Biochemistry & Pharmacology Essentials for AuD

Biochemistry: study of the chemical substances and processes of living matter; central to all life sciences and pharmacology (including ototoxicity).
Biological hierarchy: atomic → molecular → cellular → tissue → organ → organism → population → ecosystem.
Atomic structure basics:
- Atomic number Z: unique identifier equal to the number of protons in the nucleus.
- In a neutral atom, protons = electrons, so $N<em>p = N</em>e = Z$ .
- Ions: formed by gain or loss of electrons; charges create cations (positive) or anions (negative).
- Common ions in the body/cochlea: Na⁺, K⁺, Cl⁻.
- Electrolytes: substances that conduct electricity in solution; essential for cellular function.
Electron shells (capacity): the first four shells have maximum capacities: $2, 8, 18, 32\,$ electrons respectively.
Ions and electroneutrality:
- If an atom loses electrons, it becomes a positively charged ion (cation).
- If it gains electrons, it becomes a negatively charged ion (anion).
- Example: Na⁺ (Z=11) has 10 electrons; Cl⁻ (Z=17) has 18 electrons.
Ionic compounds and salts:
- Electrostatic attraction between oppositely charged ions forms ionic compounds (e.g., NaCl).
- Common body/cochlear ions: Na⁺, K⁺, Cl⁻.
Molecules, compounds, mixtures:
- Molecule: smallest unit of a pure substance with all properties; 2+ atoms linked by bonds.
- Compound: combination of < 2 elements bonded in a reproducible way (e.g., $\mathrm{H_2O}$ ).
- Mixture: two or more elements/compounds physically intermixed; separable by physical means; may retain properties of components; non-uniform mixtures (e.g., oil and water).
Radicals vs stability:
- Atoms are most stable when outer electron shell is full.
- Uncharged atom may be unstable if outer shell not full; this instability is described as a radical.
- Free radicals can damage molecules; linked to aging and cancer risk.
Chemical structure concepts:
- Chemical bond: attraction allowing formation of substances with two or more atoms; numerous bond types.
- Structural formula depicts how atoms are arranged within a molecule.
- Proteins are biomolecules formed by polypeptide chains of amino acids.
Types of chemical bonds:
- Covalent bonds: sharing of electrons between nonmetals; strongest and most stable; typically not directly involved in drug receptor interactions; example: C–O.
- Hydrogen bonds: between a hydrogen attached to N/O/S and another electronegative atom; weaker than covalent/ionic; raise boiling points; key in DNA Ha bonds, protein structure, enzyme-substrate interactions.
- Ionic bonds: electrostatic attraction between oppositely charged ions; transfer of electrons (metal to non-metal); stronger than hydrogen but weaker than covalent; important in drug-receptor attraction.
- Van der Waals forces: weak, distance-dependent interactions; dependent on size/shape; important for drug-receptor contact at close range.
Redox (oxidation-reduction):
- Redox pair consists of oxidation and reduction reactions occurring together.
- Oxidation: loss of electrons; Reduction: gain of electrons; half-reactions combine to form the full reaction.
- In metals, oxidation forms cations; non-metals gain electrons to become anions.
Oxidative stress:
- Imbalance between reactive oxygen species (ROS) production and antioxidant defenses.
- Excess ROS damages proteins, lipids, DNA; linked to aging, neurodegeneration, diabetes, cancer, atherosclerosis, etc.
- Antioxidants (endogenous and dietary) protect cells; Glutathione (GSH) is a key intracellular antioxidant.
- Glutathione: reduced form $\mathrm{GSH}$ donates electrons; liver synthesis is essential for systemic protection; important for auditory-vestibular system; otoprotective strategies may boost glutathione action.
Inflammation & tissue injury:
- Inflammation is the immune response of vascular tissue to harmful stimuli (pathogens, trauma, chemicals).
- It is essential for wound healing but can become chronic, leading to tissue damage and disease.
- Cardinal signs: heat, redness, swelling (edema), pain, loss of function.
Enzymes:
- Enzymes are protein catalysts that speed up biochemical reactions.
- Substrates bind to the enzyme’s active site; products are formed after the reaction.
- Enzymes typically end with the suffix -ase (e.g., lactase, acetylcholinesterase).
- Enzyme activity is influenced by inhibitors, activators, temperature, pH, and substrate concentration.
Enzyme-substrate interactions:
- Specific shapes lead to enzyme-substrate specificity; fit can be exact or small structural adjustments allow multiple substrates.
Receptors & ligands:
- Receptor: protein that enables communication between cell and external environment; ligands (hormones, neurotransmitters, drugs) bind and modulate cell function.
- Binding forces: ionic bonds, hydrogen bonds, and van der Waals forces.
- Some ligands block receptors without triggering a response (e.g., calcium channel blockers act as plugs).
Receptors and membrane topology:
- Transmembrane receptors span the cell membrane and mediate signal transduction.
Hormones vs Neurotransmitters:
- Hormones: chemical messengers (peptides or steroids) released into bloodstream; slower, widespread effects; essential for growth/metabolism; examples: thyroid hormone, cortisol, estrogen, testosterone.
- Neurotransmitters: chemical messengers for neuron-to-cell signaling at synapses; rapidly released after action potential; terminated by reuptake.
Neurotransmitter classification:
- Excitatory: epinephrine, norepinephrine (increase likelihood of firing).
- Inhibitory: serotonin, GABA (decrease likelihood of firing).
- Some (e.g., acetylcholine, dopamine) can be excitatory or inhibitory depending on receptor type.
Neurotransmitter functions:
- Acetylcholine: voluntary movement via skeletal muscles.
- Norepinephrine: wakefulness/arousal via sympathetic pathways.
- Dopamine: movement, motivation, reward, addiction.
- Serotonin (5-HT): memory, emotion, sleep, temperature regulation.
- GABA: major inhibitory neurotransmitter in CNS.
- Glycine: spinal reflexes and motor control.
- Glutamate: primary excitatory neurotransmitter.
Neuromodulators:
- Substances that modulate neuronal activity diffusely; role in pain; dopamine and nicotine related to addiction; Substance P modulates pain.
Local (paracrine) chemicals:
- Histamine: local immune responses and allergies.
- Prostaglandins: regulate inflammation, blood flow, clotting, labor; act locally at tissue damage sites.
Why study pharmacology in AuD:
- ~2,000 drugs and >400 potential ototoxic side effects; can impact audiology assessment and management.
- Adverse drug reactions may cause hearing loss, tinnitus, vestibular dysfunction, vertigo, cognitive effects, and test inaccuracies.
- Audiologists are integral to healthcare teams: diagnose, prevent, and manage ototoxic effects; timelines/linkages help explain test results and discrepancies.
Audiology case history (practice):
- Key questions: current medications (dose and frequency); condition treated; duration of use; establish timeline between medication onset and symptoms.
- OTC and herbal products can cause ototoxic effects; ask about them as well.
- Be aware of medications causing neurological side effects that could complicate testing.
Quick recall tips:
- Remember the major bond types and their relative strengths: Covalent > Ionic > Hydrogen > Van der Waals.
- Oxidative stress is about ROS balance; GSH is a central defender in cells.
- Inflammation signs guide diagnosis and determine chronicity.
- AuD relevance: drugs can affect cochlea, vestibular system, cognition, and test reliability; know how to obtain a pharmacological history.