What is pharmacology?

What is Pharmacology?

Pharmacology is the scientific discipline that studies how chemical substances (drugs) interact with living organisms, encompassing both what the drug does to the body (pharmacodynamics) and what the body does to the drug (pharmacokinetics). 1

Core Subdivisions of Pharmacology

Pharmacodynamics: Drug Effects on the Body

• Pharmacodynamics examines the biochemical and physiological effects of drugs and their mechanisms of action, including how drugs alter bodily functions by interacting with macromolecular components like receptors. 2, 3
• The dose-response relationship is the fundamental concept, describing how drug effects depend on concentration at the receptor site. 3
• Primary pharmacodynamic studies investigate the mechanism of action and effects related to the desired therapeutic target, typically conducted during drug discovery using in vitro receptor binding assays and in vivo animal disease models. 1
• Secondary pharmacodynamic studies examine "off-target" effects unrelated to the intended therapeutic target, particularly relevant for small molecules rather than biologics which have high target specificity. 1
• Drugs do not create new effects but instead modulate existing bodily functions—they can only alter the rate at which physiological processes proceed. 2

Pharmacokinetics: Body Effects on the Drug

• Pharmacokinetics provides quantitative assessment of absorption, distribution, metabolism, and excretion (ADME) of drugs once they enter the body. 1, 4, 5, 6
• Route of administration affects drug entry into the bloodstream and onset of action, with first-pass metabolism significantly reducing bioavailability for oral medications. 4
• Hepatic metabolism is the primary site where drugs are chemically modified, with genetic variations (such as CYP2D6 polymorphisms) causing dramatic differences in how patients metabolize medications. 4
• Renal elimination is the primary route for drug removal, though liver disease affects drug elimination more dramatically than kidney dysfunction. 4
• Drug half-life determines dosing frequency, with 4-5 half-lives required to reach steady-state concentrations—explaining why antidepressants and mood stabilizers require weeks for full therapeutic effects. 4

Specialized Pharmacology Branches

Safety Pharmacology

• The core battery of safety pharmacology studies assesses effects on cardiovascular, respiratory, and central nervous systems before human exposure. 1
• Supplemental assessments of carcinogenic potential are conducted only when warranted for drugs intended for long-duration use or with special safety concerns. 1

Toxicokinetics

• Toxicokinetics generates pharmacokinetic data during toxicity testing to interpret toxicity findings and their relevance to human clinical safety. 1
• When a metabolite represents greater than 10% of total drug-related exposure at steady-state and appears disproportionately higher in humans versus animal species, additional non-clinical characterization is required. 1

Pharmacogenomics

• Pharmacogenomics evaluates the influence of genetics on drug response, with genetic polymorphisms affecting enzyme expression and activity. 1, 5

Drug Classification Systems

By Chemical Nature

• Drugs exist as solids (paracetamol), liquids (alcohol), or gases (oxygen). [@user context@]
• Molecular weight determines administration route: medium-sized molecules work best, while large proteins/antibodies cannot be swallowed due to gastric digestion and require injection. [@user context@]

By Source

• Plant-derived drugs (morphine from poppies, caffeine) represent the oldest source. [@user context@]
• Animal-derived drugs include hormones like insulin and thyroxine. [@user context@]
• Microbial-derived drugs encompass most antibiotics (penicillin from fungi/bacteria). [@user context@]
• Mineral-derived drugs include iron for anemia and magnesium for heartburn. [@user context@]
• Synthetic drugs are manufactured from scratch in laboratories (most modern medications). [@user context@]
• Biotechnology-derived drugs are produced using DNA technology and genetic engineering of living systems. [1, @user context@]

By Nomenclature

• Chemical name: Describes molecular structure (lengthy, technical). [@user context@]
• Generic (non-proprietary) name: Official worldwide designation (e.g., paracetamol)—this is what clinicians should use to avoid confusion. [@user context@]
• Brand (proprietary) name: Company-assigned marketing name (e.g., Tylenol, Panadol)—one drug may have dozens of brand names. [@user context@]

Drug-Drug Interactions (DDIs)

Mechanisms and Clinical Significance

• A DDI occurs when one medication pharmacokinetically or pharmacologically influences another, differing from anticipated effects of each agent alone, potentially altering absorption, distribution, metabolism, or excretion. 1
• Pharmacodynamic DDIs occur when one medication modifies another's pharmacological effect in additive, synergistic, or antagonistic fashion. 1
• Approximately 2.8% of hospital admissions result directly from DDIs, though actual incidence is likely underestimated as medication issues are often reported as adverse drug reactions. 1
• Drug interactions increase exponentially with polypharmacy: 10.9% of patients experience interactions with 2-4 drugs, while 80.8% experience interactions with ≥10 drugs. 7

Critical Interaction Examples

• CYP3A4 inhibitors (azole antifungals, macrolide antibiotics, HIV protease inhibitors) significantly increase concentrations of substrate drugs, causing hypotension and syncope. 7
• CYP3A4 inducers (carbamazepine, phenytoin, rifampin, St. John's wort) substantially reduce substrate drug concentrations, decreasing efficacy. 7
• Grapefruit interacts with most statins, increasing blood levels when taken concurrently. 1
• Antioxidant vitamins adversely interact to reduce niacin's antiatherosclerotic benefit. 1

Specialized Drug Formulations

Nanoparticle Pharmacology

• For nanoparticle formulations, the pharmacokinetic disposition depends on the carrier rather than the parent drug until drug release occurs. 1
• Encapsulated or conjugated drug represents an inactive prodrug that must be released to become active. 1
• Released drug (also called legacy drug or warhead) consists of protein-bound or free drug with pharmacokinetics identical to non-carrier formulations. 1
• Sum total refers to encapsulated/conjugated drug plus released drug. 1

Clinical Application Principles

Patient-Specific Factors Affecting Drug Response

• Age, sex, lifestyle, genetic polymorphisms, and disease states (hepatic/renal impairment, cardiac failure) affect drug metabolism and response. 1
• Elderly patients often require dose adjustments due to age-related changes in body composition affecting drug distribution and elimination. 1, 4
• Body weight and renal function adjustments optimize tolerance, particularly in elderly patients, women, and smaller-sized men. 1
• Ethnic groups demonstrate varying toxicity rates to certain medications, requiring knowledge-based prescribing adjustments. 1

Monitoring and Safety Considerations

• Adequate drug concentrations must reach the target site for therapeutic effects, with suboptimal concentrations potentially explaining treatment failures. 4
• Missed doses have different clinical impacts depending on drug half-life, requiring tailored patient monitoring strategies. 4
• Medications affecting liver enzymes can dramatically alter concentrations of other drugs, necessitating dose adjustments when adding or removing medications. 4
• Systematic monitoring of treatment response and adverse effects using pharmacokinetic principles to interpret timing and patterns is essential. 4