Pharmacology Terminology

Why This Matters

Pharmacology terminology isn't just vocabulary to memorize—it's the conceptual framework you'll use to understand every drug you encounter throughout your career. These terms explain why a drug works, how it moves through the body, and what determines whether it helps or harms a patient. You're being tested on your ability to connect these concepts: understanding that bioavailability, half-life, and therapeutic index all influence dosing decisions, or recognizing how agonists and antagonists produce opposite effects at the same receptor.

Master these terms and you'll be able to predict drug behavior, anticipate interactions, and make clinical decisions with confidence. Don't just memorize definitions—know what principle each term illustrates and how it connects to the bigger picture of drug therapy. When you see a question about why one drug requires more frequent dosing than another, you should immediately think half-life and clearance. That's the level of understanding that separates strong exam performance from struggling through recall.

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The Journey of a Drug: Pharmacokinetics (ADME)

Pharmacokinetics answers the question: "What does the body do to the drug?" These four processes—absorption, distribution, metabolism, and excretion—determine how much drug reaches its target and how long it stays active.

Pharmacokinetics

• The study of ADME processes—absorption, distribution, metabolism, and excretion working together as a system
• Determines onset, intensity, and duration of drug effects based on how quickly and completely each process occurs
• Clinical applications include calculating dosing intervals, adjusting for organ impairment, and predicting drug accumulation

Absorption

• Entry into the bloodstream from the administration site—this is where bioavailability begins
• Route of administration matters: IV bypasses absorption entirely, while oral drugs face the GI tract and first-pass metabolism
• Factors affecting absorption include drug formulation, pH at the absorption site, and presence of food or other substances

Distribution

• Dispersion throughout body compartments—the drug travels from blood into tissues where it can act
• Protein binding is critical: only unbound (free) drug can cross membranes and produce effects
• Volume of distribution ($V_d$) indicates whether a drug stays in the blood or spreads widely into tissues

Metabolism

• Biotransformation primarily in the liver—enzymes (especially cytochrome P450) chemically modify drugs
• First-pass metabolism can significantly reduce bioavailability of oral drugs before they reach systemic circulation
• Active metabolites may be more potent, less potent, or toxic compared to the parent drug

Excretion

• Elimination from the body, primarily via kidneys (urine) but also through bile, lungs, and sweat
• Renal function directly impacts clearance—impaired kidneys mean slower elimination and potential toxicity
• Enterohepatic recirculation can prolong drug effects when drugs excreted in bile are reabsorbed from the intestine

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Measuring Drug Behavior: Key Parameters

These quantitative measures help clinicians make precise dosing decisions. Understanding these parameters allows you to predict how a drug will behave and adjust therapy accordingly.

Half-life

• Time for plasma concentration to decrease by 50%—typically written as $t_{1/2}$
• Determines dosing frequency: drugs with short half-lives need more frequent dosing to maintain therapeutic levels
• Steady state is reached after approximately 4-5 half-lives of consistent dosing

Bioavailability

• Fraction of administered dose reaching systemic circulation—expressed as a percentage or decimal ($F$)
• IV administration = 100% bioavailability by definition; oral bioavailability varies widely due to absorption and first-pass effects
• Formulation differences explain why generic and brand-name drugs may have slightly different effects

Therapeutic Index

• Ratio of toxic dose to effective dose: $TI = \frac{TD_{50}}{ED_{50}}$
• Higher TI = safer drug with more room for dosing error; low TI drugs (like warfarin, lithium, digoxin) require careful monitoring
• Narrow therapeutic window drugs are high-yield exam topics because small dose changes can cause toxicity or treatment failure

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How Drugs Produce Effects: Pharmacodynamics

Pharmacodynamics answers the question: "What does the drug do to the body?" This involves receptor interactions, signal transduction, and the relationship between dose and response.

Pharmacodynamics

• Study of drug mechanisms and effects—how drugs interact with biological targets to produce therapeutic outcomes
• Receptor theory is central: most drugs work by binding to specific protein targets
• Encompasses potency, efficacy, and selectivity—all testable concepts for comparing drugs within a class

Receptor

• Protein targets that recognize and respond to ligands—drugs, hormones, neurotransmitters
• Major receptor types: ion channels (fast), G-protein coupled receptors (moderate), enzyme-linked receptors, and nuclear receptors (slow)
• Receptor density and sensitivity can change with chronic drug exposure, explaining tolerance and sensitization

Agonist

• Binds and activates receptors to produce a biological response mimicking endogenous ligands
• Full agonists produce maximal response; partial agonists produce submaximal response even at full receptor occupancy
• Examples: morphine (opioid receptor), albuterol ($\beta_2$-adrenergic receptor), insulin (insulin receptor)

Antagonist

• Binds but does not activate receptors—blocks the action of agonists without producing its own effect
• Competitive antagonists can be overcome by increasing agonist concentration; non-competitive antagonists cannot
• Examples: naloxone (reverses opioid overdose), propranolol (blocks $\beta$-adrenergic effects), atropine (blocks muscarinic effects)

Dose-Response Curve

• Graphical representation of the relationship between drug concentration and effect magnitude
• Key features: threshold dose, $ED_{50}$ (dose producing 50% maximal effect), and maximal efficacy (ceiling)
• Comparing curves reveals relative potency (horizontal shift) and efficacy (vertical difference in maximum)

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Drug Effects: Intended and Unintended

Not all drug effects are therapeutic. Understanding the spectrum from predictable side effects to dangerous adverse reactions helps you anticipate and manage clinical problems.

Side Effect

• Unintended effect occurring at therapeutic doses—often predictable based on the drug's mechanism
• May be tolerable or even useful: diphenhydramine causes drowsiness (side effect) but is marketed as a sleep aid
• Severity ranges from minor annoyances to reasons for discontinuation

Adverse Drug Reaction (ADR)

• Harmful, unintended response at normal doses—more serious than typical side effects
• Type A reactions are dose-dependent and predictable; Type B reactions are idiosyncratic and unpredictable (allergies, genetic variations)
• Reporting ADRs contributes to post-marketing surveillance and drug safety databases

Drug Interaction

• One drug altering the effect of another—can occur at pharmacokinetic or pharmacodynamic levels
• Pharmacokinetic interactions: one drug affects absorption, metabolism, or excretion of another (e.g., grapefruit juice inhibiting CYP3A4)
• Pharmacodynamic interactions: additive, synergistic, or antagonistic effects when drugs act on similar pathways

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Chronic Drug Exposure: Adaptation and Dependence

The body doesn't passively accept drug exposure—it adapts. These concepts explain why drug effects change over time and why stopping certain drugs causes problems.

Tolerance

• Decreased response requiring higher doses—the same dose produces less effect over time
• Mechanisms include receptor downregulation, increased metabolism, and physiological compensation
• Cross-tolerance occurs between drugs acting on the same system (e.g., alcohol and benzodiazepines)

Dependence

• Physiological or psychological adaptation to a drug's presence—the body now requires the drug to function normally
• Physical dependence manifests as withdrawal symptoms; psychological dependence involves craving and compulsive use
• Not synonymous with addiction—patients on chronic opioids for pain may be dependent but not addicted

Withdrawal

• Symptoms emerging when a drug is reduced or stopped in a dependent individual
• Opposite of drug effects: opioid withdrawal causes pain and diarrhea (opposite of analgesia and constipation)
• Severity varies from uncomfortable (caffeine withdrawal headache) to life-threatening (alcohol or benzodiazepine withdrawal seizures)

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Foundational Concepts

These overarching terms provide the framework for everything else in pharmacology.

Drug

• Any substance that alters physiological function—used for diagnosis, treatment, prevention, or cure of disease
• Classification systems organize drugs by chemical structure, mechanism of action, or therapeutic use
• Natural, semi-synthetic, or fully synthetic origins all contribute to the modern pharmacopeia

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Quick Reference Table

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Self-Check Questions

1. A patient takes an oral medication that undergoes extensive first-pass metabolism. Which two pharmacokinetic concepts explain why the effective dose might be higher than for an IV formulation?

2. Compare and contrast competitive and non-competitive antagonists. How would increasing the dose of an agonist affect each type?

3. A drug has a half-life of 6 hours. How long until steady state is reached with regular dosing, and why does this matter clinically?

4. Explain why a patient with chronic pain might exhibit both tolerance and physical dependence to opioids. How are these phenomena related but distinct?

5. If an FRQ presents two drugs with different dose-response curves and asks you to compare them, what specific features would you analyze to discuss potency and efficacy?