by T lymphocytes
Treatment for oran specific autoimmune disease
reduce inflammation
= corticosteroids, anticytokine therapies
- Effects reduce the severity of tissue reactions that promote inflammation
- Large dosages produce significant atrophy of the lymphoid tissues throughout the body
Why are steroids considered for Organ Specific autoimmune diseases?
- suppress the growth of lymph tissues
2. decrease T lymphocytes and antibodies produced from B lymphocytes
Why does steroid treatment for organ specific autoimmune disease increase susceptibility to infection?
Large dosages produce significant atrophy of lymphoid tissues throughout the body.
- This decreases the production of T lymphocytes and antibodies from the lymph tissues, which decreases immunity and increases susceptibility to infection
Main ideas for autoimmune disease treatment
Reduce inflammation (steroids)
Antagonists (blockers) to cytokines
-**Immunosuppressvie drugs are used to inhibit T cell responses
T or F, Goals of therapy for autoimmune disease RA are curative
False, therapy goals are palliative
- Reduce joint inflammation and swelling
- relieve pain and stiffness
- encourage normal function
Which two drugs are cornerstones of treatment for the autoimmune disease RA
Aspirin and NSAIDS are cornerstones
- reduce inflammation (swelling), pain and fever
List the adverse effects of aspirin on autoimmune disease
- Adverse gastrointestinal effect
- Effects on kidney
- retention of sodium and water
- may cause hyperkalemia
- Special senses adverse effects
- *Tinnitus is sign of toxicity to aspirin
- Respiratory system
- Toxic levels may cause central respiratory paralysis = respiratory acidosis
What is the sign of toxicity to aspirin
Tinnitus
Name some oral complications of aspirin and NSAIDS
Prolonged bleeding
Oral aphthous ulceration/Aphthous stomatitis
Action of sulfasalazine (Azulfidine)
Interferes with prostaglandin synthesis
Indication of sulfasalazine (Azulfidine)
Used for treatment of RA in patients with inadequate response to aspirin and NSAIDS
Side effects of sulfasalazine (Azulfidine)
headache, photosensitivity, GI distress, anorexia
Is it ok to use celebrex with aspirin?
Yes, OK to use with low dose aspirin
List the adverse cardiovascular risks of celebrex
- increased risk for stroke
- Monitor patient’s blood pressure when used with antihypertensives = decrease effectiveness of BP meds
- Increased risk for heart attack
Celebrex is contraindicated in what patients
- Aspirin/NSAID allergic patients
2. Allergic to sulfonamides
Define DMARDS
Disease-modifying anti-rheumatic drugs
In what patients are DMARDS used
Used for treatment of RA and OA
Patients who do not respond to COX-2 inhibitors
How quickly do DMARDS act?
Slow onset of action
- May take 3-4 months to see effects
Name the 4 preparations of DMARDS
- Immune modulator
- Antimalarials
- Penicillamine
- Gold compounds
List the immune modulator drug names
- methotrexate
2. leflunomide (Arava)
How long does a response occur to methotrexate after starting treatment?
Response within 3-6 weeks
- faster than other DMARDS
What are the two indications for methotrexate?
- High dose = chemotherapy
2. Low dose = immune modulator for autoimmune diseases
List the adverse effects of methotrexate
- Most common = mucosal ulcerations, nausea
- Chronic use =
- Cytopenias - depression of WBC count
- Cirrhosis of liver
- Acute pneumonia-like syndrome
Mechanism of leflunomide (Arava)
Inhibits pyrimidine synthesis, resulting in anti-proliferative and anti-inflammatory effects
Effects of leflunomide (Arava)
- reduces pain and inflammation
- Slows progression of structural damage
What is the drug of choice for severe RA or psoriatic arthritis (unresponsive to NSAIDS)
methotrexate
Most common side effects of leflunomide (Arava)
headache
diarrhea
nausea
Describe the purpose for anticytokine therapies and why the would be effective
IL-1b and TNF-a are “pro inflammatory cytokines” involved in pathogenesis of RA.
- When secreted by macrophages, the cytokines stimulate synovial cells to proliferate and produce collagenous, which degrees cartilage, stimulates bone resorption and inhibits proteoglycan synthesis
- *Drug antagonists to these cytokines are effective in treating RA
Name the anticytokine therapy drugs
- etanercept (Enbrel)
- TNF alpha blocker - infliximab (Remicade)
- TNF alpha blocker - adalimumab (Humira)
- TNF alpha blocker - anakinra (Kineret)
- Interleukin-1 receptor antagonist
Indication of etanercept (Enbrel)
Moderate to severe RA
Side effects and risks of Enbrel
Risk: risk for activation of hepatitis and tuberculosis in carriers
Side effects:
- headache, injection site reaction, upper respiratory tract infections
Mechanism of action for infliximab (Remicade)
Inhibits progression of structural damage and improves physical function in patients with moderate to severe disease
What occurs with long-term use of infliximab?
associated with developing antibodies against the drug, unless the drug is combine with methotrexate
Side effects of infliximab
infections leading to pneumonia, cellulitis; blood dyscrasias
Indication for Humira
Treatment of moderate to severe RA in patients with inadequate response to one or more DMARDS
Humira causes what effects?
decreases signs and symptoms, and structural damage
Side effects of Humira
Headache, Nausea, rash, injection site reaction
Indication for anakinra (Kineret)
Treatment of moderate to severe RA in patients who have failed one or more DMARDS
Anakinra (Kineret) causes what effects
Slows degradation of cartilage and bone loss
Side effects of anakinra (Kineret)
headache, injection site reaction, infections
Name the Antimalarial drugs
- chloroquine (Aralen)
2. hydroxychloroquine (Plaquenil)
Indications of Antimalarial drugs
Treatment of RA that is unresponsive to NSAIDS
- may be used in combination with aspirin and/or corticosteroids
Effects of antimalarials
Slow progression of erosive bone lesions
Side effects of Antimalarial drugs
Severe effects/toxicity!
- severe eye damage
- blue-black intramural pigmentation
Action of Penicillamine
chelating agent (also used as antidote for heavy metal poisoning)
Effects of Penicillamine
Slows the progression of bone destruction and RA
Mechanism for Penicillamine
Depresses circulating IgM rheumatoid factor, depresses T-cell activity
Indication for Penicillamine
Used for RA treatment after gold salts have failed, but before use of corticosteroids
Side effects of Penicillamine
dermatologic, nephritis, aplastic anemia
Oral complications with penicillamine
Infection
Delayed healing
Prolonged bleeding
Oral ulcerations
