Pharmacogenomics and Chemotherapy Review

Comprehensive flashcards covering Pharmacogenomics, Antimicrobial mechanisms, and Antineoplastic (cancer) pharmacology based on lecture study guides.

Pharmacogenetics

The study of the role of inheritance in the variation in drug response.

Pharmacogenomics

The use of knowledge regarding a patient's DNA to enhance pharmacotherapy, maximize drug efficacy, and reduce adverse effects.

Human Genome Project (Pharmacogenomic Statistics)

Findings including $3$ billion nucleotides, $25,000$ to $30,000$ genes, and the discovery that people differ by one nucleotide every $1,000$.

BCHE (Butyrylcholinesterase)

A genetic variant that causes a decreased rate of acetylcholine metabolism, affecting the response to succinylcholine.

NAT2 (N-acetyltransferase 2)

An enzyme where genetic variation leads to fast or slow acetylators, affecting Phase 2 conjugation reactions.

Probe Drug (Debrisoquine)

A substance used to measure the urinary metabolite ratio to classify patients as poor, extensive, or ultrarapid metabolizers.

CYP2D6 Ultrarapid Metabolizer

An individual who may have up to $13$ copies of the CYP2D6 gene, potentially leading to a codeine overdose or respiratory depression.

AmpliChip CYP450 Array

A DNA testing method used for genotyping metabolic activity, specifically testing for CYP2D6 and CYP2C19.

TPMT (Thiopurine S-methyltransferase)

A Phase II enzyme that metabolizes 6-mercaptopurine and azathioprine; patients with the TPMT*3A variant may require only $1/10$ to $1/15$ of the standard drug dose.

ALOX5 Variation

A germ-line DNA variation (promoter tandem repeat polymorphism) where patients lacking one copy of the 5-repeat do not respond well to zileuton.

Germ-line DNA Variation

Inherited genetic differences that are passed to offspring, such as those found in the ALOX5 gene.

Somatic DNA Variation

Tumor-specific mutations that are not passed to offspring, such as gain-of-function mutations in EGFR.

Warfarin (Polygenic Variation)

A drug whose effects are influenced by both pharmacokinetic variation (CYP2C9) and pharmacodynamic variation (VKORC1).

Idiosyncratic Drug Reaction

A drug variation not caused by differences in metabolism or target, but by unique patient physiology, such as G6PD deficiency reacting to sulfonamides.

Drug Rescue

The process of obtaining FDA approval for a drug that failed clinical trials by identifying and treating only the specific genetic group that responds well to it, such as Bucindolol.

Ethnic Drugs

Drugs or dosing recommendations based on genetic differences common in certain ethnic groups, such as BiDil for heart failure in African-Americans.

Unique Target

A mechanism of selective targeting where the drug's target is not present in the host at all, resulting in the least toxicity.

Selective Toxicity

The ability of a drug to inhibit a pathway or target critical for a microbe or cancer cell's survival without affecting host pathways.

Bacteriostatic

Antimicrobial activity that inhibits bacterial growth without killing the bacteria, relying on the host's immune system for removal.

Bactericidal

Antimicrobial activity that results in the direct killing of bacteria.

Davis Model

The explanation of the bactericidal activity of Aminoglycosides, where mRNA misreading leads to incorrect protein incorporation and irreversible membrane damage.

Mycobacteria Cell Wall

A cell wall containing mycolic acid, requiring acid-fast staining rather than standard Gram staining.

Peptidoglycan (Murein)

A component of the bacterial cell wall that maintains osmotic pressure and is the target of various cell wall synthesis inhibitors.

Beta-lactam Antibiotics

A class of drugs including penicillins, cephalosporins, monobactams, and carbapenems that inhibit transpeptidase (penicillin-binding proteins).

Cefotetan

A 2nd-generation cephalosporin that can cause a disulfiram-like reaction and interfere with vitamin K-dependent clotting factors.

Aztreonam

A monobactam antibiotic active only against Gram-negative bacteria that is used for patients with severe penicillin allergies.

Meropenem

A broad-spectrum carbapenem antibiotic that has the potential to cause seizures.

Pseudomembranous Colitis

Severe colon inflammation caused by Clostridioides difficile overgrowth following the use of broad-spectrum antibiotics like Clindamycin.

Flucytosine

A fungal nucleic acid synthesis inhibitor that is selective because fungi possess cytosine permease, which mammalian cells lack.

Amphotericin B

A polyene macrolide that binds to ergosterol to form membrane pores, causing leakage of cell contents and fungal death.

Mitotoxicity Hypothesis

The theory that higher metabolic activity causes increased susceptibility to drugs interfering with growth, though some normal tissues recover better than cancer cells.

Log Cell Kill Model

A model based on first-order kinetics stating that each dose of chemotherapy kills a constant fraction of cancer cells.

Methotrexate

A non-selective DHFR inhibitor used in cancer treatment that prevents the regeneration of tetrahydrofolate (THF).

Folinic Acid Rescue (Leukovorin)

A method used after methotrexate treatment to bypass DHFR and rescue normal cells by allowing nucleotide synthesis to resume.

5-Fluorouracil (5-FU)

A thymidylate synthase inhibitor used primarily for colorectal cancer; its prodrug form is Capecitabine.

Hydroxyurea

A ribonucleotide reductase inhibitor used for leukemias and sickle cell disease that can be leukemogenic with prolonged use.

Platinum Compounds

Drugs like Cisplatin and Carboplatin that bind DNA through platinum coordination to form cross-links and block replication.

Bleomycin

An antitumor antibiotic that chelates iron and produces free radicals to cause single- and double-strand DNA breaks.

Vinca Alkaloids (e.g., Vinblastine)

Cancer drugs that bind to $\beta$-tubulin to prevent microtubule polymerization and mitotic spindle formation.

Taxanes (e.g., Paclitaxel)

Drugs that bind to the inside of microtubules to stabilize them and prevent depolymerization, arresting cells in mitosis.

Abraxane

An albumin-bound formulation of paclitaxel used for metastatic breast cancer to reduce toxicity and improve drug delivery.

Imatinib

A tyrosine kinase inhibitor that selectively inhibits the BCR-ABL fusion kinase in Chronic Myelogenous Leukemia (CML).

Sirolimus (Rapamycin)

An mTOR inhibitor used for renal cell carcinoma that promotes cell cycle inhibition and inhibits angiogenesis.

Bortezomib

The only FDA-approved proteasome inhibitor; it inhibits the 20S catalytic subunit to treat multiple myeloma.

Bevacizumab

A VEGF antibody that inhibits angiogenesis signaling to prevent tumor growth in metastatic tumors.

Rituximab

A monoclonal antibody tailored to recognize CD20 on mature B cells, used for B-cell non-Hodgkin's lymphoma.