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Pharmacology

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Pharmacology is the scientific study of how chemical substances, especially drugs, interact with living systems. It asks what a drug does to the body and what the body does to the drug, and it links chemistry, physiology, and medicine.[1]

This article is for education only and is not medical advice. Talk to a qualified clinician about any medication.

Pharmacology and pharmacy

Pharmacology and pharmacy are related but distinct. Pharmacology is a research science that explains how drugs work, why they cause side effects, and how new medicines are discovered. Pharmacy is a health profession focused on preparing, dispensing, and monitoring medicines for patients.

Pharmacokinetics

Pharmacokinetics describes the movement of a drug through the body, usually summarized by the acronym ADME. Absorption is the passage of a drug from its site of administration into the blood. Distribution is its spread into tissues and fluids. Metabolism is its chemical transformation, mostly in the liver, where the cytochrome P450 family of enzymes oxidizes many drugs into forms that are easier to remove. Excretion is the final elimination of the drug and its metabolites, mainly through the kidneys and bile.

Two measures summarize much of this behavior. Bioavailability is the fraction of a dose that reaches the systemic circulation unchanged; an oral dose may lose a large share to incomplete absorption and first pass metabolism in the liver. The elimination half-life is the time needed for the plasma concentration to fall by half, and it helps determine how often a drug must be given. Induction or inhibition of cytochrome P450 enzymes is a common source of drug interactions.

Pharmacodynamics

Pharmacodynamics describes what a drug does once it reaches its target. Most drugs act on proteins such as receptors, enzymes, ion channels, and transporters. An agonist binds a receptor and activates it, while an antagonist binds the receptor and blocks activation by other molecules.

A dose-response curve plots the size of an effect against drug concentration. Potency refers to the amount of drug needed to produce a given effect, so a more potent drug reaches the same effect at a lower dose. Efficacy refers to the maximum effect a drug can produce, regardless of dose. The therapeutic index compares the dose that causes toxicity with the dose that produces the desired effect, and a narrow index means the margin for safe use is small.

Drug discovery and development

Modern drug development begins with target identification, the choice of a molecule or pathway linked to a disease. Researchers screen compound libraries, refine promising hits, and test candidates in cells and animals during preclinical studies. Clinical testing proceeds in phases.[2] Phase 1 studies give the drug to a small group to assess safety and pharmacokinetics. Phase 2 studies examine effectiveness and side effects in people with the condition. Phase 3 studies compare the drug with existing treatment or placebo in larger populations. If the evidence supports a favorable balance of benefit and risk, the FDA can approve the drug for a specific indication. Phase 4 postmarketing studies and pharmacovigilance, the ongoing analysis of adverse event reports, continue after approval because rare effects may appear only with wide use.

Subfields

Clinical pharmacology studies drug effects in humans and guides rational prescribing. Toxicology studies the harmful effects of chemicals, including drugs at excessive doses. Pharmacogenomics examines how genetic variation, such as differences in cytochrome P450 genes, changes individual responses to drugs. Neuropharmacology studies drugs that act on the nervous system. Pharmacoenvironmentology examines how drugs and their metabolites enter and affect the environment after use.

History

In the early twentieth century, Paul Ehrlich proposed the idea of a magic bullet, a chemical that would strike a disease agent while sparing the host, and his laboratory developed arsphenamine as a treatment for syphilis. In 1928 Alexander Fleming observed that a Penicillium mold killed bacteria, which led to the mass production of penicillin in the 1940s. In the late 1950s and early 1960s, the sedative thalidomide was linked to thousands of severe birth defects, mostly in Europe. In response, the United States passed the Kefauver-Harris Amendments of 1962, which required manufacturers to provide evidence of effectiveness from adequate and well controlled studies before approval.[3]

Pharmacology of aging

Geroscience is a research field built on the idea that aging biology itself is the largest risk factor for many chronic diseases, such as heart disease and dementia. It asks whether drugs acting on shared aging mechanisms could delay several conditions at once. This section describes that research neutrally; none of these compounds is approved to treat aging.

The National Institute on Aging supports the Interventions Testing Program, which tests candidate compounds in genetically heterogeneous mice at three independent sites.[4] Rapamycin, an inhibitor of the nutrient sensing kinase mTOR, extended median and maximum lifespan in both male and female mice, including when treatment began late in life. Acarbose also extended lifespan in both sexes, while 17-alpha-estradiol and canagliflozin extended lifespan in males only. Metformin given alone did not produce a significant lifespan extension in its program test.

Senolytics are compounds that selectively remove senescent cells, which stop dividing and release inflammatory signals. In a 2018 study supported by the National Institute on Aging, a combination of dasatinib and quercetin cleared senescent cells, improved physical function, and extended remaining lifespan in naturally aging mice.[5]

Metformin, a long used diabetes medication, is the focus of the planned Targeting Aging with Metformin trial, known as TAME. Its design calls for a placebo controlled study of about 3000 older adults aged 65 to 79, with a primary outcome built from a composite of several age related diseases. The composite outcome reflects a regulatory challenge: drugs are approved for specific disease indications, and aging is not classified as a disease indication. Researchers designed TAME in consultation with the FDA partly to test whether such a framework could support future trials of drugs aimed at aging biology.[6]

  • Explain the difference between potency and efficacy using two hypothetical drugs with different dose-response curves.
  • How might inhibition of a cytochrome P450 enzyme by one drug change the half-life and safety of a second drug?
  • Write an essay on how the thalidomide disaster reshaped the evidence required for drug approval.
  • Why do clinical trials proceed in phases rather than testing a new drug in a large population at once?
  • What are the scientific and regulatory arguments for and against treating aging as a drug indication?
  • Prompt idea: ask an AI assistant to compare the mechanisms of rapamycin and senolytics in mice, and then check each claim against primary sources.
  • Why might a compound extend lifespan in male mice but not in female mice, and what does this imply for study design?
  • Prompt idea: ask an AI assistant to draw an ADME diagram for an oral drug and label where bioavailability is lost.

Readings from Wikipedia

See also

References

  1. ↑ "Pharmacology", Encyclopaedia Britannica.
  2. ↑ "The Drug Development Process", U.S. Food and Drug Administration.
  3. ↑ "Promoting Safe and Effective Drugs for 100 Years", U.S. Food and Drug Administration.
  4. ↑ "Supported Interventions", Interventions Testing Program, National Institute on Aging.
  5. ↑ "Senolytic drugs reverse damage caused by senescent cells in mice", National Institute on Aging, 9 July 2018.
  6. ↑ "Targeting Aging with Metformin (TAME)", Innovation in Aging, via PubMed Central, National Library of Medicine.
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