Drugs for Treatment of Ear, Eye, Nose, and Throat Problems

Question 1

Allergic Rhinitis Drugs delivered locally as nasal spray

Answer 1

Drugs delivered locally as nasal spray

• Antihistamines
• Antimuscarinics
• Cromolyn compounds
• Topical corticosteroids
• Nasal decongestants
• Sympathomimetic Agents
• alpha-adrenergic agonists

Question 2

Antihistamine Action

Answer 2

Question 3

Antihistamines:
H1 Receptor Antagonists

Answer 3

Several structural classes

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

Question 4

Histamine H1 antagonists

Answer 4

Question 5

Histamine H1 - Receptor Blockers

Answer 5

Question 6

Clinical Indications 1

Answer 6

• Acute and Chronic Allergic Rhinitis
• Vasomotor rhinitis
  
  • antimuscarinic effects help
• Eosinophilic nonallergic rhinitis
• Viral Upper Respiratory Infection
  
  • antimuscarinic effects help

Question 7

Clinical Indications 2

Answer 7

• Urticaria
• Allergic conjunctivitis
• Anaphylactic reactions
  
  • adjunct to epinephrine
• Motion sickness and nausea
• Insomnia

Question 8

Key Drugs - 1st Generation

Answer 8

• Diphenhydramine (Benadryl)
• Chlorpheniramine (Chlor-Trimeton)
• Others
  
  • Dimenhydrinate (Dramamine)
  • Cyclizine (Marezine)
  • Hydroxyzine (Atarax)
  • Meclizine (Bonine)
  • Promethazine (Phenergan)

Question 9

Key Drugs - 2nd generation

Answer 9

• Cetirizine (Zyrtec)
  
  • $63.29 (2003 price for 30 day supply)
• Fexofenadine (Allegra)
  
  • $84.62
• Loratadine (generic, Claritin, Alavert)
  
  • $21.30, $27.30, $16.50
• Desloratadine (Clarinex)
  
  • $69.74
• Azelastine (Astelin) Intranasal spray
  
  • $71.48

Question 10

Key Points - 2nd generation

Answer 10

• 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.

Question 11

Clinical Effects

Answer 11

• All antihistamines are effective for relieving:
  
  • sneezing
  • nasal itching
  • nasal discharge (rhinorrhea)
• Not very effective for relieving:
  
  • congestion
  • add decongestant

Question 12

Side Effects 1

Answer 12

• 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

Question 13

Side Effects 2

Answer 13

• Sedation - antimuscarinic effect
  
  • 1st generation only
• CNS
  
  • dizziness, tinnitus, nervousness, insomnia, fatigue, blurred vision
  • 1st generation only
• GI
  
  • nausea, vomiting, loss of appetite
• Dry mouth – (antimuscarinic effect)
  
  • 1st generation only
• Urinary retention –
  
  • (antimuscarinic effect) 1st generation only

Question 14

Decongestants

Answer 14

• alpha-adrenergic agonists
• cause vasoconstriction, reduce edema
• available as nasal spray or oral tablets
  
  • Pseudoephedrine
    
    • prescription, or behind the counter restrictions
  • Phenylephrine
  • Naphazoline
  • Oxymetazoline
  • Tetrahydrozoline
  • Xylometazoline

Question 15

Decongestants

alpha-adrenergic agonists

Answer 15

• alpha-adrenergic agonists
  
  • Effective only for relief of nasal congestion and not sneezing, itching, or discharge
  • 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

Question 16

Antitussives

Answer 16

• Opioids: central suppression of cough reflex
  
  • Codeine
  • Dextromethorphan
• Non-opioids:
  
  • Benoxinate - local anesthetic
  • Diphenhydramine - antihistamine

Question 17

Expectorants

Answer 17

• 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.

Question 18

Other Therapy for Rhinitis

Answer 18

• Ipratropium bromide
  
  • vasomotor rhinitis
• Intranasal cromolyn sodium, nedocromil
• Intranasal corticosteroids
  
  • beclomethasone dipropionate
  • budesonide
  • flunisolide
  • fluticasone propionate
  • triamcinolone acetonide

Question 19

Antimuscarinics:
Ipratropium bromide

Answer 19

• 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

Question 20

Ipratropium bromide

Therapeutic Use:

Answer 20

• Therapeutic Use:
  
  • Bronchodilation develops more slowly and is usually less intense than that produced by b-agonists.
  • Useful bronchodilation lasts up to 6 hours.
  • Principal use of ipratropium is in COPD.
  • Combined with albuterol = COMBIVENT
  • Also used intranasally (Roxane) to reduce secretions in the upper and lower respiratory tract in allergic rhinitis and chronic postnasal drip syndrome.

Question 21

Cromolyn Compounds

Answer 21

• Cromolyn sodium nasal spray (Nasalcrom)
• Cromolyn sodium (Intal)

Question 22

Antihistamines Partially Block

Answer 22

Question 23

Cromolyn Compounds

MOA

Answer 23

• 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.

Question 24

Cromolyn Compounds:
Therapeutic Use

Answer 24

• 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.

Question 25

Cromolyn Compounds: Therapeutic Use Continued

Answer 25

* Nedocromil is a newer compound, somewhat more potent than cromolyn sodium. * Nedocromil is approved for use is asthmatic patients \> 12 years old; cromolyn is approved for all ages. * Adverse effects: are infrequent and generally mild. * Used mostly in mild to moderate asthma as an added therapy or as a prophylactic alternative to inhaled steroids or oral methylxanthines.

Question 26

Intranasal corticosteroids

Answer 26

* Intranasal corticosteroids * beclomethasone dipropionate (Beconase AQ) * budesonide (Rhinocort Aqua) * flunisolide (generic, Nasarel) * fluticasone propionate (Flonase) * mometasone furoate (Nasonex) * triamcinolone acetonide (Nasacort AQ)

Question 27

Molecular Mechanism of Action

Answer 27

Question 28

Summary of immunosuppression Actions of Glucocorticoids

Answer 28

Question 29

Intranasal Corticosteroids

Answer 29

* **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.

Question 30

Intranasal Corticosteroids Side Effects

Answer 30

* Side Effects – usually mild * Dryness & irritation or burning of nasal mucosa * Sore throat * Epistaxis * Headache

Question 31

Leukotriene Modifier

Answer 31

* **_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

Question 32

Allergic Conjunctivitis Overview

Answer 32

* 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

Question 33

Allergic Conjunctivitis

Answer 33

* **_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

Question 34

Topical Ocular H1 - Antihistamines

Answer 34

* Azelastine (Optivar) * Emedastine difumarate (Emadine) * Levocabastine HCl (Livostin)

Question 35

Topical Ocular Mast Cell Stabilizers

Answer 35

* Cromolyn sodium (generic, Crolom) * Lodoxamide tromethamine (Alomide) * Nedocromil sodium (Alocril) * Pemirolast potassium (Alamast)

Question 36

H1 Antihistamine + Mast Cell Stabilizers

Answer 36

* 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.

Question 37

Antivirals

Answer 37

Question 38

Virus Anatomy

Answer 38

Question 39

Viral Infectious Process

Answer 39

Question 40

Viral Infection

Answer 40

Question 41

Antiviral Agents 1

Answer 41

* **_Amantadine_** & Rimantadine * RNA viruses * Inhibit uncoating of viral nucleic acids * Inhibit viral replication * **_Prophylaxis of type A influenza_** * Treatment initiated within 48 hours after initial appearance of symptoms is effective

Question 42

Antiviral Agents 2

Answer 42

* Oseltamivir (**_Tamiflu_**), oral * Inhibits neuraminidase of influenza A or B * Hemagglutinin on viral surface binds to host cell receptors allows virus entry * Neuraminidase on viral surface sugar from receptor. This step required for release of progeny viral particles * Also inhibits viral spread * **_Bird flu = H5N1 strain_** * Zanamivir (**_Relenza_**) * same as above, but inhaler device