BP.19 Drugs and blood clotting

Question 1

1) What are low-molecular wieght heparins?
2) what cell type is heparin found in?
3) Which chemical group in heparin binds to antithrombin?

Answer 1

1) Fragments or synthetic varieties = low-molecular weight heparins (LMWH’s)
2) mast cells
3_ sulphate group

Question 2

Describe the mechanism of action of and antiplatelet agents, eg aspirin.

Answer 2

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)

Question 3

Describe the mechanism of action of the oral anticoagulants , eg warfarin,

Answer 3

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,.

Question 4

give 3 things that can result in thrombosis

Answer 4

vascular disease e.g.atherosclerosis
prosthetic heart valves
atrial fibrillation

Question 5

What are 2 possible (baddd_ consequences of thrombosis:

Answer 5

deep vein thrombosis
pulmonary embolism
myocardial infarction

Question 6

What is the difference between a blood clot and a thrombus?

Answer 6

blood clots are in vitro, thrombus are in vivo , thombi have distinct shape (white head, read tail)

Question 7

Whats the difference between an arterial and venous thrombosus?

Answer 7

vessel wall must be atherosclerotic. arterial thrombi have large head, while venous have large tail and small head (ad give rise to emboli)

Question 8

What is the difference between a blood clot and a thrombus?

Answer 8

blood clots are in vitro, thrombus are in vivo , thrombi have distinct shape (white head, read tail)

Question 9

Whats the difference between an arterial and venous thrombus?

Answer 9

vessel wall must be atherosclerotic. arterial thrombi have large head, while venous have large tail and small head (ad give rise to emboli)

Question 10

Describe what happens in blood clotting:

2) What controls process

Answer 10

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

Question 11

What do anticoagulants do?

B) + 2.e.g., one oral

Answer 11

A) modify blood clotting mechanisms

B) heparin and oral anticoagulants e.g. warfarin

Question 12

Describe the mechanism of action of anticoagulation induced by heparin

Answer 12

requires antithrombin III (a2 globulin) for activity
AT III inactivates thrombin, IX, X, XI & XII
heparin binds to AT III to accelerate this process

Question 13

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?

Answer 13

Heparin and LMWH have immediate onset of action

2) LMWH
3) 12, 11, 9, 10.
4) 10

Question 14

Explain the importance of vitamin K in coagulation

Answer 14

required to activate

clotting factors II, VII, IX & X

Question 15

Describe how antiplatelet drugs like aspirin can inhibit blood clotting. (the summary)

Answer 15

Inhibits eicosanoid production to inhibit platelet aggregation

Question 16

What are the side effects of heparin?

2) How is overdose treated?

Answer 16

side effects include hypersensitivity & bleeding

2) by iv protamine (strongly basic protein)

Question 17

What are the side effects of heparin?

2) How is overdose treated?

Answer 17

side effects include hypersensitivity & bleeding

2) by iv protamine (strongly basic protein)

Question 18

how is vitamin K in coagulation targeted in oral anticoagulant drug therapy:

Answer 18

inhibit hepatic synthesis of vitamin K1 dependent clotting factors II, VII, IX & X

Question 19

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

Answer 19

vitamin K in coagulation

2) 1-2 days
3) 15-80hr
4) 1-20mg/day
5) rapid, almost total

Question 20

Name of oral anticoagulant

Answer 20

warfarin

Question 21

side effects of oral anticoagulants

2) treatment for overdose

Answer 21

bleeding, skin necrosis

2) vitamin K1 (iv or oral), fresh frozen plasma (thawed!)

Question 22

Is there any resistance in the population to oral anticoagulants? if so why?

Answer 22

genetically determined resistance, reduced binding to vitamin K reductases (Rost et al. 2004)

Question 23

1) does warfarin bind to plasma proteins?
2) What metabolic reactions does it undergoe:
3) how is it excreted:

Answer 23

1) yes a lot, 99%
2) ox and red
3) urinary metabolites

Question 24

How is anticoagulation medicine given in practice, considering lag periods, justify:

Answer 24

heparin and warfarin at start, then just warfarin (to cover 1-2 lag day of warfarin).

Question 25

How is effectiveness of each drug monitored: 1) heparin 2) warfarin

Answer 25

1) partial thromboplastin time (PTT) | 2) prothrombin test (expressed as INR)- should be 2-4

Question 26

What is the INR | 2) What value should it be for those on warfarin

Answer 26

the PT ratio of a test sample compared to a normal PT (derived from the log mean normal prothrombin time 2) 2-4

Question 27

Why is INR used and not thromboplastin?

Answer 27

Issue with thrombosplastin variability required standardisation (Assigned international sensitivity index (ISI) )

Question 28

TO replace warfarin we have new more direct/ more selective anticoagulants. what are they? 2) What do they target?

Answer 28

1) fsctor 10a inhibitors | 2) factor 2a inhibitors

Question 29

What effect would drugs have that decrease effect of oral anticoagulants?

Answer 29

drugs which induce cytochromes P450 e.g. rifampicin, many anticonvulsants drugs which reduce absorption e.g. sucralfate

Question 30

What effect would drugs have that increase/potentiate effect of oral anticoagulants?

Answer 30

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

Question 31

What conditions are antiplatelet drugs e.g. aspirin, hugely beneficial to?

Answer 31

largely beneficial in disorders of arterial thrombosis including acute MI and high risk MI after coronary artery bypass grafting

Question 32

Name 3 dental implications for patients on antiplatelet therapies:

Answer 32

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.

Question 33

What steps are taken by dentists to prevent excessive bleeding of patients on anticoagulant/ antiplatelet drugs:

Answer 33

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

Question 34

What steps are taken by dentists to prevent excessive bleeding of patients on anticoagulant/ antiplatelet drugs:

Answer 34

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