Some fundamental points concerning the clinical aspects of desensitization.
Continued exposure of target cells to a hormonal agonist frequently leads to a blunted response to that agonist. This process has been termed desensitization, refractoriness, tolerance or tachyphylaxis. The receptor involved in case of beta-sympathomimetics is the beta-adrenergic receptor. When the clinical aspects of beta-adrenergic receptor desensitization are considered, a number of points need serious attention: 1) the route of administration of the drug and the concentration of the drug reached at the receptor site; 2) other factors which may cause reduced responsiveness of the beta-adrenergic receptor besides beta-sympathomimetics and interfere with this process; 3) the different cell-types which are studied and thought to be representative for processes taking place at lung tissue level; 4) the in vivo parameter(s) chosen to describe desensitization; 5) the difference between normal and asthmatic subjects; 6) the mechanism behind desensitization. The paper concerns a review of these points. Since the clinical findings with respect to the induction of desensitization by beta-sympathomimetics are rather controversial, the therapeutic advice should be: use it with caution.
Bruynzeel
P L
PL
Meurs
H
H
Leferink
J G
JG
van den Berg
W
W
D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000336:Aerosols; D001249:Asthma / Q000188:drug therapy; D001980:Bronchi / Q000187:drug effects; D001993:Bronchodilator Agents / Q000494:pharmacology; D004361:Drug Tolerance; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008173:Lung Diseases, Obstructive / Q000188:drug therapy; D008214:Lymphocytes / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013618:Tachyphylaxis
D000318:Adrenergic beta-Agonists; D000336:Aerosols; D001993:Bronchodilator Agents; D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases; D007545:Isoproterenol