3 differences between inrrinsic and extrinsic causes of diseases
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Answer:
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Explanation:
While intrinsic factors act from within an individual, extrinsic factors wield their influence from the outside (i.e., they are environmental, cultural, or related to lifestyle). Extrinsic factors can have a sizeable impact on a person's health and can affect medical decision-making.
Answer:
Intrinsic factors include the genetic, physiological, and pathological characteristics of an individual; in other words, these are traits that are “intrinsic” to a person rather than being determined by that person’s environment. Intrinsic factors are central to the growing fields of pharmacogenetics, pharmacogenomics, and personalized medicine.
Genetic intrinsic factors are hard coded into a person’s DNA and include biological sex, race, and ethnicity. Genetic polymorphisms (i.e., differences in DNA sequences between individuals) are also included in this group and can be a critical consideration for certain diseases and drug types. In addition, there can be genetic differences in the diseases themselves (e.g)tumors, infections) that may require distinct treatments.
In contrast to genetic intrinsic factors, physiological and pathological intrinsic factors are not dictated by DNA but are still individual-level characteristics leading to differences in drug response that are not environmentally driven. These factors include a person’s age, organ function (e.g., liver, kidney, cardiovascular), and co-morbid diseases.
Finally, intrinsic factors also include characteristics that can be influenced by both genetics and a person’s physiology/pathology, such as height, body weight, and receptor sensitivity.
Extrinsic Factors
While intrinsic factors act from within an individual, extrinsic factors wield their influence from the outside (i.e., they are environmental, cultural, or related to lifestyle). Extrinsic factors can have a sizeable impact on a person’s health and can affect medical decision-making. Extrinsic factors as a category can be rather broad, although drug developers tend to be most concerned with a subset that includes diet, concomitant medication use, and smoking habits.
The interaction between food and drugs is a key concern for some types of medications, as some foods can alter the pharmacokinetics (PK) of certain drugs in a way that can affect patient safety and/or drug effectiveness. Grapefruit juice is awell-known example of a food that can affect drug PK.
In addition, because patients often suffer from more than one disease, they may be taking concomitant medications to treat multiple diseases. This is important because of potential drug-drug interactions, including impacts on drug exposure, safety, and effectiveness. This not only applies to prescription drugs, but also if a patient is taking an over-the-counter (OTC) drug (e.g., taking an antihistamine for a cold could inhibit drug metabolism).
Smoking can sometimes affect the PK and/or pharmacodynamics (PD) of drugs. For example, some compounds in tobacco smoke are potent inducers of drug metabolizing enzymes and can therefore increase the metabolism of certain drugs (including caffeine). Smoking can also affect how well drugs work and can increase safety risks.
Predicting a Drug’s Sensitivity to Intrinsic and Extrinsic Factors
Intrinsic and extrinsic factors can have marked effects on safety and/or efficacy for particular drugs and diseases, while others remain largely unaffected. So, is there a way to predict whether your drug is likely to be affected?
The International Council for Harmonisation (ICH) E5 guidelines summarize a number of properties that make a drug more likely to be sensitive to the influence of intrinsic and extrinsic factors. These include drugs that exhibit:
Nonlinear PK
Steep PD curve (efficacy and safety)
Narrow therapeutic range
High metabolism, especially via a single pathway
Metabolism by enzymes with known genetic
polymorphisms
Administration as a prodrug
High inter-subject variation in bioavailability
Low bioavailability
High likelihood for use with multiple concomitant medications
Pharmacokinetic, Pharmacodynamic, and Exposure-Response Considerations
The most palpable information for any drug is how the patient responds to treatment. This includes both the desirable and undesirable effects that a drug may cause. How patients respond to various drug doses is captured in the PK and the exposure-response relationship for a specific drug. Exposure-response examines the relationship between drug dose/concentration and response, which includes safety and efficacy endpoints.
For most drugs, there is marked inter-individual variability in drug exposurefollowing drug administration that can be related to intrinsic and extrinsic factors. This includes not only variability in the maximum concentrations observed (i.e., Cmax), but also the exposure to the drug over time (i.e., the area under the concentration versus time curve or AUC). This means that when the same dosing regimen is given to numerous people within the population, some may have low concentrations and be less likely to respond while others may have high concentrations and may be more likely to have an adverse event.
Explanation:
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