Dental Pharmacology Lecture 1

Front 1

What is the daily Cardiovascular aspirin therapy level peri-operatively?

Back 1

less than or equal to 325mg/day should be maintained.

Front 2

Should anti-platelet drugs such as clopidogrel (Plavix) and prasurgrel (Effient) be continued before dental surgery? What patients are on these drugs?

Back 2

Yes. Especially for patients with coronary stents. (both bare metal and drug eluting stents).

Front 3

Should anti-platelet drugs such as clopidogrel (Plavix) and prasurgrel (Effient) be continued before dental surgery? What patients are on these drugs?

Back 3

Yes. Especially for patients with coronary stents. (both bare metal and drug eluting stents).

Front 4

Patients are usually on warfarin (Coumadin to prevent what complications from what two conditions? When is an INR required?

Back 4

Warfarin is taken to prevent an emboli secondary to atrial fibrillation or deep vein thromboses (DVT's). An INR within 24 hours of a surgical procedure is required.

Front 5

When performing complex restorative care, periodontal probing, SRP, non-surgical endo, what is a safe INR? a probably safe INR?

Back 5

safe INR < 3
probably safe INR < 3.5

Front 6

What are the recommended INR values for a single or limited number of non-surgical extractions? What is the INR for surgical extrations or more involved procedures?

Back 6

Non surgical, single, or limited extractions INR preferably be 3 or less.

For surgical/involved, therapeutic INR of 2.5 or less.

Front 7

When a patient is anti-coagulated for prevention of emboli secondary to prosthetic heart valves, what is an acceptable INR range

Back 7

2.5-3.5

Front 8

What is the protocol for patients taking enoxaprin (Lovenox) an injectable anticoagulant before a surgical procedure?

Back 8

Enoxaprin should NOT be administered within 12 hours of the surgical procedure. Enoxaprin therapy is reinstituted asap after adequate hemostasis has been established.

Front 9

How long do patients usually take fondaparinux (Atrixtra) for DVT prophylaxis after lower extremity orthopedic surgery? Should dental treatment be performed?

Back 9

Usually patients take fondaparinux (Atrixtra) for 6-12 weeks after lower extremity orthopedic surgery. Dental treatment should be delayed if possible until therapy is no longer needed (6-12 weeks post surgery).

Front 10

What is the mechanism of action for Fondaparinux (Atrixtra)?

Back 10

Arixtra is a synthetic, highly sulfated pentasaccharide that binds to Anti-Thrombin II with a high affinity and causes a conformational change in ATIII significantly increasing the ability of ATIII to inactivate Factor Xa. (Anticoagulation drug)

Front 11

How many half lives/how much time does it take for Fondaparinux (Atrixtra) to be metabolized?

Back 11

3-5 half lives (2-4 days) following its last dose when patients have normal renal function.

Front 12

What is Dabigatran (Pradaxa)?
Mechanism of action?

Back 12

A direct thrombin inhibitor which inhibits both free and fibrin-bound thrombin.

Front 13

What is the reason patients are normally taking Dabigatran (Pradaxa)? Should patient take these meds before dental treatment?

Back 13

to prevent emboli secondary to atrial fibrillation. Patients with normal renal function should not take two doses of dabigatran (Pradaxa) prior to dental treatment.

Front 14

What anesthetic injections should be avoided when working on a patient who is anti coagulated?

Back 14

If possible, avoid IAN and PSA injections/block injections. Use infiltration techniques. Avaoid CN V-2.

Front 15

What are platelets?

Back 15

Platelets, or thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are small, irregularly shaped clear cell fragments (i.e. cells that do not have a nucleus containing DNA), 2–3 µm in diameter,[1] which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days. Platelets are a natural source of growth factors. They circulate in the blood of mammals and are involved in hemostasis, leading to the formation of blood clots.

Front 16

What is GP IIb/IIIa? It's main function?

Back 16

They are receptors on platelets which are the "velcro" of the platelets. They aid in platelet aggregation (platelets binding to other platelets) to form the platelet plug.

Front 17

What is Fibrin? What is it's function?

Back 17

Fibrin (also called Factor Ia) is a fibrous, non-globular protein involved in the clotting of blood. It is polymerised to form a "mesh" that forms a hemostatic plug or clot (in conjunction with platelets) over a wound site. The "fishnet" of clotting. Activation of clotting factors leads to the conversion of fibrinogen to fibrin and fibrin in the presence of Factor XIII forms the clot

Front 18

What is ASA (Aspirin)?

Back 18

Aspirin (USAN), also known as acetylsalicylic acid (/əˌsɛtəlˌsælɨˈsɪlɨk/ ə-set-əl-sal-i-sil-ik; abbreviated ASA), is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication.

Front 19

What is Clopidogrel (Plavix)?

Back 19

Clopidogrel (INN) is an oral, thienopyridine class antiplatelet agent used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease. It is marketed by Bristol-Myers Squibb and Sanofi under the trade name Plavix. The drug works by irreversibly inhibiting a receptor called P2Y12, an adenosine diphosphate (ADP) chemoreceptor on platelet cell membranes. Adverse effects include hemorrhage, severe neutropenia, and thrombotic thrombocytopenic purpura (TTP).

Front 20

What is Prasugrel (Effient)?

Back 20

Prasugrel (marketing name Effient in the US, Efient in the EU and Prasita in India) is a platelet inhibitor developed by Daiichi Sankyo Co. and produced by Ube and currently marketed in the United States in cooperation with Eli Lilly and Company for acute coronary syndromes planned for percutaneous coronary intervention (PCI).Prasugrel is a member of the thienopyridine class of ADP receptor inhibitors, like ticlopidine (trade name Ticlid) and clopidogrel (trade name Plavix). These agents reduce the aggregation ("clumping") of platelets by irreversibly binding to P2Y12 receptors. Compared to clopidogrel, prasugrel inhibits adenosine diphosphate–induced platelet aggregation more rapidly, more consistently, and to a greater extent than do standard and higher doses of clopidogrel in healthy volunteers and in patients with coronary artery disease, including those undergoing PCI".[2]

Front 21

What is Warfarin (Coumadin)

Back 21

Warfarin (also known under the brand names Coumadin, Jantoven, Marevan, Lawarin, Waran, and Warfant) is an anticoagulant. While it may be one of many drugs popularly referred to as a "blood thinner" , this is a misnomer, since it does not affect the thickness or viscosity of blood. Instead, it acts on the liver to decrease the quantity of a few key proteins in blood that normally allow blood to clotWarfarin inhibits the vitamin K-dependent synthesis of biologically active forms of the calcium-dependent clotting factors II, VII, IX and X, as well as the regulatory factors protein C, protein S, and protein Z.[2][43]

Front 22

What is INR?

Back 22

The prothrombin time (PT) and its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) are measures of the extrinsic pathway of coagulation. This test is also called "ProTime INR" and "INR PT". They are used to determine the clotting tendency of blood, in the measure of warfarin dosage, liver damage, and vitamin K status. PT measures factors I, II, V, VII, and X. It is used in conjunction with the activated partial thromboplastin time (aPTT) which measures the intrinsic pathway.

Front 23

Dabigatran (Pradaxa)

Back 23

Dabigatran (Pradaxa in Australia, Europe and USA, Pradax in Canada, Prazaxa in Japan) is an oral anticoagulant from the class of the direct thrombin inhibitors. It is being studied for various clinical indications and in some cases it offers an alternative to warfarin as the preferred orally administered anticoagulant ("blood thinner") since it does not require frequent blood tests for international normalized ratio (INR) monitoring while offering similar results in terms of efficacy. There is no specific way to reverse the anticoagulant effect of dabigatran in the event of a major bleeding event, unlike warfarin.

Front 24

What are 4 general characteristics of Normal hemostasis physiologically?

Back 24

1. Normal vessel wall integrity.
2. Adequate platelet plug formation.
3. Functioning coagulation system.
4. Normal fibrinolytic system.

Front 25

After vascular injury, describe molecularly how the platelet plug is formed and it's timeline of forming.

Back 25

Damage to the vessel wall exposes collagen causing the release of thrombin, von Willebrand's factor, ADP and epi. Causes platelet adhesion (1-2 seconds), platelet aggregation (10-20 seconds) then platelet plug formation (1-3 minutes).

Front 26

What molecule helps bind platelets to the vessel wall via which receptor?

Back 26

vWf binds platelet to vessel wall via GP Ib Receptor

Front 27

During platelet plug formation which molecules activate the platelets to start forming the platelet plug?

Back 27

Thrombin, ADP, epinephrine and exposed collagen.

Front 28

During platelet plug formation what cofactors are released to help form the platelet plug?

Back 28

Thromboxane A2 and Ca++ (Factor IV) are released.

Front 29

What molecule "recruits" more platelets during plug formation? how do the platelets bind to each other/what receptor acts as the velcro.

Back 29

Thromboxane A2 "recruits" more platelets. Platelets aggregate via GP IIb/IIIa receptor.

Front 30

During normal hemostasis what is the series of events that occur after the platelet plug is formed to clot formation. Timeline?

Back 30

after 1-3 minutes the platelet plug is formed, Thrombin (IIa) activates Fibrinogen to Fibrin causing platelet consolidation (3-5 mins). Fibrin in the presence of factor XIII forms the fibrin clot and stabilization (5-10 mins)

Front 31

What is the factor involved in the common pathway of coagulation leading to clot formation?

Back 31

Factor X is activated from the intrinsic and or extrinsic pathway. From Factor X Prothrombin is converted to thrombin --> Fibrinogen to Soluble Fibrin which interacts with Factor XIII to form the fibrin Clot.

Front 32

What are the two hemostatic factors that promote clot formation?

Back 32

vWf + collagen = platelet activation.

Tissue factor causing clot formation (which is expressed after injury)

Front 33

What two molecules are needed to cause platelet activation?

Back 33

Exposed collagen (damaged vessel wall) + vWf.

Front 34

There are molecules released from the endothelium which inhibit platelet activation/aggregation. What are two of them?

Back 34

Prostacyclin and Nitric Oxide.

Front 35

What are three anticoagulant factors which prevent clot formation during normal hemostasis?

Back 35

Antithrombin III, protein S and Thrombomodulin.

Front 36

What is the result of fibrinolysis?

Back 36

Dissolving the clot during normal hemostasis.

Front 37

What is the molecule that causes fibrinolysis?

Back 37

Tissue Plasminogen activator.

Front 38

What is a thrombosis? Is it common? What are the two different classes of thrombi?

Back 38

Thrombosis = formation of unwanted clot within a blood vessel. It is the most common abnormality of hemostasis. There are Aterial and venous thrombi

Front 39

What are three examples/diseases caused by Arterial Thrombi?

Back 39

Coronary Artery disease (CAD)
Carotid Artery disease
Peripheral vascular disease (PVD)

Front 40

What are two examples/complications of Venous thrombi?

Back 40

DVT: Deep vein thrombosis
Atrial fibrillation

Front 41

Arterial Thrombi are clots rich in what hemostatic molecule?

Back 41

Platelet rich clots (the velcro)

Front 42

Where do arterial thrombi normally form/occur? what are the three complications of arterial thrombi?

Back 42

Arterial Thrombi are platelet rich clots which occur in medium sized arteries. Atherosclerosis is etiologic. Renders surface of endothelial cell thrombogenic and causes Coranary artery disease, Peripheral vascular disease and carotid disease.

Front 43

What kind of drugs are given to treat arterial thrombi?

Back 43

Anti-PLATELET drugs.

Front 44

What are examples of anti-platelet drugs?

Back 44

Aspirin, NSAID's, Clopidogrel, Prasugrel

Front 45

Venous Thrombi are composed mainly of what hemostatic molecule?

Back 45

Fibrin Rich clots (Fishnet)

Front 46

Venous Thrombi occur in what areas? What are two examples of Venous thrombi complications?

Back 46

Venous thrombi are fibrin rich clots which occur in areas of slow blood flow causing venous stasis in the lower extremities (DVT) and Atrial fibrillation can cause venous thrombi.

Front 47

What type of medications are taken to treat venous thrombi? What are some specific examples?

Back 47

Anticoagulant drugs are given to treat venous thrombi to dissolve the fibrin rich clot. Heparin, LMWH, Warfarin/Coumadin, Dibigantran (Pradaxa), Fondaparinux (Atrixtra)

Front 48

List four drugs that are anti-coagulation drugs used to treat venous thrombi?

Back 48

Heparin, LMWH, Warfarin/Coumadin,
Dibigantran (Pradaxa), Fondaparinux (Atrixtra)

Front 49

What is an Emobolus?

Back 49

Detached blood clot moving within the bloodstream.

Front 50

What is the danger of emboli? what happens if the emboli lodges in a vessel?

Back 50

Emboli occludes ARTERIAL vessels inhibiting blood flow. Loss of blood supply distal to the site of occlusion. Leads to tissue infarction (death of tissue due to lack of oxygen).

Front 51

What are three examples of complications/deadly events that occur because of an embolus?

Back 51

Myocardial Infarction (heart attack).
Ischemic stroke
Pulmonary emobolus (prohibits O2/CO2 exchange).

Front 52

In four steps describe platelet activation to aggregation mechanism and role of thromboxane starting with the activation of platelets. (Arachidonic acid, Prostaglandin, COX1 are hints).

Back 52

Activation of platelets (via vWf + exposed collagen) liberates arachidonic acid.
Arachidonic acid is converted to prostaglandin H2 via COX1
Prostoglandin H2 results in Thromboxane A2.
Thromboxane A2 promotes platelet aggregation.

Front 53

How does Aspirin (ASA) inhibit platelet aggregation? How long is the platelet impaired?

Back 53

ASA IRREVERSIBLY inhibits the conversion of arachidonic acid to Thromboxane A2 by the INHIBITION OF COX1.

Platelet Aggregation is IMPAIRED FOR THE LIFE of the platelet.

Front 54

How does Aspirin affected the risk of thrombosis? platelet activity? How is bleeding time affected?

Back 54

Risk of (arterial) thrombosis DECREASED.
Platelet activity DECREASED
Bleeding time INCREASED up to 10 minutes.

Front 55

What is the mechanism of NSAIDs other than Aspirin?

Back 55

non-ASA NSAIDs REVERSIBLY inhibit the conversion of arachidonic acid to Thromboxane A2 by the inhibition of COX1.

Front 56

With NSAIDs, How long is platelet activity affected?

Back 56

Platelet activity is inhibited for 3-4 half lives of the specific NSAIDs (this is when the effect is functionally gone). At this point platelet activity is functionally restored. Different NSAIDs have different half lives.

Front 57

What are five NSAID's that aren't ASA. What are their approximate half lives? After 4 half lives how much drug is eliminated?

Back 57

4 half lives = 94% drug elimination.
Ibuprofen 2 hrs
Naproxen sodium (Alieve) 15 hrs
Ketoprofen 2 hrs
Flurbiprofen 7 hrs.
Diclofenac 2.5 hrs

Front 58

NSAIDs should not be taken within how many hours of ASA?
Why?

Back 58

2 hours
Not really sure, maybe because they interfere with ASA inhibition of platelets.

Front 59

Is COX1 or COX2 critical to Thromboxane A2 synthesis?

Back 59

COX1

Front 60

Do COX2 inhibitors interfere with ASA inhibition of platelets? What's a cox2 inhibitor?

Back 60

NO
Celebrex

Front 61

What are 3 Thienopyridine drugs? Are they anti-platelet or anti-coagulation?

Back 61

Anti-Platelet drugs
Clopidogrel (Plavix)
Prasugrel (Effient)
Ticlopidine (Ticlid) rarely used.

Front 62

What's the mechanism of Thienopyridines?

Back 62

IRREVERSIBLY inhibit ADP chemoreceptors (P2Y-12) on platelet cell membranes. Inhibits platelet AGGREGATION by blocking GPIIb/IIIa pathway.

Front 63

What type of drug is Clopidogel? half life? any reversal drugs? complications?

Back 63

Clopidogrel (Plavix) is a Thienopyridine. It's a prodrug requiring metabolism. Has a very long half life. No antidote for prolonged bleeding.

Complications: Thrombocytopenic purpura, neutropenia.

Front 64

What type of drug is Prasugrel (Effient)? How does it compare to clopidogrel (Plavix)?

Back 64

Theinopyridine. Newer anti-platelet drug. Prodrug.

Action is more rapid and consistent than clopidogrel (Plavix). Also lower incidence of ischemia but may have increased risk of fatal bleeding.

Front 65

What are anti-platelet drugs such as ASA and Theinopyridines used to manage?

Back 65

Acute coronary syndrome
Percutaneous coronary intervention such as angioplasty and stent placement.
Coronary Artery disease
Peripheral vascular disease,
Cardio vascular disease
post-stent placement (all arterial thrombi diseases)

Front 66

Should a patient continue anti-platelet drugs when receiving dental care?

Back 66

ASA and Thienopyridines should be maintained! especially for Drug Elutingn Stents!!! (DES)

Front 67

Thrombin is aka what factor?
Thrombin converts what to what?

Back 67

Thrombin = Factor IIa
Thrombin (IIa) facilitates the conversion of Fibrinogen (I) to Fibrin.

Front 68

What is Fibrin?

Back 68

Fibrin is a glycoprotein which forms a "Fishnet" clot matrix by cross linking platelets.

Front 69

The Intrinsic system is activated by what factor? What test is used to evaluate it? What two drugs work on the intrinsic system?

Back 69

Factor XII activates it.
evaluated by PTT
Heparin and LMWH

Front 70

What is the Mechanism of action of Heparin/LMWH?

Back 70

Heparin and LMWH INHIBIT Thrombin. Combines with anti-thrombin III to change conformation of anti-thrombin III. Anti-ThrombinIII then INHIBITS factor Xa and Thrombin (IIa).

Front 71

What are the important factors of the extrinsic system?
How is it evaluated?
What drug works on it?

Back 71

Factors VII, X, II (prothrombin)
PT = INR
Warfarin = Coumadin

Front 72

What are two other drugs (besides heparin and LMWH) that are thrombin inhibitors?

Back 72

Dabigatran (Pradaxa): Direct thrombin inhibitor.

Fondaparinux (Arixtra): increases the ability of Anti-Thrombin to inactivate Factor Xa

Front 73

What are the Vitamin K dependent coagulation factors?

Back 73

II, VII, X, IX
II = prothrombin
X = common pathway factor

Front 74

What are the differences b/w Heparin and LMWH?

Back 74

Heparin: Mixture of straight chain GAG's, wide range of MWs

LMWH: subset of Heparin molecules (MWs < 6000)

Front 75

What's the big picture goal of heparin and LMWH? What are they used to prevent? What are they used to treat?

Back 75

They limit the expansion of the Thrombus by preventing Fibrin formation! Employed to prevent venous thrombosis, rethrombosis. Treatment/prevent thrombotic disease: DVT, PE, Acute MI (angioplasty, stent placement).

Front 76

Heparin:
How is it administered?
Origin?
Mech?
Anticoagulation?
What test is used to evaluate?
Whereis it used?
Half life?
Bridge therapy?
What drug is used to reverse it's effects?
Complications?

Back 76

Injectable, rapid acing
Bovine, porcine origin (possible hypersensitivity).
Combines with ATIII, changes conformation and inhibits Factor Xa and Thrombin (IIa)
Variable anticoagulation.
Monitor/adjust via a PTT
Used in hospital settings.
Very short half life: Inhances peri-operative clotting.
May be used for "bridge therapy" for warfarin = coumadin
Reversed rapidly by protamine sulfate.
Complications: thrombocytopenia, undesired bleeding

Front 77

LMWH. Trade names?
Mech?
Doses?
onset?
Predictable?
When is it used?
Bridge therapy?

Back 77

Enoxaprin = Lovenox
Complexes with ATIII, inactivates Xa (does not bind aggressively to thrombin IIa)
usually dosed once or twice per day. 1.5mg/kg
More predictable anticoagulation vs heparin.
Weight adjusted dose.
Used on outpatient basis after orthopedic surgery.
May be used as bridge therapy for warfarin.

Front 78

Dabigantran (Pradaxa)
Mechanism?
Influenced by what physiological system?
What condition is treated with it?
Protocol with dental surgery?

Back 78

Direct thrombin inhibitor: inhibits free and bound thrombin.
Influenced by kidney function: creatine clearance.
Indicated for A-fib.
Usually, two doses should be with held prior to dent-alveolar surgery, restart after adequate hemostasis, no lab test.

Front 79

Fondaparinux (Atrixtra)
Mechanism?
Reversal agent?
When is it used?
Protocol with dental surgery?

Back 79

Binds to Anti thrombin with high affinity, causes a conformational change in AT which significantly increases the ability of Anti-thrombin to inactivate Factor Xa.
No reversal agent.
Typically used following lower extremity orthopedic surgery for 6-12 weeks.
Elective dental care usually deferred.

Front 80

What is the mechanism of Coumadin/Warfarin?

Back 80

Inhibits Vitamin K epoxide reductase, therefore Vitamin K is NOT regenerated which is needed for factors II, VII, X, and IX and coagulation is retarded.

Front 81

How is warfarin/coumadin transported in the blood?
drug interactions?
How is coagulation levels tested?
Onset, full effect and offset times?
How is it's effects reversed?

Back 81

Rapidly and completely absorbed. 99% bound to plasma albumin. May be displaced by other drugs or food with high vitamin K levels.
Evaluated by INR = PT
Onset = 8-12 hrs
Full effect = 2-4 days
Offset = 2-4 days
may be reversed with Vitamin K but this could take up to 24 hours.

Front 82

How do you test the intrinsic/extrinsic system and what drugs are evaluated with these tests?

Back 82

PTT: activated partial thromboplastin time. Normally 25-35 seconds. Evaluates the intrinsic system and activity of heparin/LMWH (II, X). Measures factors I, II, V, VIII, IX, X, XI, XII.

Prothrombin Time PT/INR evaluates the extrinsic system. normal 12-14 seconds. Evaluates activity of Warfarin/Coumadin (II, VII, IX, X)

Front 83

What is INR?
How is it calculated?

Back 83

International normalized raio. Used to compare PT from one lab to another.
INR = Patients PT/Mean lab PT adjusted by international sensitivity index.

With INR everyone speaks the "same language"

Front 84

What drugs should you NOT prescribe with warfarin/coumadin?

Back 84

ASA, SNSAIDs, propoxyphene.
Antifungal agents: fluconazole.
Cephalosporins, erythromycins, TCN, metronidazole, quinalones, sulfa drugs.

Front 85

When on Warfarin/coumadin what should you prescribe your patients for post op pain? What should you not prescribe them?

Back 85

Mild pain: acetaminophen
Severe pain: Vicodin (acetaminophen + opioid).
Do NOT perscribe ASA or NSAIDs due to effect on platelets.

Front 86

What are two clot stabilizing drugs that retard fibrinolysis?

Back 86

Aminocaproic acid = Amicar
Tranexamic acid = Cyclokapron

Front 87

What is the mechanism of Aminocaproic acid/amicar?

Back 87

Inhibits plasminogen activators and plasmin.
Orally administered prior to surgery and five days post op

Front 88

Tranexamic acid/Cyclokapron, what is the mechanism?

Back 88

Competitively inhibits plasminogen and directly inhibits plasmin.

Front 89

Some patients have factor deficiency's. Specific factor replacements are available. What is used to treat vW disease?

Back 89

Desmopressin (DDAVP)