Brainscape's Knowledge GenomeTM

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


See full index

PR3154 > Haem Pharmacology > Flashcards

Haem Pharmacology Flashcards

1
Q

What is the MoA of Ticagrelor and Clopidogrel?

A

P2Y12 inhibitor
Prevents ADP from binding to P2Y12 receptor → prevent activation of GPIIb/IIIa receptors, platelet recruitment and aggregation

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

Is ticagrelor reversible? What about clopidogrel?

A

Ticegrelor is reversible, clopidogrel is irreversible

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

True or false:
Ticagrelor has a longer duration than clopidogrel

A

False
Duration of ticagrelor is 2-3 days, whereas duration of clopidogrel is 7-10 days

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

ADRs of ticagrelor and clopidogrel

A

Bleeding, bronchospasm, dyspnea, hypotension

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

Ticagrelor is metabolised by ____ while clopidogrel is metabolised by ______

A

Ticagrelor: CYP3A4
Clopidogrel CYP2C19

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

DDIs
List some examples of CYP inhibitors and inducers of ticagrelor

A

CYP3A4 Inhibitors: clarithromycin, ritonavir, ketoconazole, itraconazole

CYP3A4 inducers: dexamethasone, phenobarbital, phenytoin, carbamazepine, rifampicin

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

DDIs
List some examples of CYP inhibitors and inducers of clopidogrel

A

CYP2C19 inhibitors: PPI, ketoconazole, fluxetine

CYP2C19 inducers: rifamycin

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

True or false
CYP2C19 inhibitors reduces clopidogrel’s antiplatelet effect, while CYP2C19 inducers increases antiplatelet effect

A

True
This is due to the CYP enzymes effect on metabolising clopidogrel to its active metabolite. (Clopidogrel is a prodrug)

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

True or false:
Ticagrelor can be used in pregnancy and lactating mothers

A

False!
Is contraindicated

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

What is the reversal agent of Ticagrelor?

A. Bentracimab
B. Andexanet alfa
C. Idarucizumab
D. Vitamin K

A

A

Note that bentracimab is not available in SG

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

What are some contraindications of ticagrelor and clopidogrel? There may be more than 1 answer

A. Hypersensitivity
B. Asthma
C. Varient alleles of CYP2C9
D. Moderate to severe hepatic impairment
E. Thrombocytopenia
F. Pregnancy and lactation

A

Ans: A, D, F

C: should be CYP2C19 instead
F: Is in drug points for ticagrelor, but no data for clopidogrel currently

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

What is the MoA of Aspirin?

A

Irreversible COX inhibitor (COX-1 > COX-2)
COX1i: inhibit production of TXA2, which promotes platelet aggregation (7-10 days)
COX2i: inhibit production of PGI2, which inhibits platelet aggregation (3-4 days)

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

True or false:
Duration of aspirin is 7-10 days

A

True
(COX1) Formation of new platelets and thus production of TXA2 takes 7-10 days

(COX2) Synthesis of new COX enzyme and thus production of new PGI2 takes 3-4 days

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

True or false
Aspirin has vasodilaiton side effects such as headache, hypotension, dizziness, and flushing

A

False
Dipyridamole is the only antiplatelet that has vasodilation side effects, due to inhibiting adenosine reuptake and PDEs in vascular smooth muscle

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

What is the MoA of Dipyridamole? (including off-target effect)

A
  1. Adenosine uptake inhibitor → ↑plasma adenosine activation of A2 receptors on platelets
  2. PDE3 inhibitor → ↓cAMP degradation

Both ↑cAMP within platelets → prevent degradation to AMP → inhibit platelet activation and aggregation

Off-target: Vasodilator (inhibit adenosine reuptake and PDEs in vascular smooth muscle)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

DDI
Interaction of dipyridamole with adenosine causes _______ and, and interaction with cholinesterase inhibitors cause _______

A

Adenosine: ↑cardiac adenosine levels and effects
Cholinesterase inhibitors: aggrevate myasthenia gravis

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

What is the MoA of warfarin? Include what coagulation factors it inhibits.

A

Inhibits Vitamin K Epoxide Reductase (VKOR), thus inhibiting reactivation of oxidised vit K, and inhibit the production of factors 2, 7, 9, 10, and anticoagulant proteins C and S

Active vit K activate factors 2, 7, 9, 10 in a step coupled to carboxylation of glutamic acid residues on those coagulation factors

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

What is the duration of warfarin? What determines this duration?

A

Duration: 2-5 days
Due to long half-life of factor 2 (42-72hrs)

Note: factor 7 has shortest half-life (4-6hrs)

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

Explain what is the hypercoagulable state when initiating warfarin. What is done to prevent this?

A

Warfarin inhibits production of natural anticoagulant proteins C and S. Protein C has a half life of 9hrs, while protein S has a half-life of 60hrs. Hence there would be a hypercoagulable state of approx 4-5 days.

Bridge with LMWH/ enoxaparin to prevent this hypercoagulable state.

Germ: pls help edit this explanation if needed arigatouu

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

Which enzymes metabolises warfarin?

A

CYP2C9 (S-enantiomer) and CYP3A4 (R-enantiomer)

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

DDI
Which drugs have a DDI with warfarin? (can think if they are inducers or inhibitor)

Metronidazole
Clarithromycin
Ritonavir
St John’s Wort
Bactrim
Omeprazole
Ciprofloxacin
Carbamezapine
Sodium valproate
Atorvastatin
Fluconazole
Amoxicillin
Ciprofloxacin
Phenobarbital
Furosemide
Rifampicin
Doxycycline
Amiodarone
Digoxin

A

CYP inhibitors: metronidazole, -azoles, PPIs
Adjust preemptively: bactrim, ciprofloxacin

CYP inducers: rifampicin, ritonavir, carbamazepine, barbiturates, St John’s Wort

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What drugs need to be preemptively adjusted when taken with warfarin? State what the adjusted dose is too.

A

Bactrim/ Co-trimox (25-50% reduction)
Ciprofloxacin (20-30% reduction)

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

DDI
Which drugs have a DDI with apixaban? (can think if they are inducers or inhibitor)

Metronidazole
Clarithromycin
Ritonavir
St John’s Wort
Bactrim
Omeprazole
Ciprofloxacin
Carbamezapine
Sodium valproate
Atorvastatin
Fluconazole
Amoxicillin
Ciprofloxacin
Phenobarbital
Furosemide
Rifampicin
Doxycycline
Amiodarone
Digoxin

A

CYP3A4 and P-gp inhibitors: -azole, ritonavir
CYP3A4 and P-gp inducers: carbamazepine, phenytoin, phenobarbital, St John’s Wort, rifampicin

Note: for CYP3A4 and P-gp inducers, avoid use in DVT/PE. For SPAF/ VTEP, no adjustments needed, monitor.

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

Which increases and which decreases INR?

Hyperthyroidism
Hypothyroidsim
Fluid retention due to oedematous gut
Fluid retention from HF
Fever
Liver impairment
Alcohol binge
Chronic alcoholism
Smoking
Grapefruit juice

A

Increase INR: liver impairment, fluid retention from HF (liver congestion), fever, hyperthyroidism, alcohol binge, grapefruit juice

Decrease INR: fluid retention due to oedematous gut (gut malabsorption), hypothyroidism, chronic alcoholism, smoking

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

True or false:
Warfarin cannot be used for all 3 trimesters in a pregnant woman

A

False
Warfarin C/I in 1st trimester.

Use LMWH for 1st trimester, switch to warfarin after 1st trimester, switch to LMWH 1 week before delivery

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Does warfarin have renal and liver impairment dose adjustments?

A

Only for renal, hepatic don’t have

Renal: lower dose in eGFR < 60, HD, and PD. Avoid use in Concurrent chemoradiotherapy (CCRT) and Prolonged Intermittent Renal Replacement Therapy (PIRRT)
Hepatic: NIL, monitor INR closely

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is the MoA of dabigatran, rivaroxaban, apixaban, and edoxaban?

A

Dabigatran: reversible direct thrombin inhibitor
Riva, apix, edo: competitive reversible factor Xa inhibitor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

True or false:
All DOACs undergo hepatic metabolism

A

False
Dabigatran: mainly renally cleared
Rivaroxaban, Apixaban: CYP3A4
Edoxaban: Minimally hepatically and renally cleared

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

True or false:
Apixaban can be used in Child-Pugh Score C patients

A

False
Contraindicated!

30
Q

True or false:
DOACs cannot be used in pregnancy and lactation

A

True

31
Q

Which is the order in which DOACs are most renally cleared, in ascending order.
(legend: D = dabigatran, R = rivaroxaban, A = apixaban, E = edoxaban)

A. D < R < A < E
B. R < D < E < A
C. E < A < R < D
D. E < R < A < D

A

C

32
Q

What are the reversal antidotes for DOACs?

A

Dabigatran: idarucizumab
Rivaroxaban, apixaban, edoxaban: andexanet alfa

33
Q

What is the MoA of UFH and LMWH?

A

Binds tightly to antithrombin III and causes a conformational change → exposes active site for ↑ interaction → inactivates thrombin/ facotr IIa (which converts fibrinogen to fibrin), and factors IXa, Xa, XIa, XIIIa

34
Q

True or False:
LMWH is more potent than UFH

A

True

LMWH has a higher selectivity for factor Xa, longer half-life, and higher bioavailability than UFHs

Do take note that LMWH are less selective of factor IIa/ thrombin as compared to UFHs

35
Q

What causes heparin-induced thrombocytopenia (HIT)? Does UFH or LMWH have a higher risk for HIT?

A

Heparin binds to platelet factor 4 (PF4) on activated platelet surface → ↑IgG activation against heparin-PF4 complex → HIT

Lower risk of HIT w LMWH

36
Q

True of False:
UFH cannot be used for pregnancy, while LWMH can

A

False
Both can be used in pregnancy

37
Q

What is the reversal agent for LWMH and UFH?
Extra: What is its MoA?

A

No reversal agent for LWMH!
Protamine sulfate IV infusion for UFH.
Highly basic peptide stably binds negatively charged heparin and neutralises anticoagulant properties of heparain

38
Q

True or false:
Drugs that increases risk of bleeding when taken with UFHs and LWMH include fibrinolytics, NSAIDs, and SSRIs

A

True

39
Q

What is the MoA of fibrinolytics? (tenectaplase, alteplase)

A

Recombinant tissue plasminogen activator (r-tPA)
Binds preferentially to clot-associated plasminogen → activating plasmin at the clot → plasma digests firbin, thereby dissolving the clot

40
Q

What is the reversal antidote for fibrinolytics? There may be more than one answer.
Extra: What is its MoA?

A. Tranexamic acid
B. Bentracimab
C. Fresh frozen plasma transfusion
D. Andexanet alfa
E. Aminocaproic acid

A

Tranexamic acid and aminocaproic acid

MoA: compete for lysine binding sites on plasminogen and plasmin → block interaction with fibrin

41
Q

Why are firbinolytics only used in high-risk patients? Think about its high potency and adverse effect on the clots.

A

Fibrinolytics may cause fibrin meshwork to be broken down too rapidly, resulting in clots breaking down in clumps. This increases the risk of fragments of clots in the bloodstream, thus causes embolism.

Hence avoid fibrinolytics if clot is not stable. Use antiplatelets and anticoagulants to remove unstable clot instead.

42
Q

Warfarin
What are instructions when taken with CYP inhibitors and inducers? Think which to lower dose preemptively first or monitor first.

A

CYP inhibitor: lower dose preemptively first and monitor
CYP inducer: monitor first, then dose adjust as needed

43
Q

True or false:
Apixaban can be used in dialysis

A

True
Apixaban is the only DOAC that can be used in dialysis

44
Q

True or false:
Ticagrelor is a prodrug, while clopidogrel is not

A

False!
Opposite!
Clopidogrel is a prodrug, while ticagrelor is not

45
Q

List the ADRs of oral/ parenteral iron (Hint: have acute and chronic ADRs)

A

Acute: constipation, necrotizing gastroenteritis with vomiting, abdominal pain, bloody diarrhoea → f/b lethargy, shock, dyspnea, metabolic acidosis, coma, death

Chronic: haemochromatosis with iron deposited in the heart, liver, pancreas, and other organs → causing organ failure and death

46
Q

What is used to treat iron overdose?

A

Parenteral deferoxamine/ oral deferasirox iron chelators

47
Q

List the ADRs of oral and parenteral vit B12

A

Photosensitivity
Injection site pain/rxn (when given parenterally)
HTN, hot flushing, tremor, arrhythemias secondary to hypokalemia, GI disturbances, dizziness, paraesthesia, chromaturia, acneiform and bullous eruptions, rash and itching

48
Q

True or false:
PPIs help increase the absorption of oral Vit B12

A

False!
PPIs lower their absorption

49
Q

List the ADRs of folic acid

A

GI: bitter taste, nausea, abdominal distension, flatulence
Hypersensitivity
Anorexia (rare)

50
Q

List some DDIs with folic acid

Germ: surely he doesn’t expect us to remember all right…. ded

A

↓plasma concentration of anticonvulsants (phenytoin, valproic acid, phenobarbital, carbamazepine)
↓effect of methotrexate chemotherapy
↓absorption of sulfasalazine, triamterene
↑effect of lithium
↑elimination of aspirin
Chloramphenicol and bactrim interfere w folate metabolism

51
Q

What population requires special precautions when taking folic acid?

A

Folate-dependent tumours, haemolytic anaemia, alcoholism
Women w pre-existing DM, obesity, family hx of neural tube defects, prev pregnancy affected by neural tube defect
Children, pregnancy, lactation

52
Q

What are the contraindications of folic acid?

A

Untreated cobalamin deficiency (including untreated pernicious anaemia/ lifelong vegetarians), and malignant disease

53
Q

True or false:
Folic acid has minimal liver metabolism and renal excretion

A

False
Metabolised in liver, converted to active metabolite 5 methyltetrahydrofolate, undergoes enterohepatic circulation
Excreted via urine

54
Q

True or false:
Vitamin B12 is excreted mainly by bile and urine

A

True

55
Q

What is the MoA of erythropoiesis stimulating agents?

A

Stimulate division and differentiation of erythroid progenitor cells → reticulocytes are released from bone marrow and mature into erythrocytes → regulating erythropoiesis

56
Q

True or false
IV epoetin alfa has a shorter half-life than darbepoetin alfa

A

True
Epoetin alfa t1/2 = 4-13hrs
Darbepoetin alfa t1/2 = 20-25hrs

57
Q

True or false:
ESAs are mainly metabolised by the liver

A

False
Limited metabolism occurs

58
Q

List some of the ADRs that ESAs causes. Also use the ADRs unique to epoetin alfa and darbepoetin alfa each.

A

HTN, oedema, ↑plasma count, thrombosis, stroke, hyperkalemia, seizures, myalgia, arthralgia, limb pain, GI disturbances
Epoetin alfa: pruritus
Darbepoetin alfa: dyspnoea, cough, bronchitis

59
Q

Can ESAs be used in pregnancy, lactation, and children?

A

Yes, use with caution

60
Q

What are the two contraindications of ESAs?

A

Uncontrolled HTN, hypersensitivity

61
Q

What is the MoA of Myeloid Growth Factors? I.e. Granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating facotr (GM-CSF)

A

G-CSF: Stimulates proliferation and differentiation of progenitors (neutrophils). Additionally also activates phagocytic activity and prolong survival of mature neutrophils

GM-CSF: Stimulates proliferation and differentiation of early and late granulocytic, erythroid, and megakaryocyte progenitors

62
Q

What are some examples of granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating facotr (GM-CSF)?

A

G-CSF: filgrastim, prefilgrastim (longer t1/2)
GM-CSF: sargramostim

Note: G-CSF can be combined with haematopoeitic stem cell mobiliser, plerixafor

63
Q

True or false:
GM-CSF is better tolerated than G-CSF

A

False
G-CSF better tolerated than GM-CSF

64
Q

List some ADRs of G-CSF and GM-CSF

A

G-CSF: bone pain (reversible)
GM-CSF: fever, malaise, arthralgias, myalgias
Potentially fatal: Severe sickle cell crisis, capillary leak syndrome, respiratory failure, acute respiratory distress syndrome, splenic rupture

65
Q

List which are contraindications and which require special cautions when taken with G-CSF/ GM-CSF.

A. Pre-malignant/ malignant myeloid condition
B. Acute myeloid condition
C. Chronic myeloid condition
D. Sickle-cell disease
E. Chronic myelodysplastic syndrome
F. Pneumonia/ lung infiltrates
G. Osteoporotic bone disease

A

Caution: A, B, D, F, G
C/I: C, E

66
Q

What are some examples of megakaryocyte growth factors? (3)

A

Oprelvekin (recombinant IL-11)
Romiplostim (Fc-peptide fusion protein thrombopoietin receptor agonist)
Eltrombopag (nonpeptide thrombopoietin receptor agonists)

67
Q

List some ADRs of megakaryocyte growth factors. Note that one has extra ADRs from the rest.

A

Thromboembolic events
Oprelvekin: fluid retention, peripheral oedema, dyspnoea on exertion

68
Q

True or false:
Oprelvekin must be used with caution in patients with chronic HF, at risk of developing HF, and fluid retention

A

True

69
Q

True or false:
Megakaryocyte growth factors must be used with caution in cerebrovascular disease only

A

False
Caution: cerebrovascular disease, and thormboembolism risk factors

Thromboembolism risk factors: advanced age, prolonged immobilisation, malignancies, bleeding, surgery/trauma, obesity, smoking, contraceptives, hormone replacement therapy

70
Q

True or false: Romiplostim require higher dose for patients with non-East Asian ancestry

A

False
Should be Eltrombopag instead

71
Q

What drugs causes immune thrombocytopenia?

A

Heparin, sulphonamides, carbamazepine, phenytoin, GIIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban)

PR3154 (9 decks)

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