[10.41] Drugs Used for Inflammatory Diseases of the Nose & Paranasal Sinuses V2.pdf

Allergen avoidance/environmental control, Immunotherapy, and Pharmacotherapy

What are the three main categories of treatment for Allergic Rhinitis?

Environmental control

What is an important adjunct that does not significantly control allergic rhinitis if not combined with other modalities?

Desensitization or allergy shots

What are two other names for immunotherapy?

Administration of increasing amounts of specific allergens to which the patient has Type 1 immediate hypersensitivity

What does immunotherapy involve?

Persistence of symptoms despite adequate pharmacotherapy, undesirable side effects from medications, and avoidance is difficult or impossible

What are the three indications for immunotherapy?

Pharmacotherapy

What is the mainstay of treatment for allergic rhinitis?

Antihistamines

What is the primary medication used in pharmacotherapy for allergic rhinitis?

Pharmacologic blockers (controllers)

Which category of medications reduces the allergic response?

Antihistamines, Steroids, Leukotriene receptor antagonists, and Mast cell stabilizers

What are the four examples of pharmacologic blockers or controllers?

Symptomatic (relievers)

Which category of medications reduces allergic symptoms?

Decongestants and Anticholinergic sprays

What are the two examples of symptomatic relievers?

Antihistamines

What is considered the most important medication for allergic rhinitis?

H1 antihistamine or H1 receptor antagonist

What is the standard nomenclature for antihistamines?

Inverse agonist

What is the reclassification of antihistamines that has no clinical significance?

Interference with H1 receptor activation

Through what mechanism do antihistamines provide anti-allergic and anti-inflammatory effects?

Functional classification

While they can be classified by chemical properties, what is a more useful way to classify antihistamines?

Alkylamines

Brompheniramine, Chlorpheniramine, Dimethindene, Pheniramine, and Triprolidine belong to which chemical class?

Acrivastine

Which 2nd generation antihistamine is chemically an alkylamine?

Piperazines

Buclizine, Cyclizine, Hydroxyzine, Meclizine, and Oxatomide belong to which chemical class?

Cetirizine and Levocetirizine

Which two 2nd generation antihistamines are chemically piperazines?

Piperidines

Azadine, Cyproheptadine, Diphenylpyraline, and Ketotifen belong to which chemical class?

Astemizole, Desloratadine, Ebastine, Fexofenadine, Levocabastine, Loratadine, Mizolastine, Olopatadine, and Terfenadine

Which nine 2nd generation antihistamines are chemically piperidines?

Ethanolamines

Carbinoxamine, Clemastine, Dimenhydrinate, Diphenhydramine, Doxylamine, and Phenyltoloxamine belong to which chemical class?

Ethylenediamines

Antazoline, Pyrilamine, and Tripelannamine belong to which chemical class?

Phenothiazines

Methdilazine and Promethazine belong to which chemical class?

Doxepin

Which chemical class labeled as "others" contains a 1st generation drug?

Azelastine, Emedastine, and Epinastine

Which three 2nd generation antihistamines are categorized as "others" chemically?

Sedating effect

What is the central nervous system effect characteristic of 1st generation antihistamines?

Non-sedating or mildly sedating

What is the central nervous system effect characteristic of 2nd generation antihistamines?

Drying effect

What is the cholinergic effect characteristic of 1st generation antihistamines?

Little drying effect

What is the cholinergic effect characteristic of 2nd generation antihistamines?

Degree of sedating and cholinergic effects

Clinically, how are antihistamines mostly differentiated?

Hydroxyzine

Cetirizine is a metabolite of which older medication?

Cetirizine

Levocetirizine is an enantiomer of which medication?

Loratadine

Desloratadine is a metabolite of which medication?

Terfenadine

Fexofenadine is a metabolite of which medication?

None

Which medication is considered a true 3rd generation antihistamine?

New molecules with action on H3 and H4 receptors

How is a true 3rd generation antihistamine defined?

2nd generation

Which generation of antihistamines has a longer duration of action and less frequent dosing?

2nd generation

Which generation of antihistamines has a faster onset of action?

Liposolubility

What physical property facilitates the generally good absorption of antihistamines?

Fexofenadine and Bilastine

Which two antihistamines are significantly affected by concomitant intake of food?

Active efflux transport mechanisms (P-glycoprotein or PgP) in the gut

What mechanism causes decreased absorption of certain antihistamines with food?

High-fat diet, grapefruit or orange juice, and drugs like cimetidine or verapamil

What three things decrease the absorption of fexofenadine and bilastine?

Empty stomach

When is the best time to take fexofenadine and bilastine?

Cytochrome P450 system in the liver

Where and how are most antihistamines, especially 1st generation, extensively metabolized?

Cetirizine and Levocetirizine

Which two antihistamines are excreted unchanged in the urine?

Fexofenadine

Which antihistamine is excreted unchanged in the bile?

Bilastine

Which antihistamine is excreted unchanged in the feces?

Altered liver function

What can affect the plasma concentration of most antihistamines besides cetirizine, fexofenadine, and bilastine?

Kidneys

Through which organ are most antihistamines eliminated after liver metabolism?

Fexofenadine and Rupatadine

Which two antihistamines are eliminated through the bile?

They are the same

How does the efficacy of different oral antihistamines compare at equivalent doses?

Safety profile, convenience (suitability), and cost

What three factors guide the choice of an antihistamine since efficacy is equal?

Block the neurotransmitter effect of histamine (H1) in the CNS

How do 1st generation antihistamines cause sedation?

Higher lipophilicity, lower molecular weight, and not being affected by P-glycoprotein efflux pump

What three factors allow 1st generation antihistamines high penetration of the blood-brain barrier?

Efflux pump

What type of pump is the Permeability Glycoprotein Pump (PgP)?

Brain capillary endothelial cells and intestinal epithelium

Where is the PgP efflux pump extensively distributed?

Translocate or pump substances out as they traverse the endothelium

What is the function of PgP at the blood-brain barrier?

Prolongation of Q-T interval (cardiotoxicity)

Dose-related blockade of alpha-adrenergic and muscarinic receptors by 1st generation drugs may cause what?

Dry eyes, dry mouth, urinary retention, constipation, erectile dysfunction, dizziness, and weight gain

What are seven adverse effects of 1st generation drugs due to muscarinic and alpha-adrenergic blockade?

Fexofenadine and Bilastine

Which two 2nd generation antihistamines have zero percent occupation of CNS H1 receptors?

30 percent

What is the CNS H1 receptor occupation percentage for cetirizine?

Relative lipophobicity, higher molecular weight, and being affected by P-glycoprotein efflux transport

What three factors cause 2nd generation drugs to penetrate the CNS poorly?

Diphenhydramine 50 mg

In a driving simulation, what dose of which medication impaired performance more than a blood alcohol of 0.1 percent?

Desloratadine

Which 2nd generation antihistamine is approved for use by pilots?

Terfenadine and Astemizole

Which two early 2nd generation antihistamines were withdrawn in 1997 due to cardiac toxicity?

Blockade of cardiac potassium ion currents

By what mechanism did withdrawn antihistamines cause Q-T interval prolongation?

Less drowsiness, less cholinergic effects, no cardiac toxicity, and less potential for abuse

What are the four listed advantages of 2nd generation antihistamines?

Newborns or nursing infants

2nd generation drugs have no reported adverse effects in which population?

Drowsiness, fatigue, somnolence, dizziness, cognitive impairment, memory loss, headache, dystonia, dyskinesia, agitation, confusion, and hallucinations

What are the central nervous system adverse effects of 1st generation antihistamines?

Irritability, drowsiness, or respiratory depression

What can 1st generation drugs cause in nursing infants if taken by the mother before parturition?

Sinus tachycardia, reflex tachycardia, and supraventricular arrhythmias

What are three cardiac adverse effects of 1st generation drugs?

Glaucoma or prostatic hypertrophy

In which two patient conditions are 1st generation antihistamines contraindicated?

Appetite stimulation and weight gain

What specific side effects are associated with cyproheptadine and ketotifen?

Diphenhydramine and Dimenhydrinate

Which two drugs are specifically mentioned as having reports of abuse for euphoria or hallucinations?

Sneezing, rhinorrhea, nasal itching, congestion (poorly), and itching of the throat, palate, and conjunctiva

What seven symptoms do antihistamines relieve?

Faster onset (5 to 10 minutes)

What is the advantage of topical nasal spray antihistamines over oral forms?

Nasal wash-out requiring frequent dosing (2 to 4 times a day)

What is the disadvantage of topical nasal spray antihistamines?

Stinging/burning, bad taste, and epistaxis

What are three local reactions associated with topical antihistamine sprays?

Oral or intranasal spray

What are the two preparations for glucocorticosteroids?

Nasal spray

Which steroid preparation is more frequently used to minimize systemic effects?

Blocks synthesis of mediators like leukotrienes and prostaglandins

What is the primary mechanism of action for glucocorticosteroids?

Annexin I

Corticosteroids induce the production of which Phospholipase A2 inhibitor?

Arachidonic acid

Inhibiting Phospholipase A2 prevents the formation of what?

Leukotrienes and Prostaglandins

Arachidonic acid is the precursor for which two inflammatory mediators?

Growth retardation, HPA-axis suppression, osteoporosis, hypertension, peptic ulcer, obesity, glaucoma, cataracts, diabetes, and mental disturbance

What are the potential systemic adverse reactions of corticosteroids?

Limited bioavailability

Why do topical intranasal steroid sprays have minimal or absent systemic effects?

Intranasal steroid sprays

Which medication provides better control of nasal symptoms than antihistamines or antileukotrienes alone?

Beclomethasone dipropionate, Budesonide, Fluticasone propionate, Fluticasone furoate, Triamcinolone acetonide, Mometasone furoate, and Ciclesonide

What are the seven examples of intranasal steroids listed?

Mometasone furoate and Fluticasone furoate

Which two intranasal steroids have the lowest bioavailability at 0.1 percent?

Dexamethasone

Which intranasal corticosteroid has the highest bioavailability at approximately 80 percent?

Continuous use for up to 1 year

Studies on MF and FF have shown no systemic side effects or growth retardation even after how long?

Asthma

For what condition were antileukotrienes originally developed?

Montelukast

What is the only antileukotriene approved for use in allergic rhinitis?

Selective antagonist of Type 1 cysteinyl leukotriene receptor

What is the mechanism of action for Montelukast?

Recruits T-cells/eosinophils, increases cytokines, activates APCs, increases mucus release, and increases vascular permeability

What are five effects of leukotrienes that are blocked by antagonists?

Blocks action on target cells

Antileukotrienes do not act on the arachidonic pathway directly; what do they do instead?

Adults: 10 mg OD; Children: 2.5 to 5 mg OD

What are the dosages for Montelukast in adults and children?

GI disturbance (stomach pain, diarrhea)

What is the most common adverse reaction to antileukotrienes?