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0. Clinical Pharmacology > Haematological Drugs > Flashcards

Haematological Drugs Flashcards

1
Q

Give 2 examples of anti-platelet drugs.

A

Aspirin

Clopidogrel

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2
Q

Describe the mechanism of action of aspirin (acetylsalicylic acid). (4)

A
  1. Irreversible inactivation of the COX enzyme
  2. This decreases platelet thromboxane (TXA2) and endotthelial prostaglandin (PGI2) production
  3. Decreased platelet thromboxane synthesis causes:
    a. Decreased platelet aggregation
    b. Decreased thrombus formation
  4. Decreased prostaglandin synthesis causes:
    a. Decreased nociceptive sensitisation
    b. Decreased inflammation
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3
Q

List 5 side effects of aspirin (acetylsalicylic acid).

A 
Bleeding (<1%)
Peptic ulceration
Reye's syndrome
Angio-oedema
Bronchospasm
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4
Q

What are the indications for aspirin? (2)

Discuss important pharmacokinetics/ dynamics of aspirin. (2)

What would you tell the patient when prescribing aspirin? (2)

A

INDICATIONS:
Secondary prevention of thrombotic events
Pain relief

PHARMACOKINETICS/ DYNAMICS:
Half-life is longer in higher doses
Non-linear pharmacokinetics in overdose

PATIENT INFO:
Avoid over the counter meds containing aspirin
ALWAYS prescribe a PPI with long-term aspirin

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5
Q

Describe the mechanism of action of clopidogrel. (3)

A
  1. Irreversibly blocks ADP-receptor on platelet membranes
  2. This inhibits formation of GPIIb/IIIa complex (which causes platelet aggregation)
  3. Therefore there is decreased platelet aggregation
    a. Therefore there is decreased thrombus formation
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6
Q

List 3 side effects of clopidogrel.

A

Bleeding (1-10%)
Abdominal pain
Diarrhoea (1-10%)

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7
Q

List 1 indication for clopidogrel.

Discuss the important pharmacokinetics/ dynamics of clopidogrel. (1)

What would you tell the patient when prescribing clopidogrel? (2)

A

INDICATIONS:
Secondary prevention of thrombotic events

IMPORTANT PHARMACOKINETICS/ DYNAMICS:
Avoid in liver failure

PATIENT INFO:
Never stop clopidogrel without consulting a doctor if you have an arterial stent in place
Stop clopidogrel before surgery

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8
Q

Give 1 example of a thrombolytic drug.

List 2 examples of drug names in this class.

A

Recombinant tissue plasminogen activator (rtPA)

E.g.
Tenecteplase
Alteplase

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9
Q

Describe the mechanism of action of rtPA. (3)

A
  1. Recombinant form of tissue plasminogen activator (t-PA)
  2. This converts plasminogen into plasmin
  3. Plasmin breaks down fibrin into fibrin degradation products
    a. This causes thrombolysis
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10
Q

List 4 side effects of rtPA drugs (e.g. tenecteplase).

A

Intracranial haemorrhage
Retroperitoneal bleeding
GI blood loss
Allergy/angio-oedema

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11
Q

What are the indications for rtPA? (3)
NOTE: where relevant, state time limits.

Discuss important pharmacokinetics/ dynamics of rtPA. (3)

What would you tell the patient when prescribing any rtPA drug? (3)

A

INDICATIONS:
Ischaemic stroke (within 4.5 hours)
Myocardial infarction (within 12 hours)
Massive pulmonary embolism

IMPORTANT PHARMACOKINETICS/ DYNAMICS:
Alteplase - bolus infusion
Tenecteplase - single bolus
Drug interactions with other blood-thinning drugs

PATIENT INFO:
Educate about risk to benefit ratio:
NNT: 3
BUT 1 in 20 will come to harm from bleeding (i.e. fairly common)

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12
Q

Describe the mechanism of action of unfractionated heparin. (2)

A
  1. Stimulates antithrombin III
    a. This inhibits thrombin
    b. Therefore, no thrombus formation
  2. Inhibits multiple clotting factors
    a. Therefore, no coagulation cascade
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13
Q

List 3 side effects of unfractionated heparin.

What is the risk of major bleeding?

A

Bleeding
Thrombocytopenia
Osteoporosis

Major haemorrhage risk: 3.5%

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14
Q

What are the indications for unfractionated heparin? (4)

Discuss important pharmacokinetics/ dynamics of unfractionated heparin. (5)

What would you tell the patient when prescribing unfractionated heparin? (2)

A 
INDICATIONS:
Treatment/prophylaxis of thromboembolic diseases
Induction of vitamin K antagonists
Renal dialysis
Acute coronary syndrome

IMPORTANT PHARMACOKINETICS/ DYNAMICS:

  • Administration: IV or subcut
  • Non-linear pharmacokinetics
  • Monitoring needed (aPTT)
  • Reversible with protamine
  • Duration of action: shorter than LMWH

PATIENT INFO:
Risk of bleeding
Regular blood monitoring required

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15
Q

Discuss the differences in pharmacokinetics/ dynamics of low molecular weight heparin, compared to UFH. (6)

A

Administration: subcut injection

Pharmacokinetics:

  • More predictable dose-response relationship
  • 2-3x longer half-life

Pharmacodynamics:
-Renal clearance (needs dose adjustment in renal impairment)

Other info:

  • Does NOT need regular monitoring
  • Less easily reversible with protamine
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16
Q

What type of drug is fondaparinux?

A

Synthetic heparin

17
Q

Describe the mechanism of action of fondaparinux. (1)

List 2 indications of fondaparinux.

What is the main side effect?

A

MECHANISM:

  1. Enhances activity of antithrombin
    a. Therefore prevents thrombus formation

INDICATIONS:
VTE prevention after surgery
Acute coronary syndrome

SIDE EFFECTS:
Bleeding

18
Q

Discuss important aspects of pharmacokinetics/ dynamics of fondaparinux. (5)

What would you tell the patient about fondaparinux? (2)

A

PHARMACOKINETICS/ DYNAMICS:

  • Administration: injection only
  • Once a day regimen (long half-life)
  • Renal clearance
  • Does NOT need monitoring
  • Less easily reversed

PATIENT INFO:
Risk of bleeding
Needs injection

19
Q

Give 2 examples of factor Xa inhibitors.

A

Rivaroxaban

Apixaban

20
Q

Describe the mechanism of action of rivaroxaban. (2)

List 2 side effects of rivaroxaban.

A
  1. Inhibits conversion of prothrombin to thrombin
  2. This reduces concentration of thrombin in blood
    a. This inhibits thrombus formation

SIDE EFFECTS:
Bleeding
Nausea

21
Q

What are the indications for rivaroxaban? (3)

Discuss important pharmacokinetics/ dynamics of rivaroxaban. (3)

What would you tell the patient when prescribing rivaroxaban? (1)

A

INDICATIONS:
VTE prophylaxis
VTE treatment
Thromboprophylaxis in non-valvular AF

IMPORTANT PHARMACOKINETICS/ DYNAMICS:

  • Metabolised by CYP450 (therefore drug interactions with inducers/inhibitors)
  • No need for monitoring
  • No antidote for reversal

PATIENT INFO:
Risk of bleeding

22
Q

Give 1 example of a direct thrombin inhibitor.

A

Dabigatran

23
Q

Describe the mechanism of action of dabigatran. (1)

List 2 side effects.

A
  1. Direct thrombin inhibitor: prevents conversion of fibrinogen to fibrin
    a. This prevents thrombus formation

SIDE EFFECTS:
Bleeding
Dyspepsia

24
Q

What are the indications for dabigatran? (2)

Discuss important pharmacokinetics/ dynamics of dabigatran. (4)

What would you tell the patient when prescribing aspirin? (1)

A

INDICATIONS:
VTE prophylaxis
Thromboprophylaxis in non-valvular AF

IMPORTANT PHARMACOKINETICS/ DYNAMICS:

  • Rapid onset of action
  • No food interactions; few drug interactions
  • No need for monitoring
  • No antidote

PATIENT INFORMATION:
Risk of bleeding

25
Q

Describe the mechanism of action of warfarin. (2)

A
  1. Inhibits vitamin K epoxide reductase
  2. This prevents recycling of vitamin K to its reduced form after carboxylation of factors 2, 7, 9 and 10
    a. This prevents vitamin K from activating the clotting factors a second time
    b. Therefore there is no thrombus formation
26
Q

List 3 side effects of warfarin.

A

Bleeding
Warfarin necrosis
Osteoporosis

27
Q

What are the indications for warfarin? (4)

Discuss important pharmacokinetics/ dynamics of warfarin. (5)

What would you tell the patient when prescribing warfarin? (4)

A 
INDICATIONS:
VTE treatment
Thromboprophylaxis in:
-AF
-Metallic heart valves
-Cardiomyopathy

IMPORTANT PHARMACOKINETICS/ DYNAMICS:

  • Many food/drug interactions
  • Reversible by giving vitamin K
  • Rate of metabolism varies between patients due to polymorphisms in key metabolising enzymes
  • Requires monitored loading dose
  • Requires monitoring with INR

PATIENT INFO:

  • Compliance is crucial
  • Careful with alcohol
  • Always inform doctor before starting new drugs
  • Avoid over the counter aspirin

0. Clinical Pharmacology (14 decks)

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