An Introduction to Testing for Drugs of Abuse. William E. SchreiberЧитать онлайн книгу.
Reading
Articles and reports
1 Canadian Substance Use Costs and Harms Scientific Working Group. (2020). Canadian substance use costs and harms 2015‐2017. (Prepared by the Canadian Institute for Substance Use Research and the Canadian Centre on Substance Use and Addiction.) Ottawa: Canadian Centre on Substance Use and Addiction. www.ccsa.ca/canadian‐substance‐use‐costs‐and‐harms‐2015‐2017‐report.
2 Nutt, D., King, L.A., Saulsbury, W., and Blakemore, C. (2007). Development of a rational scale to assess the harm of drugs of potential misuse. Lancet. 369: 1047–1053.
3 Nutt, D.J., King, L.A., and Phillips, L.D. (2010). Drug harms in the UK: a multicriteria decision analysis. Lancet. 376: 1558–1565.
4 US Department of Health and Human Services (HHS), Office of the Surgeon General (2016). Facing Addiction in America: The Surgeon General's Report on Alcohol, Drugs, and Health. Washington, DC: HHS https://addiction.surgeongeneral.gov/sites/default/files/surgeon‐generals‐report.pdf.
Websites
National Institute on Drug Abuse
Drugs, brains and behavior: the science of addiction
www.drugabuse.gov/publications/drugs‐brains‐behavior‐science‐addiction/introduction
Videos
2‐Minute Neuroscience – Reward system. www.neuroscientificallychallenged.com/blog/2‐minute‐neuroscience‐reward‐system.
AACC Pearls of Laboratory Medicine
Drugs of abuse testing
2 How the Body Handles Drugs
There are four steps in a drug's journey through the body: (i) absorption, (ii) distribution, (iii) metabolism, and (iv) excretion. These processes determine the time frame during which a drug can be detected in blood, urine, and other body fluids. They also determine the rate at which new compounds (i.e., metabolites) appear after a drug is taken. The study of drug absorption, distribution, metabolism, and excretion – what the body does to a drug – is called pharmacokinetics.
Absorption
Absorption is the process by which drug molecules enter the bloodstream. The rate of this process depends on the route of administration.
| Oral | When taken orally, a drug is absorbed across the mucosal lining of the stomach or small intestine before entering the blood. Onset of pharmacological effects typically occurs in 15–60 minutes, depending on the properties of the drug and its formulation (i.e., tablet vs liquid). |
| Following absorption, orally administered drugs are carried by the portal circulation directly to the liver, where they may be converted to less active metabolites before entering the systemic circulation. This “first‐pass” effect can limit the bioavailability of a drug. | |
| Example: benzodiazepines | |
| Intravenous | Intravenous (IV) injection bypasses the absorption step, as the drug is introduced directly into the circulation. The IV route provides the fastest onset of drug action. |
| Example: heroin | |
| Inhalation | Air‐borne drug molecules are pulled into the lungs, cross alveolar walls (where gas exchange takes place) and diffuse into adjacent capillaries. This happens when a drug is smoked or inhaled as an aerosol. Onset of drug effects can be very rapid. |
| Example: cannabis | |
| Insufflation | Better known as “snorting,” insufflation causes drugs to contact nasal passages, which are lined by a mucous membrane. It is a more porous barrier than skin and allows rapid diffusion of drugs into underlying blood vessels. |
| Example: cocaine | |
| Transdermal | Diffusion across skin is a slow process. Drug patches are used to deliver a constant amount of drug per unit of time and maintain stable levels in blood. |
| Example: fentanyl |
Other routes exist (e.g., sublingual, intramuscular or subcutaneous injection), but they are not typically used with illicit or diverted prescription drugs.
Distribution
Once a drug has entered the circulation, it is transported through the body and diffuses into tissues. This process is influenced by several factors.
Blood flow – drugs are more rapidly distributed to areas of the body with a high rate of blood flow. For most drugs of abuse as well as many prescription medications, the main target organ is the brain, which is well perfused (15% of cardiac output in the resting state).
Chemical structure – drugs that are lipophilic and are not ionized more readily cross lipid bilayers and enter cells.
Protein binding – when bound to plasma proteins (mainly albumin), drugs cannot freely pass through capillary walls and enter tissues. The degree of plasma protein binding therefore affects the amount of drug that reaches its target.
Drugs that are very lipid soluble may distribute into adipose tissue, accumulate there, and eventually diffuse back into the circulation. This can prolong the action of the drug, and it increases the length of time a drug or its metabolite(s) can be detected in blood or urine.
Metabolism
The purpose of metabolism is to transform lipid‐soluble compounds, which readily enter tissues, into a more water‐soluble form that can be excreted. This occurs in two phases.
Phase I – drug molecules are chemically altered by oxidation, reduction, or hydrolysis. These reactions are catalyzed by enzymes in the liver and, to a lesser extent, in other tissues. The most important drug‐metabolizing enzyme system, cytochrome P450 (CYP), contains multiple isoforms that act on a wide variety of drugs. The resulting products are usually inactive or less active than the parent drug. However, in some cases the metabolite has