Immune-related Toxicities Flashcards
Difference between true allergy and pseudoallergy in terms of components involved?
True allergy: mediators, lgE, lgG, lgM and T cells, formation of immune complexes
Pseudoallergy: mediators (histamine, PGs, kinins), does NOT involve immune system or any Ab
What are the drugs that can cause pseudoallergy? (3)
- Vancomycin
- ACE/ Sacubitril
- NSAIDs
What are the different types of hypersensitivity reactions? (6)
Which type is SLE?
- Anaphylaxis
- Serum-sickness/ drug fever
- Drug-induced autoimmunity (SLE)
- Vasculitis
- Respiratory
- Hematologic
Drugs that can cause anaphylaxis? (3)
Penicillins, NSAIDs, insulins
Drugs that can cause serum-sickness/ drug fever? (1)
Antibiotics
Drugs that cause drug-induced autoimmunity? (2)
Methyldopa → hemolytic anaemia
Phenytoin → hepatitis
Drugs that cause vasculitis? (2)
Allopurinol, Thiazide
Drugs that cause respiratory hypersensitivity? (3)
NSAIDs, Bleomycin, Nitrofurantoin
Drugs that cause SCAR? (3)
Allopurinol, anticonvulsants and sulflonamides
First-line Tx for anaphylaxis and MOA?
What should we do if the pt manages to reach the hospital? (4)
Epinephrine (adrenaline)
MOA: counteracts bronchoconstriction and vasodilation
If pt reaches hospital:
- IV fluids (restore volume/ BP)
- Intubation to save airway (if necessary)
- Norepinephrine (noradrenaline) if in shock (severe hypotension)
- Steroids, glucagon, diphenhydramine (H1) + ranitidine (H2)
Tx for SCAR?
Non-pharmacological and pharmacological?
Use of which medication is controversial?
Supportive care (similar to burn pts):
- Wound care
- Nutritional support
- Fluids
- Temperature regulation
- Pain management
- Prevention of infections
May use intravenous immunoglobulin (IVIG) or cyclosporine
Steroid use controversial
In what type of people are SLE most prevalent?
More prevalent in females, non-white > white (African descent highest)
Which drugs have the highest risk of causing SLE? (3) (HPQ)
Other drugs?
Procainamide, hydralazine, quinidine
Others: minocycline, isoniazid, methyldopa, carbamazepine, TNFα inhibitors
What are the clinical presentation (labs) of SLE in terms of blood count?
- Haemolytic anaemia: ↓ RBC
- ↓ WBC / ↓ lymphocytes
- ↓ PLT
What are the clinical presentation (labs) of SLE in terms of immunologic components?
Non-exhaustive:
- Antinuclear Ab (ANA)
- Antidouble-stranded DNA (dsDNA)
- Anti-Smith Ab (anti-Sm)
- Antinuclear ribonucleoprotein (anti-RNP)
- Low complement (C3, C4, CH50)
Name the drugs used for Tx of SLE (5) (BISHN)
- Hydroxychloroquine
- NSAIDs
- Steroids
- Biologics
- Immunosuppressants
When do we use hydroxychloroquine for SLE? MOA?
How long to achieve effects?
ALL SLE patients
MOA:
- Prevents flare
- Improves long term survival
- Anti-inflammatory, immunomodulatory and anti-thrombotic effects
- 4-8w to achieve effects
Impt ADE of hydroxychloroquine?
What must we monitor?
Retinal toxicity > 10% prevalence after 20 years use
Need retinal checks
Elaborate on NSAIDs for SLE and its ADEs
Hence what must we check before initiation?
First-line for acute s/sx
ADEs:
- Worsen kidney function
- ↑ cardiac risk
- GI bleed
Caution in worsening lupus nephritis, check kidney function beforehand
Elaborate on use of steroids for SLE (what type of steroid used?)
MOA? ADEs (systemic and topical)?
Glucocorticoids
MOA:
- Control flares
- Maintain low disease activity
ADEs (systemic):
- Osteoporosis
- Cataracts
- Glaucoma
- Hyperglycemia/ diabetes
- HTN
- Dyslipidemia
- Skin thinning
- Weight gain
- Fat redistribution
- Sleep/ mood disturbances
Topical:
- Skin atrophy
How do corticosteroids cause HPA axis suppression?
- Exogenous corticosteroids → ↓ secretion of Corticotropin-Releasing Hormone (CRH) from hypothalamus and Adrenocorticotropic Hormone (ACTH) from pituitary gland
- Overtime, HPA axis inactive (pts cannot produce own cortisols)
- End result: adrenal suppression
How much steroid use before adrenal suppression occurs?
- Doses > 5mg prednisone daily for > 3w (but actually IRL no clear “cut off”)
- Maintain suspicion as long as pts have taken corticosteroids before/ are taking it currently
Type of biologics used for SLE? (2)
MOA? What should we note about live vaccines?
Belimumab, Rituximab
MOA:
- Targets and disrupts functioning of B cells
DO NOT administer live vaccines in pts taking biologics
Name the immunosuppressants used for SLE (6)
Note: immunosuppressants are steroid sparing :)
- Cyclophosphamide (PO, IV)
- Mycophenolate
- Azathioprine
- Methotrexate
- Mycophenolate Mofetil
- Cyclosporine
- Tacrolimus
ADEs of cyclophosphamide? Who should avoid?
- Hemorrhagic cystitis
- Bladder malignancy
- INFERTILITY*
Avoid if pt has Hx of cystitis/ bladder problems
How often do you monitor labs for SLE?
What labs do you monitor?
Regular labs every 1-3 mths with active disease, 6-12 mths if stable
Monitor urinalysis, anti-dsDNA Ab, complement C3, C4 levels, C-reactive protein, full blood counts, liver function
What is a complication of SLE?
What happens during SLE?
Antiphospholipid syndrome (APS)
- High risk of clotting
- High risk of pregnancy morbidity (no. of miscarriages can also be a diagnostic criteria)
Tx of APS SLE?
- Primary thromboprophylaxis
- Secondary thromboprophylaxis
- Protective
- Primary thromboprophylaxis: aspirin
- Secondary thromboprophylaxis: thrombophylaxis
- Protective: hydroxychloroquine
Drugs used for induction of immunosuppression?
- Lymphocyte-depleting agents
- Immune modulators which prevent activation & proliferation of T cells
Lymphocyte-depleting agents:
- Antithymocyte globulin
- Alemtuzumab (off-label)
Prevent activation & proliferation of T cells:
- Basiliximab
Drug classes and drugs under each class that are used for maintenance Tx of immunosuppression?
Note: ALL need TDM!
Calcineurin inhibitors: cyclosporin, tacrolimus*
Anti-metabolites: mycophenolate*, azathioprine
Corticosteroids
mTOR inhibitors: sirolimus, everolimus
Biologics: adalimumab, belatacept
What complications can azathioprine and mycophenolate cause? (2)
- Bone marrow suppression
- Hepatotoxicity
What complications can steroids and CNI cause? (3)
- HTN
- Hyperlipidemia
- Hyperglycemia
What do we give pts for induction therapy for immunosuppression? Why?
Give biologic Tx to delay use of CNI (CNI is nephrotoxic)
What is a common combination of maintenance agents for immunosuppression?
Calcineurin inhibitor + glucocorticoids + mycophenolate
What is a combination we should avoid for maintenance agents for immunosuppression and why?
Calcineurin inhibitor + mTOR due to ↑ nephrotoxicity
How should we treat CNI-induced renal toxicity?
What should we AVOID?
First-line: DHP CCB
Avoid ACEi or diuretics
DDIs to take note of for drugs under immunosuppression maintenance Tx?
CNI (tacrolimus, cyclosporine) and mTORi → CYP3A4 and P-glycoprotein substrates
