Immune related toxicities (Anaphylaxis, Pseudoallergy, Autoimmune) IC9 Flashcards
Difference between Nonimmune Hypersensitivity and Immune Hypersensitivity (cause)
Immune: allergy, caused by igE, igM, IgG, T cells
Involve innate and adaptive immune system
Nonimmune: aka Pseudoallergy, caused by release of mediators eg. histamine, prostaglandins.
Drugs will cause the release or inhibit breakdown of these chemical mediators, causing hypersensitivity reaction
Examples of drugs and the corresponding Pseudoallergy reaction (3 points)
1) Vancomycin → Red man syndrome
Direct release of histamine
2) ACE / Sacubitril → Angioedema
Inhibition of breakdown of Bradykinin → vasodilation and increased vascular permeability
3) NSAID → induced asthma
Alter metabolism of Prostaglandins in lungs
5 types of clinical manifestations in Anaphylaxis
Serum sickness / Drug fever
Drug induced autoimmunity (SLE)
Vasculitis
Respiratory (Asthma)
Hematologic (Eosinophilia , Hemolytic anaemia, Agranulocytosis)
3 types of drug induced autoimmunity
Systemic Lupus Erythematosus (SLE)
Hemolytic anaemia (caused by Methyldopa)
Hepatitis (caused by Phenytoin)
Treatment of Anaphylaxis (immediate and hospital)
Epinephrine / Adrenaline
Counteracts bronchoconstriction and vasodilation
Ambulance / Hospital setting
IV fluids to restore volume, BP
Intubation to save airway
Norepinephrine / Noradrenaline if shock
Steroids
Glucagon (Counter inotropic effect of Beta Blockers)
Antihistamines (Diphenhydramine H1 + Ranitidine H2)
What is SCAR?
Serious Cutaneous Adverse Reaction
- serious anaphylactic reaction involving the skin
Involves DRESS, SJS, TEN
What is DRESS?
Drug Rash with Eosinophilia and Systemic Symptoms
Caused by Allopurinol and Anticonvulsants
What is TEN?
Toxic Epidermal Necrolysis
Caused by antibiotics (sulfamethoxazole)
Treatment for SCAR
Similar to burn patients
Supportive care, Wound care
Nutritional support, fluids
Difference between SJS and TEN
SJS < 10% detachment of skin
TEN > 30% detachment of skin
Cause of autoimmune diseases
Genetics + Environment (injury, smoking)
Genetics: produce self-reactive lymphocytes
Environment: Antigen from tissue injury and inflammation → Present to self-reactive lymphocytes
Why are autoimmune diseases difficult to treat (4 points)
Do not respond to treatment / Adverse reactions
Treatment for autoimmune diseases are off-label → great variability of treatment
Costly
People view autoimmune diseases as a weakness, unlikely to seek help
Risk factors for SLE (3 points)
Females > Males
African highest, Non white > White
Genetic + Environment (Smoking, infection, Drugs)
4 drugs approved for SLE
Which one should all patients receive?
Aspirin, Prednisolone, Hydroxychloroquine, Belimumab
All patients should receive Hydroxychloroquine
Which medications are teratogenic? (4 points)
Which one also reduces fertility (getting pregnant)?
Methotrexate
Azathioprine
Mycophenolate
Cyclophosphamide
Cyclophosphamide
Adverse effect of Hydroxychloroquine?
Retinal toxicity
Adverse effects of Cyclophosphamide (3 points)
Hemorrhagic cystitis
Bladder malignancy
Infertility
What does Antiphospholipid Syndrome (APS) result in?
General treatment for APS? (primary, secondary, pregnancy)
Increased clotting risk
Thromboprophylaxis
Primary: Aspirin
Secondary: Warfarin
Pregnancy: IV anticoagulant
Hydroxychloroquine has protective effect on phospholipids (from antibodies)
What does immunosuppression therapy consist of?
Induction and Maintenance phase
Induction: high potency, short course to reduce existing damage and prevent worsening of autoimmune condition.
Maintenance: Use Calcineurin inhibitors, Antimetabolites, Corticosteroids, mTOR inhibitors, Biologics
Examples of Calcineurin inhibitors
Cyclosporine
Tacrolimus
Examples of mTOR inhibitors
Sirolimus
Everolimus
Example of antimetabolites
Mycophenolate
Azathioprine
Transplant therapy (4 steps)
1) Match HLA and blood type
2) Use intensive induction therapy to avoid initial rejection eg. Biologics
3) Use multiple maintenance agents eg. Calcineurin inhibitors + Glucocorticoids + Mycophenolate
4) Reduce dosage or withdraw drug if toxicity > benefit
Complications of Immunosuppression
Immune related:
Opportunistic infections
Cancers
Nonimmune related:
Bone marrow suppression
Hepatotoxicity
Renal toxicity (with Calcineurin inhibitors, mTOR inhibitors)
Hypertension, Hyperlipidemia, Hyperglycemia (with steroids, Calcineurin inhibitors)
How is cortisol released in the body?
Effect of chronic corticosteroid therapy on body
Via HPA axis
Hypothalamus secrete CRH, Anterior pituitary release ACTH, Adrenal cortex release cortisol
Chronic corticosteroid therapy causes adrenal suppression.
Long term steroids cause negative feedback on Hypothalamus and Anterior Pituitary, cause decreased secretion of CRH and ACTH