Brainscape's Knowledge GenomeTM

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


See full index

PR3154 Haematology > Pharmacology of Haematology Drugs > Flashcards

Pharmacology of Haematology Drugs Flashcards

1
Q

4 Main Phases of Hemostasis and Thrombosis

A
  1. Vasoconstriction
  2. Primary Hemostasis (Platelet Plug)
  3. Secondary Hemostasis (Coagulation Cascade)
  4. Clot Stabilization (Fibrin Plug)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What happens during primary hemostasis?

A
  1. Platelet Adhesion to exposed collagen
  2. Platelet Activation
  3. Granule release ADP and Thromboxane A2
  4. Platelet Recruitment and Aggregation
  5. Platelet plug formation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What happens during secondary hemostasis?

A
  1. Platelet phospholipid complex expression
  2. Tissue factors released
  3. Coagulation cascade
  4. Thrombin activation
  5. Fibrin polymerization
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What happens during clot stabilization?

A
  1. Platelet contraction and trap cells
  2. Covalent crosslinks and Fibrin network mesh
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

3 Broad classifications of hematological drugs to prevent blood clots
- Phases that they target?

A
  1. Antiplatelets (Primary Hemostasis)
  2. Anticoagulants (Secondary Hemostasis)
  3. Fibrinolytics (Clot stabilization)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Subclasses and route of administrations of antiplatelets

A
  1. Dipyridamole (Adenosine reuptake inhibitor)
  2. Aspirin (Irreversible COX Inhibitor)
  3. Clopidogrel and Ticagrelor (P2Y12 inhibitors)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Subclasses and route of administrations of anticoagulants

A
  1. Warfarin (Vitamin K Antagonist)
  2. Direct-acting Oral Anticoagulants (DOACs)
  3. Parenterals (Heparin and LMWH)
  4. Hirudins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Subclasses and route of administrations of fibrinolytics

A
  1. Recombinant tissue Plasminogen Activator (RtPA) - Alteplase
  2. Kinases (Urokinase)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the MOA of Dipyridamole?

A
  • Inhibition of adenosine reuptake by circulating platelets to increase A2 receptor activation by adenosine
  • Inhibition of PDE3 activation to reduce cAMP degradation
  • Increased levels of cAMP from these 2 inhibitions increase calcium levels

LEADS to
1. Inhibition of platelet activation / aggregation
2. Vasodilation

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

How does the MOA of dipyridamole affect its clinical use (dosing and administration) and side effects?

A
  1. Adjunct medication to other antiplatelets or anticoagulants due to vasodilating effect that makes it dose limiting
  2. IV infusion for myocardial perfusion imaging
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

PK characteristics of Dipyridamole and how it affects its action and formulation of drug

A
  1. Fast absorption and onset (20-30 min)
  2. Short duration of action - 3h (Modified release)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

ADR of dipyridamole

A
  1. Headache, dizziness, hypotension, flushing
  2. GI disturbances (N/V/D)

Due to vasodilatory effect

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

Dipyridamole is contraindicated or used with caution in…

A
  1. Hypersensitivity
  2. Hypotension / Severe CAD
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Dipyridamole DDIs

A
  1. Adenosine
  2. Cholinesterase inhibitors (Aggravate myasthenia gravis)
  3. Heparin, anticoagulants and antiplatelets in combination
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the MOA of Aspirin?

A
  • Irreversible COX inhibition
  • COX-1 > COX-2
  • COX-1: TXA2 production - Restored only by new platelet formation (7-10 days)
  • COX-2: PGI2 production - Restored by synthesis of new COX enzyme (3-4h)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Why does Aspirin have greater antiplatelet activity than NSAIDs?

A

Due to its irreversible COX inhibition (NOT the selectivity of COX-1 over COX-2)

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

Why is Aspirin given low-dose for antiplatelet therapy? What is considered low vs high dose?

A

To ensure selective inhibition of COX-1 enzyme to reduce TXA2 production.

If high dose is given, the selective action is lost

Low-dose = 75-325 mg LD, 40-160 mg OD maintenance

High-dose = 500 mg - 1g

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

ADR of Aspirin

A
  1. Bleeding and bruising
  2. Upper GI events due to COX inhibition that reduces PG production that protects the stomach lining (GI Ulcers and bleed)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Contraindications of Aspirin

A
  • Caution in bleeding disorders
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Aspirin DDI

A

Combination with other antiplatelets and anticoagulants

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

MOA of P2Y12 Inhibitors

A

P2Y12 receptors are responsible for activation of glycoprotein IIa/IIIb needed for platelet recruitment and aggregation via fibrinogen

  1. Irreversible binding to ADP binding site of P2Y12 receptors - Clopidogrel
  2. Reversible binding to a non-ADP binding site of P2Y12 receptors to inhibit signaling pathway - Ticagrelor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Why does clopidogrel have a delayed onset but longer duration of action than ticagrelor?

A
  1. Interindividual variability in CYP2C19 mediated metabolism of clopidogrel - platelet function recovery time takes 7-10 days
  2. Reversible binding - platelet function recovery time takes 2-3 days
23
Q

ADR of Clopidogrel

A
  1. Haemorrhage / Bleeding / Bruising (Intracranial hemorrhage)
  2. Hypotension
  3. Dyspepsia
  4. Rash
  5. Bronchospasm
  6. Dyspnea
24
Q

Contraindications of Clopidogrel

A
  1. Hypersensitivity
  2. Active pathological bleeding
  3. Patients with Bleeding risk (Caution)
  4. Variant alleles of CYP2C19
25
Q

Clopidogrel DDI

A

Safety DDI - May increase risk of bleeding
* Warfarin
* NSAIDs and salicylates

Efficacy DDI
* Macrolides (Reduce effect)
* Strong to moderate CYP2C19 inhibitors - PPIs, fluoxetine, ketoconazole (Reduce effect)
* Rifamycins (Increase effect)

26
Q

Ticagrelor ADR

A
  1. Haemorrhage / Bleeding / Bruising (Intracranial bleed)
  2. Bradycardia
  3. Dyspnea
  4. Coughing
27
Q

Ticagrelor Contraindications

A
  1. Hypersensitivity
  2. Active pathological bleeding
  3. Patients with bleeding risk
  4. Elderly
  5. Moderate hepatic failure
28
Q

Ticagrelor DDI

A

Safety DDI - Bleeding risks
1. Anticoagulants
2. Fibrinolytics
3. Long-term NSAIDs
4. Aspirin doses >100 mg/day reduce ticagrelor effect but ↑ bleeding risk

Efficacy DDI
1. CYP3A inducers (e.g., dexamethasone, phenytoin) - Reduced effect
2. CYP3A strong inhibitors (e.g., clarithromycin, ketoconazole, etc) - Increased effect

29
Q

What is the MOA of warfarin?

A

Inhibit activation of coagulation factors II, VII, IX, X
* Inactive coagulation factors have glutamic acid residues that are carboxylated and activated by Vitamin K (hydroquinone) which is oxidized and converted to its inactive form (epoxide)
* Vitamin K epoxide reductase is responsible for converting Vitamin K back into its active form
* Warfarin inhibits the activity of VKORC1

30
Q

What can warfarin be reversed by and how does it affect its use?

A

Vitamin K
1. Reversal agent for MOA
2. DDIs and Food drug interactions
3. Monitoring of INR and PT due to interindividual variability of VKORC1 enzyme expression

31
Q

PK Characteristics of Warfarin

A
  1. Hepatic metabolism by CYP2C9 primarily
  2. Rapid absorption and onset
  3. Half-life duration of action depends on half-life of coagulation factors (e.g. II - 50h)
  4. Gene polymorphism - CYP2C9 and VKORC1 (Interindividual variability)
32
Q

Warfarin ADR

A
  1. Bleeding, Hemorrhage (Signs in stools, urine, melena, bruising, petechiae, menstruation)
  2. Hepatitis
  3. Cutaneous necrosis and infarction at breast, buttocks, extremities (3-5 days after initiation)
33
Q

Contraindications of Warfarin

A

Contraindications
1. Hypersensitivity
2. Severe renal / hepatic disease
3. Severe / malignant hypertension
4. Active bleeding, risk of bleed
5. After recent major surgery
6. Pregnancy

Cautions
1. Breastfeeding
2. Diverticulitis, colitis
3. HTN, renal, hepatic (Mild-moderate)
4. Draining tubes in any orifice

34
Q

Warfarin DDI

A

Safety DDI - Bleed
1. Paracetamol long term therapy > 2wks at high doses > 2g/day
2. NSAIDs, salicylates
3. PPI
4. Metronidazole
5. Allopurinol
6. TCM, herbs, food - Gingko, ginseng, cranberry juice, reishi mushroom

Efficacy DDI - Reduced
1. Barbiturates
2. Corticosteroids
3. Spironolactone and thiazides
4. Vitamin K rich foods, green tea

35
Q

MOA of DOACs

A

Competitive Reversible antagonists
1. Dabigatran - Inhibit Factor IIa
2. Rivaroxaban - Inhibit Factor Xa

36
Q

Reversal agents of DOACs

A
  1. Idarucizumab - Dabigatran etexilate
  2. Andexanet Alfa (Decoy protein) - Rivaroxaban
37
Q

PK Characteristics of Dabigatran vs Rivaroxaban

A

Both have rapid onset of action

Bioavailability:
* Rivaroxaban > Dabigatran

Metabolism:
* Rivaroxaban - Hepatic
* Dabigatran - Excreted unchanged

Half-life:
* Dabigatran (12-17h) > Rivaroxaban (5-9h)

38
Q

DOAC ADRs

A
  1. Bleeding
  2. GI symptoms for Dabigatran
39
Q

DOAC DDIs

A

Safety DDI - Bleeding risk
1. Antiplatelets, anticoagulants, fibrinolytics
2. NSAIDs
3. Ketoconazole (Dabigatran)
4. Pgp and CYP3A4 inhibitors (Rivaroxaban)

Efficacy DDI - Reduced
1. Rifampin (Dabigatran)
2. Pgp and CYP3A4 inducers (Rivaroxaban)

40
Q

What is the Heparin and LMWH MOA?

A

Inhibition of intrinsic pathway - Good for tubings (Contact)
* Potentiates antithrombin III and inactivates thrombin

  1. Heparin-ATIII complex inactivates Factors IIa, IXa, Xa, XIa, XIIa
  2. LMWH selective inhibition of Xa > IIa
41
Q

What is the advantage of lower molecular weight of heparin?

A
  1. Good Bioavailability
  2. Longer Half-life
  3. Lower Incidence of thrombocytopenia
  4. IV and SC administration favored over continuous infusion of heparins
42
Q

Heparin ADRs

A
  1. Bleeding
  2. Heparin-induced thrombocytopenia (Low platelet count due to PF4 binding causing IgG Ab activity) - Prefer LMWH
  3. Risk of epidural or spinal hematoma and paralysis in patients receiving epidural or spinal anesthesia or spinal puncture
43
Q

Reversal Agent of Heparin

A

Protamine sulfate - Highly basic peptide that binds to negatively charged heparin and neutralizes anticoagulant properties

Note: Incomplete reversal for LMWH

44
Q

Can heparin be used in pregnancy?

A

Yes. Does not cross placenta, not associated with fetal malformations.

45
Q

Contraindications and cautions in heparin and LMWH

A

Contraindicated in patients with:
- Hypersensitive to heparins or pork products
- Active major bleeding
- Thrombocytopenia or antiplatelet antibodies

Caution in:
- Elderly patients
- Risk of bleeding, including patients with prosthetic heart valves, major surgery, regional or lumbar block anaesthesia, blood dyscrasias, recent childbirth, pericarditis or pericardial effusion, renal insufficiency (for LMWHs)

46
Q

Heparin DDI and DFI

A

Increased bleeding risk:
1. Antiplatelets, anticoagulants, fibrinolytics
2. NSAIDs, SSRIs
3. Various herbs/foods - chamomile, fenugreek, garlic, ginger, ginkgo, ginseng.

47
Q

MOA of fibrinolytics

A

Conversion of plasminogen to plasmin needed to dissolve the clot by breaking down fibrin cross links to reverse clot stabilization

48
Q

How do -teplases differ from endogenous tPA

A

Recombinant variant of tPA = Longer half-lives

More convenient IV dosing

49
Q

What are the advantages of -teplases over kinases?

A

Preferential binding to clot-associated plasminogen

50
Q

Alteplase ADRs

A
  1. Bleeding, hemorrhage
  2. VTE, Cholesterol embolization
  3. VA, Hypotension, Edema
  4. Anaphylaxis
51
Q

Antidotes of alteplase - How do they reverse the effect?

A
  1. Tranexamic acid
  2. Aminocaproic acid

Compete for lysine binding sites on plasminogen and plasmin to prevent fibrin interaction

52
Q

Contraindications and cautions for alteplase use

A

Contraindicated:
1. Patients with active bleeding
2. Prior intracranial haemorrhage
3. Recent (within the last 3 months) intracranial or intraspinal surgery, serious head injury, or stroke.

Caution:
1. Patients with major surgery within 10 days
2. Risk of bleeding (e.g., peptic ulcer)
3. Cerebrovascular disease, mitral stenosis, AF, acute pericarditis or subacute bacterial endocarditis

53
Q

Alteplase DDIs

A
  1. Antiplatelet, anticoagulant
  2. Nitroglycerin (Reduce efficacy)

PR3154 Haematology (4 decks)

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