Martin Antihistamines/ Rhinitis lecture Flashcards
Drugs delivered locally as nasal spray
Antihistamines Antimuscarinics Cromolyn compounds Topical corticosteroids Nasal decongestants - Sympathomimetic Agents - alpha -adrenergic agonists
Antihistamines: what receptor do they work on? Describe pharmacokinetics
H1 Receptor Antagonists
Pharmacokinetics
- rapidly absorbed
- large Vd
- **2nd generation drugs do not cross BBB
- metabolized in the liver
- t1/2 most drugs = 4-6 hours
- sustained release preparations t1/2= 12-24 hrs
First generation Histamine receptor blockers can also have blocking effects where?
cholinergic (muscarinic), alpha adrenergic, serotonin receptors
Clinical Indications for antihistamines
Acute and Chronic Allergic Rhinitis
Vasomotor rhinitis
- antimuscarinic effects help
Eosinophilic nonallergic rhinitis
Viral Upper Respiratory Infection
- antimuscarinic effects help
Urticaria
Allergic conjunctivitis
Anaphylactic reactions
– adjunct to epinephrine
Motion sickness and nausea
Insomnia
Key Drugs - 1st Generation antihistamines
Diphenhydramine (Benadryl)
Chlorpheniramine (Chlor-Trimeton)
other: Promethazine
Key Drugs - 2nd generation antihistamines
Cetirizine (Zyrtec) Fexofenadine (Allegra) Loratadine (generic, Claritin, Alavert) Desloratadine (Clarinex) Azelastine (Astelin) *** Intranasal spray
Key Points - 2nd generation antihistamines
Less complete distribution to CNS
- little drug crosses BBB –therefore, much less sedation compared to 1st generation drugs
Have longer elimination t1/2 than 1st generation
- therefore, longer duration of action
Lower incidence of antimuscarinic side effects, e.g. dry mouth, dysuria, etc.
Clinical Effects of antihistamines
All antihistamines are effective for relieving:
sneezing
nasal itching
nasal discharge (rhinorrhea)
Not very effective for relieving:
congestion
add decongestant
Side Effects of 1st generation antihistamine agents
1st generation agents
- sleepiness
- interfere with learning
- decrease work productivity
- impair psychomotor performance
- increases risk of injury
Patient may be unaware of these effects
Side effects may persist morning after taking drug at bedtime
Sedation - antimuscarinic effect
CNS - dizziness, tinnitus, nervousness, insomnia, fatigue, blurred vision
GI- nausea, vomiting, loss of appetite
Dry mouth – (antimuscarinic effect)
Urinary retention –
(antimuscarinic effect)
Decongestants
a-adrenergic agonists
- Effective only for relief of nasal congestion and not sneezing, itching, or discharge
cause vasoconstriction, reduce edema
available as nasal spray or oral tablets
- Pseudoephedrine
- — prescription, or behind the counter restrictions
- Phenylephrine
Often given in combination with an H1-antihistamine
Adverse effects include insomnia, excitability, headache, nervousness, palpitations, tachycardia, arrhythmia, hypertension, nausea, vomiting, and urinary retention.
Should not be used more than 3 days in order to avoid rebound congestion and rhinitis medicamentosa
Antitussives
Opioids: central suppression of cough reflex
- Codeine
- Dextromethorphan
Non-opioids:
- Benoxinate - local anesthetic
- Diphenhydramine - antihistamine
Expectorants
Facilitate secretion or decrease viscosity of mucus to facilitate clearance of mucus secretions in airways.
- N-acetyl-cysteine breaks sulfhydryl bonds in mucus proteins; makes mucus less sticky
- Guaifenesin: claimed to facilitate removal of viscous mucus.
Potassium iodide: claimed to decrease viscosity of mucus.
Recombinant DNAse (Dornase alpha)
- useful in cystic fibrosis.
Other Therapy for Rhinitis
Ipratropium bromide
- vasomotor rhinitis
Intranasal cromolyn sodium, nedocromil
- (most effective) Intranasal corticosteroids
- beclomethasone dipropionate
- budesonide
- flunisolide
- fluticasone propionate
- triamcinolone acetonide
Ipratropium bromide
** A quaternary muscarinic receptor antagonist
If given parenterally, effects are like atropine
But, only given as *** inhaled aerosol to treat COPD
- few side effects, even when swallowed because is poorly absorbed from GI and does not cross into brain
– quaternary amine- poor diffusion across membranes
Parasympathetic - mediated bronchospasm is a significant component of airway resistance in some asthmatics and COPD patients, especially psychogenic exacerbations
Cromolyn Compounds
Cromolyn sodium nasal spray (Nasalcrom) Cromolyn sodium (Intal)
Cromolyn compounds are anti-inflammatory agents that indirectly inhibit antigen-induced bronchospasm and directly inhibit the release of histamine and other autocoids from sensitized mast cells.
May suppress the activating effects of chemoattractant peptides on eosinophils, neutrophils, and monocytes.
Cromolyn Compounds:Therapeutic Use
Cromolyn compounds do not directly relax smooth muscle, therefore they are not useful for control of acute bronchospasm.
Cromolyn compounds are primarily prophylactic. When inhaled several times daily, they inhibit both the immediate and late asthmatic responses to antigenic challenge or exercise.
Intranasal Corticosteroids
** Most effective drugs available for relief of symptoms of allergic rhinitis
Available in aqueous solution/pump spray formulations
They all reduce sneezing, itching, discharge, and congestion
Most are effective when given once daily
Take at least one week to be maximally effective.
Corticosteroid side effects
– usually mild Dryness & irritation or burning of nasal mucosa Sore throat Epistaxis Headache
Leukotriene Modifier
Montelukast (Singulair)
- Cysteinyl leukotrienes (cousins of prostaglandins) released in nasal mucosa during allergic inflammation.
- Oral montelukast blocks leukotriene receptor
- Modestly beneficial for relief of sneezing, itching, discharge, and congestion
- One study showed montelukast to be as effective as loratadine, but not as effective, alone or in combination with loratadine, as an intranasal corticosteroid
- Safe and with few side effects
Allergic Conjunctivitis
The most common form of ocular allergy
Usually associated with allergic rhinitis
– May be seasonal or perennial
Main symptom is itching
Oral antihistamines (2nd generation) usually effective
Topical antihistamine eye drops
- also effective
- may be more rapid acting
- also antiinflammatory
Allergic Conjunctivitis treatment
Antihistamine/decongestant combinations
- pheniramine/naphazoline (Visine A)
- antazoline/naphazoline (Vasocon-A)
Available * over-the-counter may be more effective than either agent alone but are * short acting and can cause rebound vasodilation with continued use
Topical OcularH1 - Antihistamines
Azelastine (Optivar) Emedastine difumarate (Emadine) Levocabastine HCl (Livostin)
Topical Ocular Mast Cell Stabilizers
Cromolyn sodium (generic, Crolom) Lodoxamide tromethamine (Alomide) Nedocromil sodium (Alocril) Pemirolast potassium (Alamast)
H1 Antihistamine + Mast Cell Stabilizers
Ketotifen fumarate (Zaditor)
Olopatadine HCl (Patanol) - These drugs are primarily antihistamines but are marketed as also having mast cell stabilizing activity. Probably all H1 antihistamines have mast cell stabilizing activity.
