Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Pharmacology for Anaesthetists > Drugs affecting coagulation > Flashcards

Drugs affecting coagulation Flashcards

1
Q

What are the two different models used to explain how haemostasis occurs

A

The classical model (intrinsic and extrinsic pathway)

The cell based model (initiation, amplification, propogation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Describe the classical model

A

Three elements:
1, Platelets
2. Coagulation cascade
3. Fibrinolysis

Subendothelial exposure –> vWF + platelet adhesion–> TXA2 (platelets) –> VC + platelet aggregation –> platelet plug interwoven with fibrinogen –> coagulation cascade to form cross linked fibrin and a stable clot.

Coagulation cascade:
Intrinsic and extrinsic pathway converge to activate factor 10 –> thrombin –> fibrin –> cross-linked plug

Intrinsic pathway

  • triggered by exposure to collagen
  • TENET: 12,11,9 + 8, Ca, PF3 –> 10
  • Lab measurement aPTT

Extrinsic pathway

  • triggered by leakage of tissue factors
  • 7 + 3 –> 10
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How do constituents of arterial and venous thrombi compare?

A

Arterial –> Rely on more platelets

Venous –> Fibrin mesh predominates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the physiological inhibitors of the classic haemostatic model

A
  1. Anti-thrombin 3: inhibits: 10a, and 2a (and 12a, 11a and 9a)
  2. Protein C + Protein S: Deactivates 8 and 5
    (Protein C activated by thrombin-thrombomodulin complex)
  3. Thrombomodulin binds thrombin to activate protein C and inactivate thrombin bound
  4. t-PA: converts plasminogen –> plasmin (fibrinolysis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Why was the cell based model developed

A

The classical model fails to effectively describe the haemostatic mechanisms on vivo (rather than in vitro).

E.g.
1. Factor 12 deficiency doesn’t result in increased bleeding tendency despite abnormal in vitro tests

  1. Factor 11 deficiency causes a bleeding tendency that is not closely related to in vitro tests
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How does the cell based model differ from the classical model

A

The cell based model places greater importance on the interaction between specific cell surfaces and clotting factors.

The cell based model proposes that coagulation is the sum of 3 processes each occurring on different cell surfaces RATHER than as a cascade:
INITIATION
- damage –> cells bear TF on surface –> small amount thrombin generated –> platelets coated in activated co-factors
AMPLIFICATION
- Platelet surface covered in cofactors –> ^^ Thrombin and amplification
PROPOGATION
- Tissue factor bearing cells and platelets now coated with coagulation factors ^^^ Thrombin –> propogation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the mechanism of action of aspirin with regards to its use in cardiovascular disease? What minimum dose is required to achieve this effect? What is the maximum daily dose

A

Irreversible inhibition of cyclo-oxygenase by acetylation within the platelet –> reduced TXA2 –> increase cAMP –> reduced degranulation platelets and reduced vasoconstriction

Minimum dose = 75mg daily
Maximum daily dose = 4g (Toxic dose > 10g)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the significance of low dose aspirin (75mg)

A

At low does it is believed that aspirin selectively inhibits platelet COX whilst preserving vessel wall COX. This prevents TXA related VC and platelet aggregation while leaving the vessel wall synthesis of PGI2 unaltered and hence vasodilated.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the chemical name of aspirin

A

acetylsalicyclic acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe the metabolic effects of aspirin

A

Usually have little significance but become significant in overdose.

ADULTS

  1. Initial respiratory alkalosis (direct stimulation resp. centres)
  2. Uncouple oxidative phosphorylation –> Increased O2 consumption + CO2 production but halted ATP production
  3. Interference with Krebs cycle enzymes –> ketoacidosis and lactic acidosis

CHILDREN
1. The resp. centre is depressed by rising aspirin levels –> Mixed resp acidosis + HAGMA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the consequence of uncoupling oxidative phosphorylation

A

Increased O2 consumption + CO2 production with halted ATP formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the difference between haemoperfusion and haemodialysis

A

Haemoperfusion - blood comes into direct contact with various absorbant materials which means it can remove toxins despite protein binding and lipophilicity

Haemodialysis - there is a concentration gradient between the blood and the solvent across the dialysis membrane.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the common features of Aspirin overdose

A
  1. Nausea, vomiting and tinnitus
  2. Resp alkalosis
  3. HAGMA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the treatment of aspirin overdose

A

Supportive: ABCDE

  1. Activated charcoal
  2. Forced alkaline diuresis
  3. Haemofiltration/haemodialysis/Haemoperfusion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Can children under 12 receive aspirin? Explain the answer

A

Children under the age of 12 can receive aspirin only if specifically indicated. E.g. Juvenile arthritis (Still’s disease).

Reye’s syndrome is an uncommon condition that has been linked to aspirin use in children.

Reye’s syndrome

  1. Widespread mitochondrial damage
  2. Liver: fatty changes –> hepatic failure with encephalopathy and cerebral oedema
  3. Mortality 40%
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is Reye’s syndrome

A

Reye’s syndrome is an uncommon condition that has been linked to aspirin use in children under 12 years of age.

Reye’s syndrome

  1. Widespread mitochondrial damage
  2. Liver: fatty changes –> hepatic failure with encephalopathy and cerebral oedema
  3. Mortality 40%
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Where is aspirin absorbed and why?

A

Stomach

Its a weak acid with pKa of 3.0 –> therefore it is mostly unionized in the stomach pH ± 2.0 and absorbed readily.

pH in mucosal cells = 7.4. Therefore ion trapping as aspirin becomes ionized at pH above its pKa (3.0)

Large surface area of small bowel allows further absorption of aspirin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the bioavailability of aspirin and why

A

50%

Half the aspirin is rapidly hydrolysed by hepatic and intestinal esterases to salicylate.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How is aspirin metabolized

A

Liver

  1. Hydrolysed by intestinal and liver esterases to salicylate
  2. Converted to salicyluric acid and glucoronide derivatives

Excreted in urine (enhanced under alkaline conditions) filtered but not re-absorbed as high pH in tubules maintains ionized state

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is dipyridamole and how does this drug affect coagulation

A
  1. PDE inhibitor –> increase cAMP –> Low calcium
  2. Prevents re-uptake of ADP
  3. Potentiates PGI2 effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Summarise the uses of clopidogrel

A
  1. Post-coronary stent therapy (prevent failure)
  2. STEMI and NSTEMI (with aspirin)
  3. Atherothrombotic prevention in PVD
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the mechanism of action of clopidogrel

A

Binds irreversibly to ADP receptor: P2Y 12 on platelets –> prevents Glycoprotein IIb/IIIa from transforming into its active form. Platelet activation and cross-linking is inhibited.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Is clopidogrel a drug?

A

No. It is a prodrug which is activated by cytochrome P450 system to form its active metabolite which blocks the P2Y12 ADP receptor irreversibly and prevents transformation of glycoprotein IIa/IIIb into active form hence preventing cross linking platelet aggregation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the dose of clopidogrel

A

300 - 600mg loading

75 mg daily

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
how long does it take for the antiplatelet effects of clopidogrel to occur
2 hours
26
How long to the antiplatelet effects of clopidogrel last and why
7 days (platelet life span). Due to IRREVERSIBLE binding to the P2Y12 receptor Bleeding time completely normalized after 10 days
27
When is it safe to perform a neuraxial block in a patient who has taken clopidogrel?
After 7 days
28
Why does clopidogrel have a variable antiplatelet effect in different individuals
Cytochrome P450 metabolism CYP3A4, CYP3A5 (primary isoenzymes CYP2C19 (also involved) - significant genetic polymorphism - Result: increased/decreased metabolism into active metabolite.
29
How does omeprazole effect the antiplatelet effect of clopidogrel
Omeprazole inhibits CYP2C19 --> reduced metabolism of clopidogrel into active form --> reduced antiplatelet effect.
30
Can clopidogrel be reversed?
There is no specific reversal agent A single dose of desmopressin for intracranial haemorrhage associated with aspirin/clopidogrel can be administered
31
What is the active metabolite of clopidogrel called
The clopidogrel thiol derivative
32
What is the T1/2 elimination constant for clopidogrel and its active thiol derivative
Clopidogrel t1/2 = 6 hours | Thiol derivative t 1/2 = 30 minutes
33
How is clopidogrel adminstered
PO
34
Regarding Clopidogrel: What is the risk reduction in unstable angina for MI What is the risk reduction for prevention of stent thrombosis?
Unstable angina MI --> 18% | Stent thrombosis --> 30 %
35
How long is clopidogel usually prescribed for post percutaneous transluminal coronary angioplasty (PTCA)? How long is aspirin given for
3 to 12 weeks | Aspirin for life
36
What is the increased bleeding risk associated with dual antiplatelet therapy
40% increased
37
What type of surgery should be performed whilst a patient is on clopidogrel
Life or Limb only
38
Describe successful management of patients with a drug-eluting coronary stent presenting for elective, non-cardiac surgery
1. Stop clopidogrel at 5 days preop 2. Admit 3 days preop 3. Tirofiban and UFH infusion until 6 hours preop 4. Restart clopidogrel day 1 postop 5. Continue aspirin throughout
39
By how much does one unit of pooled platelets raise the platelet count
± 5000 platelets/microliter Normal platelets > 150 000 platelets / microliter VEry small increase relative to normal platelet numbers
40
What are the functional platelet count targets for surgery/spinal anaesthesia, epidural and eye/neurosurgery
Spinal anaesthesia and surgery: Plts > 50 000 Epidural: Plts > 80 000 Eye/Neurosurgery: Plts > 100 000
41
Where does heparin naturally occur in the body
Lungs Liver Mast cells Arterial walls
42
Compare the molecular weight of unfractionated heparin and low molecular weight heparin
UFH: 15 000 Da LMWH: 5 000 Da
43
How does heparin act
1. INHIBITION OF COAGULATION - Enhances formation of antithrombin III - thrombin complex: Inhibits: 2a, 10a, 12a, 11a, 9a 2. INHIBIT PLATELET AGGREGATION 3. INCREASE LIPOPROTEIN LIPASE - reduces plasma turbidity 4. INCREASE VASCULAR PERMEABILITY
44
What are the uses of heparin
1. PROPHYLAXIS VTE 2. RX ACS and UNSTABLE ANGINA 3. RX critical peripheral arterial occlusion 4. PRIME extracorporeal circuits
45
How is heparin administered. Describe dosages: Prophylaxis and full anticoagulation as during cardiopulmonary bypass
IV or SC Adult dose for prophylaxis: 5000 IU SC 8 - 12 hrly For full anticoagulation: 300IU/kg or 3mg/kg
46
What is the onset of action and half life of heparin vs LMWH
Onset: immediate T1/2 UFH = 1 hour T1/2 LMWH = 4.5 hours
47
What are LMWH and what are their advantages compared to UFH
Fragments from depolymerization of heparin and have a MW of 5000 Da LMWH (vs. UFH) - More effective in inhibiting Xa - Less effective in potentiating antithrombin III Advantages - Single daily dose (longer half life) - Require less monitoring - Less effect on platelets - Reduced risk of HIT (heparin induced thrombocytopaenia) - Reduced affinity for vWF
48
What prolongs aPTT and TT
Heparin
49
Why do LMWH not need routine monitoring and when they are monitored how is this done?
More predictable plasma level and do not need monitoring routinely If monitoring necessary: anti-Xa assay.
50
Is aPTT prolonged by LMWH
No
51
What are the side effects of heparin
1. Haemorrhage 2. HIT 3. Hypotension (rapid infusion) 4. Osteoporosis 5. Alopecia
52
What do you understand by heparin induced thrombocytopaenia
Two types: Type 1. NON-IMMUNE - Within 4 days of starting therapy - Returns to normal without stopping therapy - Unknown clinical significance Type 2. IMMUNE - More severe - Occurs 5 - 14 days after starting therapy - 50% develop serious THROMBOSIS ± PE - High mortality (PE) - Formation of a complex formed between: HEPARIN - Platelet Factor 4 - IgG --> Platelet aggregation and thrombosis
53
How is the effect of heparin reversed
Protamine sulphate | - Basic cationic protein obtained from the sperm of fish
54
How much protamine is required to reverse heparin. How long does this reversal take
1mg reverse 100IU of heparin
55
Is protamine fully effective in reversing LMWH
No. But it can still be administered for partial reversal
56
What is the dosing regimen for protamine administration and reversal of enoxaparin
Time from last enoxaparin: < 8hrs: 1mg protamine for every 1mg enoxaparin > 8 and < 12 hrs: 0.5 mg protamine for every 1 mg enoxaparin 12 - 24 hours --> ? need for reversal depending on dose received and renal function
57
What is Warfarin? How does Warfarin act?
Warfarin is an Oral anticoagulant which is a derivative of coumarin. INHIBITS VITAMIN K EPOXIDE REDUCTASE complex 1 - Inhibits the synthesis of vitamin k dependent clotting factors: 2,7, 9, 10. Protein C, Protein S.
58
How long does warfarin take to work and why
Up to 3 days Warfarin has no effect on the circulating clotting factors
59
What are the side effects of warfarin
1. Haemorrhage 2. Teratogenecity 3. Drug interactions
60
What are the important drug interactions of Warfarin | NB Potentiation and inhibition of effects of warfarin
POTENTIATION OF WARFARIN effects 1. Other anticoagulant drugs --> Increase bleeding risk - NSAIDS - heparin 2. Highly protein bound drugs --> displace warfarin from protein binding sites --> higher free drug level --> increased bleeding risk - NSAIDS - Oral hypoglycaemics - Diuretics - Amiodarone 3. Broad spectrum antibiotics potentiate warfarin effects 4. Reduced Vit K intake potentiate warfarin effects 5. Cimetidine potentiate warfarin effects INHIBITION OF WARFARIN effects 1. Induction of CYP450: Barbiturates and phenytoin 2. Oestrogens: increase production of Vit K dependent clotting factors
61
How is warfarin therapy monitored
PT | Measure of factor 7 from extrinsic pathway and the factors of the final common pathway
62
What is INR
The international normalized ratio (PT patient / PT control)^international sensitivity index value The international sensitivity index value is provided by the manufacturer
63
How is the anticoagulant effect of warfarin reversed
Rapid reversal FFPs | Slower reversal: vitamin K
64
What is abciximab
Monoclonal antibody with a high affinity for the platelet glycoprotein IIb/IIIa receptor. This blocks the final common pathway of platelet aggregation.
65
What is the half life of abciximab and for how long does it remain in circulation with residual activity
T1/2 is 20 minutes Remains bound in circulation for 15 days with come residual activity
66
Give two more examples of Glycoprotein IIb/IIIa inhibitors What is their mechanism of action
Abciximab Eptifibitide Tirofiban Glycoprotein IIb/IIIa inhibitor --> blocking the final common pathway of platelet aggregation. They do not block: 1. Platelet adhesion 2. Secretion platelet products 3. Inflammatory effects 4. Secretion of thrombin
67
How do fibrinolytic agents work?
Stroptokinase Urokinase Alteplase Activate the fibrinolytic system by forming a complex with plasminogen --> plasmin --> enzymatic degradation of the fibrin clot
68
Is there a contraindication to regional and neuraxial blockade for a patient on aspirin or NSAIDS
No
69
How long prior to neuraxial anaesthesia should clopidogrel be stopped?
7 days preoperatively
70
How long should regional/neuraxial anaesthesia be delayed if unfractionated heparin has been administered SC
Minimum of 4 hours. UFH infusion can start 1 hour after the block
71
When should intravenous UFH be stopped and started before and after neuraxial blockade
Stop 4 hours before Start 1 hour afterwards
72
When should the IV catheter be removed
4 hours after last dose or the infusion has ended
73
How long should LMWH be witheld prior to regional anaesthesia And when can LMWH be recommenced subsequent to regional anaesthesia
Therapeutic dose clexane 1 mg.kg 12 hourly Stop > 24 hours before Start > 4 hours after Prophylactic dose clexane 1mg/kg daily Stop > 12 hours prior Start > 12 hours afterwards
74
Describe the pharmacokinetics of aspirin
A: Stomach (unionized) and SI (Surface Area) D: High PB 90%. Saturable. Increased free at high doses M: Hepatic --> Salicylate. Saturable --> 0 order in OD E: Salicylate + metabolites in urine. t1/2 15 mins
75
Describe the pharmacokinetics of clopidogrel
A: Intestinal D: Highly PB M: CYP450 E: 50% Renal. 50% faeces. T1/2 8 hours
76
Name the IIB/IIIa receptors. How long before normal platelet function resumes after disconstinuation of each of these drugs
Abciximab - 24 - 48 hours Ebtifibitide - 4 - 8 hours Tirofiban - 4 - 8 hours
77
Which anticoagulants are safe and used in pregnancy. Which cannot be used in pregnancy
LMWH < 36 weeks gestation UFH > 36 weeks gestation Cannot use NOACS or Warfarin in 1st trimester (exception: mechanical heart valves)

Pharmacology for Anaesthetists (37 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions