Viva C(iv)a

This viva is relevant to the objectives of Section C(iv)  of the 2017 CICM Primary Syllabus, which asks the exam candidate to "to explain receptor activity".

What is receptor regulation?
  • Receptor regulation  is the homeostatic increase or decrease in receptor activity or number, in response to activation or blockade.
How are drug receptors regulated?
  • Regulation can occur by modifying drug receptor numbers, or their function, or both.
  • Drugs (or endogenous ligands) binding to receptors produce a downstream effect
  • In most circumstances, this downstream effect triggers regulatory mechanisms
  • Regulatory mechanisms are designed to homeostatically respond to receptor activation, i.e. to dampen the response where it is exaggerated, or to amplify it where it is deficient.
What cellular mechanisms exist to regulate drug receptors?
  • There are several mechanisms of such regulation:
    • Increase or decrease of the number of receptor molecules expressed on the cell surface (or wherever the drug finds its targets)
    • Increase or decrease of the concentration of downstream secondary messenger molecules (eg. cAMP)
    • Alteration of substrate availability, eg. metaraminol and noradrenaline
Give some examples of drug receptor regulation which can be seen in clinical practice

(Numerous possible responses exist)

  • acetylcholine-associated sodium channels at the neuromuscular junction, upregulated following a stroke or paralysis
  • Opioid receptors, regulated by opioid administration
  • etc...


Webb, Nadia. "Tachyphylaxis." Encyclopedia of Clinical Neuropsychology. Springer New York, 2011. 2463-2463.

Figueras, Albert, et al. "Therapeutic Ineffectiveness." Drug safety 25.7 (2002): 485-487.

Meyboom, Ronald HB, et al. "The value of reporting therapeutic ineffectiveness as an adverse drug reaction." Drug Safety 23.2 (2000): 95-99.

Freeman, Brian, and Jeffrey Berger. Anesthesiology Core ReviewMcGraw-Hill Education, 2014.

Katz, Gregory. "Tachyphylaxis/tolerance to antidepressive medications: a review." The Israel journal of psychiatry and related sciences 48.2 (2011): 129.

De Moraes, S., and Varela De Carvalho. "On the mechanism of action of tachyphylaxis by ephedrine." Pharmacology 1.1 (1968): 53-59.

Cowan, F. F., T. Koppanyi, and G. D. Maengwyn‐Davies. "Tachyphylaxis III. Ephedrine." Journal of pharmaceutical sciences 52.9 (1963): 878-883.

Swanson, James M. "Long-acting stimulants: development and dosing.The Canadian Child and Adolescent Psychiatry Review 14.Suppl 1 (2005): 4.

Agvald, Per, et al. "Nitric oxide generation, tachyphylaxis and cross-tachyphylaxis from nitrovasodilators in vivo." European journal of pharmacology 385.2-3 (1999): 137-145.

Sage, Peter R., et al. "Nitroglycerin tolerance in human vessels: evidence for impaired nitroglycerin bioconversion.Circulation 102.23 (2000): 2810-2815.

Haney, Sarah, and Robert J. Hancox. "Rapid onset of tolerance to beta-agonist bronchodilation." Respiratory medicine 99.5 (2005): 566-571.

Barnes, Peter J. "Beta-adrenergic receptors and their regulation." American journal of respiratory and critical care medicine 152.3 (1995): 838-860.

Zuo, Yantao, et al. "Acute nicotine-induced tachyphylaxis is differentially manifest in the limbic system." Neuropsychopharmacology 36.12 (2011): 2498.

Packer, Milton, et al. "Hemodynamic and clinical tachyphylaxis to prazosin-mediated afterload reduction in severe chronic congestive heart failure." Circulation 59.3 (1979): 531-539.

Littleton, John. "Receptor regulation as a unitary mechanism for drug tolerance and physical dependence‐not quite as simple as it seemed!.Addiction 96.1 (2001): 87-101.

Orberg, PAULO K., and WILLIAM E. Sandine. "Common occurrence of plasmid DNA and vancomycin resistance in Leuconostoc spp." Applied and environmental microbiology48.6 (1984): 1129-1133.

Ehrman, Ronald, et al. "Conditioned tolerance in human opiate addicts." Psychopharmacology 108.1-2 (1992): 218-224.

Scholl, Jamie L., et al. "Individual differences in amphetamine sensitization, behavior and central monoamines.Physiology & behavior 96.3 (2009): 493-504.

Lê, A. D., and Jatinder M. Khanna. "Dispositional mechanisms in drug tolerance and sensitization.Psychoactive Drugs. Humana Press, Totowa, NJ, 1989. 281-351.

Goudie, Andrew J., and Michael W. Emmett-Oglesby. Psychoactive drugs: Tolerance and sensitization. Springer Science & Business Media, 1989.

Pandey, Subhash C. "Neuronal signaling systems and ethanol dependence." Molecular neurobiology 17.1-3 (1998): 1-15.

Huganir, Richard L., and Paul Greengard. "Regulation of receptor function by protein phosphorylation." Trends in Pharmacological Sciences 8.12 (1987): 472-477.

Harrison, Laura M., Abba J. Kastin, and James E. Zadina. "Opiate tolerance and dependence: receptors, G-proteins, and antiopiates." Peptides 19.9 (1998): 1603-1630.

Zaliauskiene, Lolita, et al. "Down-regulation of cell surface receptors is modulated by polar residues within the transmembrane domain." Molecular Biology of the Cell 11.8 (2000): 2643-2655.

Blakely, Randy D., et al. "Regulated phosphorylation and trafficking of antidepressant-sensitive serotonin transporter proteins.Biological psychiatry 44.3 (1998): 169-178.

JA, Jeevendra Martyn. "Basic and clinical pharmacology of the acetylcholine receptor: implications for the use of neuromuscular relaxants." The Keio journal of medicine 44.1 (1995): 1-8.

White, Kellie J., Crystal C. Walline, and Eric L. Barker. "Serotonin transporters: implications for antidepressant drug development." Drug Addiction. Springer, New York, NY, 2008. 193-215.

Zuo, Yantao, et al. "Acute nicotine-induced tachyphylaxis is differentially manifest in the limbic system." Neuropsychopharmacology 36.12 (2011): 2498.

Münzel, T., et al. "Evidence for enhanced vascular superoxide anion production in nitrate tolerance. A novel mechanism underlying tolerance and cross-tolerance." The Journal of clinical investigation 95.1 (1995): 187-194.

Andén, Nils‐Erik. "On the mechanism of noradrenaline depletion by α‐methyl metatyrosine and metaraminol." Acta pharmacologica et toxicologica 21.3 (1964): 260-271.