V. Leukotriene inhibitorsA. Leukotrienes • Leukotrienes (LT) are a family of eicosanoid, formed when arachidonic acid (released by phospholipids in cell membranes) is reacted upon by the lipooxygenase (LOX) enzymes.
LT’s are synthesized by a number of different cells (i.e. mast cells, macrophages) in the airways.
Three LT’s in particular, LTC4, LTD4, and LTE4 are responsible for many of the effects which occur during an attack, especially bronchoconstriction.
There are 2 categories of LT inhibitors: receptor antagonists and LT synthesis inhibitors.
Both categories are effective in blocking antigen induced (grass, cat dander, ragweed, and mixed antigens),
Neither category is as effective as inhaled corticosteroids in regard to alleviating symptoms, airway inflammation and bronchial reactivity.
However, they are equal to inhaled corticosteroids in reducing the frequency of asthma exacerbation.
An advantage the LT inhibitors have over the inhalation corticosteroids is that they are administered orally.
This is useful in patients who have poor compliance with the correct use of a MDI (children, the elderly).
B. Receptor antagonists1. montelukast (Singulair) • This works by blocking the binding of LT’s.
It’s safety and effectiveness has been demonstrated in children as young as 6 months of age. It is generally administered in the evening (PO 10 mg, children PO 4 mg).
The same adverse effects, as well as otitis, sinusitis, nausea and diarrhea are seen in children.
2. zafirlukast (Accolate) • This is similar to Singulair in that it is a receptor antagonist of leukotriene.
Specifically, it is a selective and competitive receptor antagonist of leukotriene D4 and E4 (LTD4 and LTE4), components of slow-reacting substance of anaphlaxis(SRSA).
It is administered either 1 hour before or 2 hours after meals (adults PO 20 mg, bid; children PO 10 mg bid).
C. Leukotriene synthesis inhibitor1. zileuton (Zyflo) • This drug has a different mechanism of action, it inhibits formation of leukotrienes by inhibiting the enzyme 5-lipoxygenase (5-LO).
The dosage is 400-800 mg, 2-4 times a day. It is approved for the prevention and chronic treatment of asthma in patients aged 12 years and older.
In a clinical study, patients receiving Zyflo were able to reduce their use of inhaled beta-adrenergic drugs.
Headache is the most frequently reported adverse effect. There are also a few reports of liver toxicity (elevated liver enzymes) with this drug.
VI. DecongestantsA. Decongestant actions • Decongestants act as vasoconstrictors to reduce blood flow to mucous membranes in the nose, sinuses and pharynx.
They produce vasoconstriction by stimulating alpha receptors in the smooth muscle around blood vessels
B. Oral decongestants • The most common oral decongestants are:
1. pseudoephedrine (Chlor-Trimeton, Dimetapp, Drixoral, Sudafed, Suphedrin, Triaminic, many generics).
Also found in many combination products (Actifed Cold and Sinus) which contain antihistamine/pain reliever (aspirin, acetaminophen, or ibuprofen).
The dosage is 60 mg every 4-6 hours, or 120 mg extended release every 12 hours, or 240 mg extended release, once a day.
As pseudoephedrine has been used in the illicit manufacture of methamphetamine, Federal regulations require that all OTC medications that contain pseudoephedrine be kept behind the counter in the pharmacy.
In addition, people buying these products must provide a photo ID and sign a logbook.
2. phenylephrine • Some drug companies are concerned that the Federal regulations regarding pseudoephedrine may keep people from buying their products, so they have reformulated their products by removing the pseudoephedrine and substituting phenylephrine for it.
Note the long list of medications that contain phenylephrine: • Sudafed PE, PediaCare Children’s decongestant, Actifed Cold and Allergy, Benadryl Allergy & Cold, Benadryl Allergy & Sinus, Children’s Sudafed Cough & Cold, Children’s Tylenol Plus Cold, Children’s Tylenol Plus Cold & Allergy, Excedrin Sinus Headache, Sudafed PE Nightime Nasal decongestant, Sudafed PE Sinus & Allergy, Sudafed PE Cold & Cough, Sudafed PE Multisymptom, Theraflu Cold & Cough, Theraflu Cold & Sore Throat, Theraflu Daytime Severe Cold,
Theraflu Daytime Flu & Sore Throat, Theraflu Nighttime Severe Cold, Triaminic Cold & Allergy, Triaminic Daytime Cold & Cough, Triaminic Nighttime Cold & Cough, Tylenol Allergy MultiSymptom, Tylenol Cold Head Congestion, Tylenol Cold MultiSymptom, Tylenol Cold MultiSymptom Daytime, Tylenol Cold MultiSymptom Nighttime, Tylenol Sinus Congestion & Pain Daytime, Tylenol Sinus Congestion & Pain Nighttime, Tylenol Sinus Congestion Severe, Vicks Day Quil Sinus, Vicks Day Quil Cold/Flu, Vicks Formula 44D Cough & Head Congestion Relief.
Congressman Henry Waxman, among others, have expressed concerns that these newly formulated drugs are not working well enough for their intended purpose.
In a peer-reviewed letter to the editor published in late 2006 in the Journal of Allergy and Clinical Immunology, two University of Florida researchers concluded that there is "virtually no evidence to show that phenylephrine oral nasal decongestants at the FDA-sanctioned dose of 10mg are effective”.
To address the issue, Waxman has twice called upon the US Food and Drug Administration (FDA) to launch an investigation into the use of phenylephrine in these drugs, based on a study by Schering-Plough.
According to Schering-Plough, phenylephrine was "not significantly different from placebo in decreasing nasal congestion" while pseudoephedrine was "significantly more effective," in a clinical trial involving 38 people.
Both phenylephrine and pseudoephedrine oral have a prolonged duration of action compared to topical decongestants, but they also have more adverse effects.
C. Topical decongestants • 1. Oxymetazoline (Afrin, Dristan 12 hours nasal, NeoSynephrine 12 hour, various generics). The recommended dosage for this 0.05% solution is 2-3 sprays per nostril, two times a day.
This is available in 0.25, 0.5 and 1.0% solutions. The recommended dosage is 2-3 sprays per nostril, two times a day. This nasal spray form of phenylephrine is more effective than the pill form
3. xylometazoline (Otrivin) • This is available in 0.05 and 0.1% solutions. The recommended dosage is 2-3 sprays per nostril, every 8-10 hours.
These topical decongestants are recommended for the acute treatment of congestion related to the common cold.
They should not be used for longer than 3 days, as they tend to cause rebound congestion.
VII. ExpectorantsA. Expectorant actions • Expectorants reduce the viscosity or thickness of sputum so that patients can more easily cough it up