The Path Drugs Take Through the Body

Substances can enter the body through various means. Drugs can be smoked, snorted, injected, swallowed (pills, capsules, liquids), or applied through transdermal means (applied to the skin).1^,2 Some substances can be eaten, such as marijuana.³

The method by which a drug is administered, along with other factors, determines the speed of onset of effects.⁴

The Path of Drugs in the Body

Drugs undergo four stages within the body:

1. Absorption.
2. Distribution.
3. Metabolism.
4. Excretion.

After a drug is administered, it is absorbed into the bloodstream.

The circulatory system then distributes the drug throughout the body. Then it is metabolized by the body. The drug and its metabolites are then excreted.^5,6

Step 1: Absorption

Absorption refers to the movement of a drug from its site of administration to the bloodstream.⁵ It occurs after a substance is administered, but there are several different methods in which someone can use or abuse a substance that will affect how the drug is absorbed.

The various routes of drug administration include:

• Oral administration – This includes swallowing pills, drinking a liquid, or eating a substance. In this method of administration, most of the absorption of the substance takes place in the small intestine.⁵ The drug will then move to the liver and then back into the bloodstream to be transported to its destination.7 The liver and intestinal walls metabolize many drugs, lessening how much gets to the bloodstream, a process called “the first-pass effect”, or “first pass metabolism”.^5,7,8 Because drugs delivered via other routes such as injection don’t go through first pass metabolism, it may only take a lower dose than the oral dose to achieve the intended effects (if that drug is significantly prone to the first-pass effect when given orally). This is why a doctor who is injecting a prescription may administer a lower dose than if they were prescribing the same drug in pill form.^5,7
• IV Injection—Injection into a vein – or intravenous (IV) injection – delivers the substance directly into the bloodstream.⁷ Drugs administered this way will be 100% absorbed by definition of absorption.⁶ While the effects of a drug delivered in this manner come on quickly, they also tend to dissipate quickly.⁷
• Subcutaneous Injection—A subcutaneous injection is an injection into the fatty tissue underneath the skin, which enables the substance to move to the capillaries or lymphatic vessels and into the bloodstream.⁷
• Snorting—When drugs are snorted, they are absorbed through nasal tissues into the bloodstream.9 The onset of effects from snorting is more rapid than that of oral administration but not as rapid as smoking or injection.1⁰
• Inhalation (including smoking)—Vapor or smoke goes into the lungs to be absorbed into the bloodstream as rapidly as it would if it were injected. Smoking produces an extremely rapid high, and effects dissipate quickly. An example of a rapid and short-lived high from smoking is crack cocaine. The effects are quick but go away within 5 to 10 minutes.⁹
• Transdermal administration—The misuse of drugs via this route is not as common as oral administration or injection. Substances that are administered this way may be done so through a patch applied to the skin, which allows the drug to be absorbed into the bloodstream and circulate throughout the body.¹¹ An example of a drug administered this way is the fentanyl patch.¹²

Step 2: Distribution

Once the drug is absorbed, it is carried through the body. It moves from the bloodstream to the tissues and intracellular fluids and binds to receptors. Distribution is reversible: molecules released from the receptors can travel back to the bloodstream.⁵

It is this step, distribution, that can be partially responsible for the unintended side effects of a drug. As the drug is carried throughout the body, it can also negatively impact an organ, or organs, that is not the target organ the drug is intended to reach.¹³

Before a drug can enter the central nervous system (CNS)–the brain and spinal cord–it must pass through the blood-brain barrier. This is a network of tightly woven capillaries that prevents many foreign substances from reaching the brain. Many substances are not able to effectively penetrate the CNS.^5,13

Drugs that do cross the blood-brain barrier (BBB) can have various effects, including the rush of euphoria or the “high” that is commonly associated with illicit drugs and the nonmedical use of some medications. Repeated use of drugs that are able to cross the BBB can also impact the brain in numerous other ways, such as making it hard to feel pleasure from natural rewards (leading to continued, compulsive drug use) and causing problems with executive functioning (planning, making decisions, and solving problems).¹⁴

Research has shown that use of certain drugs, such as cocaine and methamphetamine, can even change the BBB’s function over time. Use of these drugs can cause increased permeability of the BBB, making it a less effective barrier and making it easier for toxins like viruses and bacteria to enter the brain. For example, in individuals who have HIV, the use of stimulants may permit increased migration of HIV-infected leukocytes into the brain, heightening the likelihood and severity of neuroAIDS.¹⁵

Step 3: Metabolism

After the drug has been distrusted, the next phase is metabolism. This is where the drug is broken down. This takes place mostly in the body’s largest internal organ, the liver. (Note: While the liver is the primary site for drug metabolism, other organs such as the kidneys, GI tract, and lungs may also perform metabolic functions.)^13,16

During this phase, proteins called enzymes break down the drug molecules, which creates metabolites. These metabolites are usually less active chemically than the original drug molecule but may in some cases be equally as powerful or even more so.^5,13

The process of enzymatic breakdown can make it easier for the drug to be excreted, which is the final phase.¹³

Step 4: Excretion

The last phase of a drug within the body is excretion. This is the process by which drugs and their metabolites exit the body, primarily via urine or feces.^5,17 Drugs may also be excreted in sweat, saliva, breast milk, or exhaled air. A substance may be excreted in its altered, or metabolized, form or excreted intact.¹⁷