Cross-tolerance is a phenomenon that occurs when tolerance to certain drug effects results in tolerance to other drugs. It often occurs 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 prohibited substances, and sometimes both are united. Often, a person who takes a drug can tolerate a drug that has a completely different function. This phenomenon allows one to be tolerant of drugs they have never used before.
Video Cross-tolerance
Drug classification and cross-tolerance
Anxiolytics and sedatives
Excitation of GABA receptors results in the entry of negatively charged chloride ions, which hyperpolarizes neurons and makes them less likely to give rise to potential action. In addition to Gamma-Aminobutyric acid (GABA) itself, the GABA receptor A can also bind barbiturates and benzodiazepines. Benzodiazepine binding increases GABA binding and barbiturates maximizes open pore time. Both of these mechanisms allow the entry of chloride ions. When these drugs are taken together, especially with ethanol (drinking alcohol), there is an increase in disproportionate toxicity because the effects of both occur simultaneously and increase as they act on the same receptor at different locations. Convergence of GABA receptors A is why tolerance for one drug in the group will most likely cause cross-tolerance for other drugs in the group. However, barbiturates are also AMPA receptor blockers, and in addition interact with nAChR and voltage-gated calcium channels. As a result, a person tolerant to benzodiazepines is more sensitive to barbiturates than vice versa.
Antipsychotics
These drugs block dopamine receptors and some also block serotonin receptors (such as chlorpromazine, the first clinically used antipsychotic). Having been in one or more antipsychotics for a significant amount of time will dramatically reduce the sensitivity to others with similar mechanisms of action. However, antipsychotics with substantial disparities in pharmacology (eg haloperidol and quetiapine) can maintain significant efficacy.
Antidepressants and mood stabilizer
MAO inhibitors block enzyme systems that lead to increased storage of monoamine neurotransmitters. More common antidepressants such as tricyclic antidepressants and SSRIs blocking reuptake transporters lead to increased norepinephrine or serotonin levels in synapses. Mood stabilizers including lithium and many anticonvulsants, such as carbamazepine and lamotrigine, are also used for mood disorders. This will show a small zero cross-tolerance with serotonergic or lithium treatment.
Opioid analgesics
These drugs mimic three classes of endorphins, such as endomorphins, enkephalins, and dynorphins. These three classes each have their own receptor, kappa, and delta. Opioids will bind to receptors for endorphins that are chemically most similar to them. Tolerance to some effects occurs with regular use, resulting from decreased regulation of stimulated opioid receptors. Cross tolerance to analgesia may develop incompletely and less rapidly, allowing rotation between opioid drugs used to compensate somewhat for tolerance. This phenomenon is called incomplete cross tolerance .
Stimulants
Cocaine, amphetamines, methylphenidate and ephedrine block the reuptake of dopamine and norepinephrine. With increasing doses, amphetamines also cause the immediate release of these neurotransmitters.
Psychedelics
Serotonergic psychedelics act through serotonin modulation. Most of these drugs have a high affinity for the subtypes of 5-HT 2A receptors, which are known to produce their common perceptual and psychological effects.
Maps Cross-tolerance
Cross tolerance between drugs with different classifications
Sometimes cross-tolerance occurs between two drugs that do not share the mechanism of action or classification. For example, amphetamine and amphetamine stimulants have been shown to exhibit cross-tolerance with caffeine, and possibly cross-tolerance mechanisms involving dopamine receptors D 1 . Amphetamine also has cross-tolerance with pseudoephedrine, because pseudoephedrine can inhibit the taking of dopamine in the same way as amphetamine does, but it is less potent.
Alcohol is another substance that often tolerates crossovers with other drugs. The finding of cross-tolerance with nicotine in animal models suggests that it may also occur in humans, and may explain why these two drugs are often used together. A number of studies have also shown possible cross-tolerance between alcohol and marijuana.
References
Source of the article : Wikipedia
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