Physiological tolerance
Encyclopedia
Physiological tolerance or drug tolerance is commonly encountered in pharmacology
, when a subject's reaction to a drug (such as an opiate
painkiller, benzodiazepine
or other psychotropic drug) is reduced at a later time even though the dose or concentration at the effect site is the same. This means that larger doses are required to achieve the same effect. Drug tolerance can involve both psychological drug tolerance and physiological
factors. Characteristics of drug tolerance: it is reversible, the rate depends on the particular drug, dosage and frequency of use, differential development occurs for different effects of the same drug. Physiological tolerance also occurs when an organism builds up a resistance to the effects of a substance after repeated exposure. This can occur with environmental substances, such as salt or pesticides.
Tachyphylaxis
is a synonym for drug tolerance.
Pharmacokinetic Tolerance- Also known as 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
Pharmacodynamic Tolerance - Also known as Reduced responsiveness: the response to the substance is decreased by cellular mechanisms. This may be caused by a down regulation of receptor numbers
(which would change the receptor conformation), functional decoupling of receptors from G-proteins (leading to receptor desensitization), mu-opioid receptor internalization and/or receptor down-regulation (reducing the number of available receptors for morphine to act on), and upregulation of the cAMP
pathway (a counterregulatory mechanism to opioid effects) (For a review of these processes, see Koch and Hollt.) CCK
might mediate some counter-regulatory pathways responsible for opioid tolerance. CCK-antagonist drugs, specifically proglumide
, have been shown to slow the development of tolerance to morphine or any other kind of drug, including alcohol.
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
, when a subject's reaction to a drug (such as an opiate
Opiate
In medicine, the term opiate describes any of the narcotic opioid alkaloids found as natural products in the opium poppy plant.-Overview:Opiates are so named because they are constituents or derivatives of constituents found in opium, which is processed from the latex sap of the opium poppy,...
painkiller, benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
or other psychotropic drug) is reduced at a later time even though the dose or concentration at the effect site is the same. This means that larger doses are required to achieve the same effect. Drug tolerance can involve both psychological drug tolerance and physiological
Physiological tolerance
Physiological tolerance or drug tolerance is commonly encountered in pharmacology, when a subject's reaction to a drug is reduced at a later time even though the dose or concentration at the effect site is the same. This means that larger doses are required to achieve the same effect...
factors. Characteristics of drug tolerance: it is reversible, the rate depends on the particular drug, dosage and frequency of use, differential development occurs for different effects of the same drug. Physiological tolerance also occurs when an organism builds up a resistance to the effects of a substance after repeated exposure. This can occur with environmental substances, such as salt or pesticides.
Tachyphylaxis
Tachyphylaxis
Tachyphylaxis is a medical term describing a decrease in the response to a drug due to previous exposure to that drug. Increasing the dose of the drug may be able to restore the original response. In this context tachyphylaxis is a synonym for drug tolerance...
is a synonym for drug tolerance.
Mechanisms
There are two major mechanisms for tolerance:Pharmacokinetic Tolerance- Also known as 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
Pharmacodynamic Tolerance - Also known as Reduced responsiveness: the response to the substance is decreased by cellular mechanisms. This may be caused by a down regulation of receptor numbers
Morphine as an Example
Tolerance to the analgesic effects of morphine is fairly rapid. There are several hypotheses about how tolerance develops, including opioid receptor phosphorylationPhosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
(which would change the receptor conformation), functional decoupling of receptors from G-proteins (leading to receptor desensitization), mu-opioid receptor internalization and/or receptor down-regulation (reducing the number of available receptors for morphine to act on), and upregulation of the cAMP
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...
pathway (a counterregulatory mechanism to opioid effects) (For a review of these processes, see Koch and Hollt.) CCK
CCK
CCK may refer to:*Choa Chu Kang, a suburban town in Singapore*Complementary code keying, a modulation technique used in IEEE 802.11b*Cholecystokinin, a digestive hormone...
might mediate some counter-regulatory pathways responsible for opioid tolerance. CCK-antagonist drugs, specifically proglumide
Proglumide
Proglumide is a drug that inhibits gastrointestinal motility and reduces gastric secretions. It acts as a cholecystokinin antagonist, which blocks both the CCKA and CCKB subtypes...
, have been shown to slow the development of tolerance to morphine or any other kind of drug, including alcohol.
See also
- DesensitizationDesensitization (medicine)For medical purposes, desensitization is a method to reduce or eliminate an organism's negative reaction to a substance or stimulus.For example, if a person with diabetes mellitus has a bad allergic reaction to taking a full dose of beef insulin, the doctor gives the person a very small amount of...
- SensitizationSensitizationSensitization is an example of non-associative learning in which the progressive amplification of a response follows repeated administrations of a stimulus. An everyday example of this mechanism is the repeated tonic stimulation of peripheral nerves that will occur if a person rubs his arm...
- Physical dependencePhysical dependencePhysical dependence refers to a state resulting from chronic use of a drug that has produced tolerance and where negative physical symptoms of withdrawal result from abrupt discontinuation or dosage reduction...
- Mithridatization
- Reverse toleranceReverse toleranceReverse tolerance or sensitization is the phenomenon of a reversal of the side-effects from a drug, or the reduction of insensitivity caused after drug tolerance has been established, or in some cases an additional increase of effects with continued use of a single drug existing alongside or not to...
- Cross-toleranceCross-toleranceCross-tolerance refers to a pharmacological phenomenon, in which a patient being treated with a drug exhibits a physiological resistance to that medication as a result of tolerance to a pharmacologically similar drug. In other words, there is a decrease in response to one drug due to exposure to...
- Drug resistanceDrug resistanceDrug resistance is the reduction in effectiveness of a drug such as an antimicrobial or an antineoplastic in curing a disease or condition. When the drug is not intended to kill or inhibit a pathogen, then the term is equivalent to dosage failure or drug tolerance. More commonly, the term is used...
- TachyphylaxisTachyphylaxisTachyphylaxis is a medical term describing a decrease in the response to a drug due to previous exposure to that drug. Increasing the dose of the drug may be able to restore the original response. In this context tachyphylaxis is a synonym for drug tolerance...
- Multidrug resistanceMultidrug resistanceMultiple drug resistance or Multidrug resistance is a condition enabling a disease-causing organism to resist distinct drugs or chemicals of a wide variety of structure and function targeted at eradicating the organism...