IC5 Flashcards
Example of PGxdrugs causing allergies/ hypersensitivity
- Allopurinol/ Phenytoin: SJS/ TEN
- Carbamazepine: SJS/TEN/ DRESS
- Abacavir: Hypersensitivity reactions
Immediate treatment for anaphylaxis and how?
Epinephrine (adrenaline) -> To counteract bronchoconstriction and vasodilation
Treatment of anaphylaxis if managed to reach hospital/ ambulance
- IV fluids to restore volume/ BP
- Intubation if needed to save airway
- Norepinephrine (Noradrenaline) if shock
- Other agents: steroids, glucagon, ranitidine (H2) + diphenhydramine (H1)
Treatment for SCAR (serious cutaneous adverse reaction)
Treatment less defined;
Supportive care: wound care, fluids, nutritional support, pain management, temp regulation, prevention of infection;
Steroids use is controversial
Definition of autoimmune diseases and possible causes
- when the body is attacked by its own immune system
- caused by genetic / environment stimuli e.g. smoking and infection
Why are autoimmune diseases difficult to treat?
- a large proportion do not respond to treatment, do not tolerate or have adverse effects
- poorly indicated, mostly off-label use; great variability of tx
- drugs are usually costly
- stigma > viewed as a weakness > ppl less likely to seek tx
Why are autoimmune diseases difficult to treat?
- a large proportion do not respond to treatment, do not tolerate or have adverse effects
- poorly indicated, mostly off-label use; great variability of tx
- drugs are usually costly
- stigma > viewed as a weakness > ppl less likely to seek tx
Definition and possible causes of systemic lupus erythematosus (SLE)
- autoimmune disease a/w auto-antibody production
- strong genetic disposition + environmental triggers e.g. smoking, infection & certain drugs
Pathophysiology of SLE
- characterised by disorder of innate & adaptive immune system
- T & B cell activation & signalling is altered -> abnormal clearance of apoptotic debris containing nuclear material which can stimulate immune responses
- num of plasma cells increased in active SLE and these cells produce autoantibodies which cause tissue damage
Clinical presentation of SLE
- Lupus nephritis
- Neuropsychiatric lupus: psychosis, seizure, anxiety, cerebrovascular disease (stroke), cognitive dysfunction, peripheral neuropathy, confusion, etc
- Cardiovascular: pericarditis, myocarditis, accelerated atherosclerosis
Labs presentation for SLE
Full blood count: Reduced RBC, WBC & PLT
Immunologic: Anti-nuclear antibodies, Anti- ds DNA, Anti-smith antibodies, anti-nuclear ribonucleoprotein, low complement (C3, C4, CH50)
Treatment goal for SLE
- Remission/ achieve low disease activity (more realistic)
- Prevent flares & other organs, slow disease activity, reduce use of steroids, improve QoL while minimising adverse effects
- Evaluate and treat other comorbidities alongside Lupus
- Lifestyle (quit smoking) & support group
Drug treatment for SLE
- FDA-Approved drugs: hydroxychloroquine, aspirin, prednisone & belimumab
- Usually start on hydroxychloroquine (including pregnant women) > takes about 4-8w to have effect; minimal adverse effects
General pharmacologics for SLE + examples
- NSAIDs: first line for acute symptoms
- Steroids: Monotherapy or adjunctive to control flares/ maintain low disease activity; Concern over high dose/ LT use
- Biologics: targets and disrupts functioning of B cells -> Belimumab & Rituximab
- Immunosuppressant: IV/ PO Cyclophosphamide (severe organ involvement; induction); Mycophenolate (induction & maintenance); Azathioprine (alternative for maintenance)
What syndrome may also be found in SLE patients? What are the consequences and general treatment?
- Antiphospholipid syndrome; Positive for antiphospholipid antibodies
- High risk of clotting and pregnancy morbidity
Treatment: - Primary thromboprophylaxis: hydroxychloroquine + aspirin
- Secondary thromboprophylaxis: warfarin
Drug-induced lupus causes
Possible drugs: hydralazine, procainamide, quinidine, etc.
MOA: drugs bind to larger molecules like proteins to induce an immune response
Evaluation of treatment outcomes for SLE
- ADR
- development of comorbidities
- measure of disease activity
- Lab results (every 1-3 months if active; every 6-12 months if stable)
Causes of immunosuppression
autoimmune condition, stem cell / bone marrow / solid organ transplant
Complications of immunosuppression
Infections, cancer, blood disorders, hepatotoxicity, renal toxicity, 3 Highs
How does HPA axis suppression happen?
LT use of Exogenous glucocorticoids cause decreased secretion of CRH and ACTH -> Overtime, the whole HPA axis becomes inactive, and will be unable to recover its function
quickly if exogenous steroids are stopped
Anti-inflammatory and immunosuppressive effects of steroids
Reduced pain, swelling, stiffness and physical disability
Side effect of concomitant use of NSAID and steroid
Gastric ulcer
General dose of steroid that can lead to greater risk of HPA axis suppression
greater than 5 mg prednisone equivalents daily for more than 3 weeks
Side effects of steroids
- Osteoporosis/ osteonecrosis
- Cataract/ glaucoma
- adrenal insufficiency (HPA axis insufficiency)
- myopathy
- infections
- increased cardiovascular risk
- hirsutism (where women have thick, dark hair on their face, neck, chest, tummy, lower back, buttocks or thighs)
- skin thinning
- weight gain/ obesity
- fluid retention/ edema
- cushing syndrome
- insulin resistance/ beta cell dysfunction/ impaired glucose metabolism
- gastric ulcer (if used with NSAID)
