Anticoagulants Flashcards
Riveroxaban- MOA, SE (XARALTO)
Rivaroxaban is an inhibitor of activated clotting factor X (FXa) and prothrombinase activity(factor X).
>ANTITHROMBIN INDEPENDENT
> Unlike heparins, its anticoagulant effect does not require a cofactor. It indirectly inhibits platelet aggregation induced by thrombin**
SE: Nausea, vomiting, diarrhea, and an increase in liver enzymes can also occur. Pruritus and rash have been noted but are uncommon.
The drug should be avoided in patients with severe hepatic disease, a hepatic disease associated with coagulopathy, or with significant renal impairment
Apixaban–SAME AS RIVEROXABAN
Apixaban inhibits free and clot-bound Xa, as well as prothrombinase activity, which inhibits clot growth. By inhibiting FXa, apixaban decreases thrombin generation and thrombus development. It has no direct effect on platelet aggregation, but indirectly inhibits platelet aggregation induced by thrombin
Heparin=unfractionated heparin- MOA;
Heparin binds to antithrombin (AT), causing a conformational change that accelerates the binding of AT to several activated clotting factors, particularly factor Xa and factor *IIa (thrombin). This binding inactivates their procoagulant activity in the clotting cascade.
> > Heparin also inhibits the activation of factor XIII (fibrin stabilizing factor), preventing the formation of stable fibrin clots.
> > Heparin does not have fibrinolytic activity and will not lyse existing clots.
Heparin causes increased release of lipoprotein lipase, thereby increasing the clearance of circulating lipids and boosting plasma concentrations of free fatty acids
> Heparin is extensively protein bound, primarily to fibrinogen, low-density lipoproteins, and globulins. It does not appreciably cross the placenta or enter milk.
> The drug is apparently partially metabolized by the liver and also inactivated by the reticuloendothelial system
Clopidogrel- MOA, SE, how long after will return plt to normal function
> Inhibits platelet function for the lifespan of the platelet; clinically normal platelet function gradually returns 3 to 7 days after discontinuation of the medication as new platelets are released
MOA:
Clopidogrel is a prodrug and must be hepatically metabolized to form an active, highly unstable thiol compound (commonly referred to as clopidogrel active metabolite [CAM]). This compound binds selectively to the platelet surface adenosine diphosphate (ADP) receptor, P2Y12, and irreversibly alters the ADP receptor for the lifespan of the platelet. This receptor alteration reduces activation of the platelet by ADP and inhibits full activation of the glycoprotein GPIIb/IIIa complex (which is responsible for platelet binding to fibrinogen and integration into clots
> Vomiting (dogs and cats), anorexia, or diarrhea may occur; giving the drug with food may alleviate these effects in dogs and cats. Nonregenerative anemia has been reported in some cats receiving long-term clopidogrel treatment
enoxaparin=low molecular weight heparin- MOA
SE
By binding to and accelerating antithrombin, low molecular weight heparins (LMWHs) enhance the inhibition of factor Xa and thrombin. The potential advantage to using these products over standard (unfractionated) heparin is that LMWHs preferentially inhibit factor Xa and only minimally impact clotting times (prothrombin time, thrombin time, and activated partial thromboplastin time).
> ANTITHROMBIN DEPENDENT**
Asprin- Antiplatelet Agent, Nonsteroidal Anti-Inflammatory Drug (NSAID)
Aspirin inhibits cyclooxygenase (COX-1, prostaglandin synthetase), thereby reducing prostaglandin and thromboxane (TXA2) synthesis. These effects are thought to be how aspirin produces analgesia and reduces fever, platelet aggregation, and inflammation. Most cells synthesize new COX; however, platelets are not able to synthesize new COX, resulting in an irreversible inhibition of platelet aggregation.
Although aspirin does not directly inhibit COX-2, can modify COX-2 to produce the aspirin-triggered lipoxin (ATL) compound, which may have gastric mucosal protective actions. This effect may explain why aspirin tends to have reduced gastric damaging effects when used over time
SE: bleeding, renal and hepatic
> > Aspirin is rapidly absorbed from the stomach and proximal small intestine in monogastric animals. The rate of absorption is dependent on stomach content, gastric emptying times, tablet disintegration rates, and gastric pH.
> > During absorption, aspirin is partially hydrolyzed to salicylic acid, which is distributed widely throughout the body. The highest concentrations of salicylate are found in the liver, heart, lungs, renal cortex, and plasma. Aspirin’s plasma protein binding is variable depending on species as well as serum salicylate and albumin concentrations
> Salicylate is metabolized in the liver primarily by conjugation with glycine and glucuronic acid via glucuronyl transferase. Cats are deficient in this enzymatic pathway, resulting in prolonged half-lives of 27 to 45 hours; this may cause drug accumulation.
> > Kidneys rapidly excrete salicylate and its metabolites via filtration and renal tubular secretion. Significant tubular reabsorption occurs and is pH dependent. Raising urine pH to 5 to 8 can significantly increase salicylate excretion. Salicylate and metabolites may be removed using peritoneal dialysis or more rapidly by using hemodialysis.
Tissue plasminogen activator
Aminocaproic acid- MOA & contraindications:
> May be useful for treating hyperfibrinolysis in dogs and horses and postoperative bleeding in greyhounds†; efficacy for the treatment of degenerative myelopathies in dogs is questionable
Contraindicated in disseminated intravascular coagulation (DIC)
Infrequently causes GI distress
Rapid IV administration may cause hypotension and bradycardia
> > Aminocaproic acid inhibits fibrinolysis via its inhibitory effects on plasminogen activator substances and some antiplasmin activity. Much higher plasma concentrations (511.7 µg/mL) are required in dogs than in humans (122 µg/mL) to completely inhibit fibrinolysis.8 In horses, a plasma concentration of 5.8 µg/mL is sufficient to inhibit fibrinolysis.9
Aminocaproic acid is thought to affect degenerative myelopathy via its antiprotease activity, thereby reducing the activation of inflammatory enzymes that damage myelin.
reversal of heparin products & MOA & SE if given too rapidly IV
Protamine:
SE:Adverse Effects: If injected IV too rapidly: Acute hypotension, bradycardia, pulmonary hypertension, and dyspnea; hypersensitivity possible.
> > Protamine is strongly basic and heparin, strongly acidic; protamine complexes with heparin to form an inactive stable salt. Protamine has intrinsic anticoagulant activity, but its effects are weak and rarely cause problems.
fractionated heparin
