Pharmacodynamics

Non-Competitive Antagonism

TRYarışmasız Antagonizma
Also known as:Insurmountable antagonism · Noncompetitive antagonism

Antagonism that cannot be overcome by increasing the agonist concentration, because the antagonist binds irreversibly or acts at a site or step distinct from agonist binding; the maximal agonist response is reduced.

In depth

In broad usage the term covers antagonists that bind allosterically to reduce agonist efficacy, block a downstream step such as the ion channel pore (channel blockers), or bind irreversibly at the agonist site, a form some texts call irreversible competitive antagonism. The agonist dose–response curve is depressed; where spare receptors exist, a rightward shift may appear before the maximum falls.

Recovery from irreversible antagonism depends on the synthesis of new receptors (or, for platelets, the production of new cells) rather than on drug elimination, so the effect can long outlast the plasma half-life.

Clinical pearl

The active metabolite of clopidogrel blocks platelet P2Y12 receptors irreversibly, so the effect persists for the platelet lifespan; this is why it is usually withheld for several days before elective surgery.

Example drugs

Phenoxybenzamine Clopidogrel Ketamine
TRIn Turkish

Yarışmasız Antagonizma

Antagonistin geri dönüşümsüz bağlanması ya da agonist bağlanma bölgesinden farklı bir bölge veya basamak üzerinden etki etmesi nedeniyle agonist konsantrasyonu artırılarak aşılamayan antagonizmadır; agonistin maksimal yanıtı azalır.

Geniş anlamda bu terim; allosterik bağlanarak agonistin etkinliğini azaltan, iyon kanalı porunun tıkanması gibi sonraki bir basamağı engelleyen (kanal blokerleri) ya da agonist bağlanma bölgesine geri dönüşümsüz olarak bağlanan antagonistleri kapsar; sonuncusu bazı kaynaklarda geri dönüşümsüz yarışmalı antagonizma olarak adlandırılır. Agonistin doz–yanıt eğrisi basıklaşır; yedek reseptörlerin bulunduğu durumlarda maksimal yanıt düşmeden önce eğride sağa kayma görülebilir.

Geri dönüşümsüz antagonizmadan kurtulma, ilacın eliminasyonuna değil yeni reseptör sentezine (trombositlerde ise yeni hücre yapımına) bağlıdır; bu nedenle etki plazma yarılanma ömrünü belirgin biçimde aşabilir.

Klopidogrelin aktif metaboliti trombosit P2Y12 reseptörlerini geri dönüşümsüz olarak bloke eder ve etki trombositin yaşam süresi boyunca sürer; bu nedenle elektif cerrahiden genellikle birkaç gün önce kesilir.

Diğer adları:Nonkompetitif antagonizma · Aşılamaz antagonizma
Updated 24.09.2026 0 views Educational reference — verify against current sources before clinical use.

Read next

Competitive AntagonismYarışmalı Antagonizma

Reversible antagonism in which the antagonist binds to the same site as the agonist, so the block can be overcome by raising the agonist concentration; the agonist curve shifts to the right in parallel without a fall in maximal response.

 AntagonistAntagonist

A drug that binds to a receptor or other target without activating it (affinity but no efficacy) and thereby prevents or reduces the response to an agonist.

 Allosteric ModulatorAllosterik Modülatör

A ligand that binds to a site on a receptor distinct from the orthosteric (endogenous agonist) site and changes the receptor's affinity for, or response to, the orthosteric agonist.

 Spare ReceptorsYedek Reseptörler

Receptors in excess of those needed to produce a maximal response, so that a full agonist can elicit its maximal effect while occupying only a fraction of the available receptors.

 EfficacyEtkinlik

The capacity of a drug to produce a response once bound to its receptor; in clinical terms, the maximal effect (Emax) a drug can produce, however much the dose is increased.

 Mechanism-Based InhibitionMekanizma Temelli İnhibisyon

Irreversible or quasi-irreversible enzyme inactivation in which the enzyme converts the inhibitor into a reactive intermediate that binds covalently or tightly to it, so activity returns only as new enzyme is synthesized.