Current trends in asthma therapy, Part 3

Drug Store News, June 22, 1998 by Kendall. R.Ph. Shaw

                      Adrenomemetic amines

Medication     Brand name          Administration

Epinephrine    --                  subcutaneous

               Primatine           inhalation

Isoproterenol  Isuprel             inhalation

Metaproterenol Alupent             oral or inhalation

Terbutaline    Brethine, Brethaire oral, inhalation, SC

Albuterol      Proventil, Ventolin oral or inhalation

Bitolterol     Tomalate            inhalation

Pirbuterol     Maxair              inhalation

Salmeterol     Serevent            inhalation

Medication     Class

Epinephrine    A-agonist

               B-agonist

Isoproterenol  B-agonist

Metaproterenol B-agonist

Terbutaline    [B.sub.2]-agonist

Albuterol      [B.sub.2]-agonist

Bitolterol     [B.sub.2]-agonist

Pirbuterol     [B.sub.2]-agonist

Salmeterol     [B.sub.2]-agonist





                         Corticosteroids

Medication                      Brand name      Administration

Prednisone                       Deltasone           oral

Prednisolone                      Prelone            oral

                                  Medrol             oral

Methylprednisolone              Solu-Medrol           IV

                                Depo-Medrol           IM

Hydrocortisone                 Hydrocortone        oral, IV

Beclomethasone diproplonate Beclovent, Vanceril      MDI

Triamcinolone acetonide          Azmacort            MDI

Flunisolide                       AeroBid            MDI

Fluticasone                       Flovent            MDI

Care should be taken to ensure that multiple inhalers are utilized in the proper order and that an adequate amount of time is allowed after a B2-agonist and before another product is administered. This will help to maximize penetration and the benefit of the second agent. The same strategy is frequently used with multiple medications delivered via nebulizer, though multiple medications can he delivered simultaneously via nebulizer as an alternative.

Recognizing the environmental problems caused by chlorofluorocarbon propellants used in most MDIs, the Food and Drug Administration has mandated a gradual phase-out of their use to coincide with the development and market approval of CFC MDIs in compliance with the international ban on CFCs. In recent years, therapeutic problems deriving from the old standby MDIs have surfaced to prompt a second look at their design, so the demand for change from CFCs has spurred an evolutionary leap in metered-dose technology. Inhalers suffer from loss of prime; that is, the first actuation after an inhaler has been standing may deliver significantly less than a proper dose, depending on the product itself, the orientation of the canisters while stored and the duration of storage between actuations. They also can deliver inaccurate doses when the active ingredient settles out of solution or suspension and when the canister empties. Of course, the tendency of inhalers to deliver large portions of their doses to the nasophary nx rather than the lungs when used by the average patient without a spacer device of some kind is well documented. Now the CFCs have come under scrutiny concerning their effects on essential rubber components of the actuator valves in inhalers, as they tend to extract polycylic aromatic hydrocarbons, an air pollutant that shares with ozone a large measure of responsibility for exacerbations in asthmatics. It can hardly be efficacious to provide a damaging pollutant along with a dose of medication.

The metered-dose inhalers, seemingly so simple, are very complex, multi-faceted products. The canister contains not only the active ingredient suspended or dissolved in solution, but a surfactant that acts both to maintain the integrity of the suspension and to lubricate the actuator valve, and the propellant. The new hydrofluoroalkane propellants chosen to replace the CFCs have required development of new surfactants, for those used with CFCs are not sufficiently soluble in HFA. The metering valve of actuators, so essential in delivery of consistent and accurate doses, is comprised of seven or eight metal or plastic components manufactured to rigorous tolerances. HFA adversely affects the plastic parts used in these valve mechanisms, so new elastomers had to be developed for their manufacture. New surfactants tended to deliver unsatisfactorily coarse sprays, so the valve mechanisms themselves have had to be redeveloped to counter that problem.

The first entry to the "green" market is Schering's Proventil HFA. Its new propellant (hydrofluoroalkane) keeps the product fully aerosolizable in cold conditions and in any storage position to avoid underdosing and repriming and its MDI mechanism has been redesigned to spray with less force than other albuterol inhalers and to deliver a significantly more accurate and consistent dose. Other albuterol sprays on the market tend to deposit a large portion of each dose forcefully on the back of the pharynx, contributing to the waste and ineffectiveness of these products in the hands of a great many users. The reduced force of the new MDI promises to enhance the effective utilization of each dose by reducing this waste and increasing the amount actually inhaled without the aid of a spacer device.