question: Does taking 10mg of a drug every day, the same as taking 20mg every other day, when it comes to building a tolerance?
comment: No. Your body will always acclimate to things in smaller doses on a more regular basis. An example would be radiation. The same amount of Rems spread over time will have less of an impact than a massive dose at once. Or if that doesn't work for you, think sipping beer vs doing shots.
passages: Drug tolerance
  
  Drug tolerance is a pharmacological concept describing subjects' reduced reaction to a drug following its repeated use. Increasing its dosage may re-amplify the drug's effects; however, this may accelerate tolerance, further reducing the drug's effects. Drug tolerance is indicative of drug use but is not necessarily associated with drug dependence or addiction. The process of tolerance development is reversible (e.g., through a drug holiday) and can involve both physiological factors and psychological factors.
   Drugs in systemic circulation have a certain concentration in the blood, which serves as a surrogate marker for how much drug will be delivered throughout the body (how much drug the rest of the body will "see"). There exists a minimum concentration of drug within the blood that will give rise to the intended therapeutic effect (minimum effective concentration, MEC), as well as a minimum concentration of drug that will give rise to an unintended adverse drug event (minimum toxic concentration, MTC). The difference between these two values is generally referred to as the therapeutic window. Different drugs have different therapeutic windows, and different people will have different MECs and MTCs for a given drug. If someone has a very low MTC for a drug, they are likely to experience adverse effects at drug concentrations lower than what it would take to produce the same adverse effects in the general populace; thus, the individual will experience significant toxicity at a dose that is otherwise considered "normal" for the average person. This individual will be considered "intolerant" to that drug.
   The opposite concept to drug tolerance is drug reverse tolerance (or drug sensitization), in which case the subject's reaction or effect will increase following its repeated use. The two notions are not incompatible and tolerance may sometimes lead to reverse tolerance. For example, heavy drinkers initially develop tolerance to alcohol (requiring them to drink larger amounts to achieve a similar effect) but excessive drinking can cause liver damage, which then puts them at risk of intoxication when drinking even very small amounts of alcohol.
   There are a variety of factors that can affect the MTC, which is often the subject of clinical pharmacokinetics. Variations in MTC can occur at any point in the ADME (absorption, distribution, metabolism, and excretion) process. For example, a patient could possess a genetic defect in a drug metabolizing enzyme in the cytochrome P450 superfamily. While most individuals will possess the effective metabolizing machinery, a person with a defect will have a difficult time trying to clear the drug from their system. Thus, the drug will accumulate within the blood to higher-than-expected concentrations, reaching a MTC at a dose that would otherwise be considered normal for the average person. In other words, in a person that is intolerant to a medication, it is possible for a dose of 10 mg to "feel" like a dose of 100 mg, resulting in an overdose—a "normal" dose can be a "toxic" dose in these individuals, leading to clinically significant effects.
   Pharmacokinetic tolerance (dispositional tolerance) occurs because of a decreased quantity of the substance reaching the site it affects. This may be caused by an increase in induction of the enzymes required for degradation of the drug e.g. CYP450 enzymes. This is most commonly seen with substances such as ethanol.
   Pharmacodynamic tolerance begins when the cellular response to a substance is reduced with repeated use. A common cause of pharmacodynamic tolerance is high concentrations of a substance constantly binding with the receptor, desensitizing it through constant interaction. Other possibilities include a reduction in receptor density (usually associated with receptor agonists), or other mechanisms leading to changes in action potential firing rate. Pharmacodynamic tolerance to a receptor antagonist involves the reverse, i.e., increased receptor firing rate, an increase in receptor density, or other mechanisms.
   One may also develop drug tolerance to side effects, in which case tolerance is a desirable characteristic. A medical intervention that has an objective to increase tolerance (e.g., allergen immunotherapy, in which one is exposed to larger and larger amounts of allergen to decrease one's allergic reactions) is called drug desensitization.
   This type of tolerance is most evident with oral ingestion, because other routes of drug administration bypass first-pass metabolism. Enzyme induction is partly responsible for the phenomenon of tolerance, in which repeated use of a drug leads to a reduction of the drug’s effect. However, it is only one of several mechanisms leading to tolerance.
  
  Section::::Behavioral tolerance.
   Although tolerance is widely considered a passive state, there is evidence indicating it can be an energy-dependent process. Persister cells in "E. coli" can transport intracellular accumulations antibiotic using an energy requiring efflux pump called TolC.
   BULLET::::- 36% in the Royal Marsden Tamoxifen Chemoprevention Study of 1998
  
  BULLET::::- 29% in the National Surgical Adjuvant Breast and Bowel Project of 1998
  
  In March 1999, the "Adherence in the International Breast Cancer Intervention Study" evaluating the effect of a daily dose of Tamoxifen for five years in at-risk women aged 35–70 years was 
  
  BULLET::::- 90% after one year
  
  BULLET::::- 83% after two years
  
  BULLET::::- 74% after four years
  
  Section::::Health and disease management.:Diabetes.
   While most occurrences of pharmacodynamic tolerance occur after sustained exposure to a drug, instances of acute or instant tolerance (tachyphylaxis) can occur.
  
  Section::::Pharmacokinetic (metabolic) tolerance.
  
  Pharmacokinetics refers to the absorption, distribution, metabolism, and excretion of drugs (ADME). All psychoactive drugs are first absorbed into the bloodstream, carried in the blood to various parts of the body including the site of action (distribution), broken down in some fashion (metabolism), and ultimately removed from the body (excretion). All of these factors are very important determinants of crucial pharmacological properties of a drug, including its potency, side effects, and duration of action.
   There is also an aspect of drug intolerance that is subjective. Just as different people have different pain tolerances, so too do people have different tolerances for dealing with the adverse effects from their medications. For example, while opioid-induced constipation may be tolerable to some individuals, other people may stop taking an opioid due to the unpleasantness of the constipation even if it brings them significant pain relief.
  
  Section::::Examples of drug sensitivity.
  
  BULLET::::- Tinnitus after a normal dose of aspirin
  
  BULLET::::- Aspirin-exacerbated respiratory disease
  
  BULLET::::- Liver failure (possibly also kidney failure) after a normal dose of acetaminophen
   Reverse tolerance
  
  Reverse tolerance or drug sensitization is a pharmacological concept describing subjects' increased reaction (positive or negative) to a drug following its repeated use. Not all drugs are subject to reverse tolerance.
   Behavioral tolerance occurs with the use of certain psychoactive drugs, where tolerance to a behavioral effect of a drug, such as increased motor activity by methamphetamine, occurs with repeated use. It may occur through drug-independent learning or as a form of pharmacodynamic tolerance in the brain; the former mechanism of behavioral tolerance occurs when one learns how to actively overcome drug-induced impairment through practice. Behavioral tolerance is often context-dependent, meaning tolerance depends on the environment in which the drug is administered, and not on the drug itself. Behavioral sensitization describes the opposite phenomenon.
   Drug tolerance should not be confused with drug tolerability, which refers to the degree to which overt adverse effects of a drug can be tolerated by a patient.
  
  Section::::Tachyphylaxis.
  
  Tachyphylaxis is a subcategory of drug tolerance referring to cases of sudden, short-term onset of tolerance following the administration of a drug.
  
  Section::::Pharmacodynamic tolerance.
   Tolerance is a process characterized by neuroadaptations that result in reduced drug effects. While receptor upregulation may often play an important role other mechanisms are also known. Tolerance is more pronounced for some effects than for others; tolerance occurs slowly to the effects on mood, itching, urinary retention, and respiratory depression, but occurs more quickly to the analgesia and other physical side effects. However, tolerance does not develop to constipation or miosis (the constriction of the pupil of the eye to less than or equal to two millimeters). This idea has been challenged, however, with some authors arguing that tolerance "does" develop to miosis.
   Multidrug tolerance is caused by a small subpopulation of microbial cells termed persisters. Persisters are not mutants, but rather are dormant cells that can survive the antimicrobial treatments that kill the majority of their genetically identical siblings. Persister cells have entered a non- or extremely slow-growing physiological state which makes them insensitive (refractory or tolerant) to the action of antimicrobial drugs. When such persisting microbial cells cannot be eliminated by the immune system, they become a reservoir from which recurrence of infection will develop. Such non-growing bacteria have been observed to persist within mammalian cells. Indeed, it appears that persister cells are the main cause for relapsing and chronic infections. Chronic infections can affect people of any age, health, or immune status.
   The main interaction mechanism is competition for plasma protein transport. In these cases the drug that arrives first binds with the plasma protein, leaving the other drug dissolved in the plasma, which modifies its concentration. The organism has mechanisms to counteract these situations (by, for example, increasing plasma clearance), which means that they are not usually clinically relevant. However, these situations should be taken into account if other associated problems are present such as when the method of excretion is affected.
  
  Section::::Pharmacokinetic interactions.:Metabolism interactions.
   In humans, the gene ABCB1 encodes MDR1(p-glycoprotein) which is a key transporter of medications on the cellular level. If MDR1 is overexpressed, drug resistance increases. Therefore, ABCB1 levels can be monitored. In patients with high levels of ABCB1 expression, the use of secondary treatments, like metformin, have been used in conjunction with the primary drug treatment with some success.
   Cross-tolerance is a phenomenon that occurs when tolerance to the effects of a certain drug produces tolerance to another drug. It often happens between two drugs with similar functions or effects—for example, acting on the same cell receptor or affecting the transmission of certain neurotransmitters. Cross-tolerance has been observed with pharmaceutical drugs such as anti-anxiety agents and illicit substances, and sometimes the two of them together. Often, a person who uses one drug can be tolerant to a drug that has a completely different function. This phenomenon allows one to become tolerant to a drug that they have never even used before.
   Section::::Relevance to chronic infections.
   This is the opposite of drug tolerance (or drug desensitization), in which the effect or the subject's reaction decreases following its repeated use. The two notions are not incompatible, and tolerance may sometimes lead to reverse tolerance. For example, heavy drinkers initially develop tolerance to alcohol, requiring them to drink larger amounts to achieve a similar effect, but as excessive drinking can cause liver damage, this can then put this group at risk of intoxication when drinking even very small amounts of alcohol.
   In general, anything that "increases" the rate of metabolism ("e.g.", enzyme induction) of a pharmacologically active metabolite will "decrease" the duration and intensity of the drug action.
  
  The opposite is also true ("e.g.", enzyme inhibition). However, in cases where an enzyme is responsible for metabolizing a pro-drug into a drug, enzyme induction can speed up this conversion and increase drug levels, potentially causing toxicity.
  
  Various "physiological" and "pathological" factors can also affect drug metabolism.
  
  Physiological factors that can influence drug metabolism include age, individual variation ("e.g.", pharmacogenetics), enterohepatic circulation, nutrition, intestinal flora, or sex differences.
   The route of administration is important as well. Whether a drug is ingested orally, injected into a muscle or vein, absorbed through a mucous membrane, or any of the other types of administration routes, affects how quickly the substance will be metabolized by the body and thus effects the concentration of the active ingredient(s). Dose-response curves may illustrate the relationship of these metabolic effects.
  
  Section::::Medicines.
  
  Section::::Medicines.:Over-the-counter medications.
   Tolerance is expected to develop with regular methamphetamine use and, when used recreationally, this tolerance develops rapidly. In dependent users, withdrawal symptoms are positively correlated with the level of drug tolerance. Depression from methamphetamine withdrawal lasts longer and is more severe than that of cocaine withdrawal.
  
raw_presuppositions: Taking 10mg of a drug every day is the same as taking 20mg every other day. Taking 10mg of a drug every day is the same as taking 20mg every other day. Taking 10mg of a drug every day is the same as taking 20mg every other day. Taking 10mg of a drug every day is the same as taking 20mg every other day. Taking 10mg of a drug every day is the same as taking 20mg every other day. Taking 10mg of a drug every day is the same as taking 20mg every other day.
raw_corrections: Your body will always acclimate to things in smaller doses on a more regular basis. Your body will always acclimate to things in smaller doses on a more regular basis. Your body will always acclimate to things in smaller doses on a more regular basis. Your body will always acclimate to things in smaller doses on a more regular basis. Your body will always acclimate to things in smaller doses on a more regular basis. Your body will always acclimate to things in smaller doses on a more regular basis.