Pharmacology

From From code to clinic

Pharmacology (Greek, pharmakon, "drug" + suffix -logia, "the study of a subject") is the study of drugs' effects on the function of living organisms. While "pharmacology" literally means "the study of drugs", the contemporary definition of pharmacology places emphasis on the study of drugs' effects. Pharmacology lies at the interface between biology, chemistry and medicine. Pharmacology can crudely be broken into two fields: pharmacodynamics and pharmacokinetics:

Pharmacology itself has many subfields. Many medical specialties have overlaps with pharmacology, such as the interfaces between pharmacology with neurology and psychiatry (neuropsychoparhamcology), cardiology (cardiovascular pharmacology) and anesthesiology (anesthetic pharmacology). In addition, pharmacology is an intrinsic part of many medical specialties (e.g. internal medicine), and clinical pharmacology is a medical specialty devoted to pharmacology. Pharmacology is also related to the allied profession of drug preparation and dispensing (pharmacy), to the drug discovery and development process, and to the intrinsic study of drug molecules (medicinal chemistry).

Historical outline

Historically, the study of "pharmacology" has existed in various forms and concerned itself mostly with the (postulated) therapeutic effects of various naturally occurring substances. These precursors of modern pharmacology has had many names, such as traditional medicine, herbalism, and pharmacognosy. The science of pharmacology appeared in the mid-19th century, made possible by medicine and chemistry. The synthetic chemistry of the early 20th century drove an explosion of new synthetic drug classes. Concurrent major advances in biochemistry and physiology had a major part in making the pharmacology we see today. Where the 20th century's biology relied on breaking living systems into parts (reductionism), a fairly recent idea is that the results of the interactions of said parts are important (integrationism). This systems thinking has given rise to systems biology, a discipline that is heavily reliant on mathematical modeling and computer science. Another field that would not be possible without computers is biotechnology, which has allowed for the manipulation of living systems and thus the ability to coerce said systems to produce products (for example, antibiotics and novel semisynthetic drugs - "biopharmaceuticals"). Such biopharmaceuticals are a major part of modern pharmacology.


Pharmacology
Drug · Ligand · Active substance (pharmakon, active pharmaceutical ingredient (API)) · Target · Antitarget · Affinity · Efficacy · Dose · Half-life (t1/2) · Systematic drug naming · History
Pharmaceutical phase
drug reaches body
Routes of administration · Dose (dosage form, loading, maintenance) · Drug formulation (extemporaneous preparation)
Pharmacodynamics (PD)
drug affects body
Ligand · Drug target (receptor, enzyme, ion channel, transport protein) · Affinity · Efficacy · Potency · Spare receptors · Drug action · Drug effect · Agonist (full, partial, inverse) · Antagonist · Agonist-antagonist · Mechanism of action · Effectiveness · Therapeutic index · Off-target activity: pleiotropy, therapeutic, harmful (type A, type B), "dirty drug" · Interaction (drug-drug interaction) · ED50 · LD50
Pharmacokinetics (PK)
body affects drug
(L)ADME: (liberation →) absorption → distribution → metabolism → elimination · Steady state · Pharmacokinetic models · Drug metabolism and pharmacokinetics (DMPK)
Absorption:Solubility · Permeability · Bioavailability (F) · d
Distribution:Concentration (concentration-time curve, area under the curve) · Distribution volume (Vd) · Compartment models (one-compartment, two-compartment) · PBPK models · PKPD models
Metabolism:Half life (t1/2) · Prodrug · Antedrug · Parent drug · Daughter metabolite
Elimination:Clearance · Elimination kinetics order: zero (0), first (1), non-linear · Saturation
Clinical pharmacology Good clinical practice · Over-the-counter · Prescription · Off-label use · Unlicensed use · Polytherapy · Response failure · Drug discontinuation/deprescription · Polypharmacy · Response prediction · Therapeutic drug monitoring
Research and industry Hit (hit selection) · Lead (lead optimization) · Hit-to-lead · New chemical entity · First-in-class · Best-in-class · Drug pipeline · Target engagement · Druggability and "druglikeness" · Lipinski's rule of five · Eroom's law · Polypharmacology · Pharmacology and statistics · "Big pharma" · Drug approval process · Regulation · Pharmacopoeia · Drug pricing · Repurposing · "Orphans": drug, disease, receptor
Pharmaceutical research process:Preclinical trials (drug design, validation, discovery, development) → clinical trials (phases: 0, I, II, III) → post-market surveillance (phase IV)
MethodsForward (classical) and reverse pharmacology · High-throughput screening · Structure-activity relationship (QSAR) · Applicability domain · Biological assay · Receptor cloning · Computational chemistry · Computational pharmacology
Fields of pharmacology Neuro · Psycho · Neuropsych · Systems · Radio · Clinical · Anesthetic · Epidemiology · Genomic