Pharmacodynamics

Tolerance

TRTolerans
Also known as:Drug tolerance · Acquired tolerance

A gradual reduction in response to a drug with repeated or continuous exposure, so that a higher dose is needed to reproduce the original effect; it develops over days to weeks.

In depth

Pharmacokinetic (dispositional) tolerance results from reduced drug concentrations at the site of action, typically through enzyme induction (e.g. barbiturates, carbamazepine autoinduction). Pharmacodynamic tolerance results from adaptive changes in the target system: receptor desensitisation, down-regulation, altered signal transduction or homeostatic counter-regulation. Learned (behavioural) tolerance also occurs.

Tolerance may develop unevenly to different effects: with opioids it develops to euphoria, sedation and respiratory depression but little to miosis and constipation. Cross-tolerance between drugs of the same class is common. Tolerance is distinct from physical dependence and addiction, although it frequently accompanies them.

Clinical pearl

Tolerance to opioid respiratory depression is lost after a period of abstinence; people who resume their previous dose after detoxification or release from prison are at high risk of fatal overdose.

Example drugs

Morphine glyceryl trinitrate Diazepam Carbamazepine
TRIn Turkish

Tolerans

Tekrarlanan veya sürekli maruziyet sonucunda bir ilaca verilen yanıtın giderek azalması ve başlangıçtaki etkinin yeniden elde edilmesi için daha yüksek doz gerekmesidir; günler ya da haftalar içinde gelişir.

Farmakokinetik (dispozisyonel) tolerans, genellikle enzim indüksiyonu yoluyla (örneğin barbitüratlar, karbamazepinin otoindüksiyonu) ilacın etki yerindeki konsantrasyonunun azalmasından kaynaklanır. Farmakodinamik tolerans ise hedef sistemdeki uyumsal değişikliklerden, yani reseptör desensitizasyonu, down-regülasyonu, sinyal iletiminin değişmesi veya homeostatik karşı düzenlemelerden kaynaklanır. Öğrenilmiş (davranışsal) tolerans da görülebilir.

Tolerans farklı etkilere karşı eşit ölçüde gelişmeyebilir: opioidlerde öfori, sedasyon ve solunum depresyonuna karşı gelişir, ancak miyozis ve kabızlığa karşı çok az gelişir. Aynı sınıftaki ilaçlar arasında çapraz tolerans yaygındır. Tolerans, fiziksel bağımlılık ve bağımlılıktan (addiksiyon) farklı bir kavramdır; ancak sıklıkla bunlara eşlik eder.

Opioidlerin solunum depresyonu etkisine karşı gelişen tolerans bir süre kullanılmadığında kaybolur; detoksifikasyon ya da cezaevinden tahliye sonrasında önceki dozuna dönen kişilerde ölümcül doz aşımı riski yüksektir.

Diğer adları:İlaç toleransı · Edinsel tolerans
Updated 24.09.2026 1 views Educational reference — verify against current sources before clinical use.

Read next

TachyphylaxisTaşifilaksi

A rapidly developing decrease in response to a drug after repeated doses over a short period (minutes to hours), which often cannot be overcome by increasing the dose.

 Receptor Down-RegulationReseptör Down-Regülasyonu

A decrease in the number of receptors available at the cell surface or in the cell, typically in response to prolonged or excessive agonist stimulation, which reduces tissue responsiveness.

 Enzyme InductionEnzim İndüksiyonu

An increase in the amount and activity of a drug-metabolizing enzyme or transporter, usually through enhanced gene transcription, caused by repeated exposure to a drug or other xenobiotic.

 AutoinductionOtoindüksiyon

Induction by a drug of the enzymes responsible for its own metabolism, so that its clearance increases and its concentrations fall over time during continued dosing at the same dose.

 Withdrawal SyndromeYoksunluk Sendromu

A characteristic cluster of signs and symptoms that follows abrupt discontinuation, rapid dose reduction or antagonist reversal of a drug to which the body has adapted during prolonged use.

 Opioid ToxidromeOpioid Toksidromu

A clinical syndrome of opioid excess, mediated mainly by mu-opioid receptor agonism and defined by the triad of depressed consciousness, respiratory depression (reduced rate and/or depth) and miosis.