Drug Toxicity

Vocabulary flashcards covering key terms, mechanisms, target interactions, and toxicity outcomes from the Drug Toxicity lecture.

Toxication

Biotransformation that produces harmful products, also referred to as metabolic activation.

Detoxication

Biotransformations that eliminate the ultimate toxicant or prevent its formation.

Free Radical

An unstable molecule produced by certain drugs such as paraquat (PQ), doxorubicin (DR), and nitrofurantoin (NF).

Glutathione (GSH)

The body's main antioxidant containing a thiol group ($-SH$) that binds electrophiles and detoxicates metal ions like $Ag^+$, $Cd^{2+}$, $Hg^{2+}$, and $CH_3Hg^+$.

Superoxide Dismutase (SOD)

An enzyme that converts superoxide ($O_2^{\bullet-}$) to hydrogen peroxide ($HOOH$).

Hydroxyl Radical ($HO^\bullet$)

A highly reactive radical for which no enzyme exists to eliminate it, requiring the body to prevent its formation instead.

Noncovalent Binding

Interaction involving hydrogen and ionic bonds, typically seen when toxicants interact with membrane receptors, intracellular receptors, ion channels, and enzymes.

Strychnine

A toxicant found in rat poison that noncovalently blocks glycine receptors, preventing inhibitory signals and causing convulsions.

Saxitoxin

A toxicant involved in shellfish poisoning that noncovalently blocks sodium channels, preventing nerve signals and causing paralysis.

Warfarin

A blood thinner that noncovalently inhibits Vitamin K 2,3-epoxide reductase to prevent blood clotting.

Covalent Binding

A practically irreversible interaction common with electrophilic toxicants that permanently alters endogenous covalent binding.

Hydrogen Abstraction

A reaction where neutral free radicals abstract hydrogen atoms from endogenous compounds, converting them into radicals such as converting thiol ($R-SH$) to thiyl radical ($R-S^\bullet$).

Electron Transfer

A reaction type where a toxicant oxidizes endogenous molecules, such as oxidizing $Fe(II)$ in hemoglobin to $Fe(III)$, producing methemoglobinemia.

Ricin

A toxicant that acts like an enzyme to induce hydrolytic fragmentation of ribosomes, blocking protein synthesis.

Aflatoxin

A toxicant that binds to N-7 of guanine, causing guanine to pair with adenine instead of cytosine and leading to incorrect codons.

Neoantigen Formation

The process where covalent binding of xenobiotics or their metabolites to host proteins evokes an immune response.

Developmental Toxicity

Toxicity caused by exposure to chemical or physical agents before conception, during prenatal development, or postnatally until puberty.

Teratogenicity

Defects induced during development between conception and birth.

Fetal Alcohol Syndrome (FAS)

A condition caused by ethanol exposure during gestation, characterized by craniofacial dysmorphism, intrauterine and postnatal growth retardation, and retarded psychomotor and intellectual development.

Fibrosis

A pathologic condition characterized by excessive deposition of an extracellular matrix (scar tissue) of abnormal composition.

Type I Hypersensitivity

Immediate hypersensitivity mediated by IgE production, leading to mast cell degranulation and release of inflammatory mediators such as histamine and leukotrienes.

Type II Hypersensitivity

Cytotoxic hypersensitivity where a drug binds to cells and IgG antibodies trigger cell destruction through complement fixation, cytotoxic T cells, or macrophages.

Type III Hypersensitivity

Immune complex-mediated hypersensitivity where soluble antigen-antibody complexes form and deposit in tissues, initiating an inflammatory response via neutrophils.

Type IV Hypersensitivity

Delayed-type hypersensitivity where a hapten-protein complex is presented by Langerhans cells to activate T cells ($TH1$ and cytotoxic T cells) rather than antibodies.

Autoimmunity

A toxicity outcome resulting when the organism's immune system attacks its own cells, such as Methyldopa causing hemolytic anemia by acting against Rh factors on RBCs.