Block V, Pharmacology

Front 1

Function of VonWillebrand factor?

Back 1

mediates platelet adhesion to endothelial wall; mediates platelet aggregation

Front 2

Function of tissue plasminogen activator?

Back 2

mediates fibrinolysis and clot degradation

Front 3

Function of protein C and protein S?

Back 3

inhibit thrombin activation

Front 4

Currently, what is the main target of anticoagulation therapy?

Back 4

direct thrombin inhibition
lepirudin (Refludan)
bivalirudin (angiomax)
argatroban
ximelegatran

Front 5

Lovenox is an example of what kind of drug?
What is it's generic name?

Back 5

low molecular weight heparin
generic = enoxaparin

Front 6

What is important in order for heparin to have anticoagulant activity?

Back 6

a unique pentasaccharide sequence - this is the antithrombin binding site.

Front 7

general mechanism of action for heparin?

Back 7

binds to antithrombin III and CATALYZES the inactivation of thrombin (IIa) and factor Xa (mainly, also inactivates IXa and XIIa)
Inactivation of IIa occurs by formation of a ternary complex (heparin, ATIII and IIa).

Front 8

what effect does heparin have on platelets?

Back 8

binds to platelets inhibiting platelet function.

Front 9

How long must a heparin molecule be to form a ternary complex with ATIII and IIa?

Back 9

at least 18 saccharides long

Front 10

Are heparin molecules that are shorter than 18 saccharides long functional?

Back 10

Yes, they still retain anti-Xa activity.

Front 11

How does heparin have an influence at the very top of the clotting cascade?

Back 11

it induces the secretion of tissue factor pathway inhibitor by vascular endothelial cells.

Front 12

Why does heparin have decreased anticoagulant activity at low concentrations?

Back 12

it is bound to plasma proteins, endothelial cells and macrophages. (there is no free heparin left to form the ternary complex)

Front 13

What is the most effective method of dosing heparin?

Back 13

weight based dosing (better than traditional "bolus" dosing)

Front 14

Why is it important to overlap heparin therapy with warfarin 4-5 days before discontinuing heparin?

Back 14

warfarin has a very long 1/2 life: therefore it takes about 4-5 days for it to reach therapeutic strength. When therapy is overlapped it ensures there will be no breaks in anticoagulation therapy.

Front 15

How do you monitor heparin activity?
What else do you need to monitor during heparin therapy?

Back 15

with a PTT
platelet activity needs to be monitored to prevent thrombocytopenia.

Front 16

What are the 3 major adverse effects of heparin therapy?

Back 16

1. Bleeding
2. Osteoporosis (due to decr. osteoblast activity)
3. heparin induced thrombocytopenia

Front 17

What can you administer to counteract the effects of heparin?

Back 17

protamine sulfate

Front 18

What is the mechanism of heparin induced thrombocytopenia, and what are the therapeutic options?

Back 18

HIT is immune-mediated. therapeutic options include lepirudin and argatroban (direct thrombin inhibitors)

Front 19

Enoxaparin, Tinzaparin and Dalteparin belong to which drug class?

Back 19

low molecular weight heparins

Front 20

What are two major advantages of LMWH?

Back 20

1. smaller, more consistent size gives a more reliable half-life
2. decreased plasma protein, endothelial cell and macrophage binding.

Front 21

Why does LMWH not inactivate factor IIa as much as unfractionated heparin?

Back 21

LMWH is smaller (<18 saccharides), therefore it cannot form the ternary complex with IIa like unfractionated heparin can.

Front 22

Clinical indications of LMWH? (3)

Back 22

1. tx. of DVT/PE
2. unstable angina, non ST segment elevation MI
3. Prophylaxis (surgery, acute medically ill pts.)

Front 23

1. How would you monitor LMWH for renal toxicity?
2. What is renal dosing of LMWH?

Back 23

1. do anti-Xa assays to measure the activity of LMWH.
2. Renal dosing is once per day, not BID as usual

Front 24

What are some advantages of LMWH over unfractionated heparin? (6)

Back 24

1. predictable dose-dependant response
2. increased bioavailability
3. longer duration of action
4. dose independent clearance
5. decr. incidence of thrombocytopenia
6. no lab monitoring required

Front 25

What is the major drawback to fondparinux?

Back 25

no reversal agent is available and bleeding is a major complication due to it's long 1/2 life.

Front 26

What is the general MOA of Warfarin?

Back 26

Binds to and inhibits all vitamin K dependant enzymes resulting in loss of production of II, VII, IX, X; proteins C and S.

Front 27

How does warfarin inhibit recycling of vitamin K?

Back 27

it inhibits KO reductase, therefore reduction of vitamin K cannot occur

Front 28

What are the two main clinical indications for Warfarin?

Back 28

1. Primary and secondary prevention of venous thromboembolism
2. prevention of systemic embolism in patients with prosthetic heart valves or A-fib.
*both indications are chronic disorders; warfarin is never used in an acute disorder.

Front 29

How do you monotor Warfarin activity?

Back 29

1. PT time - measures the activity of factors II, VII and X. An INR is then calculated to standardize the results

Front 30

What is the target INR value that we shoot for in most of our patients?

Back 30

2.0-3.0

Front 31

What two factors would influence the dose of warfarin to initally begin with?

Back 31

1. weight (<45 kg)
2. age (>75 yrs)

Front 32

What dosage of warfarin do you start most patients on?

Back 32

5.0 mg

Front 33

What are the three main adverse effects of warfarin?

Back 33

1. bleeding (mainly intracerebral)
2. skin necrosis (rare)
3. purple-toe syndrome (rare)

Front 34

1.What would you do if your patient had an INR of 9.0?
2. What if the INR was >20?

Back 34

1. Administer vitamin K PO
2. administer vitamin K IV (life-threatening)

Front 35

Of the direct thrombin inhibitors, which are reversible and which aren't?

Back 35

Lepirudin (refludan) is the only irreversible one.
bivalirudin (angiomax) and argatroban are both reversible inhibitors.

Front 36

What is the MOA of direct thrombin inhibitors?

Back 36

they bind with thrombin and form an inactive complex.

Front 37

Do direct thrombin inhibitors have an effect on platelet function?

Back 37

No direct effect, except for inhibition of thrombin-induced platelet activation.

Front 38

What is the primary indication for direct thrombin inhibitors?

Back 38

heparin induced thrombocytopenia.

Front 39

What is scary about direct thrombin inhibitors?

Back 39

there is no antidote or reversal agent if major bleeding occurs.

Front 40

What are the four classes of antiplatelet agents?

Back 40

1. Aspirin
2. Dipyridamole
3. Thienopyridines
4. IIb/IIIa antagonists

Front 41

What is the MOA of aspirin?

Back 41

irreversible inhibition of COX-1. This results in blockage of Thromboxane A2 (TXA2) and prostaglandin I2 (PGI2) production. End result - no platelet aggregation

Front 42

What is the MOA of dipyridamole?

Back 42

inhibits phosphodiesterase which increases intracellular concentrations of cAMP. The cAMP potentiates the effects of prostacyclin (platelet deaggregation).

Front 43

What is done to make dipyridamole more effective?

Back 43

it is combine with ASA or warfarin. (ie. Aggrenox - dipyridamole and ASA)

Front 44

What are the two types of thienopyridines?

Back 44

1. Ticlopidine
2. Clopidogrel (Plavix)

Front 45

What is the MOA of thienopyridines?

Back 45

Inhibition of ADP induced platelet activation

Front 46

are tienopyridines reversible or irreversible?

Back 46

irreversible (additive benefits when used with ASA)

Front 47

Three adverse effects of thienopyridines?

Back 47

1. diarrhea, rash
2. neutropenia
3. thrombocytopenia

Front 48

Name three Glycoprotein IIb/IIIa inhibitors

Back 48

1. abciximab (reopro)
2. tirofiban (aggrastat)
3. eptifibatide (integrilin)

Front 49

What is the MOA of Glycoprotein IIb/IIIa inhibitors?

Back 49

bind to IIb/IIIa receptor. this prevents fibrin from attaching, thereby preventing platelet aggragation. It does not prevent platelet attachment to the endothelium.

Front 50

Three adverse effects of Glycoprotein IIb/IIIa inhibitors?

Back 50

1. bleeding
2. thrombocytopenia
3. allergic reactions

Front 51

physiology of physiologic thrombolysis? (3)

Back 51

1. release of tissue plasminogen activatior (t-PA)
2. t-PA converts plasminogen to ploasmin. this results in fibrin lysis and degradation of factors V and VIII
3. a2-antiplasmin is activated: this inactivates circulating plasmin to prevent systemic lysis.

Front 52

MOA of pharmacological thrombolytic agents?

Back 52

exogenous plasminogen activator, causes fibrin clot breakdown.

Front 53

Pharmacologic t-PA is known as?

Back 53

alteplase (activase)

Front 54

Which thrombolytic agent is the only indirect plasminogen activator?

Back 54

streptokinase

Front 55

Which of the thrombolytic agents is the most fibrin-specific? Which one is #2?

Back 55

most: Tenecteplase
#2: Alteplase (t-PA)

Front 56

Which of the thromblolytic agents...
1. is a naturally occuring plasminogen activator produced by the kidneys?
2. made from streptococci?
3. the lease expensive?
4. the only one indicated for inschemic stroke?

Back 56

1. Urokinase
2. Streptokinase
3. Streptokinase
4. Alteplase

Front 57

1. What are the similarities and differences between reteplase and tenecteplase regarding administration?
2. What are the indications for both?

Back 57

1. reteplase - given as 2 IV boluses 30 min. apart
tenecteplase - given as a single IV bolusf
2. Acute MI

Front 58

Hemorrhage is a major adverse effect of thrombolytics. What are the causes of this? (2)

Back 58

1. Lysis of physiological thrombi
2. Systemic lytic state

Front 59

What would systemic a2-antiplasmin depletion result in?

Back 59

a systemic lytic state (excess plasmin degrades coagulation factors)

Front 60

How would you treat a life-threatening hemorrhage caused by thrombolytics?

Back 60

you would administer:
1. aminocaproic acid (an antifibrinolytic agent)
2. a competitive inhibitor of plasminogen activators

Front 61

MOA of nitroglycerin?

Back 61

forms NO which activates guanylyl cyclase which increases cGMP leading to vasodilation

Front 62

MOA of lidocaine hydrochloride?

Back 62

antiarrythmic, analgesis
blocks Na+ ion channels required for initiation and conduction of neuronal impulses (and decreases phase 4 depolarization)

Front 63

MOA of sodium bicarbonate?

Back 63

buffers H+ excess and raises pH.

Front 64

MOA of digoxin?

Back 64

inhibits Na+/K+ activated ATP, thereby promoting mvmt of Ca++ from extracellular to intracellular cytoplasm - this strengthens myocardial contraction.
- also acts on CNS to enhance vagal tone - this slows conduction through the SA and AV nodes and provides an antiarrhythmic effect.

Front 65

MOA of Dopamine?

Back 65

dose dependant action
- low doses stimulate dopaminergic and alpha and beta receptors of the sympathetic nervous system
- large doses: mainly alpha stimulation

Front 66

what is estrogel?

Back 66

transdermal estrogen gel for vulva and vaginal atrophy

Front 67

what is Climera and ClimeraPro?

Back 67

transdermal patch to relieve postmenopause symptoms
Climera - estradiol
ClimeraPro - estradiol/levonorgestral

Front 68

What class of drug are Flutamide(Eulexin) and Bicalutamide(Casodex)?

Back 68

androgen receptor antagonists

Front 69

what is the MOA of Cyproterone acetate-progestin?

Back 69

prevents transcription of genes involved in androgen synthesis

Front 70

what is Spironolactone?

Back 70

Aldosterone inhibitor and inhibits androgen biosynthesis

Front 71

What is Ketoconazol (Nizoral)?

Back 71

antifungal agent that blocks P450 enzymes involved in steroid biosynthesis

Front 72

what is Finasteride and what is it prescribed for?

Back 72

5-alpha reductase inhibitor, prescsribed for prostate cancer (Proscar) and male pattern baldness (Propecia).

Front 73

what is Leuprolide acetate (Leupron)

Back 73

analog of GnRH
continuous administration suppresses gonadal steroidogenesis. (negative feedback lowers FSH and LH production, thereby lowering steroidogenesis)

Front 74

what is Raloxifene and what is it prescribed for?

Back 74

SERM that acts like estrogen on bone and lipids but has anti-estrogenic effects on the breast and endometrium

Front 75

MOA of lisinopril?

Back 75

inhibits ACE, results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and decreased aldosterone secretion.

Front 76

MOA of Claforan (Cefotaxime Sodium)

Back 76

Cephalosporin antibiotic:
inhibits cell wall synthesis
highly stable in the presence of beta-lactimases

Front 77

Effect of Dextromethorphan (DM)?

Back 77

elevates cough threshold
Found in OTC cough medication

Front 78

MOA of Azithromycin (Zithromax)

Back 78

binds to 50S ribosomal subunit interfering with microbial protien synthesis. Nucleic acid synthesis not affected.

Front 79

MOA of hydrochlorothiazide?

Back 79

LOOP DIURETIC
inhibits reabsorption of Na+ and Cl- in thick ascending limb of the Loop of Henle and early distal tubules. This increases urinary excretion of NaCl.

Front 80

What is atenolol?
differences between hi and lo doses?

Back 80

beta blocker
low dose: B1 selective
high dose: B1 and B2 action

Front 81

What would I prescribe Tegretol (Carbamezapine) for?

Back 81

its an anticonvulsant, I would prescribe it for seizures

Front 82

What is Mellaril (Tioridazine Hydrochloride) and what is it used for?

Back 82

antipsychotic
used to treat psychosis