It is a nonselective inhibitor of cyclooxygenase (COX) 1 and 2, the enzymes that participate in prostaglandin synthesis from arachidonic acid. Prostaglandins are hormone-like molecules normally found in the body, where they have a wide variety of effects, some of which lead to pain, fever, and inflammation. By inhibiting the synthesis of prostaglandins, indometacin can reduce pain, fever, and inflammation. Indometacin mechanism of action, along with several other NSAIDs that inhibit COX, was described in 1971.Additionally, indometacin has recently been found to be a positive allosteric modulator (PAM) of the CB1 cannabinoid receptor. By enhancing the binding and signalling of endogenous cannabinoids such as anandamide, PAMs may elicit increased cannabinergic signalling in a tissue specific manner, reducing the incidence of problematic side effects such as psychoactivity while maintaining some antinociceptive activity.Besides, indometacin has logarithmic acid dissociation constant  pKa of 3 to 4.5. Since the physiologic body pH is well above the pKa range of indometacin, most of the indometacin molecules will be dissociated into ionized form, leaving very little un-ionized form of indometacin to cross a cell membrane. If the pH gradient across a cell membrane is high, most of the  indometacin molecules will be trapped in one side of the membrane with higher pH. This phenomenon is called "ion trapping". The phenomenon of ion trapping is particularly prominent in the stomach as pH at the stomach mucosa layer is extremely acidic, while the parietal cells are more alkaline.
Bifascicular block is a conduction abnormality in the heart where two of the three main fascicles of the His/Purkinje system are blocked. Most commonly, it refers to a combination of right bundle branch block (RBBB) and either left anterior fascicular block (LAFB) or left posterior fascicular block (LPFB), with the former being more common.Some authors consider left bundle branch block (LBBB) to be a technical bifascicular block, since the block occurs above the bifurcation of the left anterior and left posterior fascicles of the left bundle branch. Diagnosis
Diagnostic criteria:Clinically, bifascicular block presents with one of two ECG patterns:
Right bundle branch block (RBBB) with left anterior fascicular block (LAFB), manifested as left axis deviation (LAD). RBBB and left posterior fascicular block (LPFB), manifested as right axis deviation (RAD) in the absence of other causes. Treatment
In those with bifascicular block and no symptoms, little with respect to treatment is needed. In those with syncope, a pacemaker is recommended. References

Olshansky B. Bradyarrhythmias – Conduction System Abnormalities. In: Arrhythmia Essentials 2e, 2017. Vijayaraman P. Clinical Cardiac Pacing, Defibrillation and Resynchronisation Therapy 5e, 2017
Goldberger A. Ventricular Conduction Disturbances.. In: Goldberger’s Clinical Electrocardiography 9e, 2018. == External links ==