What Does Medication Tolerance Mean

What Does Medication Tolerance Mean Addiction Drug Use Prescription Medications Print What Does Medication Tolerance Mean? By Michael Bihari, MD Michael Bihari, MD, is a board-certified pediatrician, health educator, and medical writer, and president emeritus of the Community Health Center of Cape Cod. Learn about our editorial policy Michael Bihari, MD Medically reviewed by Medically reviewed by Richard Fogoros, MD on December 17, 2019 Richard N. Fogoros, MD, is a retired professor of medicine and board-certified internal medicine physician and cardiologist. He is Verywells Senior Medical Advisor. Learn about our Medical Review Board Richard Fogoros, MD on December 17, 2019 Terry Vine / Getty Images More in Addiction Drug Use Prescription Medications Cocaine Heroin Marijuana Meth Ecstasy/MDMA Hallucinogens Opioids Alcohol Use Addictive Behaviors Nicotine Use Coping and Recovery Medication tolerance, or drug tolerance, occurs when the body gets used to a medication so that either more medication is needed to give the desired effect, or a different medication is needed. Depending on the drug, tolerance can develop acutely, in a manner of days, or chronically, over a number of weeks or months.?? There are several mechanisms behind tolerance, including changes in the metabolism of a drug, cellular changes, or behavioral effects. Tolerance is not always negative, and people may develop a tolerance to the side effects of a drug over time as well. Its important to understand that tolerance is not the same as dependence or addiction, but in the case of substances of misuse, such as some painkillers and alcohol, tolerance can predispose a person to these problems.?? What Is Drug Tolerance? Tolerance is defined as the diminishing effect of a medication following repeated administration at a certain dose. It is often a normal adaptive response to ingested drugs, as the body tries to maintain homeostasis or balance.?? The development of tolerance with a specific drug can vary between different people (there is a genetic influence); with other drugs a person is taking; and with underlying medical conditions that are present. Tolerance also develops at different rates for different effects of the drug. For example, with opioids, people may develop more tolerance to the euphoria caused by the drug than to the respiratory depression caused by the drug. Acute vs. Chronic Tolerance often develops chronically over many weeks but can occur rapidly as well. Tachyphylaxis is the term used to describe the very rapid onset of tolerance, such as that seen after a single dose with cocaine or LSD. Tachyphylaxis also often occurs with antidepressant medications.?? Effects vs. Side Effects As noted above, tolerance may be a negative finding, such as when a drug loses effectiveness over time, but can also be positive, such as when tolerance develops to side effects such as nausea or fatigue. In the case of allergy shots (desensitization), its the development of tolerance thats responsible for the effectiveness of the treatment.?? In some cases, the opposite of tolerance occurs (sensitization), and a drug becomes more effective with repeated use. Tolerance vs. Resistance Resistance also differs from tolerance. With resistance (such as to antibiotics or cancer drugs), resistance develops because bacteria or cancer cells make substances that lead to the drug not working. Tolerance vs. Addiction vs. Dependence The differences between tolerance, dependence, and addiction are important. Many drugs that cause tolerance do have addictive potential, but becoming tolerant does not mean a person is addicted to the drug. Similarly, dependence is defined as the occurrence of withdrawal symptoms when the drug is removed and may occur in the absence of tolerance or addiction.?? Mechanisms There are several different ways in which tolerance to a drug may develop:?? Pharmacodynamic Resistance: In pharmacodynamic, dispositional, or functional tolerance, changes at the cellular level leading to resistance. For example, binding of a drug to a particular receptor on the surface of cells (such as opioid receptors) may fail to cause the signals to be transmitted as in the past, or the body may produce fewer receptors on the surface of cells for the drug to bind with.Metabolic Tolerance: With this mechanism of tolerance, a drug may be broken down and cleared from the body before it reaches its site of action. For example, alcohol can induce the activity of liver enzymes that metabolize the drug.Behavioral or Learned Tolerance: In learned tolerance, people may become accustomed to the effect of a drug. For example, some people who are long-term drinkers can better hold their alcohol, even with the same blood concentration.Conditioned Tolerance: Environmental cues can also lead to tolerance. An example would be a person who routinely drinks at a bar havi ng better eye-hand coordination at the bar than he or she would have at home (after the same number of drinks). Examples of Medication Tolerance Medication tolerance is most often (but not always) related to drugs that affect your body’s brain and nervous system. A few examples include:?? Painkillers such as oxycodoneTranquilizers such as Valium (Diazepam)Over-the-counter sleep aids such as Benadryl (diphenhydramine) Management and Treatment How tolerance is managed depends on the particular drug, what it is being used for, and alternatives that are available. In some cases, increasing the dose may result in the drug working again (though it may also amplify tolerance at that dose).?? If a drug can be discontinued for some time, whats known as a drug holiday, it can often be restarted without tolerance (though tolerance may again occur in time). Tolerance and Cancer Treatment In some settings, such as terminal cancer, apparent tolerance to opioid medications is more often due to worsening cancer (tumor growth or new metastases) rather than tolerance to the drugs. When apparent tolerance occurs, its extremely important to rule out other potential causes of increased pain.?? Even when tolerance occurs, however, issues of possible dependence and addiction are of minor concern. While there is cross-tolerance between different opioids, this is often not complete, and changing to another drug in this class may be helpful. Many of these drugs can also be given at very high doses (there doesnt appear to be a ceiling or maximum dose), and, when increased gradually, there is less concern over problems such as respiratory depression. Tolerance and Substances of Misuse When a person first consumes a potential substance of misuse, be it alcohol, opioids or nicotine, the effects are more potent than they ever will be again. On repeated administration of this drug, a person needs larger and larger amounts to feel any desired effects thus setting up a vicious cycle of abuse, dependence, and withdrawal.  The phenomenon of needing more drugs to produce the desired effect is called tolerance.  ?? Cross-Over When a person becomes tolerant of a certain  central nervous system (CNS) depressant like alcohol, then this person usually becomes tolerant of other drugs of misuse like heroin.?? (Technically, opioids like heroin arent CNS depressants although they have depressant properties.) This phenomenon is called cross-tolerance. Dangers Tolerance can be particularly dangerous for several reasons. When tolerance develops to a different degree to different effects, the risk of overdose can be significant. This is a tragic problem with the opioid epidemic, as tolerance develops more quickly to the euphoric properties of these drugs than to the respiratory depressive properties.?? Switching between different medications in a category also raises the risk of complications. As noted, cross-over can vary, and people who switch off between drugs such as heroin, codeine, morphine, and others, may end up taking a higher dose than they had planned if there is less tolerance to the next drug. For those in recovery, tolerance can be dangerous in another way. Tolerance often decreases with time off of a drug. If a person who has been abstinent from the drug for a period of time resumes his previous level of use, a life-threatening overdose may occur.?? Finally, many abused substances are combined with other drugs for which physiological tolerance does not develop. For example, opioids may be combined with Tylenol (acetaminophen). While tolerance may develop to higher doses of the narcotic so that respiratory depression does not occur, an excess of Tylenol (even just a small excess) from products such as Vicodin (hydrocodone plus acetaminophen) could lead to liver failure. Differences in Tolerance and Susceptibility to Dependence Certain people exhibit a rapid acute tolerance or initial tolerance to a drug. These people may be at higher risk of drug dependence or substance misuse. What to Do If You Are Concerned About Tolerance If you feel that you may be experiencing tolerance to any substance of misuse, its extremely important to inform your physician and get help. Substance misuse and drug dependence can have terrible and deadly personal consequences for you, your loved ones and society as a whole. Please remember that there are health care professionals and support groups that specialize in drug treatment and are empathetic to your needs. Support in your region can be found by zip code in the  behavioral health treatment services locator hosted by the U.S. government.