Chapter 1 · Module 1 of 6 · General Principles

Introduction to Pharmacology

The foundational frameworks, nomenclature, drug development pipeline, and routes of administration that underpin all of clinical pharmacology

Every drug-body interaction is governed by two inseparable frameworks: pharmacokinetics, which tracks what the body does to a drug through absorption, distribution, metabolism, and elimination; and pharmacodynamics, which defines what the drug does to the body at its molecular target
Drugs carry three distinct names serving different purposes — chemical, generic, and brand — and generic name stems encode drug class membership, enabling class recognition from an unfamiliar name alone
Drugs originate from four source categories — natural, synthetic, semisynthetic, and biologic — each with characteristic examples and distinct regulatory and structural properties
The drug development pipeline runs from preclinical animal studies through four sequential clinical phases before regulatory approval; approximately 90 percent of compounds entering clinical testing fail, most often in Phase II
Route of administration is a primary pharmacokinetic variable: it determines bioavailability, speed of onset, and clinical applicability — matching route to clinical urgency and drug properties is a reasoning skill, not a memorization exercise

Section 1 — The PK / PD Framework

Foundational Frameworks

Pharmacokinetics and Pharmacodynamics

Pharmacokinetics (PK)

What the Body Does to the Drug

Determines how much drug reaches the target, when, and for how long

Absorption — drug enters the bloodstream
Distribution — drug moves to tissues
Metabolism — drug is chemically altered
Elimination — drug leaves the body

Pharmacodynamics (PD)

What the Drug Does to the Body

Determines the nature and magnitude of the drug's effect at its target

Binds molecular target: receptor, enzyme, channel, or transporter
Binding produces a biochemical or physiological effect
Effect magnitude relates to drug concentration at the target
Therapeutic index — ratio of toxic dose to effective dose

Extending PK/PD

Pharmacogenomics and Toxicology

Pharmacogenomics

Genetic Variation in Drug Response

Inherited differences that alter PK or PD in individual patients

Enzyme variants alter drug metabolism — poor vs. rapid metabolizers
Receptor variants alter pharmacodynamic response
Same dose, different patients → very different plasma levels or effects
Clinically tested: codeine, warfarin, clopidogrel enzyme genotyping

Toxicology and the Therapeutic Index

When Drug Becomes Poison

Boundary between therapeutic effect and toxicity is largely a matter of dose

Therapeutic index = toxic dose ÷ effective dose
Narrow therapeutic index → toxic dose close to effective dose
Requires careful monitoring and dose individualization
Classic narrow-index drugs: digoxin, warfarin, lithium

Section 2 — Drug Nomenclature and Sources

The Three-Name System

Chemical, Generic, and Brand Names

Three Names — Three Purposes

Chemical name — exact molecular structure; precise but unwieldy; not used clinically
Generic name (INN) — standardized, publicly owned; encodes drug class via stems; standard for institutional prescribing
Brand name — manufacturer-assigned; trademark-protected; multiple brands may exist for one generic after patent expiry

Four Drug Sources

Natural — plants, animals, microorganisms; morphine, digoxin, penicillin
Synthetic — entirely by chemical synthesis; most modern small-molecule drugs
Semisynthetic — natural core chemically modified for improved potency or stability; ampicillin, oxycodone
Biologic — large molecules from living cell systems; monoclonal antibodies, recombinant insulin, vaccines

Key INN Stems — Class Recognition from Name Alone

Stem	Drug Class	Examples
-olol	Beta-adrenergic blockers	Metoprolol, propranolol, atenolol
-pril	Angiotensin-converting enzyme inhibitors	Lisinopril, enalapril, ramipril
-sartan	Angiotensin II receptor blockers	Losartan, valsartan, irbesartan
-statin	HMG-CoA reductase inhibitors	Atorvastatin, simvastatin
-prazole	Proton pump inhibitors	Omeprazole, pantoprazole
-mab	Monoclonal antibodies	Rituximab, trastuzumab
-nib	Small-molecule kinase inhibitors	Imatinib, erlotinib
-floxacin	Fluoroquinolone antibiotics	Ciprofloxacin, levofloxacin
-cycline	Tetracycline class antibiotics	Doxycycline, minocycline

Section 3 — Drug Development Pipeline

From Laboratory to Approval

Clinical Trial Phases and Regulatory Pathway

Preclinical

Lab and Animal Studies

Safe enough for humans? IND application to FDA required before proceeding.

Phase I

20–100 Healthy Volunteers

Is it safe? What is the PK profile and maximum tolerated dose?

Phase II

100–500 Patients

Does it work? Preliminary efficacy and dosing. Most drugs fail here.

Phase III

Hundreds to Thousands of Patients

Better than comparator? Pivotal RCTs. NDA or BLA submitted on success.

Phase IV

Post-Approval Surveillance

What rare effects emerge in broader populations? Can prompt label changes or withdrawal.

Approximately 90% of drugs entering clinical testing do not receive approval — most commonly because of inadequate efficacy or unacceptable toxicity discovered in human trials

Section 4 — Routes of Administration

Route Determines Bioavailability and Onset

Enteral and Parenteral Routes

Enteral — via Gastrointestinal Tract

Oral

Most common, convenient, and well-studied route
Subject to first-pass metabolism in the liver before reaching systemic circulation
Bioavailability reduced by first-pass effect; onset slower than parenteral
Default for chronic therapy in patients who can swallow reliably

Enteral — Bypasses First-Pass

Sublingual

Drug absorbed into venous drainage of mouth
Liver does not see drug before it reaches systemic circulation
Rapid onset; avoids extensive first-pass destruction
Prototype: nitroglycerin (therapeutically inactive orally at standard doses)

Parenteral — 100% Bioavailability

Intravenous (IV)

Drug delivered directly into bloodstream
100% bioavailability by definition; fastest onset
Most precise plasma concentration control
First choice in emergencies and critical care

Parenteral — Tissue Injection

Intramuscular (IM) / Subcutaneous (SC)

Drug diffuses from tissue into capillaries
IM onset faster than SC; both avoid first-pass effect
SC enables depot formulations — sustained release over hours to days
Prototype depot route: insulin SC

Parenteral — Pulmonary Delivery

Inhalation

Large pulmonary surface area enables rapid absorption
Maximizes drug concentration at the airway target
Minimizes systemic exposure relative to delivered dose
Preferred for bronchodilators and inhaled corticosteroids

Parenteral — Sustained Systemic Release

Transdermal

Drug absorbed slowly through the skin
Avoids first-pass metabolism; maintains steady plasma levels
Suitable for drugs requiring 24-hour continuous delivery
Examples: fentanyl patch (pain), nicotine patch (cessation)

Author / Source	Title	Publication
Katzung BG, ed.	Basic and Clinical Pharmacology, 15th edition	McGraw-Hill, 2021
Brunton LL, Knollmann BC, eds.	Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th edition	McGraw-Hill, 2023
Ritter JM, Flower R, Henderson G, Loke YK, MacEwan D, Rang HP	Rang & Dale's Pharmacology, 9th edition	Elsevier, 2019
Relling MV, Evans WE	Pharmacogenomics in the clinic	Nature, 2015; 526(7573):343–350
Atkinson AJ Jr, Huang SM, Lertora JJL, Markey SP, eds.	Principles of Clinical Pharmacology, 3rd edition	Academic Press, 2012
Serafini M, Cargnin S, Massarotti A, Tron GC, Pirali T, Genazzani AA	What's in a name? Drug nomenclature and medicinal chemistry trends using International Nonproprietary Name publications	Journal of Medicinal Chemistry, 2021; 64(13):9297–9313
World Health Organization	The use of stems in the selection of International Nonproprietary Names for pharmaceutical substances	WHO, 2013
Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J	Clinical development success rates for investigational drugs	Nature Biotechnology, 2014; 32(1):40–51
Friedman LM, Furberg CD, DeMets DL, Reboussin DM, Granger CB	Fundamentals of Clinical Trials, 5th edition	Springer, 2015
Waller DG, Sampson AP	Medical Pharmacology and Therapeutics, 5th edition	Elsevier, 2018