Pharmacology: Hypersensitivity Flashcards
What are the general therapies for acute/chronic asthma?
Mast Cell stabilizers: Inhibit mast cell activation, degranulation
Leukotriene inhibitors: 5-lipooxygenase inhibitors and LTD4 Receptor antagonists
Bronchodilators: ß2-selective adrenocreceptor agonists, Methylxanthine drugs (PDE inhibition?), Muscarinic receptor antgonists
Inhaled corticosteroids: Anti-inflammatories
What are the different mast cell stabilizers?
Chromolyn
Nedocromil
What are the leukotriene inhibitors?
Zileuton (5-lipooxygenase inhibitors)
Montelukast, Zafirlukast (LTD4 receptor antagonists)
What are the available bronchodilators?
ß2 selective agonists:
Albuterol
Terbutaline
Metaproterenol
Piruterol
Salmeterol (long acting)
Formoterol (long acting)
Methylxanthine drugs:
Theophylline
Muscarinic antagonist:
Ipratropium
What are the available inhaled corticosteroids?
Beclomethasone
Budersonide
Ciclesonide
Flunisolide
Flutacasone
Mometasone
Triamcinolone
What is omalizumab?
Humanized mAb targeting the portion of IgE that binds to Fce Receptors
- Blocks binding of >96% free IgE to mast cells/basophils without crosslinking Ige that is already bound
- Reduces frequency and severity of moderate to severe asthma attacks and allergic rhinitis
What is the treatment for anaphylaxis?
1st: epinephrine
- non-selective a & ß adrenoreceptor agonist, rapidly reverses bronchoconstriction (ß2) and vasodilation (a1)
- IM injection
- remove antigen if possible (i.e.bee stinger)
2nd: antihistamines
- H1R antagonist (diphenhydramine) + H2R antagonist (cimetidine, ranitidine)
- treat with corticosteroids (prednisone) to block late-phase cytokine driven responses
- aggressive IV fluids to counteract hypotension
What is allergy desensitization?
Allergen-specific immunotherapy:
Repeated, increasing doses of causative agent (subcutaneous) - thought to induce Tregs to decrease sensitivity
–> Decreased sensitivity upon re-exposure (conjunctivitis test)
What is Rhogam?
Medication to prevent maternal antibody response of anti-Rh antibodies when pregnant with a Rh+ child
- Anti-Rh Ab given
What are types of drug induced type II hypersensitivity?
Occurs when reactive drug metabolite binds covalently to protein, resulting in immunogenicity (hapten-carrier effect)
Protein-drug conjugates often form on circulating blood cells - Abs that form against the conjugate activate complement and induce cell lysis:
- *Hemolytic anemia** (penicillin, sulfonamides, methyldopa)
- *Thrombocytopenia** (quinine, heparin)
- Agranulocytosis*/neutropenia (NSAIDs, phenylbutazone, carbimazole, clozapine)
- *Aplastic anemia** (chloramphenicol)
What type of hypersensivity is Drug-induced Lupus? What drugs cause it?
Type III Hypersensitivity
Symptoms:
Muslce and joint pain, swelling
fatigue
Fever
Serositis
Positive serology tests (ANA, anti-histone, etc)
Some drugs implicated:
Hydralazine
Procanamide
Methyldopa
Carbamazepine
Minocycline
Treatment: discontinue drug
What type of hypersensitivity is Stevens-Johnson syndrome?
Type IV hypersensitivity
- Cytotoxic Tcells: Direct destruction of keratinocytes
–> causes toxic epidermal necrolysis
What type of hypersensitivity is contact dermatitis?
Type IV hypersensitivity:
- T cell mediated, cytokine-driven inflammation directed through resident DCs
Why do patients prescribed carbamazepine need to be HLA tested?
HLA-B*1502 carriers are sensitive to CBZ –> They get Stevens-Johnson syndrome (T4-hypersensitivity)
- CBZ binds to the MHC Class I peptides presented on the surface of keratinocytes
- CTLs recognize the modified MHC peptide and cause cell death
