Immunopharmacology of hypersensitivity and allergy Flashcards
principles of management patient w allergy :
possible risk due to other disease:
1- —term as exacerbation
2- – term as remodelling
3- risk due to –
4- — form treatment
short
long
comobidities
side effects
1- allergenic rhinitis:
* Inflammation of the —
* Clinical symptoms:
- nasal discharge (— )
- sneezing
- congestion
- itching
2- pharmacological management for children:
* — and — should be the first-line approach
* Treatment requires a — approach (EUFOREA algorithm; American Acad. Allergy Asthma & Immunol)
nasal mucosa
rhinorrhea
eduction n avoidance
stepwise ( check pic in slide 9 ,10)
Anti-histamines for allergy: H1 receptor antagonists
cross First generation — –> – / —
Examples: Diphenhydramine (Benadryl®), Chlorphenamine (Piriton®)
Characteristics: — -acting
Side-effects: Can have — activity –> —- ; suggested — effects
blood brain barrier
dowsiness and sedation
short acting
anti muscarinic
dry mouth n neurological effects
Corticosteroids for allergy
* — nasal spray is the most effective single therapy for persistent allergic rhinitis
* Minimal side-effects if — administered , systemic glucocorticoids not recommended due to —
* Remember GCs are — at – doses, — at — doses
* Start with — dose to achieve symptomatic control –> then
“—- ” approach
* First generation agents: beclomethasone, budesonide
* Second generation agents: fluticasone propionate, ciclesonide
* Second gen have — bioavailability and therefore — side-effects
glucocorticoids
locally
systemic side effects
anti-inflammatory at low dosese
antisuppresive at high doses
highest dose
step down approach
lower
fewer
Pharmacological management of asthma:
* Up to 40% of patients with allergic rhinitis are estimated to have —
* Patient education is very important
* Drug treatment of asthma depends on – and level of –
1- Immediate symptomatic relief:
* — -acting — inhaler
(eg. albuterol)
* Combination – dose b2-agonist plus – inhaler
2- Asthma control:
* Depending on — , — regularly or as needed with combinations of inhaled short -/long-acting b2- agonist +/- inhaled —
* Can add on – receptor antagonist, and – for severe cases
concurrent asthma
severity and level of control
short
corticosteroids
severity
low dose
cortiscoteriods
severity and dose
corticosteroid
leukitreine
antibiotic
pharmacological management of asthma:
key cell: —
key mediators : – , —- , —
* Biologics useful in asthma include anti-IgE (Omalizumab/Xolair), Anti-IL4-Ra (Dupilumab/Dupixent blocks both IL-4 and IL-13 signalling), Anti-IL-5
* — antagonists are also useful
- additional inhibitors:
* IL-4 and IL-13: Dupilumab: binds IL-4 receptor, blocking the effects of both IL-4 and IL-13
* IL-5: Mepolizumab, reslizumab: bind IL-5 (chemical antagonism)
Benralizumab: bind IL-5Ra (receptor antagonism)
* IgE: Omalizumab: inhibits IgE binding to high-affinity IgE receptor (FceR1) on
mast cells and basophils
* Leukotrienes: Montelukast, zafirlukast: cysteinyl leukotriene CysLT1 receptor antagonists
Zileuton: 5-lipoxygenase inhibitor
esitnophils
key mediators as:
Cytokines that expand eosinophils (eg. IL-4, IL-5)
IgE
Leukotrienes
leukteirns receptor
drug allergy recap:
1- Type I hypersensitivity
Cell-bound — (— )
+ circulating – (allergen)
—- ACTIVATION
Eg. penicillin allergy anaphylaxis
2- Type II hypersensitivity
Cell-bound — (allergen)
+
circulating — ( – )
— & — cells
Eg. penicillin-coated RBC
antibodies to RBC haemolysis (extremely rare)
antibody
IgE
antigen
mast cell
antigen
antibody ( IgG)
macrophages n nk cells
pharmacological management of drug allergy:
if the patient has proven type 1 hypersensitivity to drugs by history or skin test we can either use —- medication or consult w immunology if — therapy is an option , or
If no alternative…consult with Immunology to see if possible
to administer the drug under tight medical supervision. The test dose might kill your patient
alternative unrelated
desensitisation
desentizatrion therapy:
* Administration of — drug–> incremental doses building up to — dose
* — or — protocols, done under specialist supervision
* — protocols required for patients with severe (anaphylactic) responses to their allergen
* Gives — tolerance only
* Usually needs to be — for medications given at intervals —
* Absolutely contraindicated in conditions involving widespread skin — (eg.Stevens-Johnson Syndrome; toxic epidermal necrolysis)
diluted
therapeutic
oral or intravenous
slower
temporary
repeated
>48
skin desquamation
1- Medical emergency allergies - anaphylaxis:
Average time to fatal
anaphylaxis (study in 2000):
30 mins: —
10-15 mins: —
5 mins: — -induced in hospitalised patients
2- the role of IgE in anaphylaxis:
Phases of IgE-mediated immune response:
1. —
2. — response
3. — response
- Anaphylaxis is a – diagnosis based on — and — involvement
ingested foods
insect stings
medication
sensitisation
acute/early
late
clinical
timing and A/B/C
phase 1 - sensitisation:
* Sensitisation can occur on – (or – !) exposure to a particular allergen
* Eg. some patients tolerate penicillin for decades, and then develop allergy in old age
* Sensitization can occur by the substance itself, or something which cross-reacts with it
(eg: Pholcodine & rocuronium)
* – and – cells process – –> – cells switch to — type —> —/ — induce — switching of – cells to produce allergen-specific– –> IgE binds – receptors on — cells (= “ — ”)
first or subsequent
APC and b cells
proces antigen
Th
TH2
IL4/IL-13
class switching
b cell
IgE
Fc
mast cells
priming
phase 2 - early acute response which takes — :
Sensitized individual is — to allergen –>
Allergen binds to – on primed – cells —> Adjacent IgE antibodies – & perturb membrane — > Mast cells “ — ”, releasing — , — etc –> Histamine binds to its – on various tissues, causing the symptoms of –
minutes
re exposed
IgE
mast cells
crosslinks
degranulate
histamines n PGs
receptors
anaphlyrixc
phase 3 - delayed late response which occurs —- so basically —- product specifically — + – which will lead to — production n — recruitment
( phase 2: drenaline auto-injector
Anti-histamines
phase 3: steroids )
cytokines
IL-4 IL-13
mucous
estnophil
emergency management of patient w anapglyalxis:
Key points:
* Immediate — & call for ambulance
* Timely use of intra-muscular — (— ), correct dosage
* Supportive measures: Position patient correctly – lie flat with legs raised unless patient is too breathless; oxygen and fluid bolus; inhaled beta agonists; resuscitation if necessary
* Mitigation of late phase effects ( — , when all else is under control)
-For patients with a history of anaphylaxis – future avoidance is key
recongniton
intra muscular adrenaline ( epinephrin )
steriods
treatment of phase 2 - early response:
Main problem: — causes rapid —- leading to — blood pressure — > —
Solution: — ASAP,—-
( anti histamines r not used as first line treatment )
* Oral anti-histamines….but only after — etc
( — is the first priority!!)
* — therapy if required – eg. short-acting beta2 agonists
* — can be used in hospital for anaphylactic shock patients who are particularly vulnerable (eg. asthmatic)
histamine
rapid vasodilation
reduced
shock
adrenaline intramuscularly
resuscitation
adrenaline
supportive
cortisteriods
treatment of phase 3 delayed response:
* —- : – usually after transfer to hospital
* Refer to — if the cause of anaphylactic shock is unclear
Intravenous corticosteroids
immunology
( info : * One size does not fit all!
Also biologics are very expensive)
