NUR306- Genomics + Pharm Day 1

Genetics

The study of the general mechanisms of heredity and the variation of inherited traits.

Genomics

The study of the function of all the nucleotide sequences present within the entire genome of a species, including both coding and noncoding regions.

Human Genome

The complete set of genes for our species, with two sets of every gene in each nucleated cell (except sex gametes).

Gene

A specific segment of DNA that contains the genetic code for a specific protein.

DNA (Deoxyribonucleic Acid)

The genetic material in a cell that contains genes; can be nuclear (from both parents) or mitochondrial (maternal only).

Chromosome

A temporary structure formed during cell division that consists of a large chunk of DNA containing many genes.

Pyrimidines in DNA

Single-ring nitrogenous bases, which are Thymine (T) and Cytosine (C).

Purines in DNA

Double-ring nitrogenous bases, which are Adenine (A) and Guanine (G).

Complementary Base Pairing Rule

Adenine (A) always pairs with Thymine (T), and Guanine (G) always pairs with Cytosine (C) to keep double helix spacing even.

Coding DNA vs. Non-coding DNA

Coding DNA contains regions that code for proteins, while non-coding DNA does not code for proteins.

Mitosis

The process of somatic (body) cell division where the DNA double helix separates and replicates exactly for identical daughter cells.

Semi-Conservative Replication

DNA replication where each newly formed double-stranded DNA molecule contains one original template strand and one newly synthesized strand.

Chromatid

One of the two longitudinal, identical halves of a duplicated chromosome that has been replicated during S phase.

S phase vs. M phase

DNA synthesis/replication occurs during the S phase, while chromosomes are pulled apart and cell division occurs during the M phase.

Primary purpose of chromosome packing

To pack DNA into 46 structures to ensure precise, correct delivery of DNA to the next cell generation.

Ploidy

The actual number of chromosomes present in a single-cell nucleus during mitosis.

Haploid Chromosome Number (1N)

A complete set of one of each chromosome (23 individual chromosomes in humans), typical of sex gametes.

Diploid Chromosome Number (2N)

A complete set of both pairs of all chromosomes (46 total chromosomes in humans).

Polyploidy

The abnormal condition of having additional whole sets of extra chromosomes in a cell nucleus.

Telomeres

Caps of telomeric DNA that hold chromosome strands together, protecting them from unraveling like shoelace aglets.

Senescence

Cellular aging where a cell permanently stops dividing due to telomeres becoming too short, though it remains metabolically active.

Apoptosis

Programmed cell death, a highly regulated self-destruction process that safely removes damaged or old cells.

Karyotype

An arranged visual map of a cell's chromosomes, ordered by size (largest to smallest) and centromere position.

Chromosome Arm Anatomy (p vs. q)

The 'p arm' is the short arm (top, from French 'petit'), and the 'q arm' is the long arm (bottom).

Chromosome Landmark Meaning: 11q13

The gene is located on chromosome 11, on the long arm (q), in region 13.

Karyotype Notation: 47, XY, +21

Indicates a male (XY) with 47 total chromosomes due to an extra chromosome 21 (Trisomy 21).

Genotype

The exact allele pair composition for any given single-gene trait.

Phenotype

The observed physical or clinical expression of a single-gene trait.

Allele

A specific variant or 'recipe' of a gene that codes for a specific trait version.

Autosomal Chromosome

Any of the 22 pairs of non-sex-determining chromosomes (identical in males and females).

Dominant Trait

A single-gene trait expressed regardless of whether the alleles are homozygous (identical) or heterozygous (different).

Recessive Trait

A single-gene trait that is expressed only when both alleles are identical (homozygous).

Homozygous vs. Heterozygous

Homozygous means having two identical alleles for a gene; heterozygous means having two different alleles.

Codominant Trait

A trait where two different dominant alleles are fully and equally expressed in the phenotype at the same time (e.g., AB blood type).

X-Linked Inheritance

Traits encoded by genes located specifically on the X chromosome; recessive disorders express fully in males (who have only one X).

Single-Gene Inheritance vs. Polygenic Inheritance

Single-gene is controlled by one gene with two alleles; polygenic is controlled by multiple genes working together (e.g., height, skin color).

Single-Gene Disorder Examples

Cystic Fibrosis (progressive mucus buildup), Huntington's disease (progressive neurodegeneration), and Sickle Cell disease.

Pharmacology vs. Clinical Pharmacology

Pharmacology is the study of drugs and living system interactions; Clinical Pharmacology is specifically the study of drugs in humans.

Therapeutics (Pharmacotherapeutics)

The medical use of drugs to diagnose, prevent, treat disease, or prevent pregnancy.

The 'Big Three' Properties of an Ideal Drug

Effectiveness (does what it's intended to do), Safety (cannot produce harmful effects), and Selectivity (elicits only the intended response).

Pharmacokinetics and the four phases

What the body does to the drug, encompassing four phases: Absorption, Distribution, Metabolism, and Excretion (ADME).

Pharmacodynamics

What the drug does to the body, including the therapeutic effect, mechanism of action, and receptor binding.

Generic Name vs. Trade Name

Generic is the official, non-proprietary name (e.g., Acetaminophen); Trade/Brand is the commercial marketing name (e.g., Tylenol).

7 Rights of Medication Administration

Right Drug, Right Patient, Right Dose, Right Route, Right Time, Right Documentation, and Right Indication.

Agonist

A drug molecule that binds to a receptor and activates it, mimicking the body's natural regulatory molecules.

Partial Agonist

A drug that mimics agonists but produces moderate, sub-maximal response levels.

Antagonist

A drug that binds to receptors to block activation by agonists; it has affinity but zero intrinsic activity.

Substrate

A drug that is chemically metabolized by a specific enzyme (such as a cytochrome P450 enzyme in the liver).

CYP Enzyme Inducer (what does it do and how does it affect substrates?)

A drug that stimulates enzyme synthesis, accelerating metabolism of substrates (decreasing their plasma levels and therapeutic effect).

CYP Enzyme Inhibitor (what does it do and how does it affect substrates?)

A drug that blocks enzyme activity, slowing substrate metabolism (increasing substrate plasma levels and risk of toxicity).

How drugs cross membranes: Direct Penetration

The most common method; because membranes are primarily made of lipids, the drug must be lipid-soluble (lipophilic).

Drug Absorption

The movement of a drug from its site of administration into the bloodstream.

Key factors that influence drug absorption

Rate of dissolution, surface area (e.g., small intestine), blood flow, lipid solubility, and pH partitioning.

Intravenous (IV) Route Advantages

Rapid onset (ideal for emergencies), precise control of blood levels, and permits large volumes or irritant drugs.

Intravenous (IV) Route Disadvantages (what must it be)

Irreversible, expensive, inconvenient, carries risks of fluid overload/infection, and the drug must be water-soluble.

Intramuscular (IM) / Subcutaneous (subQ) Advantages

Allows administration of poorly soluble drugs and depot preparations (slow release over weeks).

Oral (PO) Route Disadvantages

High absorption variability, potential inactivation by stomach acid/enzymes, and slow onset.

Drug Distribution

The movement of a drug from the bloodstream, into the interstitial space, and finally into target cells.

Distribution barriers: Abscesses vs. Tumors

Abscesses lack inner blood circulation and require surgical drainage; solid tumors have limited blood flow at their core.

Blood-Brain Barrier (BBB)

Tight junctions between brain capillary cells that prevent drug exit unless the drug is lipid-soluble or has a specific transport system.

Protein Binding (Albumin)

Reversible binding where bound drug molecules are trapped in the bloodstream because albumin is too large to exit capillary pores, delaying drug action.

P-Glycoprotein

A transporter protein (encoded by the ABCB1 gene) that actively pumps drug molecules out of cells to protect tissues from toxic build-up.

Drug Metabolism (Biotransformation)

The chemical alteration of drug structure, occurring primarily in the liver via the Cytochrome P450 (CYP) system.

CYPs 1, 2, and 3

The specific families of hepatic Cytochrome P450 enzymes responsible for metabolizing exogenous clinical drugs.

Prodrug

An inactive compound that must be chemically metabolized by liver enzymes to become an active, therapeutically effective drug.

First-Pass Effect

The rapid hepatic inactivation of highly metabolized oral drugs immediately after absorption, before they can reach systemic circulation.

Drug Excretion Paths

Removal of drugs from the body, primarily via kidneys (renal), and secondarily via breast milk, bile, feces, and lungs.

Minimum Effective Concentration (MEC) vs. Toxic Concentration

MEC is the minimum blood level needed for a therapeutic response; Toxic Concentration is the level where harmful effects occur.

Therapeutic Range

The concentration range between the Minimum Effective Concentration (MEC) and the Toxic Concentration.

Drug Half-Life (t1/2)

The time required for the total amount of drug in the body to decrease by fifty percent.

Dose-Response Relationship

Determines the minimal and maximal safe/effective doses, and the maximum clinical benefit a drug can achieve.

Affinity vs. Intrinsic Activity

Affinity is the strength of attraction between a drug and a receptor; Intrinsic Activity is the drug's ability to activate the receptor.

Receptor Selectivity Rule

The fewer receptors a drug targets, the more selective it is, resulting in fewer unwanted side effects.

Continuous Agonist Exposure (Down-regulation)

Constant receptor activation causes cells to decrease receptor numbers or desensitize them.

Continuous Antagonist Exposure (Up-regulation)

Constant receptor blockade causes cells to increase receptor numbers or become supersensitive.

Receptorless Drugs

Drugs acting via simple physical or chemical reactions rather than receptors, such as antacids and osmotic laxatives.

Grapefruit Juice Effect

Inhibits intestinal CYP3A4 enzymes, reducing drug metabolism and dangerously raising blood levels of CYP3A4 substrates (e.g., simvastatin).

Rhabdomyolysis

Skeletal muscle breakdown that can lead to acute renal failure; a potential toxicity of statins when combined with grapefruit juice.

Vitamin K and Warfarin Interaction

Vitamin K-rich foods (green leafy vegetables) synthesize clotting factors, directly antagonizing the anticoagulant action of Warfarin.

Side Effect vs. Adverse Drug Reaction (ADR)

A side effect is a nearly unavoidable secondary effect at therapeutic doses; an ADR is any unintended, noxious, and undesired effect.

Idiosyncratic vs. Paradoxical Effect

Idiosyncratic is an uncommon genetic drug response; Paradoxical is the exact opposite of the intended therapeutic response.

Iatrogenic Effect

A disease, symptom, or condition produced unintentionally by a physician, drug, or medical treatment.

Teratogenic Effect

A drug-induced birth defect.

Type I Hypersensitivity (IgE-Mediated)

IgE binds to mast cells, allergen crosslinks IgE, inducing degranulation (histamine release); causes anaphylaxis or hives.

Type II Hypersensitivity (IgG-Mediated / Cytotoxic)

IgG or IgM antibodies bind and destroy cells via complement activation (e.g., mismatched blood transfusion reaction).

Type III Hypersensitivity (Immune Complex-Mediated)

Antigen-antibody complexes deposit in tissues, activating complement and causing inflammation (e.g., glomerulonephritis).

Type IV Hypersensitivity (Cell-Mediated / Delayed)

Helper T cells secrete cytokines to activate macrophages and cytotoxic T cells (e.g., poison ivy contact dermatitis, PPD skin test).

Hepatotoxicity LFT Markers

AST (aspartate aminotransferase) and ALT (alanine aminotransferase) liver enzymes, which leak into blood when liver cells are damaged.

Hepatotoxicity signs for patient education

Jaundice (yellow skin/eyes), dark urine, light-colored stools, nausea, vomiting, malaise, and right upper quadrant abdominal discomfort.

QT Interval

An ECG measurement of the time required for the ventricles to electrically repolarize (reset) after each contraction.

Torsades de Pointes

A specific, life-threatening, rapid ventricular heart rhythm with a twisting ECG pattern, caused by QT-prolonging drugs (e.g., amiodarone).

Black Box Warning

The strongest safety warning a drug can carry and still remain on the market to alert prescribers to potential severe harm.

Pharmacogenetics vs. Pharmacogenomics

Pharmacogenetics studies how a specific gene affects drug response; Pharmacogenomics studies how the entire genome affects response.

Personalized / Precision Medicine

Using a patient's unique genomic profile to select the correct medication and dose from the start, avoiding trial-and-error.