Anticlotting drugs

Question 1

What are 4 classes of anti-platelet drugs?

Answer 1

1) NSAIDs
2) Platelet Gp2b/3A receptor blockers
3) ADP receptor blockers
4) PDE inhibitors

Question 2

What is the anti-clotting moa of aspirin?

Answer 2

Non-selective COX inhibitor → inhibit TXA2 → inhibit platelet aggregation

Question 3

What 3 clinical uses of aspirin as an anti-clotting drug?

Answer 3

1) Transient cerebral ischaemia prophylaxis
2) ↓incidence of recurrent MI
3) ↓mortality of post-MI px

Question 4

What are 2 AEs of aspirin?

Answer 4

Bleeding (↓PGI2)
Gastric upset and ulcers (↓PGE2)

Question 5

What are 2 examples of ADP receptor blockers?

Answer 5

Reversible:
Clopidogrel and Ticlopidine

Irreversible (faster onset):
Ticagrelor

Question 6

What is an example of PDE inhibitor?

Answer 6

Dipyridamole

Question 7

What are 3 examples of Gp2b/3A receptor blockers?

Answer 7

1) Abciximab (humanised mAb)
2) Eptifibatide (analogue of fibrinogen receptor-binding region)
3) Tirofiban (small molecule blocker)

Question 8

What are 4 anti-coagulant classes?

Answer 8

1) Heparin derivatives
2) Coumarin derivatives (Warfarin)
3) Lipirudin/Hirudin
4) Anti-thrombin 3

Question 9

LMW heparin have (better/worse) bioavailability and (longer/shorter) T1/2 compared to unfractionated heparin.

Answer 9

Better F
Longer T1/2

Question 10

What is the moa of heparin?

Answer 10

Bind to Anti-thrombin 3 → conformational change → allows for binding to F2a (only unfractionated) and FXa

Question 11

True or false: LMWH increases antithrombin 3’s action on both F10a and F2a.

Answer 11

False.
LMWH only increases for F10a not F2a (thrombin)

Question 12

What are 3 clinical indications of heparin?

Answer 12

1) DVT, PE, AMI
2) Revascularisation (w thrombolytics)
3) Angioplasty/coronary stents (w GP2b/3a inhibitors)
4) When anticoagulation must be used in pregnancy

Question 13

How is heparin administered?

Answer 13

IV or subcut
cannot IM → haematomas

Question 14

What are 2 AEs of heparin?

Answer 14

1) Haemorrhage
2) Thrombocytopenia
3) HS to heparins/pork products

Caution:
4) Elderly patients
5) Risk of bleeding

Question 15

What are 4 DDIs/FDis of Heparin?

Answer 15

DDIs:
1) Antiplatelet
2) Anticoagulation
3) Fibrinolytics
4) NSAIDs
5) SSRIs

FDIs:
6) Chamomile
7) Fenugreek
8) Garlic
9) Ginger
10) Gingko
11) Ginseng

Question 16

How are haemorrhages due to heparin treated?

Answer 16

1) Stop heparin therapy
2) Protamine sulfate (cationic peptide → sequester heparin)
3) Vitamin K

Question 17

(Heparin/warfarin) can be given during pregnancy.

Answer 17

Heparin

Question 18

How is warfarin administered?

Answer 18

Orally

Question 19

What is the moa of Warfarin?

Answer 19

Vitamin K reductase inhibitor (Vitamin K antagonist)
→ ↓reactivation of oxidised vitamin K to reduced form
→ ↓carboxylation/functional activation of coagulation factors 2, 7, 9, 10

Question 20

What are 3 AEs of warfarin?

Answer 20

1) Haemorrhage/bleeding
2) Hepatitis
3) Cutaneous necrosis

Question 21

When is warfarin contraindicated?

Answer 21

1) HS to drug
2) Active bleeding/bleeding risk
3) Severe or malignant HTN
4) Severe renal hepatic disease
5) Subacute bacterial endocarditis, pericarditis, pericardial effusion
6) Pregnancy

Caution in:
1) Breast-feeding
2) Diverticulitis, Colitis
3) Mild/moderate hypertension
4) Mild/moderate renal/hepatic disease
5) Drainage tubes in any orifice

Question 22

What is used to titrate the dose of warfarin?

Answer 22

1) INR
2) PT

Question 23

Why are DDIs of concern when administering warfarin?

Answer 23

Warfarin is metabolised by CYP450

Question 24

What are 4 DDIs/FDIs that ↑bleeding risk in patients on Warfarin?

Answer 24

Drugs:
1) Paracetamol
- Long term, high dose (>2g/day, >2 weeks)
2) Allopurinol
3) NSAIDs
4) Salicylates
5) PPIs
6) Metronidazole

Food:
7) Cranberry juice
8) Reishi mushrooms
9) Gingko
10) Ginseng

Question 25

What are 4 DDIs/FDIs that ↓drug efficacy in patients on Warfarin?

Answer 25

Drugs:
1) Barbiturates
2) Corticosteroids
3) Spironolactone
4) Thiazide diuretics

Food:
5) Vitamin K
6) Green tea

Question 26

Why is there so much variability in patients’ response to Warfarin?

Answer 26

1) CYP2C9
2) Vitamin K reductase complex
3) Subunit 1

Question 27

What is the moa of dabigatran?

Answer 27

Factor IIa antagonist

Question 28

What is used for the reversal of dabigatran?

Answer 28

Idarucizumab

Question 29

What is the moa of rivaroxaban?

Answer 29

Competitive reversible FXa antagonist

Question 30

What is used for the reversal of rivaroxaban?

Answer 30

Andexanet alfa

Question 31

What are 5 differences between Dabigatran and Rivaroxaban?

Answer 31

1) Target
D: FIIa
R: FXa

2) F
D: 3-7%
R: 80-100%

3) M & E
D: Urine unchanged
R: Urine and feces after hepatic

4) AEs
D: Bleeding + GI
R: Bleeding

5) DDIs:
D: ↑bleeding (antiplatelet, anticoagulant, fibrinolytics, NSAIDs, Ketoconazole)
↓level (rifampicin)
R: ↑bleeding (antiplatelet, anticoagulant, NSAIDs, P-gp, CYP3A4 inhibitors)
↓ levels (P-gp, CYP3A4 inducers)

Question 32

What are 4 thrombolytic agents?

Answer 32

1) TPA (alteplase)
2) Urokinase
3) Streptokinase
4) Anistreplase

Question 33

What is the moa of thrombolytic agents?

Answer 33

Activate plasminogen → ↑ plasmin breakdown

Question 34

What are 3 clinical indications for thrombolytic agents?

Answer 34

1) Emergency treatment of coronary artery thrombosis
2) Peripheral artery thrombosis and emboli
3) Ischemic stroke

Question 35

What is the main AE of thrombolytic agents?

Answer 35

Bleeding

Question 36

What are 2 contraindications for thrombolytic agents?

Answer 36

1) Pregnancy
2) Healing wound

Question 37

How are thrombolytic agents administered?

Answer 37

1) IV
2) Intracoronary