A number of<unk> s are available. The traditional ones (warfarin, other coumarins, and heparins) are in widespread use. Since the 2000s, a number of agents have been introduced that are collectively referred to as directly<unk> ting oral<unk> s (DOACs), novel oral<unk> s (NOACs), or non-vitamin K antagonist oral<unk> s. These agents include direct thrombin inhibitor (dabigatran) and factor Xa inhibitor (rivaroxaban, apixaban, betrixaban and edoxaban) and they have been shown to be as good or possibly better than the coumarins with less serious side effects. The newer<unk> s (NOACs/DOACs), are more expensive than the traditional ones and should be used with care in patients with kidney problems. Coumarins (vitamin K antagonists) These oral<unk> s are derived from coumarin, which is found in many plants. A prominent member of this class is warfarin (Coumadin) and was found to be the dominant<unk>  prescribed in a large multispecialty practice. It takes at least 48 to 72 hours for the<unk>  effect to develop. Where an immediate effect is required, heparin must be given concomitantly. These<unk> s are used to treat patients with deep-vein thrombosis (DVT), pulmonary embolism (PE) and to prevent emboli in patients with atrial fibrillation (AF), and mechanical prosthetic heart valves. Other examples are<unk> enocoumarol, phenprocoumon, atromentin, and phenindione. The coumarins brodifacoum and difenacoum are used as rodenticides but are not used medically. Heparin and derivative substances Heparin is the most widely used intravenous clinical<unk>  worldwide. Heparin is a naturally occurring glycosaminoglycan. There are three major categories of heparin: unfractionated heparin (UFH), low molecular weight heparin (LMWH), and ultra-low-molecular weight heparin (ULMWH). Unfractionated heparin is usually derived from pig intestines and bovine lungs. UFH binds to the enzyme inhibitor antithrombin III (AT), causing a conformational change that results in its<unk> tivation. The<unk> tivated AT then inactivates factor Xa, thrombin, and other coagulation factors. Heparin can be used in vivo (by injection), and also in vitro to prevent blood or plasma clotting in or on medical devices. In venipuncture, Vacutainer brand blood collecting tubes containing heparin usually have a green cap. Low molecular weight heparin (LMWH) Low molecular weight heparin (LMWH), is produced through a controlled depolymerization of unfractionated heparin. LMWH exhibits higher anti-Xa/anti-IIa<unk> tivity ratio and is useful as it does not require monitoring of the APTT coagulation parameter and has fewer side effects. Synthetic pentasaccharide inhibitors of factor Xa * Fondaparinux is a synthetic sugar composed of the five sugars (pentasaccharide) in heparin that bind to antithrombin. It is a smaller molecule than low molecular weight heparin. * Idraparinux * Idrabiotaparinux Directly<unk> ting oral The directly<unk> ting oral<unk> s (DOACs) were introduced on and after 2008. There are five DOACs currently on the market: dabigatran, rivaroxaban, apixaban, edoxaban and betrixaban. They were also previously referred to as "new/novel" and "non-vitamin K antagonist" oral<unk> s (NOACs). Compared to warfarin, DOACs have a rapid onset<unk> tion and relatively short half-lives; hence, they carry out their function more rapidly and effectively and allow for drugs to quickly reduce their<unk> ion effects. Routine monitoring and dose adjustments of DOACs is less important than for warfarin, as they have better predictable<unk> ion<unk> tivity. DOAC monitoring, including laboratory monitoring and a complete medication review, should generally be conducted before initiation of a DOAC, 1-3 months after initiation, and then every 6-12 months afterwards. Both DOACs and warfarin are equivalently effective but compared to warfarin, DOACs have fewer drug interactions, no known dietary interactions, wider therapeutic index, and have conventional dosing that does not require dose adjustments with constant monitoring. However, there is presently no countermeasure for most DOACs, unlike for warfarin; nonetheless, the short half-lives of DOACs will allow their effects to swiftly recede. A reversal agent for dabigatran, idarucizumab, is currently available and approved for use by the FDA. Rates of adherence to DOACs are only modestly higher than adherence to warfarin among patients prescribed these drugs, and thus adherence to<unk> ion is often poor, despite hopes that DOACs would lead to higher adherence rates. DOACs are significantly more expensive than warfarin after taking into consideration the cost of frequent blood testing associated with warfarin. Direct factor Xa inhibitors Drugs such as rivaroxaban, apixaban and edoxaban work by inhibiting factor Xa directly (unlike the heparins and fondaparinux, which work via antithrombin<unk> tivation). Also included in this category are betrixaban from Portola Pharmaceuticals, the discontinued darexaban (YM150) from Astellas, and, more recently, the discontinued letaxaban (TAK-442) from Takeda and eribaxaban (PD0348292) from Pfizer. Betrixaban is significant as it was, in 2018, the only oral factor Xa inhibitor approved by the FDA for use in<unk> utely medically ill patients. Darexaban development was discontinued in September 2011; in a trial for prevention of recurrences of myocardial infarction in addition to dual antiplatelet therapy (DAPT), the drug did not demonstrate effectiveness, and the risk of bleeding was increased by approximately 300%. The development of letaxaban was discontinued for<unk> ute coronary syndrome in May 2011, following negative results from a Phase II study. Direct thrombin inhibitors Another type of<unk>  is the direct thrombin inhibitor. Current members of this class include the bivalent drugs hirudin, lepirudin, and bivalirudin; and the monovalent drugs argatroban and dabigatran. An oral direct thrombin inhibitor, ximelagatran (Exanta) was denied approval by the Food and Drug Administration (FDA) in September 2004 and was pulled from the market entirely in February 2006 after reports of severe liver damage and heart attacks. In November 2010, dabigatran Etexilate was approved by the FDA to prevent thrombosis in atrial fibrillation. Relevance to dental treatments As in any invasive procedures, patients on<unk> ion therapy have increased risk for bleeding and caution should be used along with local hemostatic methods to minimize bleeding risk during the operation as well as post-operatively. However, with regards to DOACs and invasive dental treatments, there has not been enough clinical evidence and experience to prove any reliable adverse effects, relevance or interaction between these two. Further clinical prospective studies on DOACs are required to investigate the bleeding risk and haemostasis associated to surgical dental procedures. Recommendations of modifications to usage/dosage of DOACs prior to dental treatments are made based on the balance of the bleeding risk of each procedure and also the individual's bleeding own bleeding risks and renal functionality. With low-bleeding-risk dental procedures, it is recommended that DOACs be continued by the patient as per normal, so as to avoid any increase in the risk of thromboembolic event. For dental procedures with a higher risk of bleeding complications (i.e. complex extractions, adjacent extractions leading to a large wound, or more than three extractions), the recommended practice is for the patient to miss or delay a dose of their DOAC before such procedures so as to minimize the effect on bleeding risk. Antithrombin protein therapeutics The antithrombin protein itself is used as a protein therapeutic that can be purified from human plasma or produced recombinantly (for example, Atryn, which is produced in the milk of genetically modified goats.) Antithrombin is approved by the FDA as an<unk>  for the prevention of clots before, during, or after surgery or birthing in patients with hereditary antithrombin deficiency. Other Many other<unk> s exist, for use in research and development, diagnostics, or as drug candidates. * Batroxobin, a toxin from a snake venom, clots platelet-rich plasma without affecting platelet functions (lyses fibrinogen). * Hementin is an<unk>  protease from the salivary glands of the giant Amazon leech, Haementeria ghilianii. * Vitamin E * Alcoholic-beverage
Anticoagulant
Decongestant
Anticonvulsant
Antipyretic
Cholagogue
Antiparasitic
Antipruritic
Abirritant