How Do Drugs Work?

To understand how drugs work, one must understand the concept of drug kinetics. In short, drug kinetics refers to the actions taken by the human body to deal with a medicine. These actions involve the processes of drug absorption into the body, distribution of that drug to various tissues, metabolism (or breakdown), and excretion (or elimination). Of the above processes, absorption is the most significant.


Absorption is the process by which a drug passes from its site of administration into the circulation (bloodstream). The blood receives a drug from the site of administration and carries it to all the organs, including those on which the drug acts. The speed, ease, and degree of absorption are related to the route of administration. There are several sites at which drugs are commonly administered. They are as follows:
  • Intravenous administration (IV) - IV refers to the injection of a drug directly into the blood, most commonly into a peripheral vein.
  • Intramuscular injection (IM) - In an intermuscular injection, the drug is injected into the muscle. This type of injection may have erratic absorption. If suspended in an oil base, an IM medicine usually has a slow and even absorption. (i.e. penicillin IM)
  • Subcutaneous injection (SQ, SC) - With a subcutaneous injection, the drug is injected just beneath the skin. A subcutaneous injection provides slower absorption than an IM. (i.e. insulin)
  • Rectal administration - In this type of administration, the drug passes through the rectal lining (mucosa) into the blood. Absorption is highly variable and may cause irritation of the rectal mucosa. This route is mainly used for antinausea and antiemetic (antivomiting) drugs.
  • Oral route - This is the most commonly used route of administration for drugs. It uses the oral lining (mucosa) and the gastrointestinal tract (GI).
    • The oral mucosa administration includes sublingual (under the tongue) and buccal (in the cheek) methods. These methods provide convenient routes when rapid onset of action is required (i.e. sublingual nitroglycerin) and are convenient ways to administer drugs that are unstable in the gastointestinal environment.
    • Absorption of drugs from the GI tract depends on the drug's ability to pass across intestinal cell membranes, withstand the highly acidic environment of the stomach, and resist destruction in the liver (first-pass effect). In most cases drugs pass through cell membranes of intestines by simple diffusion, from an area of high concentration (inside the lumen of the intestines) to an area of lower concentration (bloodstream). Active transport across the GI mucosa, very much like a shuttle system, is another way some substances are absorbed (i.e. Vitamin B12). Other factors that may affect absorption of drugs include food and other medications that may inactivate the drug.


After the drug is absorbed, it is then distributed to various organs of the body. Distribution is influenced by how well each organ is perfused (supplied by blood), organ size, binding of the drug to various components of blood and tissues, and permeability of tissue membranes. The more fat-soluble a drug is, the higher its ability to pass across the cell membrane is. The blood-brain-barrier restricts passage of drugs from the blood into the central nervous system and cerebrospinal fluid. Protein binding (attachment of the drug to blood proteins) is an important consideration influencing drug distribution. Many drugs are bound to blood proteins such as serum albumin (the main blood protein) and are not available as active drugs.


Metabolism occurs via two types of reactions: phase I and phase II. The goal of metabolism is to change the active part of medications (also referred to as the functional group), making them more water-soluble and more readily excreted by the kidney. (ie. the body is trying to get rid of the "foreign" drug) Changing the molecular structure of drugs increases their water solubility and decreases their fat solubility, which speeds up the excretion of the drug in the urine. Phase I reactions involve oxidation, hydrolysis, and reduction. Oxidation and reduction processes make a molecule's charge more positive or negative than the original drug. Regardless of the positivity or negativity, a charged molecule is dissolvable in water. (blood serum is primarily water) These reactions take place primarily in the liver by enzymes known as the cytochrome p-450 enzyme system. Oxidative metabolism may result in formation of an active metabolite or inactive compound. Phase II reactions involve conjugation (which means adding another compound) to form glucuronides, acetates, or sulfates, by adding glucose, acetate, or sulfate molecules, respectively. These reactions generally inactivate the pharmacologic activity of the drug and may make it more prone to elimination by the kidney.


Excretion occurs primarily through the urine. Fecal excretion is seen with drugs that are not absorbed from the intestines or have been secreted in the bile (which is discharged into the intestines). Drugs may also be excreted in the expired air through the lungs, in the perspiration, or in breast milk. There are three processes by which drugs are eliminated through the urine: by pressure filtration of the drug through the kidney component called the Glomerulus, through active tubular secretion (like the shuttle system), and by passive diffusion from areas of high drug concentration to areas of lower concentration.

The above paragraphs explain what the human body does to the drug (pharmacokinetics). What the drug does to the body is called pharmacodynamics; this term refers to the action of the drug at the tissue-,cellular-, and molecular level. Pharmacodynamic processes are specific to and different for each drug.

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