Exam 3: Autoimmune diseases Flashcards

1
Q

What occurs during immune system dysfunction

A

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
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2
Q

What genes predispose to autoimmune disease

A

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
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3
Q

List diseases classified as familial autoimmunity:

A
  1. Thyroid disease
  2. Systemic Lupus Erythematosus
  3. Rheumatoid arthritis
  4. Multiple sclerosis
  5. type 1 diabetes mellitus
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4
Q

Autoimmune diseases are often preceded by what? (See slides 13&14 to study more..

A

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
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5
Q

How do autoantibodies initiate disease and give example of each

A
  1. Alter/inhibit receptor function (no tissue damage)
    * *Myasthenia graves = acetylcholine receptors are inhibited; neurotransmission fails, resulting in paralysis
  2. Stimulate receptors that would normally be stimulated by a hormone
    * *Hyperthyroidism = antibodies against the thyroid-stimulating receptor stimulate thyroid cells directly
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6
Q

Organ specific autoimmune disease is mediated by what cells?

A

Mediated by T lymphocytes

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7
Q

Treatment for oran specific autoimmune disease

A

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
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8
Q

Why are steroids considered for Organ Specific autoimmune diseases?

A
  1. suppress the growth of lymph tissues

2. decrease T lymphocytes and antibodies produced from B lymphocytes

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9
Q

Why does steroid treatment for organ specific autoimmune disease increase susceptibility to infection?

A

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

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10
Q

Main ideas for autoimmune disease treatment

A

Reduce inflammation (steroids)
Antagonists (blockers) to cytokines
-**Immunosuppressvie drugs are used to inhibit T cell responses

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11
Q

T or F, Goals of therapy for autoimmune disease RA are curative

A

False, therapy goals are palliative

  • Reduce joint inflammation and swelling
  • relieve pain and stiffness
  • encourage normal function
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12
Q

Which two drugs are cornerstones of treatment for the autoimmune disease RA

A

Aspirin and NSAIDS are cornerstones

- reduce inflammation (swelling), pain and fever

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13
Q

List the adverse effects of aspirin on autoimmune disease

A
  1. Adverse gastrointestinal effect
  2. Effects on kidney
    • retention of sodium and water
    • may cause hyperkalemia
  3. Special senses adverse effects
    • *Tinnitus is sign of toxicity to aspirin
  4. Respiratory system
    • Toxic levels may cause central respiratory paralysis = respiratory acidosis
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14
Q

What is the sign of toxicity to aspirin

A

Tinnitus

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15
Q

Name some oral complications of aspirin and NSAIDS

A

Prolonged bleeding

Oral aphthous ulceration/Aphthous stomatitis

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16
Q

Action of sulfasalazine (Azulfidine)

A

Interferes with prostaglandin synthesis

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17
Q

Indication of sulfasalazine (Azulfidine)

A

Used for treatment of RA in patients with inadequate response to aspirin and NSAIDS

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18
Q

Side effects of sulfasalazine (Azulfidine)

A

headache, photosensitivity, GI distress, anorexia

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19
Q

Is it ok to use celebrex with aspirin?

A

Yes, OK to use with low dose aspirin

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20
Q

List the adverse cardiovascular risks of celebrex

A
  1. increased risk for stroke
  2. Monitor patient’s blood pressure when used with antihypertensives = decrease effectiveness of BP meds
  3. Increased risk for heart attack
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21
Q

Celebrex is contraindicated in what patients

A
  1. Aspirin/NSAID allergic patients

2. Allergic to sulfonamides

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22
Q

Define DMARDS

A

Disease-modifying anti-rheumatic drugs

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23
Q

In what patients are DMARDS used

A

Used for treatment of RA and OA

Patients who do not respond to COX-2 inhibitors

24
Q

How quickly do DMARDS act?

A

Slow onset of action

- May take 3-4 months to see effects

25
Name the 4 preparations of DMARDS
1. Immune modulator 2. Antimalarials 3. Penicillamine 4. Gold compounds
26
List the immune modulator drug names
1. methotrexate | 2. leflunomide (Arava)
27
How long does a response occur to methotrexate after starting treatment?
Response within 3-6 weeks | - faster than other DMARDS
28
What are the two indications for methotrexate?
1. High dose = chemotherapy | 2. Low dose = immune modulator for autoimmune diseases
29
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
30
Mechanism of leflunomide (Arava)
Inhibits pyrimidine synthesis, resulting in anti-proliferative and anti-inflammatory effects
31
Effects of leflunomide (Arava)
- reduces pain and inflammation | - Slows progression of structural damage
32
What is the drug of choice for severe RA or psoriatic arthritis (unresponsive to NSAIDS)
methotrexate
33
Most common side effects of leflunomide (Arava)
headache diarrhea nausea
34
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
35
Name the anticytokine therapy drugs
1. etanercept (Enbrel) - TNF alpha blocker 2. infliximab (Remicade) - TNF alpha blocker 3. adalimumab (Humira) - TNF alpha blocker 4. anakinra (Kineret) - Interleukin-1 receptor antagonist
36
Indication of etanercept (Enbrel)
Moderate to severe RA
37
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
38
Mechanism of action for infliximab (Remicade)
Inhibits progression of structural damage and improves physical function in patients with moderate to severe disease
39
What occurs with long-term use of infliximab?
associated with developing antibodies against the drug, unless the drug is combine with methotrexate
40
Side effects of infliximab
infections leading to pneumonia, cellulitis; blood dyscrasias
41
Indication for Humira
Treatment of moderate to severe RA in patients with inadequate response to one or more DMARDS
42
Humira causes what effects?
decreases signs and symptoms, and structural damage
43
Side effects of Humira
Headache, Nausea, rash, injection site reaction
44
Indication for anakinra (Kineret)
Treatment of moderate to severe RA in patients who have failed one or more DMARDS
45
Anakinra (Kineret) causes what effects
Slows degradation of cartilage and bone loss
46
Side effects of anakinra (Kineret)
headache, injection site reaction, infections
47
Name the Antimalarial drugs
1. chloroquine (Aralen) | 2. hydroxychloroquine (Plaquenil)
48
Indications of Antimalarial drugs
Treatment of RA that is unresponsive to NSAIDS | - may be used in combination with aspirin and/or corticosteroids
49
Effects of antimalarials
Slow progression of erosive bone lesions
50
Side effects of Antimalarial drugs
Severe effects/toxicity! - severe eye damage - blue-black intramural pigmentation
51
Action of Penicillamine
chelating agent (also used as antidote for heavy metal poisoning)
52
Effects of Penicillamine
Slows the progression of bone destruction and RA
53
Mechanism for Penicillamine
Depresses circulating IgM rheumatoid factor, depresses T-cell activity
54
Indication for Penicillamine
Used for RA treatment after gold salts have failed, but before use of corticosteroids
55
Side effects of Penicillamine
dermatologic, nephritis, aplastic anemia
56
Oral complications with penicillamine
Infection Delayed healing Prolonged bleeding Oral ulcerations