Drugs affecting Coagulation Flashcards
Classification?
- Anti - platelet drugs.
- Thrombin inhibitors (Direct and Indirect).
- Inhibitors of coagulation (Direct-inhibiting factor 10A and indirect anti-coagulants).
- Fibrinolytic and anti-fibrinolytic drugs.
- Coagulants with local effect.
- Coagulants with systemic effect.
Explain the anti-platelet drugs.
Aspirin, Clopidogrel and Disopyridamole.
- Aspirin is a COX inhibitor meaning it inhibits thromboxane A2 function (Platelet aggregation). Hepatic metabolism to salicylic acid and some excreted in urine unchanged. Blocking platelet aggregation means less clot formation, making bleedings (GI bleedings) the main complication.
- Clopidogrel functions to inhibit ADP binding on platelet receptors, which has the effect of reducing platelet binding to fibrinogen and to each other (thrombus growth).
- Dipyridamole functions to reduce the synthesis of thromboxane A2 via inhibition of “cyclic nucleotide phosphodiesterase”. Hepatic metabolism and excretion into the feces. SHOULD NOT BE USED WITH STABLE ANGINA as the causes vasodilation of coronary arteries causing “coronary steal phenomenon”.
Explain the “INDIRECT” thrombin inhibitors.
Heparin and LMWH (low molecular weight). Heparin works in conjunction with the anticoagulant “ANTI-THROMBIN” to inhibit “clotting factor proteases” that aid coagulation cascade, the end goal is to inhibit the formation of the “fibrin clot”. Heparin speed up clotting factor protease inhibition compared to the function of anti-thrombin alone.
Administration is via intravenous route. IV injects a high dose bolus into blood stream followed by a low dose steady infusion for immediate anti-coagulant effects. The inactive metabolites are excreted in urine. Partial thromboplastin time “aPTT” (time taken for blood to clot) is at level 1.5-2.0, used to monitor the anti-coagulating activity of Heparin.
Adverse Effects: Bleeding (managed by drug discontinuation and use of “PROTAMINE SULPHATE”. The protamine sulphate itself is a weak anti-coagulant which can potentiate bleeding if over 1mg per 100 units of Heparin.
Anaphylaxis, chills, fever and urticaria (Itchy raised rash).
Uses : Heparin may be the drug of choice used in pregnancy as it does not cross the BPB, Acute thromboembolisms (DVT/PE).
Explain “DIRECT” thrombin inhibitors.
“DABIGATRAN” is the inactive parent (direct oral thrombin inhibitor) drug and “ DABIGATRAN EXTELIATE” is the active metabolite.
Functions to bind to clot bound and free plasma thrombin to reduce formation of Fibrin clot. After the formation of active metabolite = renal excretion.
Therapeutic use: Systemic embolism and strokes.
Adverse effects: Bleeding (no antidote), GI adverse effects (abdominal pain, GI bleeding, dyspepsia/indigestion and esophagitis.
Explain “DIRECT” acting anti-coagulants” (Blockers of factor 10A)
“RIVAROXABAN” (Oral factor 10A inhibitor). Preventing conversion of pro-thrombin to thrombin.
Therapeutic uses: DVT and PE
Adverse effects: Bleeding (No antidote).
Explain the “INDIRECT” anti-coagulants.
“Coumarin anti-coagulants” aka Warfarin is used for the inhibitor of co-factor vitamin K. Coagulant factors 2, 7, 9 and 10 require vit.K for their synthesis in the liver.
Rapid oral absorption, highly bound to plasma albumin (can be displaced and have prolonged effects, plasma accumulation).
Adverse Effects: Bleeding is the main one, minor bleeding can be aided by oral vit.K administrations, severe bleeding requires high dose IV vit.K administration. Warfarin has teratogenic effects, is hepatotoxic.
It takes 24 hours for administered vit.K to reverse effects of warfarin, in which time the already synthesised and circulating coagulation factors have degraded and not been replaced.
Therapeutic use : DVT/PE and stroke treatment.
Explain “FIBRINOLYTIC” drugs.
These agents stimulate the conversion of plasminogen to plasmin.
Examples are :
“STREPTOKINASE”, “ATEPLASE” and “UROKINASE”.
Formation of plasmin leads to fibrinolysis. A side effect of dissolving clots is increased formation of local thrombi. This causes an enhanced platelet aggregation to fragments of fibrin. Co-administration of fibrinolytic drugs with “ASPIRIN” or “thrombotic” like “HEPARIN” reduces these chances.
10% of Ateplase is injected via IV bolus due to short half life, other 90% as steady infusions.
Adverse effects: Haemorrhage of any clots, meaning people with healing wounds may be affected.
Explain “ANTI- FIBRINOLYTIC” drugs.
“AMINOCAPROIC ACID” (inhibitor of fibrinolysis via reduced plasmin and fibrin interaction). Oral administration and urinary excretion. Can be used in patients with haemophilia, therapy from bleeding due to fibrinolytic therapy to clear DVT for example.
Adverse effects: Formation of thrombosis due to inhibitory function, abdominal discomfort, diarrhoea and nasal stiffness.
Explain coagulants with “LOCAL” effect.
“Gelatine sponges” which act as a homeostatic device by providing coagulation factors like “thrombin” into the area. They function to absorb lots of blood at the site of bleeding but at the same time provide the coagulant to control the bleeding. (Promotors of coagulation).
Explain Coagulants with “SYSTEMIC” effect.
Calcium ions are factor IV of the coagulation system.
Side effects include nausea, constipation, upset stomach.
Vitamin K stimulates prothrombin (factor II) and factors VII, IX, and X by participating in their post ribosomal modifications within the liver.
Intravenous administration of vitamin K (water-soluble form) should be slow, because rapid infusion can produce dyspnea, chest and back pain, and even death.
