I. GENERAL PHARMACOLOGY – Self learning series -1 with Dr sheen Page # 1 unit -1, Edition 2023 south Asian

• The word pharmacology comes from:
  • Pharmacon = an active principle or drug.
  • Logus = discourse or study.
• Pharmacology is the science that studies substances that interact with living systems through chemical processes.
• These substances work mainly by binding to regulatory molecules.
• They can activate or inhibit normal body functions.
• These substances are usually given as drugs to produce beneficial therapeutic effects in patients.
• Pharmacology is a branch of medicine that combines several biomedical sciences, including:
  • Chemistry
  • Biochemistry
  • Physiology
  • Clinical medicine
• Pharmacology is both:
  • A basic science.
  • An applied science.
• Pharmacology is the foundation of rational drug therapy.
• Pharmacology studies:
  • Sources of drugs.
  • Biochemical effects of drugs.
  • Physiological effects of drugs.
  • Mechanism of action of drugs.
  • Therapeutic uses of drugs.
  • Adverse effects of drugs.
• Pharmacology also explains:
  • What effects drugs produce.
  • How drugs produce those effects.
• Example: Paracetamol
  • Lowers body temperature during fever.
  • It works by inhibiting the enzyme cyclooxygenase (COX) in the CNS.
  • This reduces the production of inflammatory mediators.
• Example: Penicillin
  • Treats certain bacterial infections.
  • It inhibits a key enzyme needed for bacterial cell wall synthesis.
  • As a result, bacterial cell walls cannot form properly.
• In 1966, the World Health Organization (WHO) defined a drug as:
  • Any substance or product used or intended to modify or study physiological systems or pathological conditions for the benefit of the patient.
• According to the New Drugs and Clinical Trials Rules, 2018 (India):
  • An Active Pharmaceutical Ingredient (API) is any substance used in a pharmaceutical formulation.
  • It provides pharmacological activity.
  • It may also directly help in:
    • Diagnosis
    • Cure
    • Mitigation
    • Treatment
    • Prevention of disease
    • Restoring normal physiological functions
    • Correcting physiological functions
    • Modifying physiological functions
  • It can be used in both humans and animals.
• Drugs are chemical substances that affect living organisms.
• Clinicians use drugs to:
  • Diagnose diseases.
  • Prevent diseases.
  • Treat diseases.
• Safe use of drugs requires knowledge of:
  • Mechanism of action.
  • Drug doses.
  • Routes of administration.
  • Adverse drug effects.
  • Drug interactions.
• Medicinal or organic chemists create a new candidate molecule called a New Chemical Entity (NCE).
• Pharmacologists test the NCE:
  • In vitro.
  • On isolated tissues.
  • In cell cultures.
  • In animals (in vivo).
  • In humans.
• Successful testing can lead to the discovery of new therapeutic drugs.
• General pharmacology includes the study of:
  • Sources of drugs.
  • Routes of drug administration.
  • Drug absorption.
  • Factors affecting absorption.
  • Drug distribution.
  • Drug biotransformation (metabolism).
  • Drug excretion.
  • Drug–receptor interaction.
  • Mechanism of drug action.
  • Adverse drug effects.
  • Preclinical evaluation.
  • Clinical evaluation.

KEY CONCEPT

• Pharmacology is the science of drugs and their effects on living systems.
• It combines chemistry, biochemistry, physiology, and clinical medicine.
• It explains drug sources, actions, uses, adverse effects, and mechanisms.
• Drugs act by interacting with regulatory molecules to activate or inhibit body functions.
• Safe drug therapy requires understanding drug action, dose, administration, adverse effects, and interactions.
• New drugs are developed by creating New Chemical Entities (NCEs) and testing them from laboratory studies to human trials.
• General pharmacology mainly covers drug sources, administration, absorption, distribution, metabolism, excretion, receptor interaction, adverse effects, and drug evaluation.

A. Branches of Pharmacology

• Pharmacology has two main branches:
  1. Pharmacokinetics
  2. Pharmacodynamics

1. Pharmacokinetics (What the body does to the drug)

• Pharmacokinetics studies what happens to a drug inside the body.
• It describes the movement of the drug through the body.
• It includes:
  • Absorption
  • Distribution
  • Biotransformation (metabolism)
  • Excretion
• Example: Chlorpromazine
  • It is absorbed faster by the parenteral route than by the oral route.
  • It binds to plasma proteins and tissue proteins.
  • It is metabolized in the liver.
  • It is excreted within 15–30 hours.

2. Pharmacodynamics (What the drug does to the body)

• Pharmacodynamics studies how a drug acts on the body.
• It explains the:
  • Molecular actions of the drug.
  • Biological actions of the drug.
  • Therapeutic actions of the drug.
• Example: Pantoprazole
  • It inhibits the proton pump (H⁺/K⁺ ATPase).
  • This decreases acid secretion in the stomach.
• The relationship between pharmacokinetics and pharmacodynamics is shown in Figure 1.1.

KEY CONCEPT

• Pharmacology has two major branches:
  • Pharmacokinetics = What the body does to the drug (Absorption, Distribution, Biotransformation, Excretion).
  • Pharmacodynamics = What the drug does to the body (Drug action and therapeutic effects).
• Chlorpromazine is an example of pharmacokinetics.
• Pantoprazole is an example of pharmacodynamics.
• Figure referenced: Figure 1.1.

B. Other Branches

1. Pharmacotherapeutics

• Pharmacotherapeutics is the branch of medicine that applies pharmacokinetic and pharmacodynamic principles in clinical practice.
• It is used for:
  • Treatment of disease.
  • Diagnosis of disease.
  • Prevention of disease.

2. Toxicology

• Toxicology is the science of poisons.
• Poisons are substances that are harmful, dangerous, or can cause death in humans and animals.
• Many drugs can act as poisons when given in large doses.
• Example: Aspirin
  • In low doses, it acts as an anticoagulant.
  • It works by inhibiting thromboxane A₂.
  • It is useful for heart patients.
  • In high doses, it can cause gastric ulceration.
  • Severe bleeding may occur and can be fatal.

3. Chemotherapy

• Chemotherapy studies the effects of drugs on microorganisms and parasites living inside the body.
• It is also used to treat cancer by targeting cancer cells.

4. Clinical Pharmacology

• Clinical pharmacology studies drugs and their clinical use.
• It provides information about:
  • Drug potency.
  • Drug usefulness.
  • Drug doses.
  • Drug toxicity.
• It helps ensure the safe clinical use of drugs.
• It includes:
  • Clinical trials of new drugs in humans.
  • Identification of adverse drug reactions.
  • Reporting of adverse drug reactions.
  • Rational use of drugs.
  • Essential drug concept.

5. Pharmacoepidemiology

• Pharmacoepidemiology studies the effects of drugs on populations.

6. Pharmacoeconomics

• Pharmacoeconomics studies:
  • Cost-effectiveness of drug treatment.
  • Cost of medications.
• It is especially important for groups such as:
  • Elderly patients.
  • AIDS patients.

7. Pharmacogenetics

• Pharmacogenetics studies genetic variations that cause different drug responses among individuals and populations.
• Some people show greater-than-normal sensitivity to standard drug doses.
• Genetic screening before prescribing may help provide individualized therapy.

8. Pharmacogenomics

• Pharmacogenomics applies genomic technologies to:
  • Discover new drugs.
  • Further study and improve older drugs.

9. Pharmacognosy

• Pharmacognosy studies drugs obtained from:
  • Plants.
  • Animals.

10. Pharmacy

• Pharmacy is the art and science of preparing suitable dosage forms for drug administration in humans and animals.
• It also involves:
  • Dispensing drugs.
  • Identification of medicinal substances.
  • Selection of medicinal substances.
  • Collection of medicinal substances.
  • Purification of medicinal substances.
  • Isolation of medicinal substances.
  • Standardization of medicinal substances.
  • Quality control of medicinal substances.

11. Clinical Pharmacy

• Clinical pharmacy is a health science in which pharmacists provide patient care to optimize drug therapy.
• It promotes:
  • Health.
  • Wellness.
  • Disease prevention.
• It is patient-oriented.
• It includes advising patients on the proper use of:
  • Prescribed drugs.
  • Over-the-counter (OTC) drugs.

12. Pharmacovigilance

• Pharmacovigilance involves:
  • Monitoring adverse drug events.
  • Detecting adverse drug events.
  • Reporting adverse drug events.
  • Taking remedial measures.

KEY CONCEPT

• Pharmacotherapeutics: Clinical use of drugs for treatment, diagnosis, and prevention.
• Toxicology: Study of poisons and toxic effects of drugs.
• Chemotherapy: Drugs used against microorganisms, parasites, and cancer cells.
• Clinical Pharmacology: Safe clinical use of drugs, including clinical trials and adverse drug reaction monitoring.
• Pharmacoepidemiology: Study of drug effects in populations.
• Pharmacoeconomics: Study of the cost-effectiveness of drug therapy.
• Pharmacogenetics: Study of genetic differences affecting drug response.
• Pharmacogenomics: Use of genomic technology in drug discovery and development.
• Pharmacognosy: Study of drugs from plant and animal sources.
• Pharmacy: Preparation, dispensing, and quality control of medicines.
• Clinical Pharmacy: Patient-centered pharmacy care and medication counseling.
• Pharmacovigilance: Monitoring, detecting, reporting, and preventing adverse drug events.

C. Definitions

1. Pharmacopoeia

• Pharmacopoeia is an official reference book.
• It contains a selected list of established drugs and medicinal preparations.
• It describes:
  • Physical properties of drugs.
  • Tests for drug identity.
  • Drug purity.
  • Drug potency.
• It sets the official standards for drug preparations.
• Some well-known pharmacopoeias are:
  • British Pharmacopoeia (BP)
  • Indian Pharmacopoeia (IP)
  • International Pharmacopoeia (IP)
  • United States Pharmacopoeia (USP)
• The description of a drug preparation in a pharmacopoeia is called a monograph.
• A monograph includes:
  • Drug description.
  • Identification characteristics.
  • Standards of purity.
  • Standards of strength.
  • Limits of impurities.
  • Drug assay method.
  • Storage instructions.
  • Other instructions.

2. National Formulary

• A National Formulary is a collection of drugs recognized as legal standards.
• It specifies the standards of:
  • Purity.
  • Quality.
  • Strength.
• It is published by the government or authorized health agency of a country.
• Examples:
  • National Formulary of India — published by the Government of India.
  • British National Formulary (BNF) — jointly published by the British Medical Association (BMA) and the Royal Pharmaceutical Society.

3. Essential Medicines

• According to the WHO, Essential Medicines are those that meet the priority healthcare needs of the population.
• These medicines should be:
  • Available at all times.
  • Available in adequate amounts.
  • Supplied in appropriate dosage forms.
  • Of assured quality.
  • Provided with adequate information.
  • Affordable for individuals and the community.
  • Available within a functioning healthcare system.

4. Orphan Drugs

• Orphan drugs are:
  • Drugs.
  • Vaccines.
  • Biological products.
• They are used for:
  • Diagnosis.
  • Prevention.
  • Treatment of rare diseases.
  • Treatment of some common diseases that are mainly found in poor countries.
• Pharmaceutical companies have little interest in developing these drugs because they provide very little commercial profit.
• Developing orphan drugs requires:
  • Very high development costs.
  • Low expected sales.
• Therefore, the development cost is often not recovered.
• In India, an orphan drug is intended to treat a disease affecting not more than 5 lakh people.
• Clinical studies in children are highly restricted because of ethical and legal reasons.
• Many rare diseases occur in children.
• Diseases affecting very small patient populations are called orphan diseases because only a few approved treatment options are available.
• Rare (or orphan) diseases affect about 6–8% of the world’s population.
• Examples of orphan diseases:
  • Infantile spinal muscular atrophy.
  • Cystic fibrosis.
  • Patent ductus arteriosus (PDA).
  • Lysosomal storage disorders.
  • Familial adenomatous polyposis (FAP).
  • Acute intermittent porphyria.
• Examples of orphan drugs:
  • Miglustat — Type 1 Gaucher disease.
  • Iloprost — Pulmonary arterial hypertension in patients with NYHA Class III or IV symptoms.
  • Bosentan — WHO Class II–IV pulmonary arterial hypertension symptoms.
  • Pegvisomant — Acromegaly.
  • Busulfan — Allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia.
• Many countries have made laws to encourage orphan drug development.
• These countries provide incentives and support for developing orphan drugs.

KEY CONCEPT

• Pharmacopoeia: Official book that sets standards for drugs and medicinal preparations through monographs.
• National Formulary: Government-approved reference that defines the legal standards of drug purity, quality, and strength.
• Essential Medicines: WHO-listed medicines that should always be available, affordable, effective, and of assured quality.
• Orphan Drugs: Drugs developed for rare diseases or diseases with little commercial interest.
• Orphan Diseases: Rare diseases affecting small populations, often with limited treatment options.
• Many governments encourage orphan drug development by providing legal and financial support.

D. Pharmacoeconomics

• Pharmacoeconomics is the description and analysis of the costs of drug therapy for healthcare systems and society.
• It helps use limited healthcare resources to provide the maximum benefit to:
  • Patients.
  • Healthcare payers.
  • Society.
• Pharmacoeconomics is used to:
  • Develop healthcare guidelines.
  • Support healthcare policy decisions.
  • Plan national health policies.
• Information from pharmacoeconomics is important for national healthcare spending.
• It helps choose the best treatment options when resources are limited.
• The main purpose of pharmacoeconomics is to:
  • Analyze healthcare costs.
  • Allocate resources appropriately.
  • Guide research and investment in specific drugs or drug groups.
  • Compare the cost of one drug or drug therapy with another.
• Pharmacoeconomics is a subdivision of health economics.

Need of Pharmacoeconomics

• Minimize healthcare expenditure while achieving the best healthcare outcomes.
• Reduce the cost of drugs and healthcare-related services.
• The relevant components are shown in Figure 1.2.
• Pharmacoeconomics considers:
  • Direct costs.
  • Indirect costs.
  • Other healthcare expenses.
• It evaluates healthcare from the perspective of:
  • Patients.
  • Healthcare providers.
  • Payers.
  • Society.
• Both direct and indirect costs are included in pharmacoeconomic analysis.
• Outcome analysis includes:
  • Clinical outcomes
    • Disease outcomes.
    • Treatment outcomes.
    • Morbidity.
    • Mortality.
  • Economic outcomes
    • Direct costs.
    • Indirect costs.
    • Tangible costs.
  • Humanistic outcomes
    • Patient preferences.
    • Quality of life.
• Different pharmacoeconomic methods are shown in Figure 1.3.

KEY CONCEPT

• Pharmacoeconomics studies the cost and value of drug therapy.
• It helps use limited healthcare resources efficiently.
• It supports healthcare guidelines, policy decisions, and national health planning.
• It compares the costs of different drugs and treatment options.
• It considers:
  • Direct costs.
  • Indirect costs.
  • Clinical outcomes (disease, treatment, morbidity, mortality).
  • Economic outcomes (direct, indirect, and tangible costs).
  • Humanistic outcomes (patient preference and quality of life).
• Pharmacoeconomics is a subdivision of health economics.

E. Sources of Drugs (Figure 1.4)

• Drugs are mainly obtained from:
  • Plants.
  • Animals.
  • Microorganisms.
  • Minerals.
• Today, most therapeutic drugs are produced from:
  • Synthetic products.
  • Semisynthetic products.

1. Animal Sources

• Drugs obtained from animals include:
  • Insulin.
  • Heparin.
  • Gonadotrophins.
  • Thyroid extract.
  • Antitoxic sera (e.g., antisnake venom).

2. Mineral Sources

• Drugs obtained from minerals include:
  • Liquid paraffin.
  • Ferrous sulfate.
  • Magnesium sulfate.
  • Magnesium trisilicate.
  • Kaolin.

3. Microorganisms (Bacteria and Fungi)

• Many important antibiotics are obtained from microorganisms, including:
  • Penicillin.
  • Streptomycin.
  • Erythromycin.
  • Polymyxin B.
  • Bacitracin.
  • Chloramphenicol.
  • Nystatin.
  • Griseofulvin.
• Other useful products produced by microorganisms include:
  • Streptokinase
    • An enzyme produced by Streptococcus pyogenes (gram-positive cocci).
  • Vitamin B₁₂ (Cyanocobalamin)
    • Produced by Streptomyces griseus.

KEY CONCEPT

• Drugs are obtained mainly from:
  • Plants.
  • Animals.
  • Microorganisms.
  • Minerals.
• Most modern drugs are synthetic or semisynthetic.
• Animal sources: Insulin, heparin, gonadotrophins, thyroid extract, antisnake venom.
• Mineral sources: Liquid paraffin, ferrous sulfate, magnesium sulfate, magnesium trisilicate, kaolin.
• Microorganisms: Produce many antibiotics and other products such as streptokinase and vitamin B₁₂.

E. Sources of Drugs (Figure 1.4)

• Drugs are mainly obtained from:
  • Plants.
  • Animals.
  • Microorganisms.
  • Minerals.
• Today, most therapeutic drugs are produced from:
  • Synthetic products.
  • Semisynthetic products.

1. Animal Sources

• Drugs obtained from animals include:
  • Insulin.
  • Heparin.
  • Gonadotrophins.
  • Thyroid extract.
  • Antitoxic sera (e.g., antisnake venom).

2. Mineral Sources

• Drugs obtained from minerals include:
  • Liquid paraffin.
  • Ferrous sulfate.
  • Magnesium sulfate.
  • Magnesium trisilicate.
  • Kaolin.

3. Microorganisms (Bacteria and Fungi)

• Many important antibiotics are obtained from microorganisms, including:
  • Penicillin.
  • Streptomycin.
  • Erythromycin.
  • Polymyxin B.
  • Bacitracin.
  • Chloramphenicol.
  • Nystatin.
  • Griseofulvin.
• Other useful products produced by microorganisms include:
  • Streptokinase
    • An enzyme produced by Streptococcus pyogenes (gram-positive cocci).
  • Vitamin B₁₂ (Cyanocobalamin)
    • Produced by Streptomyces griseus.

KEY CONCEPT

• Drugs are obtained mainly from:
  • Plants.
  • Animals.
  • Microorganisms.
  • Minerals.
• Most modern drugs are synthetic or semisynthetic.
• Animal sources: Insulin, heparin, gonadotrophins, thyroid extract, antisnake venom.
• Mineral sources: Liquid paraffin, ferrous sulfate, magnesium sulfate, magnesium trisilicate, kaolin.
• Microorganisms: Produce many antibiotics and other products such as streptokinase and vitamin B₁₂.

E. Sources of Drugs (Figure 1.4)

• Gum Resins
  • Asafetida
    • Used as a carminative.
    • Used as an antispasmodic.
• Oleo Gum Resin
  • Myrrh
    • Has local stimulant properties.
    • Has antiseptic properties.
    • Commonly used in mouthwash.
• Balsams
  • Benzoin
    • Used internally as an expectorant.
    • Used externally as an astringent.
  • Balsam Tolu
    • Used as a stimulating expectorant.
• Gums
  • Gums are secretory products of plants.
  • On hydrolysis, they produce simple sugar-like polysaccharides.
  • They are pharmacologically inert.
  • They are mainly used as:
    • Suspending agents.
    • Emulsifying agents.
  • Common examples:
    • Gum acacia.
    • Tragacanth.
• Tannins
  • Tannins are non-nitrogenous plant constituents.
  • Chemically, they are phenolic derivatives.
  • They are known for their astringent action.
  • They are commonly used in the treatment of:
    • Diarrhea.
    • Burns.
  • Important plant sources include:
    • Hirda (used in combination as Triphala).
    • Amla.
    • Behera.
    • Ashoka bark.
    • Black catechu.

KEY CONCEPT

• Asafetida (Gum resin): Carminative and antispasmodic.
• Myrrh (Oleo gum resin): Local stimulant, antiseptic, and used in mouthwash.
• Benzoin (Balsam): Expectorant internally and astringent externally.
• Balsam Tolu: Stimulating expectorant.
• Gums: Plant secretions that are pharmacologically inert and used as suspending and emulsifying agents.
• Tannins: Phenolic plant compounds with astringent action, used for diarrhea and burns.

Note: This text is part of Figure 1.4 (Sources of Drugs). MADE BY SELF LEARNING DR SHEEN