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IMF-097-03-0001-en	Beyond a statistical association, what makes a pharmacogenomic result clinically useful?	It must change a decision (whether to prescribe, which drug, starting dose, adjustment speed, or toxicity monitoring) using an accurately measured variant linked to a reproducible phenotype in the relevant context.	Integrated Medical Foundations; chapter 97, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 242ddf8b806467fd074ba75c5c762e152183461d70edcbb27c82c0d0a3aa7e42; editorial review pending	imf lang::en chapter::097 module::097-03 review::pending
IMF-097-03-0002-en	Why can reduced metabolic function raise toxicity with one drug but reduce efficacy with another?	For an active parent drug, reduced metabolism raises exposure; for a prodrug requiring activation, it lowers active-metabolite exposure, so the direction cannot be inferred without knowing the pathway.	Integrated Medical Foundations; chapter 97, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 242ddf8b806467fd074ba75c5c762e152183461d70edcbb27c82c0d0a3aa7e42; editorial review pending	imf lang::en chapter::097 module::097-03 review::pending
IMF-097-03-0003-en	How can a genetically normal metaboliser behave like a poor metaboliser?	Enzyme inhibition by another drug causes phenoconversion, so current phenotype no longer matches genotype.	Integrated Medical Foundations; chapter 97, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 242ddf8b806467fd074ba75c5c762e152183461d70edcbb27c82c0d0a3aa7e42; editorial review pending	imf lang::en chapter::097 module::097-03 review::pending
IMF-097-03-0004-en	How can variation in an antigen-presenting molecule create risk of a specific drug hypersensitivity?	The variant molecule can present a drug-related antigen to T cells, creating a strong risk of that particular reaction.	Integrated Medical Foundations; chapter 97, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 242ddf8b806467fd074ba75c5c762e152183461d70edcbb27c82c0d0a3aa7e42; editorial review pending	imf lang::en chapter::097 module::097-03 review::pending
IMF-097-03-0005-en	In causality assessment, why may rechallenge be unacceptable and dechallenge misleading?	Rechallenge strengthens inference but is unethical after a severe reaction, and improvement after stopping can mislead when disease resolves naturally or several treatments stop together.	Integrated Medical Foundations; chapter 97, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 242ddf8b806467fd074ba75c5c762e152183461d70edcbb27c82c0d0a3aa7e42; editorial review pending	imf lang::en chapter::097 module::097-03 review::pending
IMF-097-03-0006-en	Why can a severe cutaneous or systemic drug reaction progress after the drug is stopped?	Immune activation has become self-sustaining, so removing the drug no longer halts the reaction.	Integrated Medical Foundations; chapter 97, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 242ddf8b806467fd074ba75c5c762e152183461d70edcbb27c82c0d0a3aa7e42; editorial review pending	imf lang::en chapter::097 module::097-03 review::pending
IMF-097-03-0007-en	How does local exposure explain drug toxicity in the liver and kidney?	The liver meets high concentrations during first-pass metabolism, and the kidney concentrates filtrate, exposing tubules to transport-dependent toxicity and crystals; organ toxicity reflects local exposure and vulnerability.	Integrated Medical Foundations; chapter 97, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 242ddf8b806467fd074ba75c5c762e152183461d70edcbb27c82c0d0a3aa7e42; editorial review pending	imf lang::en chapter::097 module::097-03 review::pending
IMF-097-03-0008-en	Why does enzyme inhibition act quickly while induction develops and resolves slowly?	Inhibition usually begins as inhibitor concentration rises, whereas induction requires the amount of enzyme protein to change.	Integrated Medical Foundations; chapter 97, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 242ddf8b806467fd074ba75c5c762e152183461d70edcbb27c82c0d0a3aa7e42; editorial review pending	imf lang::en chapter::097 module::097-03 review::pending
IMF-097-03-0009-en	How can several sedatives dangerously depress breathing without any pharmacokinetic interaction?	Their effects combine at a shared physiological outcome, so they jointly depress consciousness and ventilation without changing one another's concentrations.	Integrated Medical Foundations; chapter 97, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 242ddf8b806467fd074ba75c5c762e152183461d70edcbb27c82c0d0a3aa7e42; editorial review pending	imf lang::en chapter::097 module::097-03 review::pending
IMF-097-03-0010-en	Why can serum creatinine look normal in an older adult with low filtration?	When muscle mass is low, serum creatinine can stay normal despite low filtration, masking the reduced renal reserve common in older adults.	Integrated Medical Foundations; chapter 97, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 242ddf8b806467fd074ba75c5c762e152183461d70edcbb27c82c0d0a3aa7e42; editorial review pending	imf lang::en chapter::097 module::097-03 review::pending
IMF-097-03-0011-en	Why should untreated maternal illness not be treated as a zero-risk alternative in pregnancy?	Maternal disease carries its own risk, and because evidence is mostly observational, uncertainty can itself cause harm when effective treatment is withheld; drug risk must be compared against it.	Integrated Medical Foundations; chapter 97, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 242ddf8b806467fd074ba75c5c762e152183461d70edcbb27c82c0d0a3aa7e42; editorial review pending	imf lang::en chapter::097 module::097-03 review::pending
IMF-097-03-0012-en	Why does blaming an individual for a medication error without examining workflow fail to improve safety?	It preserves the conditions, such as similar names, confusing units, or incomplete reconciliation, that produced the error; systems should make the intended action easy and dangerous action difficult.	Integrated Medical Foundations; chapter 97, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 242ddf8b806467fd074ba75c5c762e152183461d70edcbb27c82c0d0a3aa7e42; editorial review pending	imf lang::en chapter::097 module::097-03 review::pending
IMF-097-03-0013-en	What does regulatory approval mean, and why can regulators reasonably reach different decisions?	Approval means evidence supports a favourable benefit-risk balance for a defined indication, population, dose, and product, not complete knowledge; available treatments, endpoints, mandates, and tolerance of uncertainty differ.	Integrated Medical Foundations; chapter 97, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 242ddf8b806467fd074ba75c5c762e152183461d70edcbb27c82c0d0a3aa7e42; editorial review pending	imf lang::en chapter::097 module::097-03 review::pending
IMF-097-03-0014-en	Why must a newly detected drug risk be judged by absolute frequency, not relative risk alone?	A dramatic relative risk may mean a small absolute excess, whereas a modest relative increase in a common serious outcome may matter greatly.	Integrated Medical Foundations; chapter 97, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 242ddf8b806467fd074ba75c5c762e152183461d70edcbb27c82c0d0a3aa7e42; editorial review pending	imf lang::en chapter::097 module::097-03 review::pending