Brainscape's Knowledge GenomeTM

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


See full index

Pharm Exam 4 > Hockerman Lectures Exam 4 > Flashcards

Hockerman Lectures Exam 4 Flashcards

1
Q

How does t-PA activate plasminogen?

A

It cleaves a arg-valine bond to create plasmin

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

What type of protein is t-PA?

A

Serine Protease

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

What 2 enzymes inhibit t-PA?

A

PAI-1 and PAI-2

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

What does aminocaproic acid inhibit?

A

The conversion of Plasminogen to Plasmin

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

What are the indications of Thrombolytic Therapy?

A

Acute MI (ASAP), Acute Ischemic Thrombotic Stroke (W/in 3hrs after excluding ICH), Pulmonary Embolism

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

What are the thrombolytic drugs?

A
  1. Alteplase 2. Reteplase 3. Tenecteplase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Which thrombolytic lacks the fibrin binding domain?

A

Reteplase

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

Which thrombolytic is more fibrin specific than t-PA?

A

Tenecteplase

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

Which thrombolytic is more potent and faster onset?

A

Reteplase

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

Which thrombolytic has a longer t1/2?

A

Tenecteplase

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

What is the underlying pathophysiology of the increase in t1/2 and enhanced activity of tenecteplase?

A

2 point mutations

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

When does streptokinase degrade a clot?

A

When it forms a 1:1 complex w/ plasminogen

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

All anti-fibrinolytics are derivatives of what?

A

Lysine; b/c plasmin binds to fibrin through a lysine binding site

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

How do antifibrinolytics work?

A

They are lysine analogs that bind to the receptor on plasminogen and plasmin

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

Which anti-fibrinolytic is more potent?

A

Tranexamic acid is 10X more potent than aminocaproic acid

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

Why is it difficult to break up clots that have formed post anti-fibrinolytic therapy?

A

The clots that form do not have plasminogen localized to the clot so the clot specific drugs (fibrin binding domains) don’t work as well on these clots

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

What induces the expression of Gp2b/3a receptors on plts?

A

ADP, 5-HT, and TXA2 when released from capsules

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

What cmpds released from plts are potent vasoconstrictors?

A

5-HT and TXA2

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

Which of the COX enzymes are more for inflammation?

A

COX2

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

When does hemostasis return to normal after ASA therapy abatement?

A

36 hrs

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

What ADP receptor is targeted by drugs?

A

P2Y12 - it is a Gi PRC that inhibits Adenylate Cyclase

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

What are the ADP receptor inhibitors?

A

Ticlopidine, Clopidogrel, Prasurgrel, and Ticagrelor

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

How do Ticlopidine and Clopidogrel Work?

A

They irreversibly block ADP receptor P2Y12 and prevent subsequent activation of Gp2b/3a

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

What is a risk of Ticlopidine?

A

TTP

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

When do you use the thienopyridine class of ADP receptor inhibitors?

A

ACS, Acute MI, PVD, Coronary Stenting Procedures

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

How does Ticlopidine cause TTP?

A

It induces Abs against ADAMTS13

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

What is the reversible P2Y12 Inhibitor?

A

Ticagrelor; it binds to an allosteric site

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

What is special about Ticagrelor?

A

It does not require bioactivation and has a fast onset of action

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

How does prasugrel work?

A

It is metabolized by CYP3A4/2B6 to an active metabolite and forms an irreversible disulfide bond w/ the P2Y12 receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Why does clopidogrel have variable efficacy among pts?

A

It is activated by CYP2C19 and this enzyme has variable expression among pts.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Why does prasugrel have a more predicatble response than clopidogrel?

A

It is activated by CYP3A4/2B6 which has more predictable expression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What are the Gp2b/3A receptor Inhibitors?

A

Eptifibatide, Tirofiban, Abciximab

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Why does Eptifibatide have a short duration of action?

A

It is a peptide and can be broken down (6-12hrs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Which of the Gp2b/3a inhibitors are reversible?

A

Eptifibatide and Tirofiban

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What is the half life of Tirofiban?

A

2 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What is the use of Tirofiban?

A

Combined w/ Heparin for tx of ACS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What is Abciximab?

A

Fab fragment of chimeric human/murine monoclonal Ab

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Why does Abciximab have a inc. risk of bleeding?

A

Long duration of action

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Uses of Abciximab?

A

Prevent thromboembolism in PCI and combined w/ t-PA for tx of acute MI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What are the phosphodiesterase inhibitors?

A

Dipyridamole and Cilostazol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What is the fxn of PDE inhibitors?

A

Inhibit plt. Aggregation

42
Q

When do you use cilostazol?

A

Intermittent claudication

43
Q

What are the Protease Activated Receptor Inhibitors?

A

Vorapaxar and Atopaxar (both in trials)

44
Q

Why are PAR inhibitors important?

A

They prevent plts from being activated by thrombin

45
Q

What are the 2 types of proteins for clotting factors?

A

Serine proteases and Glycoproteins

46
Q

What are the glycoproteins?

A

They are the proteins used as cofactors for activation of proteases: 8,5,3, Protein S and to bind and inhibit thrombin Antithrombin III

47
Q

Why is gamma-carboxylation important for coagulation?

A

Ca2+ can bind to the carboxylated residues and allow the cofactors to interact w/ the phospholipid membrane

48
Q

Which isomer of Warfarin is the most potent?

A

S

49
Q

What are all derivatives of Coumarin Anticoagulants?

A

Water soluble lactones

50
Q

What Enzyme does coumarins inhibit?

A

Vit. K Epoxide Reductase which regenerates oxidized Vit. K back into its active form

51
Q

Where is Warfarin Metabolized?

A

Liver CYP2C9 with variable expression

52
Q

How can you counter Warfarin OD

A

Vit K in mild cases and FFP in severe cases

53
Q

Why should you not use Warfarin in pregnancy?

A

It can freely pass through placenta and inc. risk of spontaneous abortion

54
Q

What are the birth defects associated w/ Warfarin?

A

Nasal hypoplasia and abnormal bone formation

55
Q

What is the fxn of antithrombin 3

A

Inactivates thrombin and 10a, (7a& 9a) to some extent

56
Q

Which anticoagulant is effective immediately?

A

Heparin (and effect disapears quickly as well)

57
Q

What is the antidote for heparin OD?

A

Protamine sulfate which binds heparin tightly and inactivates

58
Q

How does Heparin induce TP in a pt?

A

Develops 7-12 days after therapy and abs form to platelet PF4-Heparin complex

59
Q

What is the charged group on Heparin that interacts w/ antithrombin III

A

Sulfate Groups

60
Q

Which heparins have the higher incidence of HIT?

A

Long-chain Heparins

61
Q

What are the LMWH?

A

Dalteparin, Enoxaparin, and Tinzaparin

62
Q

What are the benefits of LMWH over std Heparin?

A

Inc. bioavailability from SQ route, longer t1/5 = 4 hrs so less frequent dosing, and don’t need to monitor clotting

63
Q

How does the MOA of LMWH differ from Std Heparin?

A

It doesn’t bind and inhibit thrombin as well

64
Q

What is a benefit of Fondaparinux therapy?

A

t1/2 of 17-21 hrs

65
Q

What are the orally available Factor 10a inhibitors?

A

Revaroxaban and Apixaban

66
Q

MOA of Rivaroxaban and Apixaban?

A

Direct inhibition of active site of Factor 10

67
Q

What are 2 risks of Rivaroxaban and Apixaban?

A

Need to reduce dose in renal impaired pts and inc. risk of stroke w/ discontinuation

68
Q

What are the direct thrombin inhibitors?

A

Lepirudin, Desirudin, Bivalirudin, Argatroban, and Dabigatran

69
Q

Why are Lepirudin and Desirudin so specific for direct inhibition of thrombin?

A

Bivalent binding to active site and exosite I

70
Q

Which Direct thrombin inhibitors bind irreversibly to thrombin?

A

Lepirudin & Desirudin

71
Q

Which direct thrombin inhibitors can induce a hypersensitivity rxn?

A

Lepirudin and Desirudin b/c they are proteins

72
Q

What is the MOA of Bivalirudin?

A

It reversibly binds to the catalytic site and the exosite 1 of thrombin

73
Q

What is the use of Bivalirudin?

A

PCI b/c it has a rapid onset and short duration

74
Q

What is the clinical use of Argatroban?

A

HIT

75
Q

Where does argatroban bind?

A

Reversibly to the active site of thrombin

76
Q

Which direct thrombin inhibitor is a prodrug?

A

Dabigatran

77
Q

What is ApoA1

A

Structural in HDL, produced in liver and intestine, mediates reverse cholesterol transport

78
Q

What is ApoB-100?

A

Structural in VLDL, IDL, LDL

79
Q

What is ApoB-48

A

Structural in Chylos and produced in the intestine

80
Q

What is ApoE?

A

Ligand for LDL receptor remnant receptor; sequesters Chylos, IDL to liver

81
Q

What is the key measurement in asseccing risk of CVD?

A

Ratio of Total Cholesterol to HDL-Cholesterol

82
Q

What ratio of Total cholesterol to HDL-Cholesterol is assoc. w/ inc. CVD risk?

A

> 4.5

83
Q

What is the MOA of Bile acid binding Resins?

A

They inhibit reabsorption of Bile acid by exhanging Cl- for bile acid like a chromatography column, and they upregulate LDL receptors on the liver

84
Q

What is cholestipol?

A

Bile acid binding resin

85
Q

What is the MOA of Ezetimibe?

A

It inhibits cholesterol absorption from the intestines by inhibiting HPC1L1 transporter conformational change for clatherin internalization

86
Q

How do Statins upregulatin hepatic LDL receptors?

A

They allow for SREBP and SCAP to be transported from the ER surface to the golgi where S1P and S2P can cleave the TF to go to nuc and upregulate

87
Q

What statins are metabolized by CYP3A4

A

Lovastatin, Simvastatin, and Atorvastatin

88
Q

What statins are metabolized by CYP2C9

A

Fluvastatin and Rosuvastatin

89
Q

How is Pravastatin exreted?

A

Sulfation

90
Q

Which stating is least likely to have drug-drug interactions?

A

Pravastatin

91
Q

What is Juxtapid?

A

It inhibits assembly of ApoB containing Lipoproteins

92
Q

What is the use of Juxtapid?

A

Familial Hypercholeterolemia - LDLR mutation

93
Q

What is the MOA of mipomersen?

A

It hybridizes ApoB-100 mRNA in the liver for degredation; it is a phosphorothioate anti-sense oligonucleotide inhibitor

94
Q

What fibrate must undergo bioactivation?

A

Fenofibrate to Fenofibric acid

95
Q

What is the MOA of fibrates?

A

They bind to PPAR-_ and regulate gene transcription w/ retinoic acid receptor; this clears TGs from the blood

96
Q

Why do you need to be careful using statins w fibrates?

A

Both cause rhabdo

97
Q

What is an important drug interaction w/ fibrates?

A

Potentiate the action of Warfarin

98
Q

What are the benefits of omega-3 FA intake?

A

They are used as substrates to produce TxA3 (less potent at stimulating plt aggregation) and PGI3 which is equipotent as prostacyclin

99
Q

What is the MOA of Niacin?

A

Inc. lipase activity, dec hepatic VLDL production, inc HDL levels

100
Q

What is a very effectivce drug for inc HDL levels

A

Niacin

101
Q

How can you tx the flushing and itching assoc w/ Niacin?

A

Take a Cox inhibitor b/c mediated by prostaglandins

102
Q

How does Niacin inhibit the breakdown of TG to FFA?

A

Activates GPR109a receptor

Pharm Exam 4 (3 decks)

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