Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CPT + Prescribing > Antiplatelets + fibrinolytics > Flashcards

Antiplatelets + fibrinolytics Flashcards

1
Q

Give some examples of thromboembolic diseases

A
  • DVT, PE
  • AF consequence
  • TIA, ischaemic stroke
  • MI (NSTEMI/STEMI)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Give the definitions of thrombus and embolus

A

Thrombus:

Clot adhered to vessel wall, at local site

Embolus:

Intravascular clot distal to site of origin (eg PE)

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

Distinguish between venous and arterial thrombosis

A

VENOUS:

  • Associated with stasis of blood and/or damage to veins
  • Less likely to see endothelial damage (eg DVT in lower limbs)
  • High red blood cell + fibrin content, LOW PLATELET CONTENT

ARTERIAL:

  • Forms at site of atherosclerosis, following plaque rupture
  • Low fibrin content, much HIGHER PLATELET CONTENT

Varying platelet contents of arterial and venous thrombi dictate drugs initially offered

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

Describe how a healthy endothelium is maintained (with platelets in their resting state)

A
  • Prostacyclin (PGI2) produced and released by endothelial cells- INHIBITS PLATELET AGGREGATION
  • PGI2 binds to platelet receptors, increasing cAMP in platelets​
  • Increased cAMP = decreased Ca2+
  • Thus, preventing platelet aggregation
  • Reduction in platelet aggregatory agents
  • Stabilises GPIIb/IIIa receptors- maintains inactive resting state

Inactive GPIIb/IIIa receptor required for resting platelet (glycoprotein receptor)

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

Provide an outline of platelet activation and aggregation

A
  • Creation of a thrombus has a similar process to normal clot formation (pathological stimulus vs physical trauma- damaged endothelium)
  • Atherogenic pathway; fibrous cap, plaque rupture, thrombus formation
  • Platelet adhesion at damaged endothelium– cascade of signalling molecules
  • Chemical mediators released by activated platelets; thromboxane A2, ADP, serotonin, PAF (pt activating factor) - lead to plt aggregation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the roles of Ca2+ and GPIIb/IIIa receptors in platelet activation and aggregation

A
  • Release of platelet granules- ADP, thromboxam A2, PAF, thrombin
  • Initiates activation and aggregation through GPIIb/IIIa receptors + fibrinogen – ACTIVATED GPIIb/IIIa RECEPTORS
  • Activated platelets bound to collagen of sub-endothelium cause increase in Ca2+ levels
  • Increased calcium + decreased cAMP in platelets
  • Plt aggregation via Vwf + thrombin (finrinogen to fibrin)
  • CASCADE + AMPLIFICATION IN PLTs

Elevated Ca2+ causes:

  • Release of plt granules
  • Activation of thromboxane A2 synthesis
  • Activation of GPIIb/IIIa receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the main target of antiplatelet drugs?

A

Reduction of pathological platelet aggregation

To reduce CV events + mortality

Disrupting various stages of signalling cascade

Effective in the arterial circulation, where anticoagulants have little effect

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

Distinguish between the drug classes used to prevent arterial and venous thrombi

A

ARTERIAL:

Platelet rich, arterial, white thrombi: ANTIPLATELET + FIBRINOLYTIC DRUGS

VENOUS:

Lower pletelet content, red, venous thrombi: PARENTERAL ANTICOAGULANTS (heparins), ORAL ANTICOAGULANTS (warfarin)

Combination can be used in some pt’s for secondary prevention

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

What do antiplatelet agents target?

A

Pt activation + aggregation

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

Describe the mechanism of action of cyclo-oxygenase inhibitors

A
  • Normally, potent platelet aggregating agent thromboxane A2 is formed from arachidonic acid by COX-1
  • Aspirin: inhibits (acetylates) COX-1 mediates production of TXA2 + reduced plt aggregation
  • IRREVERSIBLE INHIBITION OF ENZYMATIC CONVERSION (aspirin irreversibly inhibits COX-1)
  • Aspirin = a salicylate compound, thus has ability to acetylate COX-1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Give an example of a cyclo-oxygenase inhibitor

A

Aspirin

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

Why does aspirin not completely inhibit platelet aggregation?

A

As there are other mechanisms and mediators, independent of COX-1, by which platelets can aggregate

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

Distinguish between the doses of aspirin required for anti-platelet vs analgesic effects

A

Anti-platelet action: at low non-analgesic doses (75mg) - baby aspirin

Analgesia: loading, higher dose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Give some properties of aspirin

A

Higher doses inhibit endothelial prostacyclin (PGI2)- imp consideration in stable resting patients

Absorbed by passive diffusion, hepatic hydrolysis to salicylic acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Give some warnings/contraindications of aspirin

A
  • Bleeding time prolonged- haemorrhagic stroke, GI bleeding (peptic ulcer); thus balance vs risk of bleeding
  • Reye’s syndrome - avoid aspirin in <16 yr/olds
  • Hypersensitivity to aspirin
  • 3rd trimester pregnancy - premature closure of ductus arteriosus into ligamentum arteriosum
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is Reye’s syndrome?

A

**Post viral infection + aspirin given on top

Hepatic + brain oedema

May be fatal

Reye’s (Reye) syndrome is a rare but serious condition that causes swelling in the liver and brain. Reye’s syndrome most often affects children and teenagers recovering from a viral infection, most commonly the flu or chickenpox.

Taking aspirin to treat such an infection greatly increases the risk of Reye’s

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Give an important interaction/consideration of aspirin

A

Other antiplatelet + anticoagulants - additive/synergistic effect

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

Why does antiplatelet COX-1 inhibition last the lifespan of a platelet (7-10 days)?

A

As platelets lack nuclei; thus unable to produce more COX once inhibited

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

Describe the consequence of COX-1 polymorphisms on the effect of aspirin in some people

A

COX-1 polymorphisms result in lack of efficacy of aspirin in some pt’s

As there is a differing ability of aspirin to acetylate COX-1

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

Give some indications for the use of aspirin

A
  • Secondary prevention of stroke + TIA (post-ischaemic events)
  • Secondary prevention of acute coronary syndromes (ACS)- NSTEMI, STEMI, unstable angina
  • Post primary percutaneous coronary intervention (PCI) + stent to reduce ischaemic complications
  • Secondary prevention of MI in stable angina or peripheral vascular disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How is aspirin often prescribed?

A

Often co-prescribed with other agents; depending on pt’s age, presentation of ACS etc

22
Q

Describe the dose and frequency of aspirin generally used for secondary prevention of ACS

A

Initial once only 300mg chewable loading dose of aspirin

To reduce incidence of re-occlusion

23
Q

Describe the dose and frequency of aspirin generally used for secondary prevention of acute ischaemic stroke

A

Initial 300mg daily for 2 weeks

To reduce incidence of re-occlusion

24
Q

Which other type of medication should be considered in high risk patients on long term aspirin use?

A

Gastric protection

PPIs

25
Q

Describe the mechanism of action of ADP receptor antagonists

A
  • Inhibit binding of ADP to P2Y12 receptor (on platelet)
  • Thus, inhibit activation of GPIIb/IIIa receptors
  • INDEPENDENT OF COX PATHWAY

Decrease Ca2+ in platelet, thus inhibit plt aggregation

Inhibit ADP mediated platelet aggregation

26
Q

Give 3 examples of ADP receptor antagonists

A

Clopidogrel

Prasugrel

Ticagrelor

(All orally)

27
Q

Compare the properties and actions of clopidogrel, prasugrel and ticagrelor

A

Clopidogrel + prasugrel = irreversible inhibitors of P2Y12

Pro-drugs - hepatic metobolites (need to be metabolised into active state)

Clopidogrel - slow onset of action (5-6 hrs for full effect) without loading dose; inter-individual variability in antiplatelet action

Ticagrelor + prasugrel = more rapid onset (1-2 hrs post oral dose)

Ticagrelor acts REVERSIBLY at DIFFERENT SITE to clopidogrel - has active metabolites

28
Q

Give some warnings/contraindications of ADP receptor antagonists

A
  • Bleeding
  • GI upset; dyspepsia, diarrhoea
  • Thrombocytopaenia (low plt’s)
  • Hepatic + renal impairment - caution; as metabolised from pro to active drug
29
Q

Give some important interactions/considerations of ADP receptor antagonists

A
  • Clopidogrel required CYPs for activation; drugs interfering- omeprazole (PPI), ciprofloxacin, erythromycin, SSRI’s
  • CYP 2C19 invl
  • Thus, need to consider use of other PPI’s with clopidogrel
  • Ticagrelor can interact with CYP inhibitors and inducers - CYP 3A4
  • Caution when co-prescribed with other antiplatelet + anticoagulant agents or NSAIDS– BLEEDING, peptic disease
30
Q

Which drug needs stopping 7 days prior to surgery?

A

Clopidogrel -

Risk vs benefit - to allow time for drug to wear off

(Ticagrelol 5 days before?)

31
Q

Give some indications for clopidogrel (ADP receptor antagonist)

A
  • Monotherapy where aspirin contraindicated
  • NSTEMI pt’s for up to 12 mths (PPCI considerations)
  • STEMI with stent- for up to 12 mths - stop before CABG (high vs low risk pt’s)
  • Ischaemic stroke + TIA - long term secondary prevention

RISK OF CARDIOVASCULAR EVENTS VS BLEEDING RISK

32
Q

Give an indication for using prasugrel with aspirin

A

ACS patients undergoing PCI, up to 12 mths

33
Q

Provide an outline of the evidence (PLATO study) done to compare the use of ticagrelor or clopidogrel with aspirin

A

TICAGRELOR significantly reduced rate of death from vascular causes

Ticagrelor: currently licensed in combination with aspirin for p_revention of atherothrombotic events in ACS for UP TO 12 MTHS_

34
Q

Describe the mechanism of action of glycoprotein IIb/IIIa inhibitors

A
  • Monoclonal antibody
  • Blocks binding of fibrinogen and von Willebrand factor (vWf)
  • Antibody blocks GPIIb/IIIa receptors leading to 80% reduction in aggregation

Abciximab binds irreversibly to the GPIIb/IIIa receptors and blocks the binding of fibrinogen

35
Q

Give an example of a glycoprotein IIb/IIIa inhibitor

A

Abciximab - IV injection with bolus

Antibody blocks GPIIa/IIIb receptors

Leads to 80% reduction in aggregation- bleeding risk greater than other agents

36
Q

Why do glycoprotein IIb/IIIa inhibitors have a greater associated bleeding risk compared to the other agents?

A

As they target the final common pathway where there is more complete plt aggregation

Thus, there are not many other mechanisms by which platelets can aggregate (as with COX inhibitors)

Hence, a substantial reduction in platelet aggregation (80%)– increased bleeding risk

37
Q

Give some warnings/contraindications and important interactions/considerations of glycoprotein IIb/IIIa inhibitors

A
  • BLEEDING (fuller antipletelet effects) - dose adjustment for body weight, thrombocytopaenia, hypotension, bradycardia
  • Caution with other antipletelet + anticoagulant agents

Specialist use in HIGH RISK PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY PATIENTS

38
Q

OVERVIEW

A
39
Q

Give an example of a phosphodiesterase inhibitor

A

Dipyridamole

40
Q

Describe the mechanism of action of phosphodiesterase inhibitors (dipyridamole)

A
  • Dipyridamole inhibits cellular reuptake of adenosine- increased plasma adenosine- inhibits platelet aggregation via A2 receptors
  • Normally, phosphodiesterases breakdown cyclic nucleotides, thus with a phosphodiesterase inhibitor, cAMP degradation is prevented
  • Dipyridamole also acts as a phosphodiesterase inhibitor which prevents cAMP degradation- inhibits expression of GPIIb/IIIa (increased cAMP, decreased Ca2+, reduced plt aggregation)

PHOSPHODIESTERASE 5 AND 3 INHIBITION

41
Q

Give some warnings/contraindications and any important interactions/considerations of phosphodiesterase inhibitors (dipyridamole)

A
  • Flushing, headache, hypersensitivity
  • Caution with antihypertensives (side effects), antiplatelets, anticoagulants
42
Q

Give some uses of phosphodiesterase inhibitors (dipyridamole)

A

Secondary prevention of ischaemic stroke + TIA

Adjunct for prophylaxis of thromboembolism following valve replacement

43
Q

Briefly describe the mechanism of action of fibrinolytic agents (thrombolysis/clot busters)

A

Fibrinolytics dissolve fibrin meshwork of thrombus

Fibrin clot into fibrin degradation products

44
Q

Give 2 examples of fibrinolytics and explain how they work

A

Streptokinase; promotes plasminogen production

Alteplase; plasminogen activator- promotes conversion of plasminogen into plasmin

45
Q

What does plasmin do?

A

Breaks down fibrin clot into fibrin degradation products

46
Q

What does tranexamic acid do?

Give some of its uses

A

Inhibits fibrinolysis - inhibits fibrin clot breakdown

Is used to treat heavy bleeding during your menstrual period. Tranexamic acid works by slowing the breakdown of blood clots, which helps to prevent prolonged bleeding. It belongs to a class of drugs known as antifibrinolytics.

Tranexamic acid has been found to be an excellent affordable nonhormonal treatment option for women with HMB and should be considered during major gynecological surgery.

47
Q

Which fibrinolytic is used in acute ischaemic stroke <4.5 hours of presentation?

A

Alteplase

48
Q

Give another use of fibrinolytics

A

Following acute MI diagnosis acutely vs primary PCI

49
Q

Give some warnings/contraindications of fibrinolytics eg streptokinase and alteplase

A
  • Bleeding
  • Streptokinase can only be used once- as antibodies develop to streptococci (hence not effective on 2nd use)
  • Intracranial haemorrhage needs ruling out
50
Q

When is coronary angiography with primary PCI indicated as the preferred coronary reperfusion strategy instead of thrombolysis for acute STEMI?

A

PRIMARY PCI IF:

Presentation is within 12 hrs of onset of symtoms

AND

Primary PCI can be delivered within 120 mins of the time when fibrinolysis could have been given

51
Q

What class of drug should be offered to all patients post MI once they are haemodynamically stable?

A

ACEi

CPT + Prescribing (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions