1. ANTI-ALLERGY Medication
About 1 in 10 suffer from some type of allergy:
pollen, poison ivy, food, cosmetics, drugs (penicillin), chemicals
About 1 in 15 suffer asthma:
NA ALLERGY DEATHS: ~ 5000/y ASTHMA
~100/y FOOD
~40-100/y STINGS
~300/y PENICILLIN
Pollen, for example, contains an ANTIGEN (ALLERGEN) which reacts with one of the antibody proteins in the blood
eg. IgE (Immunoglubulin E)

3. Antigen-Antibody complex causes release of stored HISTAMINE from mast cells, which then goes to H-1 sites, and triggers the inflammation cycle that causes hay fever symptoms:
1. Dilates blood capillaries: skin red, warm and itchy
Capillaries leak water and plasma proteins: swelling, inflammation and HIVES
Bronchial muscle spasms and constriction: ASTHMA
Stimulates glands: produces nasal fluids, mucus, tears, saliva
(opposite effect of atropine)
5. Dilated blood vessels: blood pressure drop but normally no effect on heart

4. Strategies: AVOID, DESENSITIZE, or block receptor sites with anti-histamine
HISTAMINE: note the N-C-C-C-N sequence/shape
Older anti-histamines: side effect DROWSINESS
(mild sleeping pills)
Pyribenzamine Phenergan Benadryl Chlortripolon

5. Also used in travel (motion sickness) pills:
eg. Dramamine, Gravol, etc.
all use a salt of benadryl and a chlorinated caffeine derivative
Other ones are Cyclizine, Meclizine (Calmonal, Anti-vert, Sea-Legs)
Dramamine (OTC) Cyclizine Meclizine
(dimenhydrinate) “Marzine, Marezine” “Bonamine”

6. 2nd Generation ALLERGY DRUGS (LESS DROWSY): SELDANE
Seldane does not cross the blood brain barrier: non-sedating
First prescription antihistamine to relieve the symptoms of allergic rhinitis (1985) without causing drowsiness
After Seldane was approved, FDA began receiving reports of fatal and serious instances of cardiac arrhythmias:
Drug interactions between Seldane and erythromycin or ketoconozole – in the presence of these antibiotics, Seldane accumulated in the blood, resulting in serious cardiac side effects
Withdrawn from the market in 1997
Hismanal: similar side effects, more interactions: withdrawn 1999

7. ALLEGRA (fexofenadine)
is a metabolism product of
Seldane without the side effects
REACTINE (cetirizine) is another
popular non-drowsy antihistamine

8. Other anti-histamines:
Desloratadine: Aerius (Can) Clarinex (US)
Loratidine: Claritin
Azatidine: Optimime Trinalin
Cyproheptidine: veterinary use

9. OTHER APPROACHES CROMOLYN (Nalcrom, Allergochrom, Nasalcrom, Opticrom)
Powder sprayed into nose: prevents release of stored histamine from mast cells
not a cure, management at bad times of year
also available orally as Nalcrom for food allergies: 200 mg x 4 / day, 20 min before meals

10. LEUCOTRIENE RECEPTOR ANTAGONISTS
Leucotrienes are produced in a similar manner to the prostaglandins, and they promote powerful wind-pipe contractions and inflammation
Accolate (zafirlukast) Astra-Zeneca
blocks the leucotriene D4 and E4 receptors [LTD4 and E4]
(2 x 20mg/day)

11. Salbutamol (Ventolin) ~3h Salmeterol (Serevent) ~12h
THE BRONCHODILATOR DRUGS FOR ASTHMA
(doses usually ~ mg/spray)
Salbutamol (Ventolin) ~3h
Salmeterol (Serevent) ~12h

12. b-agonists: activate adenylcyclase enzyme = increases c-AMP (cyclic adenosine monophosphate)
c-AMP activates phosphorylation of HO-containing amino acids (tyrosine, serine and threonine) which causes the enzyme to change shape = release of Ca2+ ions from their storage sites = relaxation of muscles
Lungs have PDE-4's that destroy c-AMP so one strategy is to look for PDE-4 inhibitors that maintain higher levels of c-AMP
(compare with effects of Viagra on PDE-5 to keep c-GMP elevated)
Egs. of long acting b-agonists include Salmeterol and Foradil (formoterol, shown below)

13. Note: inhaled corticosteroids in low doses are considered
a better long term strategy than using beta-agonists
Eg. Flovent (Advair, Flonase, Flunase....)
= fluticasone propionate: