Intro to Pharmacology

• Pharmacology can be defined as the study of substances that interact with living systems through chemical processes, especially by binding to regulatory molecules and activating or inhibiting normal body processes.
• Drug - any substance that brings about a change in biologic function through its chemical actions
• Drugs may be chemicals administered to

  • achieve a beneficial therapeutic effect on some process within the patient (Ex. Losartan - antihypertensive)
  • or for their toxic effects on regulatory processes in parasites infecting the patient (Ex. Mebendazole - anthelmintic)
• PHARMACOLOGY is the study of drugs, their sources, their nature, and their properties
• DRUG refers to a chemical substance of known structure, other than a nutrient or an essential dietary ingredient which, when administered to a living organism, produces a biological effect.

  May be:

  • synthetic chemicals
  • Chemicals obtained from plants or animals
  • Products of genetic engineering
• Genetic engineering is the transfer of DNA from one organism to another using biotechnology. The organism receiving the DNA is said to be genetically modified (GM)
• Medicines are drugs prepared in different dosage forms (liquid, solid, semisolid) quantifying the right amount of drug for achieving a therapeutic outcome.
• Medical pharmacology - the science of substances used to prevent, diagnose, and treat disease
• Toxicology - deals with the undesirable effects of chemicals on living systems, from individual cells to humans to complex ecosystems
• Poisons are drugs that have almost exclusively harmful effects.
• Paracelsus (1493–1541) famously stated that “the dose makes the poison, ” = any substance can be harmful if taken in the wrong dosage
• Toxins are usually defined as poisons of biologic origin, ie, synthesized by plants or animals, in contrast to inorganic poisons such as lead and arsenic.
• Pharmacokinetics explains what our body does to the drug once it is taken.
• Absorption - The movement of the drug from the site of administration to the systemic circulation (bloodstream). Due to its anatomical structure, the organ which is the most important site of drug absorption is the small intestine.
• Distribution is the process by which drug diffuses or is transferred from intravascular space (systemic circulation/ bloodstream) to extravascular space (body tissues/ site of action)
• Metabolism (aka Biotransformation) The chemical conversion or transformation of drugs into compounds which are easier to eliminate. Liver is the principal site of drug metabolism.
• Excretion - The removal of unchanged drug from the body via renal, biliary, or pulmonary processes. Major pathway of excretion is via the kidney.
• Pharmacodynamics is the study of the biochemical and physiologic effects of drugs.
• Pharmacogenomics — the relation of the individual’s genetic makeup to his or her response to specific drugs
• PHARMACODYNAMICS – the actions of the drug on the body.
• PHARMACOKINETICS – the actions of the body on the drug.
• In most cases, the drug molecule interacts as an agonist (activator) or antagonist (inhibitor) with a specific target molecule that plays a regulatory role in the biologic system.
• This target molecule is called a receptor.
• Drugs may be synthesized within the body (eg, hormones) or may be chemicals not synthesized in the body (ie, xenobiotics).
• The receptor concept has important practical consequences for the development of drugs and for arriving at therapeutic decisions in clinical practice.

  1. Receptors largely determine the quantitative relations between dose or concentration of drug and pharmacologic effects.
  2. Receptors are responsible for selectivity of drug action.
  3. Receptors mediate the actions of pharmacologic agonists and antagonists
• PHYSICAL NATURE OF DRUGS:

  To interact chemically with its receptor, a drug molecule must have the (SiESA): appropriate size, electrical charge, shape, and atomic composition.
• Furthermore, a drug is often administered at a location distant from its intended site of action, eg, a pill given orally to relieve a headache.
• practical drug should be inactivated or excreted from the body at a reasonable rate so that its actions will be of appropriate duration
• Drugs may be solid at room temperature (eg, aspirin, atropine), liquid (eg, nicotine, ethanol), or gaseous (eg, nitrous oxide). These factors often determine the best route of administration.
• Alimentary canal - Enteral:

  1. Oral
  2. Sublingual
  3. Rectal
• Nonalimentary canal - Parenteral: (IISIT)

  1. Intravascular (intravenous and intra-arterial)
  2. Intramuscular
  3. Subcutaneous
  4. Intradermal (Skin)
  5. Transdermal
• Other routes of administration:

  1. Inhalation
  2. Intranasal
  3. Intrathecal / Intraventricular
  4. Topical
  5. Intra-articular
• Enteral administration (administering a drug by mouth) is the safest and most common, convenient, and economical method of drug administration.
• In Enteral, drug may be swallowed, allowing oral delivery, or it may be placed under the tongue (sublingual), or between the gums and cheek (buccal), facilitating direct absorption into the bloodstream
• Most drugs absorbed from the GI tract enter the portal circulation and encounter the liver before they are distributed into the general circulation.
• These drugs undergo first-pass metabolism in the liver, where they may be extensively metabolized before entering the systemic circulation
• Oral drugs are

  • easily self-administered, and toxicities and/or overdose of oral drugs may be overcome with antidotes, such as activated charcoal.
  • However, the pathways involved in oral drug absorption are the most complicated, and the low gastric pH inactivates some drugs.
  • some drugs are absorbed in the stomach but DUODENUM is often the major site because of its larger absorptive surface (100 m2)
• SMALL INTESTINE:

  • includes (DJI) duodenum, jejunum, and ileum
  • contains folds called as folds of kerckbing, result in 3 fold increase in surface area.
  • these folds possess finger like projections called villi which increase the surface area 30 times.
  • from the surface of villi protrude several microvilli which increase the surface area 600 times.
  • blood flow is 6-10 times that of stomach
  • pH range is 6-7.5 , favorable for most drugs to remain unionised.
• Small intestine is the major site for absorption of most drugs due to its large surface area.
• Sublingual / Buccal allows the drug to diffuse into the capillary network and to enter the systemic circulation directly.