pharmacology

BASIC PRINCIPLES OF PHARMACOLOGY

INTRODUCTION

• Presenter: Prof. Kwasi A. Bugyei

• Affiliation: Dept of Medical Pharmacology, University of Ghana Medical School, Korle-Bu, Accra

DEFINITION OF PHARMACOLOGY

• Etymology: Pharmacology derives from Greek; 'pharmakon' means drug, and 'logos' means knowledge or discourse.

• Understanding:

  • All knowledge pertaining to drugs.

  • The science focused on the action of drugs on biological systems, encompassing plants, animals, and human beings.

PHARMACOLOGY AS A DISCIPLINE

• Definition:

  • The study of interaction between living systems (biological systems) and small molecules (chemicals), especially xenobiotics and endogenous substances.

• Interaction:

  • Defined as a mutual relationship where drug effect interacts with body effect.

DIVISIONS OF PHARMACOLOGY

1. Pharmacokinetics (PK):

   • How the body handles drugs.

     • Includes ADME: Absorption, Distribution, Metabolism, Excretion

2. Pharmacodynamics (PD):

   • How drugs affect the body.

     • Involves mechanisms of action (physiological/biochemical).

BASIC PRINCIPLES

1. Active Principle:

   • Every drug has an active principle causing pharmacological effects (therapeutic, side, or toxic).

2. Receptor Binding:

   • Most drugs bind to receptors, which come in various types.

3. Dose-Effect Relationship:

   • A relationship exists between dose and effect (response).

4. Congeners:

   • Drugs with similar chemical structures tend to have similar effects but varying potency.

5. Inter-individual Variability:

   • Drug response varies among individuals within a population.

6. Drug Group Naming:

   • Drugs are grouped, e.g., antihypertensives, with names based on their uses and characteristics, such as the management of hypertension.

THE DRUG

• Origins of the term 'Drug':

  • Derived from Dutch "droog" meaning dry; French "drogue" meaning dry herb.

• Definition:

  • Small chemical molecules that induce changes in physiological or biochemical processes in the body.

  • Can have toxic effects on organisms invading the body.

DRUG EXAMPLES

• Students should identify drugs based on the provided definition, including:

  • (list of examples to be supplied by students)

DRUG AND POISON

• Definition of a Poison:

  • Any substance with a toxic effect, can also be a drug in certain circumstances.

• Difference Between Drugs and Poisons:

  • Drugs have a safety dose range, whereas poisons typically have little or no safety dose range, leading to toxicosis even at small doses.

• When does a drug become a poison?

  • Overdose

  • Prolonged administration of the recommended dose

  • Incorrect administration route

USES OF DRUGS

• Medical Uses:

  • Treatment (e.g., antibiotics)

  • Diagnosis (e.g., edrophonium)

  • Prevention (e.g., vaccines, antibiotics)

• Other Uses:

  • Socio-economic purposes (e.g., antifertility drugs)

  • Recreational purposes (e.g., marijuana, alcohol)

SOURCES OF DRUGS

• Categories of Sources:

1. Natural Sources:

   • Biological: from animals (e.g., insulin, heparin), plants (e.g., morphine, reserpine, artemether), microorganisms (e.g., antibiotics).

   • Non-biological: from minerals (e.g., MgSO4, Ca(HCO3)2).

2. Synthetic Sources:

   • Drugs manufactured solely from chemicals with no natural additions (e.g., sulphonamides, procaine, corticosteroids, methotrexate).

3. Semisynthetic Sources:

   • Combining natural and synthetic components (e.g., Co-amoxiclav = Clavulanic acid + Amoxicillin).

4. Genetically Engineered Drugs:

   • DNA recombinant techniques (e.g., insulin produced by transgenic animals).

5. Immunological Sources:

   • Produce drugs (e.g., vaccines) by using antigens and antibodies.

6. Serological Sources:

   • Derived from antiserum/antivenins (e.g., snake antivenins).

PHARMACOKINETICS

• Definition of Pharmacokinetics:

  • Refers to how the body handles drugs through ADME factors:

  1. Absorption:

  • Movement of the drug from the site of administration into circulation.

  1. Distribution:

  • Movement of the drug from circulation to the tissues.

  1. Metabolism:

  • Chemical conversion of the drug into more polar compounds.

  1. Excretion:

  • Elimination of drugs from the body via renal, biliary, or other processes.

DRUG ADMINISTRATION

• Routes of Administration:

  • Enteral: Via the gastrointestinal tract.

  • Parenteral: Bypasses the gastrointestinal tract.

FORMULATIONS OF DRUGS

• Common forms:

  • Tablets, Oblets, Capsules, Caplets, Pills, Suppositories, Pessaries, Suspensions, Solutions, Syrups, Liniment, Lotions, Gels, Bitters, Creams.

FACTORS INFLUENCING DRUG ABSORPTION

• Routes of drug administration determine the site or surface area of absorption, impacting the effective concentration of the drug in circulation.

DRUG ADMINISTRATION ROUTES

• Enteral Routes:

  1. Oral (PO)

  2. Naso-gastric

  3. Oro-gastric

  4. Buccal

  5. Sublingual

  6. Rectal

• Parenteral Routes:

  • Injection routes (IV, Epidural, IM, Intraosseous, SC, Intra-arterial, Intraperitoneal, Intrasynovial, Intrathecal) and non-injection routes (Topical, Transdermal, Inhalational).

DRUG DISTRIBUTION

• Definition:

  • The transfer of a drug from systemic circulation to various tissues within the body, which includes:

  • Site of action

  • Storage depot

  • Organs for drug metabolism

  • Organs/routes for drug elimination

• Types of Drug Tissues:

  1. Plasma Protein Binding

  2. Cellular Reservoirs

  3. Fat as Reservoir/Depot

  4. Bone/Teeth as reservoirs

• Plasma Protein Binding:

  • Drug-binding dynamics with plasma proteins such as albumin (for acidic drugs) and α1-acid glycoprotein (for basic drugs).

• Distribution to Placenta:

  • Modern understanding indicates the placenta does not effectively exclude drugs, as seen in the thalidomide disaster.

DRUG BIOTRANSFORMATION (METABOLISM)

• Definition:

  • Refers to the biological transformation of drugs from less polar to more polar substances to enhance elimination.

• Purpose:

  • Convert drugs into polar substances, promoting excretion. Importantly, biotransformation does not equal detoxification.

• Reasons for Biotransformation:

  1. Inert parent drugs can convert into active drugs (prodrugs).

  2. Metabolites might exhibit increased, reduced, or no activity compared to the parent compound.

  3. Some metabolites can potentially have adverse effects or toxicity.

ENZYMES IN DRUG BIOTRANSFORMATION

• Enzymes catalyze all biotransformation reactions, which include:

  1. Microsomal Enzymes

  2. Non-microsomal Drug Metabolizing Enzymes

• Variability in rate among individuals is observed due to genetic polymorphism affecting biotransformation rates.

EXCRETION

• Definition:

  • Process of transferring drugs (parent compounds or metabolites) from the body into the external environment. Polar drugs are more efficiently excreted, although non-polar drugs may also be efficiently excreted through lungs.

• Principal Excretory Organs:

  • Kidneys (primary), liver, mammary glands, lungs, intestinal tract, skin (sweat glands), salivary glands, and lacrimal glands.

KIDNEY FUNCTION IN EXCRETION

• The kidney receives about 25% of cardiac output, facilitating drug excretion through nephrons, enhancing the organ's excretory capabilities.

RENAL EXCRETION

• Polar drugs and metabolites are usually excreted in urine. Some drugs may be expelled unchanged in urine.

HEPATO-BILIARY EXCRETION OF DRUGS

• Two Pathways:

  1. Drugs directly enter hepatocytes and are secreted unchanged into bile, eventually reaching feces.

  2. Drugs can be transformed into metabolites, then secreted into bile leading to prolonged drug effect.

PULMONARY EXCRETION

• Particularly significant for volatile drugs (e.g., anesthetics). The lungs provide a large surface area for effective excretion.

OTHER ROUTES OF EXCRETION

• Include excretion through milk (risk to nursing babies), saliva, sweat, and tears.