This Is A Pharmaceutical Tests About Anticoagulants

Proteins C and S are dependent on Vitamin K for synthesis. Vitamin K is essential for the production of blood clotting proteins, including proteins C and S. These proteins play a crucial role in regulating blood clotting and preventing excessive clot formation. Without sufficient Vitamin K, the synthesis of proteins C and S would be impaired, leading to an increased risk of abnormal blood clotting. Therefore, Vitamin K is necessary for the proper functioning of proteins C and S in the body.

Warfarin has a 35 hour half-life! It is well absorbed by the oral route and is 99% bound to plasma proteins (albumin).

Protamine is a small, positively charged molecule that binds with heparin. Dosages is based on the level of heparin - must be dosed to titrate 1:1 with heparin, taking into account the different half lives of the drugs. Adverse effects of protamine are anticoagulation (acts as an anticoagulant if administered without heparin) and anaphylactic shock (derived from fish sperm).

Warfarin acts thru competitive inhibition of vitamin K reductase - blocks the synthesis of factors II, VII, IX, X, and protein C and S - results in lack of gamma carboxylation of the factors (gamma carboxylation allows calcium to bind, which is necessary for activation and platelet binding).

Mechanim of action: irreversible inhibition of cyclooxygenase (COX-1 and COX-2). COX-1 is ubiquitously present in all cells - inhibiting COX-1 inhibits the synthesis of thromboxanes which inhibits platelet aggregation. COX-2 is not present on platelets.

Increased half-life because the plasminogen activator inhibitor doesn't degrade these as quickly. Only specific approved indications.

Heparinase in liver.

LMWHs are cleared renally. Less interactions with platelets means less risk of HIT! (Still can't use in patients who have had HIT.) Additional benefits include little monitoring (don't have to be in the hospital), self-administration SQ.

Estrogen therapy increases the synthesis of clotting factors and can cause ischemic strokes. Protein C and S help keep clot formation in balance.

abciximab (Reopro) = murine-human chimeric antibodies. eptifibatide (Integrelin) = synthetic peptide form. tirofiban (Aggrastat) = synthetic peptide forms.

Gout - low doses of aspirin increase uric acid levels - competes for excretion of uric acid. Salicylism - aspirin is an acid - use sodium bicarb to treat - excrete in anionic form.

Heparin metabolites are excreted in the kidneys. The kidneys play a vital role in the excretion of waste products and metabolites from the body. Heparin, a medication used as an anticoagulant, undergoes metabolism in the liver and is then excreted primarily through the kidneys. The kidneys filter the blood and remove waste products, including heparin metabolites, through urine. Therefore, the correct answer is kidneys.

Streptokinase forms a non-enzymatic complex with circulating plasminogen which catalyzes thrombolytic reactions - used IV and infused directly into coronary arteries *(less than 6 hours for MI)*

The correct answer is A, D, and E. Low molecular weight heparins (LMWHs) are a type of anticoagulant medication. Enoxaparin (Lovenox), dalteparin (Fragmin), and tinzaparin (Innohep) are all examples of LMWHs. Warfarin and coumadin, on the other hand, are not LMWHs.

Hypersensitivity is due to animal origin. Osteoporosis and alopecia are only seen in long-term use - 2-3 months. Hemorrhage is the major concern. Thrombocytopenia = hepairin induced (HIT) platelet aggregation - heparin antibody develops 7-14 days after start of treatment. Thromboembolism is induced by HIT.

Heparin is the drug of choice for pregnant women because it does not cross the placental membrane.

Fondaparinux (Arixtra) inhibits factor Xa in conjunction with antithrombin. Factor Xa is a key enzyme in the coagulation cascade that plays a crucial role in the formation of blood clots. By inhibiting factor Xa, Fondaparinux prevents the formation of blood clots and reduces the risk of thromboembolic events.

indicated in arterial thromboembolism prophylaxis

Clopidogrel (Plavix) is indicated in thrombosis and coronary artery disease - side effects include a low risk of TTP (thrombotic thrombocytopenia purpura), bleeding, hypersensitivity, abdominal pain, constipation - resistance to clopidogrel (Plavix) can be seen if the patient has a defect in CYP450 enzymes - prodrug doesn't get converted to active form.

Cannot be administered orally - large and negative. Cannot be administered IM - hematoma. Only IV and SQ.

LMWH (Low Molecular Weight Heparin) inactivates Xa (Factor Xa) but has little inactivation at IIa (thrombin) via antithrombin because the chains of LMWH are shorter compared to heparin. Thrombin has a higher molecular weight and requires longer chains to bind effectively. Therefore, LMWH primarily targets and inhibits Xa, which is involved in the formation of blood clots, while having minimal effect on thrombin. This is different from heparin, which can inhibit both Xa and IIa.

Fondaparinux (Arixtra) is a LMW Heparin Derivative that does not originate from unfractionated heparin. It is a synthetic pentasaccharide identical to the antithrombin binding region of heparin.

activates plasminogen bound to platelets and endothelial cells (relatively clot specific) - not very antigenic (unless allergic to E. coli) - inhibited by t-PA inhibitor - short half-life of 5-10 minutes - long infusion of 90 min. infusion - higher intracranial bleeding risk but no hypotension (which can be an issue with streptokinase).

Acts as reversible antagonists of glycoprotein IIb/IIIa - the receptor on the platelet for adhesive proteins such as fibrinogen and von Willebrand factor. Maximally inhibit the final common pathway involved in platelet adhesion, activation, and aggregation.

Collagen is exposed after tissue injury, which activates platelets. von Willebrand factor is then released, attracting platelets to the site of injury. Platelets secrete serotonin and thromboxane A2, causing vasoconstriction. Finally, platelets secrete ADP, which attracts more platelets to the site of injury. Therefore, the correct order is C, A, D, B.

It is large and negatively charged and cannot cross the membrane to be absorbed.

Phytonadione (K1) can be given orally, IV, or SC and it competes with warfarin. Transfusion of fresh frozen plasma provides a lot of fresh clotting factors.

We want plasmin associated with the clot (bound) - systemic lysis can occur when plasmin is present in circulating plasma - it will destroy clotting factors in addition to clots!

Warfarin takes out the synthesis of inactivated factors but you need to wait for the body to get rid of the activated factors before seeing the effects of warfarin. Activated IIa has the longest half life, at 60 hours.

Heparin acts as an anticoagulant by way of antithrombin (a protease inhibitor) - antithrombin inhibits factors Xa, thrombin (IIa), and IXa, XIa, and XIIa. Heparin therefore inhibits conversion of prothrombin to thrombin (via inhibition of Xa) and fibrinogen to fibrin (via inhibition of IIa).

Synthetic drivative of arginine - direct reversible thrombin inhibitor by blocking the catalytic site - treats thrombosis in HIT - IV administration - metabolized by the LIVER so don't have to worry about renally compromised patients.

Inhibits platelet activation by increasing cellular cyclic AMP by inhibiting a phosphodiesterase that degrades cAMP.

Barbiturates increase metabolism by inducing degradation enzymes. Rifampin increases metabolism by inducing CYP450 enzymes. Vitamin K competes for binding (role of foods). Estrogens increase factors VII and X which increases the synthesis of coagulation factors. Estrogens also decrease the synthesis of antithrombin. Cholestyramine - binds fat soluble vitamins and so eliminates warfarin if given concurrently

Only 3 AAs different from alteplase - 20-24 minute half-life - more resistant to t-PA circulating inhibitors - highest fibrin selectivity - wont have as many issues with extraneous plasminogen formation.

Synthetic derivative - IV administration - renal elimination so must use caution in renally compromised patients.

Newest of the group - direct thrombin almost irreversible inhibitor - can be used in HIT patients - SQ so more useful - renal elimination, use caution.

A deficiency in Prothrombin (factor II) or in Stuart-Prower factor (factor X) can be caused by liver disease and vitamin K deficiency. Liver disease can impair the liver's ability to produce these clotting factors, leading to a deficiency. Vitamin K is essential for the production of these factors, so a deficiency in vitamin K can also result in a deficiency of Prothrombin and Stuart-Prower factor. Therefore, both liver disease and vitamin K deficiency can contribute to a deficiency in these clotting factors.

"Tissue factor" or thromboplastin is released from endothelial wall - starts the extrinsic pathway ("tissue factor pathway" - a factor from outside the vascular system is required.
Contact of blood with collagen starts the intrinsic pathway of blood ("contact activation pathway") - all clotting factors required to start the pathway are present within the vascular system.

(I'm not sure why, but according to my notes, emphasis was placed on the importance of this point...)

If patient has had a previous strep infection or has been given streptokinase before, the patient will have antibodies to streptokinase that will cause an allergic reaction or neutralization of streptokinase).

Acetylsalicylic acid - platelets - reduce platelet aggregation - displacement of warfarin from albumin (get more unbound, active aspirin and more free warfarin too). Acetaminophen - high dose and long term - inhibits warfarin degradation - competition for CYP1A2 and 3A4. Antibiotics - (broad spectrum) gut flora - bacteria in the stomach synthesize vitamin K - reducing the amount of vitamin K produced means there is less for warfarin to compete with so it is able to work better. Antibiotics - sulfonamides - compete in plasma albumin binding.

Fetal bone defects are due to lack of gamma carboxylation of osteocalcein.

Dipyridamole and aspirin formulation (Aggrenox) is recommended for use with prosthetic heart valves in combination with aspirin. Technically A would be true too but is not the most important difference between the two. More platelet inhibition is seen with cilostazol than with aspirin or dipyridamole.

Thyroid - increased metabolism of clotting factors so there are less clotting factors around. Miconazole - is able to cross the membrane and affect warfarin enzymes - inhibits CYP450 - increased warfarin levels. Gemfibrozil - competes for plasma proteins.

Cilostazol would likely be prescribed for a patient with atherosclerosis in the legs causing intermittent claudication. Cilostazol is a medication that helps improve blood flow by dilating the blood vessels and reducing platelet aggregation. It is specifically indicated for the treatment of intermittent claudication, which is characterized by pain, cramping, and weakness in the calf muscles during physical activity such as walking. Aspirin, Dipyridamole, and Niacin may have other uses, but Cilostazol is the most appropriate choice for this particular condition.

Heparin releases a clearing factor (a lipoprotein lipase) - this lipase hydrolyzes triglycerides in chylomicrons.

Dosing by IV and is expensive - renal elimination so use caustion in renally compromised patients.

This is also the order for activating thrombin - tenectaplase the least and reteplase the most.

Reteplase is clot specific but less so than alteplase - not very antigenic - 13-16 min. half-life - 2 separate 2 minute IV bolus separated by 30 min. - bleeding risk.

Drugs are infused - rapid acting - and rapidly reversed after stopping infusion - major side effect: bleeding.