Martin Antihistamines/ Rhinitis lecture

Question 1

Drugs delivered locally as nasal spray

Answer 1

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

Question 2

Antihistamines: what receptor do they work on? Describe pharmacokinetics

Answer 2

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

Question 3

First generation Histamine receptor blockers can also have blocking effects where?

Answer 3

cholinergic (muscarinic), alpha adrenergic, serotonin receptors

Question 4

Clinical Indications for antihistamines

Answer 4

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

Question 5

Key Drugs - 1st Generation antihistamines

Answer 5

Diphenhydramine (Benadryl)
Chlorpheniramine (Chlor-Trimeton)

other: Promethazine

Question 6

Key Drugs - 2nd generation antihistamines

Answer 6

Cetirizine (Zyrtec)
Fexofenadine (Allegra)
Loratadine (generic, Claritin, Alavert)
Desloratadine (Clarinex)
Azelastine (Astelin) *** Intranasal spray

Question 7

Key Points - 2nd generation antihistamines

Answer 7

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 8

Clinical Effects of antihistamines

Answer 8

All antihistamines are effective for relieving:
sneezing
nasal itching
nasal discharge (rhinorrhea)

Not very effective for relieving:
congestion
add decongestant

Question 9

Side Effects of 1st generation antihistamine agents

Answer 9

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)

Question 10

Decongestants

Answer 10

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

Question 11

Antitussives

Answer 11

Opioids: central suppression of cough reflex

• Codeine
• Dextromethorphan

Non-opioids:

• Benoxinate - local anesthetic
• Diphenhydramine - antihistamine

Question 12

Expectorants

Answer 12

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 13

Other Therapy for Rhinitis

Answer 13

Ipratropium bromide
- vasomotor rhinitis

Intranasal cromolyn sodium, nedocromil

• (most effective) Intranasal corticosteroids
• beclomethasone dipropionate
• budesonide
• flunisolide
• fluticasone propionate
• triamcinolone acetonide

Question 14

Ipratropium bromide

Answer 14

** 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 15

Cromolyn Compounds

Answer 15

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.

Question 16

Cromolyn Compounds:Therapeutic Use

Answer 16

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 17

Intranasal Corticosteroids

Answer 17

** 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 18

Corticosteroid side effects

Answer 18

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

Question 19

Leukotriene Modifier

Answer 19

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 20

Allergic Conjunctivitis

Answer 20

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 21

Allergic Conjunctivitis treatment

Answer 21

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 22

Topical OcularH1 - Antihistamines

Answer 22

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

Question 23

Topical Ocular Mast Cell Stabilizers

Answer 23

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

Question 24

H1 Antihistamine + Mast Cell Stabilizers

Answer 24

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 25

Antivirals: Amantadine & Rimantadine

Answer 25

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 26

Oseltamivir

Answer 26

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