BP.19 Drugs and blood clotting Flashcards
1) What are low-molecular wieght heparins?
2) what cell type is heparin found in?
3) Which chemical group in heparin binds to antithrombin?
1) Fragments or synthetic varieties = low-molecular weight heparins (LMWH’s)
2) mast cells
3_ sulphate group
Describe the mechanism of action of and antiplatelet agents, eg aspirin.
platelet-derived TXA2 promotes aggregation
endothelium-derived PGI2 inhibits aggregation
aspirin irreversibly inhibits COX-mediated synthesis of both
endothelium can synthesise new COX, platelets cannot
net effect is an increase in PGI2 and inhibition of platelet aggregation
(OVERALL: inhibits eicosanoid production to inhibit platelet aggregation)
Describe the mechanism of action of the oral anticoagulants , eg warfarin,
warfarin inhibits vitamin K reductase required to form vit. K from oxidised vit . K. Sma eenzyme is required to make reduced Vit K from Vit. K,.
give 3 things that can result in thrombosis
vascular disease e.g.atherosclerosis
prosthetic heart valves
atrial fibrillation
What are 2 possible (baddd_ consequences of thrombosis:
deep vein thrombosis
pulmonary embolism
myocardial infarction
What is the difference between a blood clot and a thrombus?
blood clots are in vitro, thrombus are in vivo , thombi have distinct shape (white head, read tail)
Whats the difference between an arterial and venous thrombosus?
vessel wall must be atherosclerotic. arterial thrombi have large head, while venous have large tail and small head (ad give rise to emboli)
What is the difference between a blood clot and a thrombus?
blood clots are in vitro, thrombus are in vivo , thrombi have distinct shape (white head, read tail)
Whats the difference between an arterial and venous thrombus?
vessel wall must be atherosclerotic. arterial thrombi have large head, while venous have large tail and small head (ad give rise to emboli)
Describe what happens in blood clotting:
2) What controls process
complex series of enzymatic activations
produces active clotting factors from precursors
cascade mechanism which results in production of fibrin
2) Controlled by enzyme inhibitors and fibrinolysis
What do anticoagulants do?
B) + 2.e.g., one oral
A) modify blood clotting mechanisms
B) heparin and oral anticoagulants e.g. warfarin
Describe the mechanism of action of anticoagulation induced by heparin
requires antithrombin III (a2 globulin) for activity
AT III inactivates thrombin, IX, X, XI & XII
heparin binds to AT III to accelerate this process
Describe rate of onset of heparin and LMWH
2) Which one of the 2 has more consistent activity?
3) Which clotting factors does Heparin inhibit activation of?
4) which clotting factors does LMWHs inhibit activation of?
Heparin and LMWH have immediate onset of action
2) LMWH
3) 12, 11, 9, 10.
4) 10
Explain the importance of vitamin K in coagulation
required to activate
clotting factors II, VII, IX & X
Describe how antiplatelet drugs like aspirin can inhibit blood clotting. (the summary)
Inhibits eicosanoid production to inhibit platelet aggregation
What are the side effects of heparin?
2) How is overdose treated?
side effects include hypersensitivity & bleeding
2) by iv protamine (strongly basic protein)
What are the side effects of heparin?
2) How is overdose treated?
side effects include hypersensitivity & bleeding
2) by iv protamine (strongly basic protein)
how is vitamin K in coagulation targeted in oral anticoagulant drug therapy:
inhibit hepatic synthesis of vitamin K1 dependent clotting factors II, VII, IX & X
What do oral anticoagulant drug therapy target?
2) What is the lag-period?
3) What is the half life of warfarin ( a type of oral anticoagulant):
4) dose of warfarin given?
5) describe rate of absorbtion
vitamin K in coagulation
2) 1-2 days
3) 15-80hr
4) 1-20mg/day
5) rapid, almost total
Name of oral anticoagulant
warfarin
side effects of oral anticoagulants
2) treatment for overdose
bleeding, skin necrosis
2) vitamin K1 (iv or oral), fresh frozen plasma (thawed!)
Is there any resistance in the population to oral anticoagulants? if so why?
genetically determined resistance, reduced binding to vitamin K reductases (Rost et al. 2004)
1) does warfarin bind to plasma proteins?
2) What metabolic reactions does it undergoe:
3) how is it excreted:
1) yes a lot, 99%
2) ox and red
3) urinary metabolites
How is anticoagulation medicine given in practice, considering lag periods, justify:
heparin and warfarin at start, then just warfarin (to cover 1-2 lag day of warfarin).
How is effectiveness of each drug monitored:
1) heparin
2) warfarin
1) partial thromboplastin time (PTT)
2) prothrombin test (expressed as INR)- should be 2-4
What is the INR
2) What value should it be for those on warfarin
the PT ratio of a test sample compared to a normal PT (derived from the log mean normal prothrombin time
2) 2-4
Why is INR used and not thromboplastin?
Issue with thrombosplastin variability required standardisation (Assigned international sensitivity index (ISI) )
TO replace warfarin we have new more direct/ more selective anticoagulants. what are they?
2) What do they target?
1) fsctor 10a inhibitors
2) factor 2a inhibitors
What effect would drugs have that decrease effect of oral anticoagulants?
drugs which induce cytochromes P450 e.g. rifampicin, many anticonvulsants
drugs which reduce absorption e.g. sucralfate
What effect would drugs have that increase/potentiate effect of oral anticoagulants?
drugs which decrease platelet aggregation e.g. aspirin
drugs which inhibit cytochrome P450 e.g. co-trimoxazole
drugs which inhibit the reduction of vitamin K e.g.cephalosporin antibiotics
What conditions are antiplatelet drugs e.g. aspirin, hugely beneficial to?
largely beneficial in disorders of arterial thrombosis including
acute MI and high risk MI
after coronary artery bypass grafting
Name 3 dental implications for patients on antiplatelet therapies:
NSAID interaction with antiplatelet function of aspirin – delay NSAID for 1-2 hours.
Increased risk of bleeding following minor dental surgery with low dose aspirin.
Increased risk of mucosal damage and bleeding with combined NSAIDs.
What steps are taken by dentists to prevent excessive bleeding of patients on anticoagulant/ antiplatelet drugs:
Awareness of edge of haemorrhagic state, treatment performed if patient in therapeutic dose range and adequate pre- and post-operative observation and care available
Use of local haemostatic measures e.g. sutures, pressure packs, haemostatic agents including vitamin K
Awareness of drug-drug interactions
What steps are taken by dentists to prevent excessive bleeding of patients on anticoagulant/ antiplatelet drugs:
Awareness of edge of haemorrhagic state, treatment performed if patient in therapeutic dose range and adequate pre- and post-operative observation and care available (Patients requiring dental surgical procedures in primary care and who have an
International Normalised Ratio (INR) below 4.0 should continue warfarin therapy
without dose adjustment.)
Use of local haemostatic measures e.g. sutures, pressure packs, haemostatic agents including vitamin K
Awareness of drug-drug interactions