drug hypersensitivity, allergies, immune-mediated toxicities Flashcards
Describe the laboratory clinical presentations of SLE
full blood count: low RBC (hemolytic anemia), WBC, lymphocytes and platelets
immunologic: positive for Anti-nuclear antibody, Anti-Smith antibody, Anti-dsDNA antibody, Anti-Ribonucleoprotein antibody, low complement (C3, C4, CH50)
Describe the clinical presentations of SLE and the complications involved
Facial rash (butterfly pattern)
Arthritis (joint swelling, tenderness and pain in the wrists, hands, ankles)
Lupus nephritis (leading to renal failure)
Cardiovascular disease (pericarditis, myocarditis, accelerated atherosclerosis)
Neuropsychiatric lupus (stroke, cerebrovascular disease, anxiety, seizures, cognitive dysfunction, confusion, peripheral neuropathy, psychosis etc.)
Name the four drugs approved by FDA for use in treatment of SLE
Hydroxychloroquine (all patients, incl. pregnant women should be on hydroxyhloroquine), prednisolone, aspirin, belimumab
Name the S/E of systemic glucocorticoids
osteoporosis (patient should receive osteoporosis preventive therapy), cataract, glaucoma, hypertension, hyperlipidemia, hyperglycemia/diabetes, fat maldistribution, weight gain, thinning of skin, sleep/mood disturbances
Name the S/E of topical glucocorticoids
skin atrophy, spider veins, dermatitis
Name the S/E of hydroxychloroquine
retinal toxicity (>10% in patients who use it for over 20 years; risk increases with doses of >5mg/kg/day, more than 5 years of therapy, renal or macular disease or concurrent tamoxifen use), gastric intolerance, rash, skin hyperpigmentation
Name the S/E of belimumab
infusion reactions, hypersensitivity, nausea, diarrhea, fever, nasopharyngitis, bronchitis, pain in extremities, insomnia, depression, migraine
Name the S/E of cyclophosphamide (IV/PO)(immunosuppressant; induction therapy)
hemorrhagic cystitis (greater risk with oral as compared to IV, decrease with hydration and mesna), bladder malignancy, infertility, myelosuppression, opportunistic infections
Name the S/E of mycophenolate mofetil (immunosuppressant; induction and maintenance therapy)
N/V/D (gastrointestinal effects may limit use and compliance, less symptoms with enteric coated form), myelosuppresion, hepatotoxicity
Name the S/E of azathioprine (immunosuppressant; alternative to mycophenolate for maintenance therapy)
hepatotoxicity, myelosuppression
(test thiopurine methyltransferase - TPMT before starting as toxicity is greatly enhanced if deficient)
Name the S/E of methotrexate
hepatotoxicity, pulmonary toxicity, hematologic toxicity, stomatitis (inflammation of the oral mucosa, presenting with ulcers)
Name the S/E of rituximab
infusion reactions, infections, neutropenia, mucocutaneous reactions, fever, fatigue, progressive multifocal leukoencephalopathy
Which of the drugs used for SLE are safe in pregnancy?
Hydrochloroquine (not more than 5mg/kg/day calculated using actual body weight) & Azathioprine
the rest: cyclophosphamide decreases fertility, and is teratogenic esp. in the 1st trimester, mycophenolate mofetil/methotrexate are teratogenic, steroids can cause gestational diabetes, pre-eclampsia, hyperglycemia, hypertension and should be minimized in pregnancy
Name the drugs with the highest risk of developing SLE
Procainamide, hydralazine, quinidine
Name the anti-phospholipid antibodies found in those with anti-phospholipid syndrome (APS) in SLE patients (found in 40% of SLE patients)
APA: lupus anticoagulant, anti-cardiolipin, anti-beta2 glycoprotein 1
What is the general treatment for anti-phospholipid antibody positive patients?
non-pregnant:
primary thromboprophylaxis: aspirin
secondary thromboprophylaxis: warfarin
pregnant:
primary thromboprophylaxis: aspirin
secondary thromboprophylaxis: parental anticoagulants, e.g. heparin (warfarin is CI in pregnancy)
note: hydroxychloroquine has some protective effects as it suppresses some clotting factors
Describe the monitoring regime for SLE:
monitor for adverse drug reactions, development of co-morbidities, measures of disease activity (SLEDAI, BILAG), regular labs every 1-3 months with active disease, every 6-12 months if stable
labs: urinalysis (assess renal function), anti-dsDNA antibodies, complement C3 and C4 levels, c-reactive protein, full blood count, liver function test
- ANA, anti-Sm, anti-RNP do not need to be repeated with each visit, as the levels do not fluctuate with disease activity
What is are the common combinations for maintenance immunosuppression therapy for organ transplantation?
most common: calcineurin inhibitor (cyclosporin/tacrolimus) + mycophenolate + corticosteroids
other options: calcineurin inhibitor (cyclosporin/tacrolimus) + mTOR inhibitors (sirolimus/everolimus) -> however, the increased risk for nephrotoxicity limits its use
*calcineurin inhibitor is nephrotoxic, and toxicity worsens when it is combined with a mTOR inhibitor
What are the common drugs used for induction immunosuppression therapy for organ transplantation?
lymphocyte depleting agents to cause cell lysis: antithymocyte globulin (ATG) and alemtuzumab (off-label)
immunomodulator to prevent activation and proliferation of T cells: Basiliximab
What are the common drugs used for maintenance immunosuppression therapy for organ transplantation? (by pharmacological class)
calcineurin inhibitors: *cyclosporin, *tacrolimus
S/E: nephrotoxicity (worse when combined with mTOR inhibitor), hypertension, hyperlipidemia, hyperglycemia
antimetabolites: *mycophenolate, azathioprine
S/E: bone marrow suppression, hepatotoxicity
mTOR inhibitors: *sirolimus, *everolimus
biologics: adalimumab, belatacept
corticosteroids
Describe the HPA axis suppression by long term use of corticosteroids
HPA axis: Hypothalamus-pituitary-adrenal axis (cortisol production pathway/control)
hypothalamus produces CRH (corticotropin releasing hormone), which stimulates the anterior pituitary to produce ACTH (adrenocorticotropic hormone), which stimulates the adrenal cortex to secrete cortisol
The introduction of exogenous glucocorticoids stimulates negative feedback loops which decrease the production of CRH and ACTH, thus leading to HPA Axis suppression. When exogenous glucocorticoids are stopped, the HPA axis is unable to recover its function quickly, leading to adrenal insufficiency.
Who are at greater risk for adrenal insufficiency?
Patients who are on corticosteroids with a dose greater than 5mg of prednisolone once daily equivalent, for more than 3 weeks. But all patients taking long term steroids should have a tapered withdrawal and a degree of suspicion of adrenal insufficiency should be maintained in all patients who are taking or have taken corticosteroids
