Flashcards in Dyslipidemia, anticoagulants Deck (73):
What does cholesterol produce?
Cell Membranes, bile acids, steroid hormones
(Lipoproteins = triglycerides + cholesterol)
What might you find on a physical exam of someone with hyperlipidemia?
Xanthelasma: fatty deposits on hands, arm, face
Circumferential arcus: white ring around eyelid/iris (fat)
PVD: shiny extremities, discoloration of skin, hairlessness
If fasting, which lab results do you look at to determine if someone has hyperlipidemia, if they don't fast which lab results do you look at?
Fasting: Total cholesterol, LDL, HDL, TAGs
Not fasting: total and HDL
If total is more than 200 mg/dl or HDL less than 40, test again with fasting
What total cholesterol levels are desirable vs. borderline vs. high?
Desirable: less than 200 mg/dl
High: over 240
What levels of HDL are considered high vs. low?
High: over 60
Low: under 40
What levels of LDL are considered optimal, near optimal, borderline high, high, and very high?
Optimal: less than 100
Near optimal 100-129
Borderline high: 130-159
Very high: over 190
What is primary hyperlipidemia?
Genetic heterozygous condition resulting in elevated total cholesterol (over 200) or triglycerides (over 500)
These patients are prone to pancreatitis
What is secondary hyperlipidemia?
Hyperlipidemia caused by diseases or drugs
Diabetes, hypothyroid, obstructive liver disease, chronic renal failure, alcohol, HIV/AIDS, obesity
Drugs: progestins, corticosteroids, anabolic steroids
Who is screened for hyperlipidemia? How often? What tests are done?
Adults over 20
Every 4-6 years
Fasting lipoprotein profile: total cholesterol, LDL, HDL, triglycerides
ALT, DK, HbA1c
Estimated 10 year ASCVD risk
What do the newest guidelines from the ACC/AHA focus on regarding hyperlipidemia?
Lower cholesterol by improving overall health as number one focus, if that doesn't work then add medication
What factors elevate and lower HDL?
Elevate: alcohol, saturated fats, weight loss
Lower: low fat diet, sugar, excess calories, polyunsaturated fats
What factors elevate and lower LDL?
Elevate: saturated fat, trans fatty acids, dietary cholesterol
Lower: MUFAs, complex carbs, and soy
What factors elevate and lower cholesterol?
Elevate: saturated fats, trans-fatty acids
Lower: substituting MUFAs and complex carbs for saturated fats, soy
What factors elevate and lower triglycerides?
Elevate: alcohol, sugar, high carb diet, excess calories
Lower: weight loss, fish oils
What are the 4 categories established indicating statin therapy for secondary prevention of ASCVD?
1. Clinical ASCVD
2. LDL over 190
4. Over 7.5% estimated 10-year ASCVD risk
How do HMG-CoA Reductase Inhibitors work? (AKA statins)
Inhibit the rate-limiting enzyme in the formation of cholesterol
Interrupts the process that the body is storing fats
Effect is to decrease LDLs, decrease TGs, and increase HDLs
For someone with clinical ASCVD, at what age should they receive high vs. moderate-intensity statins?
75 or older = high intensity statins
Under 75 = moderate intensity statins
What are bile acid sequestrants? Name a few
Work by binding bile acids in the intestine, resuting in the liver using hepatic cholesterol to producce more bile acids
Effect is to decrease LDLs and increase HDLs
Cholestyramine (Questran), Colestipol, Colesevelam
Note: these make the patient have oily poops
How does nicotinic acid (niaspan, niacin) work?
Reduces the production of VLDLs
Effect is to reduce LDLs, TGs, and increase HDLs
Note: it causes flushing, sweating
How do fibric acid derivatives work? Name a few
Fibrates reduce the synthesis and increase the breakdown of VLDLs
Effect is to reduce LDLs, decrease TGs, and increase HDLs
Gemibrozil (lopid), fenofibrate, clofibrate
How does eztimibe (zetia) work?
Works by inhibiting cholesterol and phytosterol absorption from the brush border of the intestines
No effect on fat soluble vitamins (A,D,E,K)
No effect on CYP450
Used in combination with a statin
Not used as often because of coronary side effects
What can happen with patients taking statins and fibric acids together?
Increased risk of myopathy
Contraindicated with severe hepatic disease
What can happen with patients taking statin and niacin?
Increased risk of hepatic dysfunction
Name some drug interactions with lovastatin and simvastatin
Who is at greater risk of myopathy?
Age over 80
Small body frame and frail
Impaired renal/hepatic system
What drugs combined with statins increase risk of myopathy?
HIV protease inhibitors
What drugs should pregnant and nursing women avoid related to hyperlipidemia? What is the only safe drug they can take?
Fibric acid derivatives
Bile acid-binding resins are the only safe drugs during pregnancy (oily poop drugs!)
How quickly does primary hemostasis start working?
Occurs immediately (seconds-minutes) in response to a vessel injury that results in a "platelet plug"
How does primary hemostasis work?
Exposed subendothelial collagen attracts circulating platelets, which then adhere to each other. These platelets adhere, degranulate, and aggregate
Promoted by a group of pro-coagulants (von willebrand factor, clotting factor VIII, ADP), causes localized vasoconstriction
How do platelets activate, degranulate and aggregate in primary hemostasis?
Adhered platelets activate and change shape forming pseudopods (like an "arm" that grabs platelet to form a platelet plug) and release thromboxane A2
Platelets degranulate, releasing a variety of biochemicals.
Aggregation begins, using fibrinogen and vWF and a connecting agent
What agents are released during degranulation?
Serotonin, histamine (vasoconstrict)
Thromboxane (vasoconstrict, degranulate platelets)
ADP (makes plasma membrane sticky, degranulates platelets)
Clotting factors Va, VIIIa, IXa
Platelet factor 4 (heparin neutralizing factor, enhances clot formation)
What is secondary hemostasis?
Takes minutes to hours and results in fibrin clot formation
The fibrin clot is a meshwork of protein that acts as a net to collect other cells and stabilize the platelet plug. Then the net retracts and fibrin strands shorten to trap the platelets.
Each clotting factor is converted to its active form until fibrin ends the coagulation cascasde
Once the coagulation process is activated, what natural anticoagulants regulate this process?
What mediates lysis in the fibrinolytic system?
Plasmin, activated by coagulation and inflammation substances
Plasmin splits fibrin and fibrinogen into fibrin degradation products
Name some oral and IV antiplatelet medications
Oral: aspirin, ticlopidine, clopidogrel (plavix), prasugrel, ticagrelor
IV: abciximab, eptifibatide, tirofiban
What is aspirin? What is the normal dosage?
COX inhibitor, prevents production of thromboxane A
The action is irreversible, lifespan of a platelet is 10 days
Dosage 81-325 mg every day
CV (blunts effect of ACEI, b-blockers, diuretics due to prostaglandin inhibition)
Asthmatics (increased leukotrienes which increase bronchoconstriction
Increased bleeding with other anticoagulants (treat with platelet transfusion)
What class ticlopidine (ticlid) and clopidogrel (plavix)? How do they work and why are they used?
Thienopyridine that blocks ADP receptor on platelet and inhibits fibrinogen from binding
Used for prevention of ischemic events (for patients with aspirin intolerance)
Plavix is also used in combination with aspirin
Why is hardly anyone on ticlipidine (ticlid) anymore?
Clopidogrel (plavix) precautions?
Metabolized by CYP2C19, genetic predisposition to poor metabolism along this pathway, may require increased dosing
Dose adjustment for renal/hepatic disease
What is prasugrel (effient)? How does it compare to clopidogrel?
New thienopyridine that has greater prevention of platelet aggregation than clopidogrel but more fatal events and higher risk of bleeding during CV surgery
What is ticagrelor (brilinta) and how does it compare to clopidogrel?
Allosteric antagonist, blocks ADP receptors from a different binding site
Reduces death rates after MI more than clopidogrel
BUT, there is a higher rate of non-procedure related bleeding and higher incidence of fatal intracranial hemorrhage compared to clopidogrel
Used in combo therapy with ASA, precaution: hepatic dysfunction
What are GPIIb/IIIKa inhibitors? What are they used for? Name a few
Block the GPIIb/IIIa receptor, preventing fibrinogen binding
Used for acute coronary syndrome and PCI
Abciximab (ReoPro), eptifibatate (integrillin), tirofiban (agrastat)
Why would you use Abciximab vs eptifibatide? How would you treat bleeding?
Abciximab for ACS with planned PCI, most prolonged effects
Eptifibatide for the same thing, dosage based on serum creatinine (decreased dosage for creatinine 2-4)
For bleeding, reverse with platelets if they are on abciximab, just discontinue the drug if they are on eptifibatide or tirofiban
When are antiplatelets stopped before surgery and restarted?
7-10 days before surgery, resume 24 hours after surgery
Clopidogrel should be stopped 5 days before surgery
Patients at high risk for cardiac events should not discontinue
How does heparin work? What are the uses?
It is a heterogenous mixture of polysaccharide chains
Activates Antithrombin III which increases inhibition of Thrombin IIa and Factor Xa by 1000-fold
Uses: DVT/PE tx, DVT prophylaxis, ACS, warfarin contraindicated
True/False: Heparin has an inability to inhibit clot-bound thrombin.
TRUE, this is a major drawback of heparin use
When heparin causes bleeding, what is the reversal?
Protamine 1 mg/ 100 units of heparin given OR 50mg bolus of protamine
Type 1 vs. Type 2 HIT
Type 1: non-immune mediated, benign, mild drop in platelets, usually within 4 days of heparin tx, NOT associated with thrombosis
Type 2: immune mediated, starts 5-14 days of heparin tx, reduction in platelets less than 150k or decrease by 50% of baseline
What is HITT?
10-25% of cases
Thrombocytopenia with thromboembolism
Venous (more common): DVT, PE, gangrene, dural sinus thrombosis
Arterial: cerebral infarction, limb ischemia, skin necrosis, MI, gut, renal, adrenal infarction
What lab tests help diagnose HIT?
ELISA assay (measures titer of IgG to heparin)
C-serotonin release assay (detects platelet activation, not readily available)
Don't delay treatment waiting for labs!!
Stop heparin and start argatroban (or another non-heparin anticoagulant)
How does a low molecular weight heparin (enoxaparin/lovenox) work? What is it used for?
Binds with Antithrombin III and inhibits factor Xa
Uses: DVT prophylaxis (40mg qd), ACS (1mg/kg q12h), VTE tx
LMWH precautions? (exoxaparin/lovenox)
Pregnant women (monitor anti-Xa levels)
Obese pt (needs weight based)
NOT recommended for renal insufficiency
Spine surgery pt or epidural
Fondaparinux (arixtra): class of drug, how does it work, what are the uses?
Synthetic factor Xa inhibitor
Binds with anti-thrombin III to potentiate Xa inhibition (no effect on IIa)
Uses: ACS, PE/DVT tx, DVT prophylaxis (7.5 mg)
What are argatroban and lepirudin used for? What is bivalirudin used for? What class are these drugs?
IV direct thrombin IIa inhibitors
Argatroban and lepirudin for HIT
Bivalirudin for PCI
Note lepirudin ad desirudin can only be used once due to anaphylaxis issues
IV direct thrombin IIa inhibitors interactions? Treatment of bleeding?
Interactions: increased bleeding with anticoagulants, thrombolytics, antiplatelets
Treatment of bleeding: stop infusion, can give Factor VII, FFP, and cryoprecipitate
How does warfarin work? What is it used for?
Interferes with production of Vitamin K-dependent clotting factors (II, VII, IX, X) and interferes with carboxylation of natural anticoagulants (Protein C and S)
Uses: prevention clot/embolis with DVT, Afib, and mechanical heart valves, long term tx of VTE
Warfarin dosing is based on ____ (lab value). Start with 5-10 mg/day. Overlap with heparin/LMWH for ___ days
Therapeutic INR is 2-3
Overlap for 1-2 days
List warfarin adverse effects and interactions
Adverse effects: Bleeding, birth defects, cutaneous necrosis. Use caution in NSAIDs and antiplatelets
Interactions: Increases effect of amiodarone, cimetidine, acetaminophen, and phenylbutazone. Decreases effect of sucralfate, cholestyramine, spironolactone, barbituates, and Vit K foods
Reversal/treatment of bleeding with warfarin therapy?
Note: FFP's INR is 1.5 so it can't help more than that
If warfarin is d/c for surgery, how long before surgery is it d/c and how long post-op until it is resumed?
5 days before surgery d/c
12-24 hours post-op resume
Bridging with heparin up until 4 hours of surgery is a possibility too
Dabigatran (pradaxa): drug class, uses?
Direct thrombin inhibitor IIa (new oral anticoagulants)
Uses: prevents stroke for Afib and treats DVT/PE
Dabigatran (pradaxa) advantages and disadvantages?
Adv: no routine monitoring, predictable pharmacokinetics, less diet/drug interactions, rapid peak (1 hr), short half-life (12 hrs)
Disadv: high cost, bid dosing, no antidote, no assay for monitoring effect, no long term data
Rivaroxaban (xarelto): class, use?
Class: direct factor Xa inhibitor
Use: stroke/embolism prevention in Afib, prevents DVT, treats PE/DVP
Rivaroxaban (xarelto): advantages/disadvantages?
Adv: no routine, monitoring predictable pharmacokinetics, less diet/drug interactions, rapid peak (2.5-4h), short half-life (7-11h)
Disadv: high cost, no antidote, no assay, no long term data
Apixaban (eliquis): class, use?
Class: direct factor Xa inhibitor
Use: stroke/embolism prevention in Afib, prevent DVT, tx DVT/PE
Apixaban (eliquis): advantages/disadvantages?
Adv: no routine monitoring, predicable pharmacokinetics, less diet/drug interactions, rapid peak (3h), short half-life (12h)
Disadv: high cost, bid dose, no assay, no long term data, reversed ONLY with prothrombin complex concentrate
How do fibrinolytics work? Name some.
Plasminogen activators convert plasminogen to plasmin
Plasmin causes fibrinolysis
Streptokinase, urokinase, tPA, recombinant tPA (alteplase, reteplase), tenecteplase (TNK-ase)
Acute ischemic stroke
Urokinase used for CVC de-clotting and PE
Fibrinolytic absolute contraindications?
Previous hemorrhagic stroke
Ischemic stroke within 3 mo
Active internal bleeding
Aortic dissection (CXR r/o wide mediastinum)
Significant head/facial trauma within 3 mo
Fibrinolytic relative contraindications?
Uncontrolled HTN (180/110)
Severe chronic HTN
Current use of anticoagulants (INR over 2.5)
Non-compressible vascular puncture