Global Journal of Medical Research, A: Neurology & Nervous System, Volume 23 Issue 3

a) Absorption and Distribution Regardless of the quantity of a drug one ingests, the drug remains outside the body until it is absorbed through the intestinal wall. This absorption process can be affected by many factors, including drug solubility, intestinal membrane permeability, digestive enzyme activity, and food intake [85]. Drug absorption can also be affected by a person’s emotional state, as stress tends to reduce intestinal absorption [86]. Furthermore, once in the bloodstream, the drug must cross the blood-brain barrier (BBB) before it can bind to its target receptors in the brain. Passage through the BBB can be affected by several factors, including the chemical properties of the drug, whether or not the drug is bound to plasma proteins, and the electrical charge of the drug [87]. While most small lipophilic drugs may cross the BBB by simple diffusion, others may pass through aqueous channels or require either mediated diffusion or active transport. Additionally, only free (non- protein-bound) molecules are available to cross the BBB via transendothelial diffusion, and fat-soluble drugs may be absorbed into fatty tissue, thus reducing their bioavailability. Together, all of these time-dependent factors contribute to the 20-40-minute delay in the onset of action of most medications. Obviously, the route of administration is also important, as absorption can be facilitated by direct inhalation of a drug, chewing and sublingual holding of a drug, or injection of a drug subcutaneously, intramuscularly, or intravenously. Thus, numerous factors can affect the speed and extent to which a drug actually reaches its target receptors. b) Mechanism of Action Because the number of different pathological processes that can occur in the human body far outnumber the assortment of ways that those processes can be expressed clinically, many different pathological processes can precipitate the same signs and symptoms. This highlights the importance of fit between drug selection and pathological process in determining the dosage requirements of a particular drug. The more that a drug’s pharmacological effects can correct, offset, or compensate for the abnormality that is driving the patient’s symptoms, the more efficiently the drug will work and, thus, the less of the drug that will be needed to express its therapeutic effects. c) Receptor Affinity In order for most drugs to exert their therapeutic effects, the molecules of the drug, like keys fitting into locks, must bind to and activate their target receptors. Although most receptors within a species are very similar in size and shape, there are also minor differences, just as there are in one’s head-size, hand- size, and foot-size. This can affect the ability of specific drugs to bind to and activate their target receptors. The better the fit between the drug and the receptor, the more likely the drug is to exert its therapeutic effects. Also, the greater the drug’s affinity for the receptor, the less of the drug that will be needed to maintain its therapeutic effect. However, a drug can also cause side effects if it binds to off-target receptors. This underscores the importance of finding the sweet spot when dosing psychotropic drugs. d) Metabolism and Excretion Immediately after a drug enters the bloodstream, the processes of distribution, metabolism, and excretion begin. Hence, dosing requirements can depend highly on fat solubility, liver enzyme activity, and glomerular filtration rates. Total blood volume and body weight also contribute to dosing requirements; however, these two factors generally pale in comparison to the many other factors that affect the dosing requirements of a drug. VI. T he N eed for I ndividualized D osing With all of the aforementioned factors influencing the dosage of a drug that is needed to achieve a therapeutic effect and, conversely, unwanted side effects, there is clearly a need for individualized dosing of any drug that is prescribed. Yet most prescribers simply initiate treatment at the “recommended” starting dose or lowest available dosing strength. Clearly, however, this fails to align with the complexity and unpredictability of patient-specific factors. Then again, even if a prescriber were to take into consideration all of the aforementioned factors, there would still be no reliable way to determine how those factors come together to predict the therapeutic dose (and side effect dose) of a given drug for a given individual. In recent years, however, various new pharmacogenomic tests have been developed to help clinicians determine which medications would be best tolerated by which patients. The problem is that these tests, though genetically-based, fail to incorporate the many other factors besides drug metabolism that influence the dosing requirements of a particular drug for a particular patient. Dosing requirements would also depend upon the degree of fit between the drug’s primary mechanism of action and the type of pathology that is being treated. This has been particularly problematic in psychiatry due to the lack of clarity about what pathological process is being treated and the continued reliance on symptoms rather than pathology as a guide to pharmacotherapy. This reiterates the importance of replacing the current (symptom-based) approach to psychiatric diagnosis and treatment with a pathology-based approach. 29 Year 2023 Global Journal of Medical Research Volume XXIII Issue III Version I ( D ) A © 2023 Global Journals A Precision Medicine Approach to the Treatment of Psychiatric Disorders