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 (neuropsychopharmacology), 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).

Definitions

Drug

The word "drug" is of uncertain origin. One speculation[1] is that it comes from the Middle Dutch drogue waere, meaning "dry wares", in the sense of "(dry) drugs and spices"[1]. A drug is a chemical substance of known structure that is not a nutrient or dietary ingredient, and that has a biological effect when administered to a living organism. This definition has some important aspects:

  • The fact that a drug is a chemical substance says nothing of its origin. "Chemical" does not necessarily mean man-made: drugs can be synthetic, obtained from plants or animals, or be products of genetic engineering.
  • To be a drug, a substance has to be administered as a drug (exogenous). However, many substances are also produced and released in living organisms (endogenous). A substance being endogenous does not preclude it from being a drug, given that it is administered exogenously: insulin, erythropoietin and thyroxine are endogenous hormones that are also drugs.
  • Popular use of the word drug refers to illegal drug, often those with psychoactive (mind-altering) or addictive ("repeated use despite negative consequences") properties. The pharmacological use of the word includes illegal and legal substances, the latter including drugs used in a therapeutic context. Such therapeutic drugs have many names: "medicinal products", pharmaceutical drugs, or just "medicines".
  • That a drug should not be a nutrient or dietary ingredient is not a watertight definition: certain dietary subtances are used as drugs, such as iron and vitamins.
  • A distinction can be made between the actual medicinal product that is administered, and the substance in said product that produces the desired effect. This substance is known as the active substance, active substance (API), or active drug The medicinal product - such as a pill - can include other things than the active substance, called excipients (this includes stabilisers and solvents)

Per the above definition, a drug should have a biological effect. Here one can distinguish between the biochemical actions by which a drug works (drug action), and the more readily observable, physiological consequences of the drug’s action (drug effect).

Drug action and effect

Pharmacology has two major divisions: pharmacodynamics and pharmacokinetics. The drug action and effect are described by pharmacodynamics. The process of a drug reaching its site of action and subsequent breakdown falls under pharmacokinetics. These two divisions are abbreviated to PD and PK, respectively, and certain areas of study that combine both divisions are sometimes called PKPD (i.e., "PKPD modeling").

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.

References

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