Introduction to Pharmacology



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Chapter 1 : Introduction to Pharmacology



Introduction arrow_upward


  • Pharmacology is a science which deals with the study of drugs and their action on human body.
  • Pharmacology studies the effects of drugs and how they exert their effects.
  • Pharmacology has 2 main divisions:
    • Pharmacokinetics: What the body does to the drug?
    • Pharmacodynamics: Studies the mechanisms by which drugs work.

    Pharmacokinetics arrow_upward


  • It is defined as a process by which drugs are metabolized and eliminated through body.
  • Pharmacokinetics process is divided into 4 parts:
    • Absorption
    • Distribution
    • Metabolism
    • Elimination

    Absorption arrow_upward


  • Absorption is movement of the drug from its site of administration into the circulation.
  • Absorption involves several phases:
    • Oral absorption.
    • Subcutaneous and Intramuscular absorption.
    • Absorption through topical sites like skin, cornea, mucous membranes etc.


    Distribution arrow_upward


  • Distribution is the dispersion or dissemination of substances throughout the fluids and tissues of the body.
  • Drug has to be distributed to its target (where it will act).
  • The extent of distribution of a drug depends on:
    • Lipid solubility.
    • Ionization at physiological pH.
    • Extent of binding to plasma and tissue proteins.
    • Presence of tissue-specific transporters.
    • Differences in regional blood flow.
  • Factors affecting drug distribution:
    • Lipid: Water partition coefficient of drug.
    • pKa (acid dissociation constant) value of the drug.
    • Degree of plasma protein.
    • Affinity for different tissues.
    • Fat: Lean body mass ratio, which can vary with age, sex, obesity.
    • Diseases like cardiac heart failure, uremia, and cirrhosis.

    Metabolism arrow_upward


  • Drug metabolism is the biochemical modification of pharmaceutical substances by living organisms, usually through specialized enzymatic systems.
  • It has 2 phases:
    • Phase I (Fictionalization): These enzymes modify the drug chemically by processes such as oxidation, reduction and hydrolysis or by the removal and addition of an active group.

    Oxidation

  • This reaction involves addition of oxygen, or removal of hydrogen.
  • Reduction

  • This reaction is the converse of oxidation and involves cytochrome P-450 enzymes working in the opposite direction.
  • Hydrolysis

  • This is a cleavage of drug molecule by taking up a molecule of water.
  • Cyclization

  • This is a formation of ring structure from a straight chain compound.
  • Decyclization

  • This is opening up of ring structure of the cyclic drug molecule.

    • Phase 2 (Conjugation): Conjugation reactions involve the addition of molecules naturally present in the body to the drug molecule.

    Glucuronide formation

  • Compounds with a hydroxyl or carboxylic acid group are easily conjugated with glucuronic acid.
  • This is derived from glucose.
  • Sulfation

  • The phenolic compounds and steroids are sulfated by sulfotransferase.
  • Glutathione Conjugation

  • It is a minor pathway.
  • Glycine Conjugation

  • Salicylates and other drugs having carboxylic acid group are conjugated with glycine.
  • Methylation

  • The amines and phenols can be methylated.
  • Acetylation

  • Compounds having amino or hydrazine residues are conjugated with the help of acetyl coenzyme-A.


  • Elimination arrow_upward


  • Remaining drug or parts of drug will be eliminated via kidneys, lungs, bile, and skin. This process is known as elimination.
  • Elimination takes place by 4 ways:

  • By Lungs

  • Only occurs with highly volatile or gaseous agents
  • By Skin

  • Small amounts of few drugs can pass through the skin and excreted via sweat.
  • By Bile

  • After most psychoactive drugs are processed by the liver, they are usually less fat soluble, less capable of being reabsorbed, and therefore capable of being excreted in urine.
  • By Kidney

  • Excrete most of the products of body metabolism through kidney
  • Closely regulate the levels of most of the substances found in body fluids
  • Psychoactive drugs are often reabsorbed out of the kidneys, so the liver has to enzymatically transform the drugs; so with minimal reabsorption, they can exit via urine.



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