19. Anticoagulants Flashcards
(43 cards)
1
Q
Why do dentists know about drugs and clotting?
A
- thrombo-embolic diseases are a major cause of death in developed countries
- drugs used to affect blood clotting modify blood coagulation or platelet adhesion/activation
- haemorrhage and bleeding in GIT, mucus membranes, gingiva and urinary tract are side effects
- since patients take anticoagulants are on the edge of a haemorrhagic state, must take precautions in surgical procedures
2
Q
Define ‘haemostasis’
A
spontaneous arrest of blood loss from damaged blood vessels
- essential to life
3
Q
Steps of haemostasis
A
- vasoconstriction
- platelet adhesion and aggregation (eicosanoids)
- fibrin formation (coagulation system vs fibrinolytic system)
4
Q
Define ‘thrombosis’
A
unwanted formation of haemostatic plug of thrombus within blood vessel or heart
5
Q
Why can thrombosis occur?
A
- vascular disease e.g atherosclerosis
- prosthetic heart valves
- atrial fibrillation
6
Q
Consequences of thrombosis
A
- deep vein thrombosis
- pulmonary embolism
- myocardial infarction
7
Q
How does a thromboembolus can look layered. This is typical of a thrombus where?
A
- large vein of pelvis
- lower extremity
8
Q
Explain role of atheroma and the thrombus in a lumen
A
- atheroma plaques narrow the lumen significantly
- then thrombus occludes completely
9
Q
Difference in a clot vs thrombus
A
- clot forms in vitro - amorphous
- thrombus forms in vivo - distinct structure (white head, red tail)
10
Q
2 types of thrombus
A
- arterial
- venous
11
Q
Features of an arterial thrombus
A
- atherosclerotic
- large head
- platelets
12
Q
Features of venous thrombus
A
- normal
- large tail, small head
- gives rise to emboli
13
Q
Define ‘blood clotting’
A
- complex series of enzymatic activations
- produces active clotting factors from precursors
- cascade mechanism which results in production of fibrin
14
Q
What controls blood clotting?
A
- enzyme inhibitors
- fibrinolysis
15
Q
Role of anticoagulants
Examples
A
- modify blood clotting mechanisms
- heparin and oral anticoagulants like warfarin
16
Q
Intrinsic pathway of clotting
A
- triggered by exposure of collagen in damaged vessels
- factor 12 activates 11 activates 9
- vWF activates 8
17
Q
How long does blood clotting take?
A
under 5 mins
without any help
18
Q
Extrinsic pathway of clotting
A
- triggered by damaged tissue which releases 3
- which activates 7
- 3 and 7 together activate 9
19
Q
Explain the common pathway
A
- factor 9 activates 10
- 10 causes prothrombin to become thrombin/factor 2 which activates 13
- thrombin activates fibrinogen to fibrin
20
Q
What positive feedback occurs in clotting cascade?
A
- thrombin reinforces intrinsic pathway by activating 11
- activated 10 activates 7 and 3
21
Q
What is heparin?
A
- a parenteral anticoagulant
- family of sulphated mucopolysaccharides
- sulphate groups required for binding to antithrombin
- fragments or synthetic varieties - low-molecular weight heparins (LMWHs)
22
Q
Where is heparin found?
A
in secretory mast cells
23
Q
How to get heparin?
A
extracted from animal liver
24
Q
Explain the pharmacodynamics of heparin
A
- requires antithrombin III (a2 globulin) for activity
- AT III inactivates thrombin, IX, X, XI and XII
- heparin binds to AT III to accelerate this process
- LMW heparins more consistent
- all types have immediate onset of action
25
Explain pharmacokinetics in heparin
- inactive orally - not absorbed through GI tract
- administered with iv or sc for LMWHs
- short half life of less than an hour (low doses), 2 hours for higher doses but LMWH have longer duration of action
- eliminated mainly by renal excretion
26
Side effects of heparin
- hypersensitivity
- bleeding
27
How to treat heparin overdose?
iv protamine
- strongly basic protein
28
Explain pharmacodynamics of warfarin
- inhibits hepatic synthesis of vitamin K1 - dependent clotting factors II, VII and X
- 1-2 day long period
- genetically determined resistance, reduced binding to vitamin K reductases
29
Side effects of warfarin
- bleeding
- skin necrosis
30
How to treat a warfarin overdose
- vitamin K1 (iv or oral)
- fresh frozen plasma (thawed)
31
How does warfarin work as a mode of action?
- 2, 7, 9 and 10 need to be carboxylated and oxidised with oxygen, carbon dioxide and glutamic acid to delta-carboxyglutamic acid residues
- this enables vitamin K reduced form (hydroquinone) to vitamin K oxidised form (epoxide)
- it goes back to quinone then hydroquinone when reduced
- warfarin targets vitamin K reductase at both stages of this reduction to keep it reduced and all the activation of clotting factors can't happen
32
Pharmacokinetics of warfarin
- dose is highly variable (1-20mg/day)
- absorption - rapid, almost total
- plasma protein binding around 99%
- metabolism - oxidation and reduction
- excretion - urinary metabolites
- half life - 15 to 80 hrs
33
Use of anticoagulants in clinical practice
- starts usually with combination of heparin and oral coag like warfarin
- heparin rapidly effective - monitored through partial thromboplastin time
- warfarin takes 1-2 days for full effect - monitored with prothrombin test (in INR)
- heparin covers lag period and can be then withdrawn
34
How to monitor anticoagulant therapy?
- fasting blood taken to establish PT ratio
- issue with thromboplastin variability required standardisation - assigned international sensitivity index (ISI)
- patients PT is expressed as INR - internalised normalised ratio
- INR is PTpt/PTref to the power of ISI
35
Typical warfarin INR value
2-4
36
Why are new anticoags better?
- dont need antithrombin
- directly act and act quicker therefore
37
Drugs that potentiate effect of oral anticoags
- drugs that decrease platelet aggregation e.g aspirin
- drugs that inhibit cytochrome P450 e.g co-trimoxazole
- drugs that inhibit reduction of vitamin K e.g cephalosporin antibiotics
38
Drugs that decrease effect of oral anticoags
- drugs that induce cytochromes P450 e.g rifampicin, many anticonvulsants
- drugs which reduce absorption e.g sucralfate
39
How is aspirin an antiplatelet drug?
- inhibits eicosanoid production to inhibit platelet aggregation
- platelet-derived TXA2 promotes aggregation and endothelium derived PGI2 inhibits aggregation
- aspirin irreversibly inhibits COX-mediated synthesis of both
- endothelium can synthesise new COX, platelets cannot
- net effect increases PGI2 and inhibits platelet aggregation
40
When is aspirin beneficial as an anticoag?
- disorders of arterial thrombosis
- includes acute MI and high risk MI
- after coronary artery bypass grafting
41
Anticoags in a dental patient - how is this considered?
- every effort made to avoid treatment - use preventative care
- awareness of those, treatment performed if patient in therapeutic dose range and adequate pre- and post-treatment operative observation and care available
- use of local haemostatic measures like sutures, pressure packs, haemostatic agents like vitamin K
- awareness of drug-drug interactions
42
Dental implications for patients medicated with antiplatelet therapies
- NSAID interaction with antiplatelet function of aspirin - delay NSAID for 1-2 hrs
- increased risk of bleeding following minor dental surgery for low dose aspirin
- increased risk of mucosal damage and bleeding with combined NSAIDS
43
Dental implications for patients medicated with anticoagulants
- antibiotics enhance anticogaluant activity (esp metrodinazole, tetracycline)
- NSAIDs contraindicative in postoperative pain and inflammation management - high risk of ulcerative bleeding
