allergic and hypersensitivity Flashcards
definition of allergies
- immunologically mediated hypersensitivity reaction to a substance in a sensitised person
- it is a response of immune system to the antigenic substance leads to host tissue damage, manifesting as an organ-specific or generalised systemic reaction
why is the percentage of adverse reactions event hard to determine?
- unreported cases
- Unable to differentiate between non immune drug hypersensitivity reaction and immune drug hypersensitivity
why is the percentage of adverse reactions event hard to determine?
- unreported cases
- Unable to differentiate between non immune drug hypersensitivity reaction and immune drug hypersensitivity
what are the drugs that are commonly a/w allergic/allergic like rxns? (10)
penicillin, sulfonamide, anticonvulsant (phenytoin), chemo agents containing platinum, radiocontrast media, chlorhexidine, ACEi/ARB, biologics, NSAIDs, insulin
what is drug hypersensitivity reactions
adverse events that clinically resemble drug allergy but have not yet been proven to be associated with an immune response
- Adverse events include symptoms which are similar to drug allergy
- Drugs can cause the release of mast cell and basophil derived mediators by a pharmacologic or physical effect rather than IgE (immune response)
are DHRs and drug allergies the same?
no
what is the difference between DHRs and drug allergies?
dhr: release of mast cell and basophil derived mediators by a pharmacologic or physical effect (non-immune mediated)
drug allergies: release IgE (immune mediated)
what are the drugs that can cause DHRs + reactions + reasons?
- vancomycin - When infused too rapidly will cause “Red man syndrome”. This is due to the direct release of histamine
- ACEi/Sacubitril - Angioedema. ACEi causes Inhibition of breakdown of bradykinin. Accumulation of bradykinin leads to inflammation, vascular permeability and vasodilation
- NSAIDs - Asthma. This is due to the altered metabolism of prostaglandins and it causes bronchoconstriction, leading to asthma
what are the effectors of allergic reactions?
major components of innate and adaptive immune systems
which includes:
cellular elements (T & B cells, macrophages, neutrophils, mast cells, platelets),
immunoglobulins (esp IgE),
complements (cascade of proteins) and
cytokines
what are the effectors of DHRs?
pharmacologically active chemical mediators
eg: histamine,
platelet-activating factor (PAF) –> trigger platelet aggregation and clots, prostaglandins (PG),
thromboxanes,
leukotrienes
classifications of allergic reactions
type 1 - immediate hypersensitivity
type 2 - antibody mediated diseases
type 3 - immune complex-mediated diseases
type 4 - T cell mediated diseases
list the clinical manifestations of DHRs (6)
- anaphylaxis,
- serum sickness/drug fever
- drug induced autoimmunity - SLE
- vasculitis ,
- respiratory
- hematologic
describe signs of anaphylaxis (5)
- skin
- Hives (urticaria), itching, flushed skin, Swelling of lips, tongue, throat, face - airway *
- Tightness + swelling of the throat, horseness, scratchy throat, Trouble breathing, wheezing, chest tightness - central nervous system
- Anxiety, headache, dizziness, confusion, tunnel vision, fainting - cardiovascular system *
- Chest pain, Low blood pressure (hypotension), Rapid heart rate + weak pulse - GI tract
- Nausea, abdominal cramping, vomiting and diarrhea
what are the 3 serious cutaneous adverse reactions (SCAR)?
- drug rash with eosinophilia and systemic symptoms (DRESS)
mucocutaneous disorders - stevens-johnson syndrome (SJS)
- toxic epidermal necrolysis (TEN)
definition of DRESS (drug rash with eosinophilia and systemic symptoms)?
Triad of rash, eosinophilia and internal organ involvement (all 3 factors)
what are the drugs that cause DRESS?
- Allopurinol
- Anticonvulsant
is the mortality rate of DRESS higher than SJS/TEN?
yes, higher than SJS, but lower than TEN
definition of SJS/TEN?
- Progressive bullous or “blistering” disorders that constitute dermatologic emergencies
- Progress to include mucous membrane erosion which could affect internal organs and epidermal detachment (skin starts falling out)
which is more serious SJS/TEN?
TEN Greater than 30% detachment of body surface area vs 10% (SJS)
drugs that cause SJS/TEN?
Antibiotics, Especially sulfonamides
why some people predisposed to drug allergies/hypersensitivity?
Genetically determined human leukocyte antigen (HLA) alleles increases susceptibility to several drug hypersensitivity syndromes
Genetic factors can also influence the metabolic deactivation of drugs via phase 1 & 2 metabolism
Example of drugs people are hypersensitive to + rxn
- Abacavir –> hypersensitivity reactions
- Allopurinol –> SJS/TEN
- Carbamazepine/phenytoin –> SJS/TEN
- Carbamazepine –> DRESS
Do we do pharmacogenomics testing on every patient?
no, not all. only selected drugs, you must do level 1 testing for:
1. Abacavir for HIV
2. Allopurinol for gout and hyperuricimia
3. Carbamazepine, phenytoin for epilepsy (seizures)
4. Sulphasalazine for juvenile arthritis/autoimmune disease
Level 1 testing to make sure that the patient has the allele before we can give the drug
purpose of treatment of anaphylaxis + drugs to give
purpose: Prompt treatment to restore respiratory and CVS function
- epinephrine (adrenaline) - counteract bronchoconstriction and vasodilation
after reaching ambulance/hosp:
1) IV fluids to restore volume/BP
2) Intubation if necessary to save airway (open because pt already has bronchoconstriction)
3) Norepinephrine (nonadrenaline) if shock - A strong vaso-constrictor
Other agents that might be used: Steroid, Glucagon, Diphenhydramine (H1) + ranitidine (H2) –> to block release of histamines
treatment of SCAR
Management is similar to burn patients: Providing supportive care
1. Wound care
2. Nutritional support
3. Fluids
4. Temperature regulation
5. Pain management
6. Prevention of infections (giving antibiotics)
Steroids use is controversial
definition of autoimmune disease
Refer to conditions when the body is attacked by own immune system
examples of autoimmune diseases (9)
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Systemic vasculitis
- Psoriasis
- Sjogren’s syndrome
- Graves disease
- Type 1 DM
- Scleroderma
- Multiple sclerosis
risk for autoimmune disease
Genetic background and environmental stimuli such as smoking and infection can increase risk for developing an autoimmune disorder
Why are autoimmune diseases difficult to treat? (4)
- many pt do not respond to treatment, lose response to treatment, do not tolerate, have adverse reactions to the treatment
- most drugs are off label (poorly indicated) - which means that they are not indicated for autoimmune disease. There is great variability of treatment among centres and specialists
- expensive drugs. because very few drugs are available.
- people may be less likely to seek help due to stereotype - weakness
definition of SLE (systemic lupus erythematosus)
Is an autoimmune disease associated with auto-antibody production - multisystem disease
is the mortality rate for SLR higher than general population?
yes because body undergo constant inflammation
who needs immunosuppressants?
- Autoimmune conditions
- Solid organ transplants - for life
- Stem cell/bone marrow transplants eg Blood cancers , Bone marrow issue
2 types of use of immunosuppressants
- induction
- maintenance
induction use of immunosuppressants
- High potency
- Short course therapy given ASAP
- Prevent acute rejection with lymphocyte-depleting therapy
- Examples:
Basiliximab
Alemtuzumab
classes of maintenance immunosuppressants
1, Calcineurin inhibitors
2. Antimetabolite
3. Corticosteroids
4. mTOR inhibitors
5. Biologics
examples of each class of maintenance immunosuppressants
- Calcineurin inhibitors - Cyclosporin, Tacrolimus
- Antimetabolite - Mycophenolate, Azathioprine
- Corticosteroids
- mTOR inhibitors - Sirolimus, Everolimus
- Biologics - Adalimumab
6 complications of immunosuppressants
- increased risk of infection + opportunistic infections
- cancers
- blood disorders
- hepatotoxicity (especially mycophenolate and azathioprine)
- renal toxicity (Especially cyclosporin and tacrolimus)
- hypertension, hyperlipidemia, hyperglycemia (Especially calcineurin and mTOR inhibitors )
steroid withdrawal with respect to HPA axis suppression
- Exogenous glucocorticoids cause decreased secretion of CRH (Corticotrophin-releasing hormone) and ACTH (Adrenocorticotropic hormone)
- Overtime, the whole HPA axis becomes inactive. Adrenal gland will also become smaller.
- Hence, if the patient stopped taking steroids, the HPA axis will not be able to recover its function quickly, causing adrenal suppression and patients will experience steroid withdrawal symptoms.
can HPA axis suppression be reversed?
yes but needs time
how much steroid use is too much?
no clear cut off, but >5mg prednisolone daily for more than 3 weeks is > what the adrenal glands produces everyday –> risk of adrenal suppression
what are the 3 drugs that commonly cause anaphylaxis?
penicillins, NSAIDs and insulins
what are the class of drugs that commonly cause drug fever?
antibiotics
what are the 2 drugs that commonly cause vasculitis?
allopurinol, thiazide
what are the 3 drugs that commonly cause respiratory related allergic reactions?
- NSAIDs causes asthma
- Bleomycin and nitrofurantoin causes acute infiltrative and chronic fibrotic pulmonary reactions
what is the drug that cause development of autoimmune hemolytic anemia?
Methyldopa
what is the drug that cause development of autoimmune hepatitis?
Phenytoin
what complications need to look out for in immunosuppressant drugs especially in mycophenolate and azathioprine?
hepatotoxicity
renal toxicity is most severe in which immunosuppressant?
cyclosporin and tacrolimus
