<unk> , a non-steroidal anti-inflammatory drug (NSAID), has similar mode of action when compared to other drugs in this group. 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,<unk>  can reduce pain, fever, and inflammation.<unk>  mechanism of action, along with several other NSAIDs that inhibit COX, was described in 1971. Additionally,<unk>  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,<unk>  has logarithmic acid dissociation constant pKa of 3 to 4.5. Since the physiologic body pH is well above the pKa range of<unk> , most of the<unk>  molecules will be dissociated into ionized form, leaving very little un-ionized form of<unk>  to cross a cell membrane. If the pH gradient across a cell membrane is high, most of the<unk>  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. Therefore,<unk>  are trapped inside the parietal cells in ionized form, damaging the stomach cells, causing stomach irritation. This stomach irritation can reduce if the stomach acid pH is reduced.<unk> 's role in treating certain headaches is unique compared to other NSAIDs. In addition to the class effect of COX inhibition, there is evidence that<unk>  has the ability to reduce cerebral blood flow not only through modulation of nitric oxide pathways but also via intracranial precapillary vasoconstriction.<unk>  property of reducing cerebral blood flow is useful in treating raised intracranial pressure. A case report has shown that an intravenous bolus dose of<unk>  given with 2 hours of continuous infusion is able to reduce intracranial pressure by 37% in 10 to 15 minutes and increases cerebral perfusion pressure by 30% at the same time. This reduction in cerebral pressure may be responsible for the remarkable efficacy in a group of headaches that is referred to as<unk> -responsive headaches", such as<unk> iopathic stabbing headache, chronic paroxysmal hemicranial, and exertional headaches. On the other hand, the activation of superior salivary nucleus in the brainstem is used to stimulate the trigeminal autonomic reflex arc, causing a type of headache called trigeminal autonomic cephalgia.<unk>  inhibits the superior salivatory nucleus, thus relieving this type of headache. Prostaglandins also cause uterine contractions in pregnant women.<unk>  is an effective tocolytic agent, able to delay premature labor by reducing uterine contractions through inhibition of prostaglandin synthesis in the uterus and possibly through calcium channel blockade.<unk>  readily crosses the placenta and can reduce fetal urine production to treat polyhydramnios. It does so by reducing renal blood flow and increasing renal vascular resistance, possibly by enhancing the effects of vasopressin on the fetal kidneys. Other modes of action for<unk>  are: * it inhibits motility of polymorphonuclear leukocytes, similar to colchicine * it uncouples oxidative phosphorylation in cartilaginous (and hepatic) mitochondria, like salicylates * it has been found to specifically inhibit MRP (multidrug resistance proteins) in murine and human cells
Indometacin
Methylergometrine
Ergometrine
Xylometazoline
Alclometasone
Drostanolone propionate
Ethinylestradiol sulfonate
Chloroxylenol