Tranamic Mechanism of Action

Anti-Fibrinolytic/Non-Steroidal Anti-Inflammatory Drug.
Pharmacology: Mechanism of Action: Tranexamic acid is a competitive inhibitor of plasminogen activation and at much higher concentrations, a non-competitive inhibitor of plasmin i.e. actions similar to aminocaproic acid. Tranexamic acid is about 10 times more potent in vitro than aminocaproic acid.
Tranexamic acid binds more strongly than aminocaproic acid to both the strong and weak receptor sites of the plasminogen molecule in a ratio corresponding to the difference in potency between the compounds. Tranexamic acid in a concentration of 1 mg per mL does not aggregate platelets in vitro. Tranexamic acid in concentration up to 10 mg/mL blood has no influence on the platelet count, the coagulation time or various coagulation factors in whole blood or citrated blood from normal subjects. On the other hand, tranexamic acid in concentrations of 10 mg and 1 mg/mL blood prolongs the thrombin time.
Mefenamic acid is an analgesic preparation with anti-inflammatory properties.
Pharmacokinetics: The plasma protein binding of tranexamic acid is about 3% at therapeutic plasma levels and seems to be fully accounted for by its binding to plasminogen. Tranexamic acid does not bind to serum albumin. Absorption of tranexamic acid after oral administration in human represents approximately 30 to 50% of the ingested dose. The peak plasma level after 1 g orally is 8 mg/L and 2 g, 15 mg/L, both obtained three hours after dosing.
After an intravenous dose of 1 g, plasma concentration time curve shows a triexponential decay with a half-life of about 2 hours for the terminal elimination phase. The initial volume of distribution is about 9 to 12 liters. Urinary excretion is the main route of elimination via glomerular filtration. Overall renal clearance is equal to overall plasma clearance (110-116 mL/min) and more than 95% of the dose is excreted in the urine as the unchanged drug. Excretion of tranexamic acid is about 90% at 24 hours after intravenous administration of 10 mg/kg body weight. After oral administration of 10 to 15 mg per kg body weight, the cumulative urinary excretion at 24 hours is 39% and at 48 hours, 41% of the ingested dose or 78% and 82% of the absorbed material. Only a small fraction is metabolized. After oral administration, 1% of the dicarboxylic acid and 0.5% of the acetylated compound are excreted.
An antifibrinolytic concentration of tranexamic acid remains in different tissues for about 17 hours and in the serum, up to 78 hours. Tranexamic acid passes through the placenta. The concentration in cord blood after an intravenous injection of 10 mg/kg to pregnant women is about 30 mg/L, as high as in the maternal blood. Tranexamic acid diffuses rapidly into joint fluid and the synovial membrane. In the joint fluid, the same concentration is obtained as in the serum. The biological half-life of tranexamic acid in the joint fluid is about 3 hours.
The concentration of tranexamic acid in a number of other tissues is lower than in blood. In breast milk, the concentration is about one-hundredth of the serum peak concentration. Tranexamic acid concentration in cerebrospinal fluid is about one tenth of that of the plasma. The drug passes into the aqueous humor, the concentration being about one tenth of the plasma concentration. Tranexamic acid has been detected in semen where it inhibits fibrinolytic activity but does not influence sperm migration.
Mefenamic acid is an analgesic preparation with anti-inflammatory properties. Mefenamic acid is known to have a peripheral anti-inflammatory effect and has also shown antipyretic action.
The pharmacological activity of mefenamic acid may be due in part of its ability to inhibit the synthesis of prostaglandins. Mefenamic acid also inhibits the action of exogenous prostaglandins on uterine muscle, uterine tube contraction and ovarian cyclic AMP and progesterone formulation in animal models.
Pharmacokinetics and Metabolism: Mefenamic acid is well absorbed from the gastro-intestinal tract. Peak plasma concentrations occur in about 2 to 4 hours, with a half-life of 2 to 4 hours. Plasma levels are proportional to dose, following multiple doses, with no drug accumulation. Mefenamic acid is extensively bound to plasma proteins. Over 50% of the dose may be recovered in the urine as unchanged drug or conjugated metabolites.