Drug Removal

Drugs are eliminated from the body either unchanged as the parent drug or as metabolites (a changed form of the drug). Organs that excrete drugs eliminate polar compounds (water soluble) more readily than components with high lipid (fat) solubility. The exception to this premise is the lungs. Lipid soluble drugs are not readily eliminated until they are metabolized to more polar compounds.

Possible sources of excretion include:

•  Breath

•  Urine

•  Saliva

•  Perspiration

•  Feces

•  Milk

•  Bile

•  Hair

The kidney is the most important organ involved in the elimination of drugs and their metabolites. substances excreted in the feces usually involve orally ingested unabsorbed drugs or metabolites excreted in the bile that are not reabsorbed from the intestinal tract. Excretion of drugs in milk is relevant because excreted drugs can produce drug toxicity in the nursing infant. Pulmonary excretion (through breathing) is important as it pertains to the elimination of anesthetic gases and vapors, as well as alcohol.

Excretion through the kidneys

The kidneys are a pair of bean-shaped organs, each a little smaller than the fist and weighing about 0.25 pounds. They lie on the back of the abdominal cavity at the level of the lower ribs. They act as a pressure filter. On its way through the kidneys the blood is filtered. The liquid or "primary urine" consists of a considerable amount of the blood's water, together with all substances dissolved in this water (including drugs). The kidneys reabsorb most of the water and some of the dissolved substances. Components that are fat-soluble tend to diffuse back into the bloodstream.

The kidneys perform two major functions:

•  They excrete most of the end-products of body metabolism (including drugs); They closely regulate the levels of most of the substances found in body fluids.

•  Substances that must be excreted include the end-products of body metabolism, as well as sodium, potassium, and chloride, which frequently accumulate in the body in excess quantities. The kidneys must also be capable of conserving water, sugar, and the necessary quantities of sodium, potassium and chloride.

Since drugs are small particles dissolved in the blood, they too are usually filtered into the kidneys and then reabsorbed back into the bloodstream. Water is reabsorbed from the kidney into the bloodstream to a much greater extent than most drugs, so the drugs become more concentrated inside the kidney than they are in the blood. In order for the kidney to eliminate drugs from the body, the drug must somehow be prevented from being reabsorbed from the urine into the bloodstream. The drug must be chemically changed into a compound that is less fat-soluble and therefore less capable of being reabsorbed.


This process of converting fat-soluble drugs into water soluble metabolites that can be excreted by the kidney is carried out in the liver. Usually (but not always) the process of metabolism decreases the pharmacological activity of a drug. Even though a metabolite might remain in the body (awaiting excretion), it would usually be pharmacologically inactive or less active and would not produce the effects of the parent drug to the same extent. Many drugs can increase the rate at which an enzyme system metabolizes a variety of drugs, thereby increasing the speed with which a drug is eliminated. Certain drugs induce an increase in enzyme activity. This process can decrease the pharmacological response to certain agents metabolized in the liver. For example, phenobarbital stimulates the production of enzymes that normally metabolize the anti-coagulant warfarin. Thus phenobarbital decreases the effect of warfarin by increasing the metabolism of warfarin. Some drugs can also stimulate their own metabolism. This is one mechanism to explain why increasing doses of a drug must be administered in order to produce the same effect that smaller doses produced earlier. Regarding the placental barrier referred to earlier, the fetus may excrete drugs through the umbilical cord back into the bloodstream of the mother. The mother can then eliminate the drug through the liver and kidneys. After delivery, however, the newborn baby is no longer attached to the mother and must deal on its own with any drug in its blood. Unfortunately, the newborn baby has few drug metabolizing enzymes in the liver and the kidneys may not yet be fully functional. This means, that the infant has great difficulty metabolizing and excreting drugs.

Biliary and fecal excretion

Many metabolites of drugs created in the liver are excreted into the intestinal tract in the bile. Hence the intestine is not only a site of absorption but it is also a site of excretion. The net excretion by this route may be greatly reduced by subsequent reabsorption into the bloodstream of fat-soluble compounds further along the intestines. In this case drugs will undergo the process of excretion all over again and the drug effect is prolonged. This excretion/reabsorption phenomenon is called enterohepatic cycling. Metabolites may be excreted in the feces. More commonly, they are reabsorbed into the blood and ultimately excreted in the urine.

Excretion by other routes

Minute amounts of drugs are excreted into sweat, saliva and tears. Drugs excreted into the saliva enter the mouth, where they are usually swallowed. Their fate thereafter is the same as drugs taken orally. Some drug concentrations in the saliva parallel those found in the plasma.Since breast milk is more acidic than blood plasma, basic compounds may become slightly concentrated in this location. Although excretion into hair and skin occurs in small quantities, it does have forensic significance.

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