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IC5 Immune-mediated toxicities > Management of immune-mediated toxicities > Flashcards

Management of immune-mediated toxicities Flashcards

1
Q

Treatment of anaphylaxis is to restore respiratory and CVS function (breathing difficulties, fast heart rate).
What is the drug of choice for treatment?

A

Epinephrine (adrenaline)
- Vasoconstriction to increase BP, increase CO
- Bronchodilation to relax airways

*Epipen - IM injection

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2
Q

What treatment options can be given for anaphylaxis for pt in hospital?

A

IV fluid - restore volume/BP
Intubation - open airways
Norepinephrine (noradrenaline) - vasoconstriction

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3
Q

What are some other drugs that may be given in anaphylaxis?

A

Steroids - anti-inflammatory, immunosuppression

Glucagon - incr blood sugar levels

Diphenhydramine (H1) + Ranitidine (H2) - block all histamine pathways

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4
Q

Treatment of SCAR is less defined, and involves supportive care for symptoms presented. What might this entail?

A

Wound care, nutritional support, fluids, temp regulation, pain management, prevention of infection

*Steroids use is controversial

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5
Q

What might increase the risk of developing autoimmune disorders?

A
  1. Genetic background
  2. Environmental stimuli (e.g., smoking, infection)
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6
Q

Systemic Lupus Erythematosus (SLE) is an autoimmune disease associated with _____ production.

A

Auto-antibody

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7
Q

SLE is a multisystem disease that affects many tisues and organs, what are some of the most common causes for death with SLE?

A

Cardiovascular, renal, infections

**Kidney transplant

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8
Q

SLE is characterized by disorders of the innate and adaptive immune system. Describe the pathophysiology of SLE.

A
  1. 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.
  2. 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)

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9
Q

What is the clinical presentation of SLE?

A

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

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10
Q

What are some lab used for the diagnosis of SLE?

A

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

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11
Q

What are 6 treatment goals of Lupus?

A
  1. Prevent flares
  2. Prevent other organ involvement
  3. Slow disease activity
  4. Reduce use of steroids
  5. Improve QoL
  6. Minimize ADEs
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12
Q

What are the 4 FDA approved drugs for treatment of SLE?

A
  1. Aspirin - anti-inflammatory
  2. Prednisone - anti-inflammatory + immunosuppression
  3. Hydroxychloroquine
  4. Belimumab - targets B cells
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13
Q

All SLE pt including pregnant women should receive this drug. What is this drug and what are its benefits?

A

Hydroxychloroquine
- prevent flares, improve long term survival
- anti-inflammatory, immunomodulatory, anti-thrombotic (prevent clots)
- minimal adverse effects
- takes 4-8 weeks to have effects

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14
Q

What are 4 general pharmacologic classes used in treatment of SLE?

A
  1. NSAIDs - 1st line for acute symptoms, caution in ARGH - lupus nephritis, cardiac risk, GI bleed, asthma
  2. Steroids - control flares and maintain low disease activity, rapid onset, concerns with high dose or long term use
  3. Biologics - Belimumab, Rituximab targets B cells
  4. Immunosuppressants
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15
Q

Name the 3 immunosuppressants commonly used and whether they are for induction or maintenance.

A
  1. Cyclophosphamide (IV/PO) - induction, for serious organ involvement
  2. Mycophenolate - induction + maintenance
  3. Azathioprine - maintenance
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16
Q

Name the SLE syndrome associated with high risk of clots and pregnancy morbidity

A

Antiphospholipid syndrome (APS)

  • Antiphospholipid antibodies target phospholipids, cause blood to clot
17
Q

What is the treatment for Antiphospholipid Syndrome (APS) - thromboprophylaxis?

A

Primary thromboprophylaxis: hydroxychloroquine + aspirin

Secondary thromboprophylaxis: warfarin

18
Q

10-15% of SLE is drug-induced lupus. What is a possible MOA in which drugs can cause lupus?

A

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

19
Q

What are some drugs with highest risk of causing drug-induced lupus?
What is the primary treatment for drug-induced lupus?

A
  1. Procainamide - antiarrhythmic
  2. Hydralazine - vasodilator for hypertension
  3. Quinidine - antiarrhythmic

STOP treatment, consider symptomatic treatment

20
Q

Evaluation of therapeutic outcome for SLE includes evaluating ADR, comorbitities, disease activity, and labs.

How often should labs be assessed?

A

Every 1-3 months in active disease, 6-12 months if stable

21
Q

What labs should be assessed to evaluate therapeutic outcomes of SLE treatment?

A

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

22
Q

What are the characteristics of induction for immunosuppression?

A

High potency
Short course therapy

=> to reduce existing damage, prevent worsening
=> prevent acute rejection after transplantation (lymphocyte-depleting therapy - Basiliximab, Alemtuzumab)

23
Q

Recognize the following maintenance drugs for immunosuppression

A

Calcineurin inhibitors - cyclosporin, tacrolimus

Antimetabolites - mycophenolate (induction + maintenance), azathioprine

Corticosteroids

mTOR inhibitors - sirolimus, everolimus

Biologics - adalimumab

24
Q

What are the complications of immunosuppression?

What are the drug effects of immunosuppressants?

A

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)

25
Q

What are the therapeutic effects on corticosteroids?

A

Anti-inflammatory
Immunosuppressive effect

=> reduce pain, swelling, stiffness, physical disability

Decrease endothelial dysfunction, decrease permeability

26
Q

Name 5 side effects of corticosteroids

A
  • Infections
  • Myopathy
  • Osteoporosis (growth suppression)
  • Neuro-psychiatric symptoms, HPA insufficiency (anxiety, mood change)
  • Weight gain, fluid retention, edema
  • Cushing syndrome (redistribution of fats - buffalo hump, moonface)
  • Increased risk of diabetes (impaired glucose metabolism, insulin resistance, B cell dysfunction)
  • Skin thinning, poor wound healing
  • Gastric ulcer (w concomittant NSAID)
  • Cataract, glaucoma
  • Incr CVD risk (hypertension, increase lipids)
27
Q

Pituitary gland releases adrenocorticotropic hormones (ACTH) aka corticotropin in response to corticotropin releasing hormone/factor (CRH/CRF) from hypothalamus.

What does ACTH stimulate?

A

ACTH stimulates the release of cortisol from adrenal cortex.

CRH => ACTH => Cortisol

28
Q

Explain the mechanism of HPA axis suppression, what happens overtime as a result?

A

Exogenous corticosteroids exert negative feedback on the hypothalamus and the anterior pituitary.

This causes decreased release of corticotropin-releasing hormones CRH from the hypothalamus and decreased release of adrenocorticotropic hormones ACTH from the anterior pituitary. This then decreases the release of endogenous cortisol from the adrenal glands.

Overtime, HPA axis becomes inactive, adrenal glands shrink and atrophy, eventually stops producing cortisol.
=> Adrenal suppression

29
Q

What are the symptoms of adrenal suppression?

A

Fatigue, muscle weakness, LOA, weight loss, abdominal pain

30
Q

The adrenal gland produces an amount of steroids equivalent to _mg per day

A

5mg

31
Q

What situations put pt at risk for adrenal insufficiency?

A

Supraphysiologic dose of >5mg prednisone equivalents daily, for more than 3 weeks

*Adrenal insufficiency has also been reported in pt taking <5mg prednisone equivalent with tapered withdrawal

THUS, maintain suspicion for ALL pt who are taking/have taken corticosteroids

IC5 Immune-mediated toxicities (2 decks)

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