Tachyphylaxis
Tachyphylaxis is a medical term describing an acute (sudden) decrease in the response to a drug after its administration.[1] Tachyphylaxis can occur both after an initial dose of medication or after an inoculation with a series of small doses. Increasing the dose of the drug may be able to restore the original response.[2] This can sometimes be caused by depletion or marked reduction of the amount of neurotransmitter responsible for creating the drug's effect, or by the depletion of receptors available for the drug or neurotransmitter to bind to. This depletion is caused by the cell's reducing the number of receptors in response to their saturation. Examples: Amphetamine, ephedrine, MDMA (indirectly acting drugs)
Contents |
[edit] Characteristics
Tachyphylaxis is characterized by the rate sensitivity: The response of the system depends on the rate with which a stimulus is presented. To be specific, a high-intensity prolonged stimulus or often-repeated stimulus may bring about a diminished response also known as desensitization.
[edit] Molecular interaction
In biological sciences, molecular interactions are the physical bases of the operation of the system. The control of the operation, in general, involves interaction of a stimulus molecule with a receptor/enzyme subsystem by, typically, binding to the macromolecule A and causing an activation or an inhibition of the subsystem by forming an activated form of the macromolecule B. The following schematic represents the activity:
p
A --------> B
Where p is the activation rate coefficient. It is customary that p is called a rate constant, but, since the p stands for measure of the intensity of the stimulus causing the activation, p may be variable (non-constant).
The above scheme is only the necessary condition for the rate sensitivity phenomenon, and other pathways of deactivation of B may be considered, with the subsequent return to the inactive form of the receptor/enzyme A. Examples[3][4][5] offer particular use of such (mathematical) models in endocrinology, physiology and pharmacology.
[edit] Examples
[edit] Calcitonin
Calcitonin demonstrates tachyphylaxis in 2–3 days when being used to treat hypercalcemia of malignancy. This reaction is anticipated and calcitonin is given along with biphosphonates, which have their maximum effect in 2–3 days.
[edit] Hormone replacement
Hormone replacement when used in menopausal women in the form of estrogen and progesterone implants is cited as having potential to lead to tachyphylaxis, but that citation is based on a single study done in 1990[6] and no followup research is available to support this interpretation.
[edit] Psychedelics
Psychedelics such as LSD-25 and psilocybin-containing mushrooms demonstrate very rapid tachyphylaxis. In other words, one may be unable to 'trip' two days in a row. Some people are able to 'trip' by taking up to three times the dosage, yet some users may not be able to negate tachyphylaxis at all until a period of days has gone by.[7]
[edit] Centrally-acting analgesics
In a patient fully withdrawn from centrally-acting analgesics, viz. opioids, going back to an intermittent schedule or maintenance dosing protocol, a fraction of the old tolerance level will rapidly develop, usually starting two days after opioid therapy is resumed and, in general, leveling off after day 7. Whether this is caused directly by opioid receptors modified in the past or effecting a change in some metabolic set-point is unclear. Increasing the dose will usually restore efficacy; relatively rapid opioid rotation may also be of use if the increase in tolerance continues.
[edit] Beta-2 adrenergic receptor gene
Gene encoding the beta-2 adrenergic receptor (ADRB2) is situated on chromosome 5q31.[8] Individuals who are homozygous for the Gly16 form of the beta-2 adrenergic receptor gene have attenuated responses and more rapid tachyphylaxis to adrenergic bronchodilator medications than do those with the wild type, homozygous Arg16 form of the gene.[9][10]
[edit] Nicotine
Nicotine may also show tachyphylaxis over the course of a day, although the mechanism of this action is unclear.[11]
[edit] Other examples
- Nitroglycerine demonstrates tachyphylaxis, requiring drug-free intervals when administered transdermally
- Repeated doses of ephedrine may display tachyphylaxis, since it is an indirectly acting sympathomimetic amine, which will deplete noradrenaline from the nerve terminal. Thus, repeated doses result in less noradrenaline released than the initial dose.
- Hydralazine displays tachyphylaxis if given as a monotherapy for antihypertensive treatment. It is administered with a beta-blocker with or without a diuretic.
- Metoclopramide is another example.
- Dobutamine, a direct-acting beta agonist used in congestive heart failure, also demonstrates tachyphylaxis.
- Desmopressin used in the treatment of type 1 von Willebrand disease is, in general, given every 12–24 hours in limited numbers due to its tachyphylactic properties.
[edit] Intervention and reversal
[edit] Intranasal decongestants
Chronic use of intranasal decongestants (such as oxymetazoline), leads to tachyphylaxis of response and rebound congestion, caused by alpha-adrenoceptor mediated down-regulation and desensitization of response. Oxymetazoline-induced tachyphylaxis and rebound congestion are reversed by intranasal fluticasone.[12]
[edit] See also
[edit] References
- ^ Bunnel, Craig A. Intensive Review of Internal Medicine, Harvard Medical School 2009.
- ^ Lehne, R. 2007, PHARMACOLOGY FOR NURSING CARE, Saunders/Elsevier, St. Louis, p.79
- ^ Ekblad EBM, Ličko V (1984). "A model eliciting transient response". American Journal of Physiology 246: R114–21.
- ^ Ličko V, Raff H (1985). "Rate Sensitivity of Blood Pressure to Hypoxia". Journal of Theoretical Biology 112 (4): 839–45. doi:10.1016/S0022-5193(85)80065-5. PMID 3999765.
- ^ Ličko V (1985). "Drugs, Receptors and Tolerance". Pharmacokinetics and Pharmacodynamics of Psychoactive Drugs. pp. 311–322. ISBN 0-931890-20-9.
- ^ "nal.usda.gov". http://grande.nal.usda.gov/ibids/index.php?mode2=detail&origin=ibids_references&therow=240075.
- ^ Isabel H, Miner EJ, Logan, CR. Cross tolerance between d-2-brom-lysergic acid diethylamide (BOL-148) and the d-diethylamide of lysergic acid (LSD-25). Psychopharmacologia 1959;1:109-16.
- ^ Kobilka BK, Dixon RA, Frielle T, Dohlman HG, Bolanowski MA, Sigal IS et al. (1987). "cDNA for the human beta 2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor". Proc Natl Acad Sci U S A 84 (1): 46–50. doi:10.1073/pnas.84.1.46. PMC 304138. PMID 3025863. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=304138.
- ^ Israel E, Drazen JM, Liggett SB, Boushey HA, Cherniack RM, Chinchilli VM et al. (2000). "The effect of polymorphisms of the beta(2)-adrenergic receptor on the response to regular use of albuterol in asthma". Am J Respir Crit Care Med 162 (1): 75–80. PMID 10903223.
- ^ Tan S, Hall IP, Dewar J, Dow E, Lipworth B (1997). "Association between beta 2-adrenoceptor polymorphism and susceptibility to bronchodilator desensitisation in moderately severe stable asthmatics". Lancet 350 (9083): 995–9. doi:10.1016/S0140-6736(97)03211-X. PMID 9329515. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9329515.
- ^ Zuo Y, Lu H, Vaupel DB, Zhang Y, Chefer SI, Rea WR et al. (2011). "Acute Nicotine-Induced Tachyphylaxis Is Differentially Manifest in the Limbic System". Neuropsychopharmacology 36 (12): 2498–512. doi:10.1038/npp.2011.139. PMC 3194077. PMID 21796109. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21796109.
- ^ Vaidyanathan S, Williamson P, Clearie K, Khan F, Lipworth B (2010). "Fluticasone reverses oxymetazoline-induced tachyphylaxis of response and rebound congestion". Am J Respir Crit Care Med 182 (1): 19–24. doi:10.1164/rccm.200911-1701OC. PMID 20203244. http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20203244.
[edit] External links
|
|||||||||||||||||
