Management of immune-mediated toxicities Flashcards
Treatment of anaphylaxis is to restore respiratory and CVS function (breathing difficulties, fast heart rate).
What is the drug of choice for treatment?
Epinephrine (adrenaline)
- Vasoconstriction to increase BP, increase CO
- Bronchodilation to relax airways
*Epipen - IM injection
What treatment options can be given for anaphylaxis for pt in hospital?
IV fluid - restore volume/BP
Intubation - open airways
Norepinephrine (noradrenaline) - vasoconstriction
What are some other drugs that may be given in anaphylaxis?
Steroids - anti-inflammatory, immunosuppression
Glucagon - incr blood sugar levels
Diphenhydramine (H1) + Ranitidine (H2) - block all histamine pathways
Treatment of SCAR is less defined, and involves supportive care for symptoms presented. What might this entail?
Wound care, nutritional support, fluids, temp regulation, pain management, prevention of infection
*Steroids use is controversial
What might increase the risk of developing autoimmune disorders?
- Genetic background
- Environmental stimuli (e.g., smoking, infection)
Systemic Lupus Erythematosus (SLE) is an autoimmune disease associated with _____ production.
Auto-antibody
SLE is a multisystem disease that affects many tisues and organs, what are some of the most common causes for death with SLE?
Cardiovascular, renal, infections
**Kidney transplant
SLE is characterized by disorders of the innate and adaptive immune system. Describe the pathophysiology of SLE.
- T and B lymphocyte activation and signaling is altered in SLE, resulting in abnormal clearance of apoptotic debris containing nuclear material. These nuclear materials are capable of stimulating immune responses.
- As a result, number of plasma cells is increased in active SLE. These plasma cells produce autoantibodies against the nuclear material. These autoantibodies cause tissue damage => multisystem disease
FYI: SLE is a type 3 immune complex mediated disease (immune complex deposit in tissues)
What is the clinical presentation of SLE?
Disease fluctuate with periods of remission, flares, and progression.
Multi-organ involvement:
- Skin: butterfly rash
- Blood: low blood count, high BP
- Heart: endocarditis, atherosclerosis
- Kidneys: blood in urine
- Lungs: pleuritis, penumonitis, pulmonary emboli
- Muscles & joints: pain, swelling
- Others: hair loss, high fever, abnormal headache, severe abdominal pain
**
Lupus nephritis - mesangial
Neuropsychiatric Lupus - stroke, anxiety, seizures, confusion, peripheral neuropathy
Cardiovascular - pericarditis, myocarditis, atherosclerosis
What are some lab used for the diagnosis of SLE?
Full Blood Count: dcr RBC, dcr WBC, dcr PLT
=> Hemolytic anemia, thrombocytopenia
Immunologic: Autoantibodies against nuclear materials
=> Antinuclear antibody, Antidouble stranded DNA, Anti-smith antibody, Anti-RNP, low complement
What are 6 treatment goals of Lupus?
- Prevent flares
- Prevent other organ involvement
- Slow disease activity
- Reduce use of steroids
- Improve QoL
- Minimize ADEs
What are the 4 FDA approved drugs for treatment of SLE?
- Aspirin - anti-inflammatory
- Prednisone - anti-inflammatory + immunosuppression
- Hydroxychloroquine
- Belimumab - targets B cells
All SLE pt including pregnant women should receive this drug. What is this drug and what are its benefits?
Hydroxychloroquine
- prevent flares, improve long term survival
- anti-inflammatory, immunomodulatory, anti-thrombotic (prevent clots)
- minimal adverse effects
- takes 4-8 weeks to have effects
What are 4 general pharmacologic classes used in treatment of SLE?
- NSAIDs - 1st line for acute symptoms, caution in ARGH - lupus nephritis, cardiac risk, GI bleed, asthma
- Steroids - control flares and maintain low disease activity, rapid onset, concerns with high dose or long term use
- Biologics - Belimumab, Rituximab targets B cells
- Immunosuppressants
Name the 3 immunosuppressants commonly used and whether they are for induction or maintenance.
- Cyclophosphamide (IV/PO) - induction, for serious organ involvement
- Mycophenolate - induction + maintenance
- Azathioprine - maintenance
Name the SLE syndrome associated with high risk of clots and pregnancy morbidity
Antiphospholipid syndrome (APS)
- Antiphospholipid antibodies target phospholipids, cause blood to clot
What is the treatment for Antiphospholipid Syndrome (APS) - thromboprophylaxis?
Primary thromboprophylaxis: hydroxychloroquine + aspirin
Secondary thromboprophylaxis: warfarin
10-15% of SLE is drug-induced lupus. What is a possible MOA in which drugs can cause lupus?
Small drug molecules bind to larger proteins, and induce immune response
**Drug-induced lupus is an idiosyncratic reaction precipitate by interplay of genetics and environmental factors
What are some drugs with highest risk of causing drug-induced lupus?
What is the primary treatment for drug-induced lupus?
- Procainamide - antiarrhythmic
- Hydralazine - vasodilator for hypertension
- Quinidine - antiarrhythmic
STOP treatment, consider symptomatic treatment
Evaluation of therapeutic outcome for SLE includes evaluating ADR, comorbitities, disease activity, and labs.
How often should labs be assessed?
Every 1-3 months in active disease, 6-12 months if stable
What labs should be assessed to evaluate therapeutic outcomes of SLE treatment?
Anti dsDNA antibodies
- Should decrease (unable to achieve cure - 0)
- More specific for SLE than ANA, should decrease with treatment response
- ANA, anti-Sm, and anti-RNP levels do not fluctuate with disease activity, hence only used for diagnosis, tests not repeated
Complements
- Complement count should increase back to normal levels with treatment response
FBC
- low blood count should improve
CRP
- can be too high or too low, inflammatory marker
Liver function test
Renal function/urinalysis
What are the characteristics of induction for immunosuppression?
High potency
Short course therapy
=> to reduce existing damage, prevent worsening
=> prevent acute rejection after transplantation (lymphocyte-depleting therapy - Basiliximab, Alemtuzumab)
Recognize the following maintenance drugs for immunosuppression
Calcineurin inhibitors - cyclosporin, tacrolimus
Antimetabolites - mycophenolate (induction + maintenance), azathioprine
Corticosteroids
mTOR inhibitors - sirolimus, everolimus
Biologics - adalimumab
What are the complications of immunosuppression?
What are the drug effects of immunosuppressants?
Associated with weakened immune system:
1. Infections
2. Cancer
3. Blood disorders (low blood count - leukopenia, thrombocytopenia)
Drug effects:
4. Hepatotoxicity (antimetabolites - mycophenolate, azathioprine)
5. Renal toxicity (calcineurin inhibitors - cyclosporin, tacrolimus)
6. Hypertension, hyperlipidemia, hyperglycemia (calcineurin inhibitors, mTOR inhibitors)
