Goodman & Gilman's The Pharmacological Basis of Therapeutics¶
Brunton, L. L., Hilal-Dandan, Randa, & Knollmann, B. C. (2018). Goodman & Gilman's The Pharmacological Basis of Therapeutics. McGraw-Hill.
Cited by¶
17 citations across 17 artifacts.
Each citation links to the sentence it supports in the citing article.
Primes¶
- Bioaccumulation
- … on maintaining tissue concentration within a therapeutic or safe window through dose adjustment and periodic biomonitoring, an approach codified across the cardiovascular and antiarrhythmic chapters of Goodman & Gilman's The Pharmacological Basis of Therapeutics (Brunton, Hilal-Dandan, & Knollmann, 2018, 13th ed.).
This sourceCanonical pharmacology reference covering chronic management and therapeutic drug monitoring of long-half-life cardiac drugs (amiodarone, digoxin)
- … on maintaining tissue concentration within a therapeutic or safe window through dose adjustment and periodic biomonitoring, an approach codified across the cardiovascular and antiarrhythmic chapters of Goodman & Gilman's The Pharmacological Basis of Therapeutics (Brunton, Hilal-Dandan, & Knollmann, 2018, 13th ed.).
- Dose-Response Relationship
- Every dose-response articulation, as systematized in the canonical pharmacological reference of Brunton, Hilal-Dandan, and Knollmann (2018), specifies (1) the dose metric—concentration, cumulative exposure, rate, scheduling pattern—and its measurement scale (often logarithmic because response varies over orders of magnitude); (2) the response metric and its measurement (quantal responses—yes/no at population level—versus graded responses within individuals; therapeutic effect versus adverse effect); (3) the functional form—linear, sigmoidal (Hill equation, log-logistic), threshold, U-shaped (hormetic), biphasic—that best describes the observed relationship and its theoretical grounding; and (4) the key parameters of the curve: ED50 or EC50 (dose producing 50% of maximal response), Emax (maximal response), slope factor (Hill coefficient), and threshold or no-observed-effect level.
This sourceCanonical pharmacology reference; supports D47-017 (a dose-response articulation specifies the dose metric and scale, the response metric, the functional form, and the curve's key parameters: ED50/EC50, Emax, Hill slope, threshold). NOTE: the pre-existing annotation about phenytoin/CYP2C9 saturable metabolism is mis-pasted from another prime and does not describe the D47-017 claim.
- Every dose-response articulation, as systematized in the canonical pharmacological reference of Brunton, Hilal-Dandan, and Knollmann (2018), specifies (1) the dose metric—concentration, cumulative exposure, rate, scheduling pattern—and its measurement scale (often logarithmic because response varies over orders of magnitude); (2) the response metric and its measurement (quantal responses—yes/no at population level—versus graded responses within individuals; therapeutic effect versus adverse effect); (3) the functional form—linear, sigmoidal (Hill equation, log-logistic), threshold, U-shaped (hormetic), biphasic—that best describes the observed relationship and its theoretical grounding; and (4) the key parameters of the curve: ED50 or EC50 (dose producing 50% of maximal response), Emax (maximal response), slope factor (Hill coefficient), and threshold or no-observed-effect level.
- Elasticity
- In medicine, dose–response elasticity frames the therapeutic window: steep elasticity near a threshold means a narrow window.
This sourceFrames the dose–response curve and therapeutic window — a steep dose–response slope near threshold means a narrow window.
- In medicine, dose–response elasticity frames the therapeutic window: steep elasticity near a threshold means a narrow window.
- Gain Control
- In endocrine and homeostatic systems receptor downregulation and sensitivity changes retune responses to ambient hormone levels, with pharmacological tolerance as the same pattern.
This sourceThe standard pharmacology text; describes receptor downregulation and desensitization as adaptive responses to sustained agonist exposure and the basis of pharmacodynamic tolerance — cellular gain control on hormone/drug signaling, with tolerance and drug-holiday resets as the same pattern.
- In endocrine and homeostatic systems receptor downregulation and sensitivity changes retune responses to ambient hormone levels, with pharmacological tolerance as the same pattern.
- Potentiation
- It stands as the direct opposite of tolerance, with which it shares structural logic but inverted direction: both are time-dependent response changes under repeated exposure, but potentiation amplifies while tolerance dampens.
This sourceCanonical pharmacology reference: documents phenytoin as the archetypal case of saturable hepatic CYP2C9 metabolism producing non-linear pharmacokinetics, dose-dependent half-life, and the transition from first-order to zero-order elimination near therapeutic concentrations.
- It stands as the direct opposite of tolerance, with which it shares structural logic but inverted direction: both are time-dependent response changes under repeated exposure, but potentiation amplifies while tolerance dampens.
- Receptor Saturation
- As Brunton, Hilal-Dandan, and Knollmann (Goodman & Gilman, 2018) describe in their treatment of phenytoin pharmacokinetics,
This sourceCanonical pharmacology reference: documents phenytoin as the archetypal case of saturable hepatic CYP2C9 metabolism producing non-linear pharmacokinetics, dose-dependent half-life, and the transition from first-order to zero-order elimination near therapeutic concentrations.
- As Brunton, Hilal-Dandan, and Knollmann (Goodman & Gilman, 2018) describe in their treatment of phenytoin pharmacokinetics,
- Synergy and Antagonism
- The isobologram framework precisely quantifies both directions and permits dose-optimization without trial-and-error.
This sourceCanonical pharmacology reference: documents phenytoin as the archetypal case of saturable hepatic CYP2C9 metabolism producing non-linear pharmacokinetics, dose-dependent half-life, and the transition from first-order to zero-order elimination near therapeutic concentrations.
- The isobologram framework precisely quantifies both directions and permits dose-optimization without trial-and-error.
- Therapeutic Window
- The width of this window is a defining property of the intervention and a first-class design target.
This sourceCanonical pharmacology reference: documents phenytoin as the archetypal case of saturable hepatic CYP2C9 metabolism producing non-linear pharmacokinetics, dose-dependent half-life, and the transition from first-order to zero-order elimination near therapeutic concentrations.
- The width of this window is a defining property of the intervention and a first-class design target.
- Tolerance
- A time-indexed sequence of identical exposures produces responses whose magnitude declines progressively across the sequence, formalized—as Brunton, Hilal-Dandan, and Knollmann (2018) develop in their treatment of receptor pharmacology—as a rightward shift of the dose-response curve, where the dose required to achieve a target effect (e.g., 50% maximum response) increases over time.
This sourceCanonical reference for clinical pharmacology: develops tolerance as rightward shift of the dose-response curve driven by receptor downregulation, enzyme induction, and behavioral compensation; chapters on opioid analgesics treat rotation, dose holidays, and adjuvant strategies as mechanism-specific responses to tolerance.
- A time-indexed sequence of identical exposures produces responses whose magnitude declines progressively across the sequence, formalized—as Brunton, Hilal-Dandan, and Knollmann (2018) develop in their treatment of receptor pharmacology—as a rightward shift of the dose-response curve, where the dose required to achieve a target effect (e.g., 50% maximum response) increases over time.
Domain-specific¶
- Contraindication
- The prohibition rule is the restriction itself, which clinical medicine codes in two gradations: absolute contraindications (the treatment must not be given under the conditioning context, with no room for compensating adjustments) and relative contraindications (the risk-benefit ratio worsens enough to require serious alternative consideration or protective co-intervention, but clinical judgment may still permit the treatment with appropriate safeguards)
This sourceStandard reference for the risk-benefit framing that defines a contraindication; the absolute-versus-relative gradation is clinical convention rather than a distinction this text or the FDA labelling rule (21 CFR 201.57(c)(5)) formally draws. Covers the beta-blocker/asthma and ACE-inhibitor/pregnancy contraindications and their mechanisms; the live-vaccine limb rests on the CDC/ACIP General Best Practice Guidelines for Immunization, which bar live vaccines in most forms of altered immunocompetence because of uninhibited growth of the attenuated organism.
Supported in partVerified against the source
- The prohibition rule is the restriction itself, which clinical medicine codes in two gradations: absolute contraindications (the treatment must not be given under the conditioning context, with no room for compensating adjustments) and relative contraindications (the risk-benefit ratio worsens enough to require serious alternative consideration or protective co-intervention, but clinical judgment may still permit the treatment with appropriate safeguards)
- Cumulative Dose
- Doxorubicin (an anthracycline chemotherapy agent) is dosed per treatment cycle in milligrams per square metre of body-surface area, and each individual infusion is generally well tolerated
This sourceDoxorubicin's per-cycle dosing in mg/m2 of body-surface area and the tolerability of an individual infusion.
- Doxorubicin (an anthracycline chemotherapy agent) is dosed per treatment cycle in milligrams per square metre of body-surface area, and each individual infusion is generally well tolerated
- First-Pass Metabolism
- This route-dependence is load-bearing for clinical practice: oral morphine doses are roughly three times larger than intravenous doses of equivalent effect, and oral propranolol requires ten times the intravenous dose
This sourceThe oral-to-intravenous dose multipliers for morphine (about 3x) and propranolol (about 10x) as the clinical reading of hepatic extraction.
- This route-dependence is load-bearing for clinical practice: oral morphine doses are roughly three times larger than intravenous doses of equivalent effect, and oral propranolol requires ten times the intravenous dose
- Metabolic Inactivation
- In pharmacology and toxicology the process is typically organised into phase-I reactions — predominantly cytochrome P450-mediated oxidation, together with reduction and esterase-mediated hydrolysis, that introduce or unmask a functional group — and phase-II conjugation reactions — glucuronidation, sulfation, glutathione conjugation, or acetylation — most of which add a polar moiety, increasing water solubility and enabling renal or biliary excretion of the now-inactive metabolite, whereas acetylation inactivates without substantially changing lipophilicity
This sourceThe phase-I (functionalisation) / phase-II (conjugation) organisation of drug metabolism, with conjugation generally increasing polarity for renal or biliary excretion. Bioactivation as the converse of inactivation, with codeine O-demethylation to morphine by CYP2D6 and acetaminophen's reactive hepatotoxic metabolite (NAPQI) at high dose as standard examples.
- In pharmacology and toxicology the process is typically organised into phase-I reactions — predominantly cytochrome P450-mediated oxidation, together with reduction and esterase-mediated hydrolysis, that introduce or unmask a functional group — and phase-II conjugation reactions — glucuronidation, sulfation, glutathione conjugation, or acetylation — most of which add a polar moiety, increasing water solubility and enabling renal or biliary excretion of the now-inactive metabolite, whereas acetylation inactivates without substantially changing lipophilicity
- Neurotransmission
- Cellular neurophysiology — the EPSP/IPSP account of how synapses compute, receptor pharmacology, and short-term facilitation and depression at single connections. Systems neuroscience — the diffuse dopaminergic, serotonergic, cholinergic, and noradrenergic projections that globally bias circuit gain, the broadcast layer distinct from point-to-point transmission. Neuropharmacology — virtually every psychoactive drug acting on a named step in the chain: SSRIs at reuptake, benzodiazepines at GABA-A, opioids at their receptor
This sourceEstablishes the molecular sites of action asserted here: SSRIs as inhibitors of the presynaptic serotonin transporter (reuptake), benzodiazepines as positive allosteric modulators at the GABA-A receptor, and opioids as agonists at the mu/delta/kappa opioid receptors.
- Cellular neurophysiology — the EPSP/IPSP account of how synapses compute, receptor pharmacology, and short-term facilitation and depression at single connections. Systems neuroscience — the diffuse dopaminergic, serotonergic, cholinergic, and noradrenergic projections that globally bias circuit gain, the broadcast layer distinct from point-to-point transmission. Neuropharmacology — virtually every psychoactive drug acting on a named step in the chain: SSRIs at reuptake, benzodiazepines at GABA-A, opioids at their receptor
- Pharmacodynamic Antagonism
- The structural mechanism is characterised by four sub-types that name the geometry of the opposition. Competitive antagonism: both agents bind the same receptor site, the agonist and antagonist competing for occupancy; the antagonist is displaceable by higher agonist concentrations, the dose-response curve shifts rightward without reducing the maximum achievable response, and the antagonism is surmountable — naloxone competing with opioids at the mu receptor is the canonical reversal-agent example.
This sourceCompetitive antagonism as same-site competition by a drug that lacks intrinsic efficacy and shifts the agonist dose-response curve rightward, with naloxone reversing opioid effects. Naloxone as an opioid antagonist that blocks opioid effects intravenously and flumazenil as a benzodiazepine-receptor antagonist.
Supported in partVerified against a saved copy of the source
“One is simple competitive antagonism, whereby a drug that lacks intrinsic efficacy”
- The structural mechanism is characterised by four sub-types that name the geometry of the opposition. Competitive antagonism: both agents bind the same receptor site, the agonist and antagonist competing for occupancy; the antagonist is displaceable by higher agonist concentrations, the dose-response curve shifts rightward without reducing the maximum achievable response, and the antagonism is surmountable — naloxone competing with opioids at the mu receptor is the canonical reversal-agent example.
- Potency
- The morphine-versus-codeine comparison is exactly this diagnostic: a roughly tenfold lower analgesic ED50 for morphine is read off the dose axis
This sourceStandard pharmacology text documenting codeine's exceptionally low affinity for opioid receptors and its dependence on conversion to morphine for analgesia. Standard pharmacology text documenting codeine's exceptionally low receptor affinity and its dependence on metabolic conversion to morphine.
Supported in partVerified against a saved copy of the source
“Codeine has an exceptionally low affinity for opioid”
- The morphine-versus-codeine comparison is exactly this diagnostic: a roughly tenfold lower analgesic ED50 for morphine is read off the dose axis
Mechanisms¶
- Dosage Window Protocol
- This is the therapeutic window
This sourceDefines the pharmacological dose-response, therapeutic-index, and safety-margin concepts that bound beneficial and harmful drug exposure.
- This is the therapeutic window
Verification¶
Does it exist? Not checked yet. This entry carries no identifier to resolve. It was extracted from the citation as written in the article, normalized, and deduplicated against the rest of the registry.
Does it back the claim? Read against the text for 3 of 17 citations: 3 supported in part. Each verdict is shown under its citation below, with what in the work backs the sentence.
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Links previously used in the corpus¶
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- https://www.mheducation.com/highered/product/goodman-gilman-s-the-pharmacological-basis-of-therapeutics-brunton-knollmann.html ×1
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