Anti-Allergy Drugs Flashcards
Systemic Allergies
- hayfever & rhinitis
- asthma (allergic/extrinsic component)
- dermatitis (contact+)
- food/GI allergies
- anaphylaxis
- Allergies to inhaled substances
- Contact allergies
- Ingested (food) allergies
- Drug allergies
- Insect allergies
Types of ocular allergies
- hayfever allergic conjunctivitis – seasonal, most common (98%)
- vernal (kerato)conjunctivitis – chronic, relatively rare (<2%)
- giant papillary conjunctivitis – not a true allergic reaction- contact
lens repeated mechanical irritation - atopic keratoconjunctivitis - chronic, relatively rare (<2%)
- contact dermatitis
- blepharoconjunctivitis – staphylococcus aureus infection
Systemic Allergic Responses
- Allergic rhinitis
- Contact dermatitis
- Local/Generalized swelling & hyperemia
- Anaphylaxis
- Wheezing (asthma-like symptoms)
Hypersensitivity Reactions: Type I (immediate or anaphylactic)
- antigen - IgE antibody reaction (mast cells/basophils)
- rapid response
Type II (cytotoxic/complement dependent)
antigen interaction with cell-bound antibodies
(drug induced autoimmune reactions)
Type III (toxic complex/immune complex)
precipitation of antigen-antibody complex
(serum sickness, arthus/vasculitis)
Type IV (cell-mediated/delayed)
- interaction antigen with sensitized T-lymphocytes
- mediator release including cytokines/chemokines
- slow reaction (24 - 48 hours)
Ex) contact dermatitis, drug reactions
Common Allergic Mediators
*histamine
* serotonin
* heparin
* Prostaglandins (PGD2)
* cytokines (TNF-a, TNF-b, IL-2)
* leukotrienes (SRSA, LTD4, CysLT1)
* eosinophilic chemotactic factor (Eotaxin)
* platelet activating factor (PAF)
* complement cascade
* IgE
Early Phase (seconds-minutes) allergic mediators
Mast Cell Degranulation: Histamines, Prostaglandins, Leukotrienes
Late Phase (6 hrs-48 hrs) allergic mediators
Leukocyte (Eosinophils), Lymphocyte infiltration
Central role of T-lymphocytes in prolonged/chronic responses “Adaptive Immune Response”
Th1 and Th2 Helper Lymphocytes Responses
Th1: cellular response, delayed response
Th2: humoral response, B-cells, antibodies, allergen recognition, cytokine release
Main Drug Classes of Anti-Allergy Drugs
- Decongestants
- Antihistamines
- Mast Cell Stabilizers
- Anti-IgE monoclonal antibodies
- Anti-inflammatory drugs (Steroids, NSAIDS)
Ocular & Upper Respiratory Allergies: Common Symptoms
Ocular Allergies
* itchy eyes
* watery eyes*
* congestion*
* swelling
* mucous discharge
* papillary hypertrophy - also generalized irritation
Allergic Rhinitis
* runny nose/rhinorrhea
* congestion
* stuffiness
* mucous discharge
Decongestants Options - Symptomatic
alpha-adrenergic (sympathomimetic) agonists
Phenylephrine (more a1-selective)
* Imidazoles (more a2 -selective, potent, minimal miosis, reduced
rebound congestions)
* Naphazoline (max effect at 0.02%)
* Oxymetazoline (potent)
* Tetrahydrozoline (tachyphylaxis)
- vasoconstriction (WHY?)
- reduced hyperemia
- decongestant action
when to use decongestants?
conjunctival hyperemia
mild allergies (conjunctival, nasal)
-avoid where possible avoid where possible for rebound congestion (nasal spray addiction)
Adverse reactions & Contra-indications of anti-allergy drugs
adverse reactions
-rebound congestion, less problematic imidazoles
-conjunctival reactions
-mydriasis
contrindications
-cardiovascular disease
-hyperthyroidism
-diabetes
Potential drug interactions
- Monoamine Oxidase (MAO) inhibitors (depression) +
- Trycyclic Antidepressants TCAs (depression) +
- atropine (ocular) +
- methylphenidate (ADS, Ritalin) + “sympathectomizing drugs” (e.g. reserpine, neuronal blockers; hypertension)
- a-adrenergic antagonists (benign prostatic hyperplasia)
- beta blockers (variable)
- general anesthesia (variable)
Histamine & Allergies Effects
Triple response of histamine (red, flush, wheel)
* capillary dilatation (heat & flare)
* vasodilatation (precapillary beds)
* vasoconstriction (venules)
* edema/chemosis (swelling)
* itch
Antihistamines for Allergies: Receptors & Potential Sites of Action
H1 receptors (mainly on smooth muscles)
* blood vessels (sm M)*
* bronchi (sm M)*
* GI (sm M)
* CNS/nerves
* mucous membranes
H2 receptors
* blood vessels*
* heart
* GI parietal cells (regulates stomach pH)
* mast cells (feedback inhibition)
* CNS
Pharmacology of H1 antagonists
- Inhibit Allergic Reactions
- itch, pain
- capillary dilatation, edema
- Sedation (1st generation, not 2nd generation)
* Sleep aids
* Excitation in some children - Antinausea and antiemetic actions (1st generation)
* Diphenhydramine, Promethazine, Meclizine - Antiparkinsonism effects
- Antimuscarinic actions
* atropine-like effects - Adrenergic receptor blocking actions
- Serotonin blocking actions
- Local anesthesia
* Block sodium and potassium channels - Other actions
* Inhibit mast cell release, glycoprotein transporters
Specific Features of Newer Topical Ophthalmic Anti-HA Drugs
adjunct mast cell stabilizer action
* azelastine
* epinastine
* olopatadine (also basophils?)
* ketotifen (decreases eosinophil chemotaxis)
* alcaftadine
Main Side-Effects of Topical Anti-HA Products
- burning, stinging
- Pupil dilatation (except olopatadine)
- Allergies (long term use, formulation)
- Headache (newer products)
- Safety newer products not fully established (all category C)
* Young children(<3yr)
* Pregnant women (teratogenic effects)
Uses of Oral Antihistamines
- augment topical therapy (especially if severe)
- generalized allergic response
- lid myokymia (topical & oral)-anti-muscarinic activity
- anti-nausea (CNS activity)
2nd generation
* less anti-muscarinic activity
* less lipid soluble
* additional activities?
Side-effects of Oral Anti-HA Drugs
mediated by
* H 1, 2, 4 receptors elsewhere
* other receptors (muscarinic, adrenergic, serotonin)
* common effects (anti-HA +/- antimuscarinic)
* sedation (potential excitation in young children)
* GI & urinary disturbances
* dry throat, mouth, bronchi
* palpitations & dysrhythmias
* ocular antimuscarinic effects (example?)
* nonsedating (2nd Generation) Anti-HA tend to have:
* low anticholinergic activity (dry mouth, fatigue, drowsiness 5-20%)
* minimum anti-emetic activity
* Headaches (cetirizine 16%)
Drug Interactions: Oral Drugs
- alcohol!!
- other CNS depressants - sedatives, opioids, analgesics
- additive with
* anticholinergics- adrenergic agonists
* MAOIs
* Phenothiazines (TCA)
- adrenergic agonists
- inhibition
* adrenergic antagonists - TD50
* grapefruit juice & P450 inhibitors
Contra-indictaions of anti-allergy drugs
-nursing, pregnant
-GI, UT disease, narrow angles
-cardiac safety -cardiac toxicity, additive effects antifungals, macrolides
mast cell stabilizer drugs
- cromolyn sodium
- lodoxamide tromethamine
- nedocromil sodium
- pemirolast
Mast Cell Stabilizers effects
- prevent release of mediators from mast cell
- calcium mechanism
- mechanisms for anti-allergy effect
- inhibition of sensory nerve firing (chloride channel)
- inhibition eosinophil accumulation
- reduced IgE production (B lymphocytes)
- generally no intrinsic AH/VC/anti-inflammatory action
New versus Old Mast Cell Stabilizers
- newer ones generally more potent than cromolyn
* Lodoxamide – 2,500 more potent that cromolyn - additional actions
* nedocromil - direct antagonism (HA, Leukotrienes) - pemirolast - inhibition eosinophils (chemotaxis, mediator release)
Ophthalmic & Other Applications: Mast Cell Stabilizers
- seasonal allergies (including asthma)
- keratoconjunctivitis
- conjunctivitis
- GPC (compatibility with contact lenses?)
- most useful in generally allergic patients (ocular allergy + e.g. asthma, eczema hay fever)
- reduce/terminate corticosteroid therapy
Adjunct, Newer & Alternative Treatments
- Anti-IgE antibodies
- NSAIDs
- Corticosteroids
- Immunosuppressive drugs
- Leukotriene receptor antagonists, CysLT1
- Homeopathic options
- Immunotherapy
