CVS Drugs Part 1 Flashcards
Antiplatelet/Antithrombotic Drugs & Anti-Arrhythmic Drugs
First step in platelet aggregation
damage to endothelium causes platelets to become activated which cover and adhere to exposed subendothelial surface -> platelet adhesion
Second step of platelet aggregation
activated platelets release chemical mediators including thromboxane A2, ADP, serotonin, and PAF -> platelet activation
Third step of platelet aggregation
platelets are recruited forming platelet plug -> platelet aggregation
Intrinsic pathway factors
activation of factors XII, XI, IX, and VIII leading to activation of factor X
Extrinsic pathway factors
activation of factors III (tissue factor) and VII leading to activation of factor X
Common pathway factors
activation of factor X through extrinsic and intrinsic pathways leading to conversion of prothrombin (factor II) to thrombin (factor IIa), activation of factor XIII, and conversion of fibrinogen (factor I) to fibrin (factor Ia) resulting in fibrin clot formation
fibrinolysis
break down of a fibrin clot by plasmin after conversion of plasminogen to plasmin
Aspirin MOA
antiplatelet drug that irreversibly inhibits COX-1 enzyme inhibiting platelet aggregation (by inhibition of thromboxane A2 synthesis from prostaglandins)
Aspirin clinical indications
- primary and secondary prevention of heart attack and stroke in patients previously diagnosed with CAD, DM, PVD, CVA, and TIA
- in DAPT combined with P2Y12 ADP inhibitor (clopidogrel) recommended after CABG, PCI, stroke, and TIA (for 2 weeks)
Aspirin contraindications
intracranial, intramedullary, or posterior eye surgeries
Aspirin adverse effects
GI bleeding (especially in the elderly) and tinnitus
Clopidogrel MOA
antiplatelet drug that is an irreversible P2Y12 ADP receptor inhibitor causing inhibition of platelet activation
Clopidogrel clinical indications
1st line drug for prevention of atherosclerotic events in recent MI, CVA, unstable angina, ACS, and coronary angioplasty
- used in DAPT combined with aspirin for 1-6 months in BMS, 12 months in DES,12 months in ACS, and 10-21 days in TIA/minor ischemic strokes (not in major CVA d/t bleeding risk)
Clopidogrel contraindications
do not use during episodes of active bleeding, in patients with a history of bleeding, history of vascular disease including stable angina, prior TIA or stroke, and PAD
DAPT score associated with favorable benefit/risk ratio for prolonged DAPT
score of greater than or equal to 2
risk factors that increase DAPT score
tobacco smoking, diabetes, MI at presentation, prior PCI or MI, stent diameter <3 mm, paclitaxel-eluting stent, CHF or LVEF <30% (+2), and saphenous vein graft PCI (+2)
Clopidogrel pharmacokinetics
prodrug that is metabolized by CYP 2C19, onset = 2 hours (effects last 5 days)
clopidogrel drug interactions
omeprazole which inhibits CYP (if PPI needed, use pantoprazole)
Ticagrelor (Brilinta) MOA
only antiplatelet drug that is a reversible P2Y12 ADP receptor inhibitor
Ticagrelor pharmacokinetics
administered orally and is not metabolized by CYP (not a prodrug like clopidogrel), has fastest onset = 1-3 hours
Ticagrelor clinical indications
- 2nd line for prevention of atherosclerotic events in recent MI, CVA, unstable angina, ACS, and coronary angioplasty
- used in DAPT combined with aspirin
Prasugrel (Effient) MOA
antiplatelet drug that is an irreversible P2Y12 ADP receptor inhibitor with increased antiplatelet activity
Prasugrel clinical indications
used in combination with aspirin in ACS and after MI and stroke (not used routinely)
Prasugrel contraindications
increased risk of bleeding (especially >75 yo)
Ticlopidine MOA
antiplatelet drug that is an irreversible P2Y12 ADP receptor inhibitor causing inhibition of platelet activation
Ticlopidine clinical indications
TIA patients and patients with a prior history of stroke - no longer sold in the US due to life-threatening hematologic adverse effects (requires CBC every 2 weeks for 4 months)
Ticlopidine adverse effects
thrombocytopenia, agranulocytosis, and TTP
Ticagrelor adverse effects
increased aches and pains when combined with statins
Abciximab MOA
humanized monoclonal antibody that is an antiplatelet drug and GP IIb/IIIa receptor inhibitor that also binds to vWF and fibrinogen inhibiting platelet aggregation
Abciximab clinical indications
used in ACS patients who do not respond to conventional therapy within 24 hours and with aspirin and heparin during balloon angioplasty, coronary stent placement, and PCI to prevent further clot formation
Abciximab pharmacokinetics
administered IV and reaches peak effect after 30 minutes persisting 24 hours after stopping
Tirofiban MOA
antiplatelet drug and GP IIb/IIIa receptor inhibitor that also binds to vWF and fibrinogen inhibiting platelet aggregation
Tirofiban clinical indications
rarely used to reduce the rate of thrombotic CV events in NSTEMI with PCI
Tirofiban pharmacokinetics
administered IV with rapid onset and short duration of action (effects last 4-8 hours after IV stops), excreted in kidneys
Tirofiban contraindications
patients with history of bleeding including recent trauma or surgery, history of thrombocytopenia with previous tirofiban use, and history of bleeding diathesis
Tirofiban adverse effects
thrombocytopenia (must monitor aPTT)
Eptifibatide MOA
antiplatelet drug and GP IIb/IIIa receptor inhibitor that also binds to vWF and fibrinogen inhibiting platelet aggregation
Eptifibatide clinical indications
same as Tirofiban and interchangeable depending on insurance
Dipyridamole MOA
antiplatelet drug that inhibits adenosine deaminase and phosphodiesterase (and conversion of cAMP to AMP) inhibiting platelet aggregation and resulting in vasodilation
Dipyridamole clinical indications
rarely used but when used is in fixed combination with aspirin (Aggrenox) for secondary prevention of stroke - Clopidogrel and aspirin works as well and is safer
Cilostazol MOA
antiplatelet and vasodilatory drug that inhibits phosphodiesterase (and conversion of cAMP to AMP) inhibiting platelet aggregation and resulting in vasodilation
Cilostazol clinical indications
intermittent claudication (legs) in PVD (also increases HDL and decreases TG)
Cilostazol contraindications
heart failure
Cilostazol adverse effects
headache, GI upset, drug interactions due to metabolism by CYP
things to caution when prescribing antiplatelet drugs
patients taking other antithrombotic drugs, platelet-inhibiting supplements including fish oil, Dong quai, garlic, ginger, gincko, ginseng, and green tea
Unfractionated heparin MOA
indirect thrombin inhibitor that binds to and activates anti-thrombin creating a complex that leads to inactivation of thrombin (factor IIa) and intrinsic clotting factors IXa and Xa, inhibiting the formation of fibrin
Unfractionated heparin clinical indications
used in acute settings in treatment of PE, DVT, TIA, and ACS (MI) and sometimes used initially in the treatment of atrial fibrillation or prosthetic valves, and in hemodialysis and heart/lung bypass machine
Unfractionated heparin pharmacokinetics
administered IV or SC with rapid onset and short half life = 2 hours - must use lower dose with impaired kidney function
Unfractionated heparin contraindications
do not use with NSAIDs due to the risk of bleeding and renal dysfunction
Unfractionated heparin adverse effects
frequent bleeding, osteoporosis, hyperkalemia, transiently elevated transaminases, HIT (must monitor platelets and PTT)
Unfractionated heparin antidote
protamine sulfate (1 mg neutralizes 100 U heparin)
LMW heparin MOA
indirect thrombin inhibitor that binds to and activates anti-thrombin creating a complex that leads to inactivation of thrombin (factor IIa) and clotting factors IXa and Xa, inhibiting formation of fibrin
LMW heparin pharmacokinetics
administered SC with onset of 1-2 hours and half-life of 4 hours
LMW heparin contraindications
spinal or epidural catheters
Enoxaparin (Lovenox) clinical indications
a LMW heparin that is used in the treatment of DVT/PE and for DVT prophylaxis in knee and hip replacement surgeries as well as abdominal surgeries (safe in pregnancy), can also be used to bridge patients starting on warfarin until INR reaches satisfactory level
Enoxaparin adverse effects
peripheral edema, less HIT and osteoporosis compared with heparin
Dalteparin clinical indications
used primarily in patients with malignancy and more effective than warfarin in reducing recurrent embolic events
Dalteparin adverse effects
peripheral edema, less HIT and osteoporosis compared with heparin
Warfarin MOA
anticoagulant that inhibits Vitamin K, a co-factor in carboxylation/activation of clotting factors II, VII, IX, and X, inhibiting fibrin formation
Warfarin pharmacokinetics
administered orally, is absorbed rapidly and binds 99% to albumin, the onset of action is delayed (3-4 days) due to the time it takes to degrade clotting factors, metabolized by CYP enzymes, crosses the placenta
Warfarin clinical indications
used most commonly prophylactically to prevent thrombosis in atrial fibrillation, atrial flutter, prosthetic heart valves, and recurrent DVT, and perioperatively with TKA and THA, also used in the treatment of DVT/PE to prevent the thrombus from growing while body dissolves the fibrin plug
Warfarin adverse effects
bleeding
Warfarin antidote
Vitamin K infusion
Warfarin contraindications
pregnancy
recommended PT/INR for Warfarin
between 2-3 except for with mechanical heart valves which needs to be 2.5-3.5
Warfarin drug interactions
CYP inducers will reduce warfarin activity (Carbamazepine, Phenobarbital, Phenytoin, Rifampin, Vitamin K, Cholestyramine, Colestipol) and CYP inhibitors will increase warfarin activity and bleeding (Aspirin, Heparin, Antibiotics - decrease gut bacteria vitamin k production)
Foods rich in Vitamin K
asparagus, broccoli, Brussels sprouts, collard greens, kale, kiwi, lettuce, soybeans, spinach, Swiss chard
Dabigatran MOA
direct thrombin inhibitor = first warfarin alternative
Dabigatran clinical indications/advantages
used in prophylaxis of thrombosis similar to warfarin but with reduced drug/food interactions and risk for intracranial bleeding, superior to warfarin in patients with poor INR control - does not require INR monitoring
Dabigatran pharmacokinetics
administered orally, onset of action = 2-3 days (faster than warfarin)
Dabigatran adverse effects
more GI bleeding and heartburn than warfarin but less intracranial bleeding, discontinuation can cause rebound thrombosis
Dabigatran antidote
Idarucizumab (Praxbind)
Argatroban MOA
direct thrombin inhibitor that binds to thrombin and inhibits the conversion of fibrinogen to fibrin
Argatroban pharmacokinetics
administered IV only, must decrease dose in patients with hepatic impairment
Argatroban clinical indications
used as anticoagulant prophylaxis or treatment for HIT and also in PCI if a patient is at risk of HIT with heparin agent (must monitor ACT when being used)
Fondaparinux MOA
binds to and activates anti-thrombin causing direct inhibition of factor Xa (no direct effect on thrombin)
Fondaparinux clinical indications
used similar to a heparin in the treatment of DVT/PE and as DVT prophylaxis in orthopedic surgery, can be used as alternative to heparin in patients with history of HIT
Fondaparinux administration
SC injection
Rivaroxaban (Xarelto) MOA
direct inhibitor of factor Xa
Rivaroxaban clinical indications
used in prophylaxis and treatment of DVT/PE and stroke prevention in non-valvular atrial fibrillation
Rivaroxaban adverse effects
has the highest risk of the Xa inhibitors for GI bleeding and more liver/kidney toxicity but lower rates of serious and fatal bleeding than warfarin
Rivaroxaban administration
oral once daily
Apixaban (Eliquis) MOA
direct inhibitor of factor Xa
Apixaban clinical indications
used in prophylaxis of DVT/PE and stroke prevention in non-valvular atrial fibrillation, better than warfarin and safer than Rivaroxaban (DOC)
Apixaban adverse effects
less bleeding than warfarin
Apixaban administration
oral twice daily
Alteplase (tPA) MOA
endogenously activates the conversion of plasminogen to plasmin by activating protease and preferentially activates plasminogen bound to fibrin (avoiding systemic activation) which breaks down fibrin clots in arterial system
Alteplase clinical indications
administered IV for acute stroke, MI, and PE
Alteplase half-life
5 minutes
adverse effects of fibrinolytics
hemorrhage by destruction of therapeutic clots as well as pathologic clots is the biggest risk
Anistreplase MOA
purified human plasminogen and bacterial streptokinase that has been acylated to protect the enzyme active site which catalyzes the conversion of plasminogen to plasmin
Anistreplase clinical indications
administered IV in the treatment of acute MI (not used much anymore)
Urokinase clinical indications
treatment of acute PE (not used much anymore)
Reteplase (r-PA)
genetically engineered smaller derivative of tPA administered IV for acute MI
Tenecteplase (TNK-tPA)
genetically engineered smaller derivative of tPA with a higher affinity for fibrin than tPA
Tenecteplase clinical indications
administered IV for acute MI
Tenecteplase half-life
20-24 minutes
Reteplase half-life
13-16 minutes
Cardiac arrhythmia
an electrical activity that deviates from normal cardiac rhythm as a result of an abnormality in impulse formation and/or impulse conduction which can result in reduced cardiac output (occurs in over 80% of patients with an acute MI, 50% of anesthetized patients, and up to 25% of patients treated with digoxin)
common causes of arrhythmias
ischemia, scarred tissue, hypoxia (sleep apnea), acidosis or alkalosis (sepsis), electrolyte disturbances, excessive catecholamine exposure (cocaine use), autonomic disturbances, and drug toxicities
P wave on EKG
atrial depolarization followed by contraction
QRS complex on EKG
ventricular depolarization followed by contraction
T wave on EKG
ventricular repolarization followed by refilling
Phase 0 of action potential
rapid influx of Na+ causing rapid depolarization
Phase 2 of action potential
efflux of Ca2+ causing contraction of atrial or ventricular muscle and a relatively stable plateau in membrane potential
Phase 3 of action potential
rapid efflux of K+ causing repolarization (drugs that delay repolarization prolong the ERP)
Phase 4 of action potential
membrane potential remains stable (myocardium cells) or undergoes spontaneous depolarization where the membrane potential gradually rises until threshold potential is reached (SA node cells)
Class Ia drugs effects on action potential
slow phase 0 depolarization in ventricular muscle fibers resulting in increased ERP and action potential duration
Class Ib drugs effects on action potential
slow phase 0 depolarization and accelerate phase 3 repolarization in ventricular muscle fibers resulting in decreased ERP and action potential duration
Class Ic drugs effects on action potential
markedly slow phase 0 of repolarization in ventricular muscle fibers and have no effect on ERP or action potential duration
Class II drugs effects on action potential
slow phase 4 spontaneous depolarization resulting in decreased impulse automaticity, chronotropy, dromotropy, and inotropy of the myocardium and prolonged repolarization at the AV node
Class III drugs effects on action potential
slow phase 3 repolarization resulting in increased ERP and action potential duration
Class IV drugs effects on action potential
slow phase 4 spontaneous depolarization resulting in slowed conduction in the SA and AV node cells and decreased impulse automaticity and conduction in vascular smooth muscle and the myocardium
Quinidine clinical indications/pharmacokinetics
Class Ia drug that is administered orally used uncommonly to convert atrial, AV junctional, and ventricular tachyarrhythmias to NSR or to prevent arrhythmias (historically used to treat malaria)
Quinidine adverse effects
blurry vision, tinnitus, headache, vertigo (cinchonism), psychosis and also has some mild, alpha-adrenergic and anticholinergic actions
Procainamide clinical indications/pharmacokinetics
Class Ia drug that is administered IV only and used uncommonly to treat acute atrial or ventricular arrhythmias or hemodynamically stable SMVT (largely replaced by amiodarone in clinical practice)
Procainamide adverse effects
hypotension, lupus like syndrome
Lidocaine clinical indications/pharmacokinetics
Class Ib drug that is administered IV only and used to terminate active ventricular tachycardia/ventricular fibrillation (ACLS) and in the prevention of ventricular fibrillation after cardioversion in setting of acute ischemia (not used in prevention due to risk of mortality)
Lidocaine adverse effects
CNS changes - nystagmus, drowsiness, and slurred speech
Mexiletine clinical indications
Class Ib drug that is used in chronic preventative treatment of ventricular arrhythmias in patients prone to VT
Mexiletine adverse effects
nausea and vomiting, has a narrow therapeutic index
Flecainide clinical indications/pharmacokinetics
Class Ic drug that is administered orally and used to treat patients with otherwise normal hearts who are prone to atrial fibrillation or flutter
Flecainide adverse effects
blurry vision, nausea, may cause severe exacerbation of arrhythmia in patients with pre-existing VT and previous MI and ventricular ectopy
Propafenone clinical indications
Class Ic drug that is used to control rhythm in atrial arrhythmia including atrial fibrillation and flutter and can be used to prevent paroxysmal SVT in patients with AVRT
Propafenone adverse effects
has beta-blocking effects so can cause bronchospasms - use cautiously in asthmatics
Beta-blockers anti-arrhythmic clinical indications/pharmacokinetics
administered oral or IV (except for Esmolol = IV only) and used to treat tachyarrhythmias caused by increased sympathetic activity - atrial flutter and fibrillation and AVNRT, also can be useful in preventing recurrent infarction and sudden death due to ventricular arrhythmias in patients recovering from acute MI
Metoprolol clinical indications
cardioselective beta-blocker that is most widely used in the treatment of cardiac arrhythmias
Esmolol clinical indications
very short-acting cardioselective beta-blocker with fast onset used IV to abort arrhythmias
Class III drugs adverse effects on EKG
QT prolongation that increases the risk of torsades de pointes
Amiodarone clinical indications
Class III drug that has features of all four drug classes administered oral or IV, used in the treatment of hemodynamically stable SMVT as well as pulseless VT/VF (ACLS), highly effective in the treatment and prevention of SVT, especially atrial fibrillation and also approved for prevention of recurrent ventricular arrhythmias in at-risk patients
Amiodarone adverse effects
symptomatic bradycardia and heart block in patients with known sinus or AV nodal disease, peripheral vasodilation and hypotension, pulmonary fibrosis!! (required PFT monitoring), thyrotoxicity and hepatotoxicity!! (required LFT and TSH monitoring)
Class Ia drugs adverse effects on EKG
QT prolongation and widened QRS complex
Amiodarone contraindications
long-term treatment in YOUNGER patients
Dronedarone clinical indications/pharmacokinetics
Class III drug that is administered orally and only used clinically to maintain NSR in patients with atrial arrhythmias, less effective than amiodarone
Dronedarone contraindications
patients with symptomatic HF
Sotalol clinical indications/pharmacokinetics
Class III drug that is a nonselective beta-blocker used to treat life-threatening ventricular arrhythmias (ACLS) and for cardioversion and maintenance of NSR in patients with atrial fibrillation (with telemetry in hospital setting)
Sotalol contraindications
patients with long QT
Verapamil clinical indications/pharmacokinetics
Class IV drug that is administered IV to terminate SVT and administered orally or IV for rate control in atrial fibrillation and atrial flutter (rarely able to covert atrial fibrillation/flutter to NSR)
Diltiazem clinical indications/pharmacokinetics
Class IV drug that is administered orally or IV and used for managing supraventricular arrhythmias and rate control in atrial fibrillation/flutter (less side effects than with verapamil)
Verapamil/Diltiazem adverse effects
HF, 3rd-degree AV block, bradycardia as well as hypotension
Amiodarone half-life
25-110 days
Amiodarone pharmacokinetics
administered orally or IV and metabolized by CYP3A4 so can interact with many drugs
Digoxin MOA
inhibits the sodium/potassium-ATPase pump resulting in a shortened refractory period in atrial and ventricular myocardial cells and a prolonged refractory period/diminished conduction velocity in the AV node
Digoxin clinical indications
used to control ventricular response rate in atrial fibrillation and atrial flutter but has a narrow therapeutic index (may be DOC for rate control in patients with heart failure and atrial fibrillation)
Digoxin pharmacokinetics
administered orally or IV with loading dose prior to maintenance dosing, needs therapeutic level monitoring
Digoxin adverse effects
at toxic doses, it may cause ectopic ventricular beats resulting in VT or VF
Adenosine MOA
inhibits AV nodal conduction and increases AV nodal refractory period
Adenosine clinical indications/pharmacokinetics
administered IV bolus and is DOC (very effective) for prompt conversion of paroxysmal SVT to NSR - duration of action = 10-15 seconds
Adenosine adverse effects
flushing, SOB, and chest pain
Atropine clinical indications
administered IV to abort life-threatening bradycardia due to medication toxicity/OD, 2nd-degree heart block, and complete heart block
First-line treatment of Afib
rate control with CCB (Class IV) alone or in combination with beta-blocker (Class II), if heart failure is present- digoxin may be of value
Rhythm control of Afib in patients with normal heart
DC cardioversion is the first choice therapy but an anti-arrhythmic agent like Flecainide (Class I) can be used as a form of cardioversion
Rhythm control of Afib in patients with HF with low EF and/or hypertension
Amiodarone = first line
Rhythm control of Afib in patients with CAD
Sotalol = first line
Rhythm control of Afib in patients with mild HF (mild LVH, HFpEF) that do not convert to NSR with cardiac ablation or with established persistent Afib
Flecainide or Sotalol = first line, Amiodarone = second line
Absolute refractory period (ARP)
time during which another stimulus will not lead to another AP (phases 0,1,2)
Relative refractory period (RRP)
interval following ARP in which a 2nd stimulus is inhibited but not impossible (phases 2 and 3)
Effective refractory period (ERP)
time in which a cell does not produce a new AP (phases 0,1,2,3)
early afterdepolarizations (EADs)
disturbed impulses that occur during phase 3 of action potential and interfere with normal impulse formation
delayed afterdepolarizations (DADs)
disturbed impulses that occur during phase 4 of the action potential and interfere with normal impulse formation
EAD triggers
anything that causes QT prolongation (blockage of rapidly activating delayed rectifier potassium channels due to drugs or congenital syndrome), especially slow heart rates and hypokalemia, which can result in torsades de pointes (V Tach), tachycardia, and other arrhythmias
DAD triggers
excess accumulation of intracellular calcium especially fast heart rates which can result in ventricular tachycardia, digitalis toxicity, excess catecholamines, and myocardial ischemia
Torsades de pointes
disturbance of impulse formation caused by QT prolongation which can lead to ventricular tachycardia
Wolff-Parkinson-White Syndrome
serious disturbance of impulse conduction caused by the failure of an impulse to die out after normal activation (typically due to an obstacle and availability of another circuit) and creating an additional repetitive impulse at the AV node
Lipoproteins containing apo B-100
LDL, VLDL, and chylomicrons
role of HDL
made up of mostly cholesterol and acts as a scavenger to take up cholesterol from peripheral tissues and triglycerides from degradation of VLDL - does not contain apo B-100
role of VLDL
secreted by liver and functions to export triglycerides to peripheral tissues
role of chylomicrons
formed in the intestine and function to carry triglycerides of dietary origin, unesterified cholesterol, and cholesteryl esters
primary hyperlipidemia
genetically determined (familial; hereditary)
secondary hyperlipidemia
acquired due to other conditions such as hypothyroidism, nephrotic syndrome, drugs, DM, alcohol, gout, chronic renal failure
total cholesterol goal
less than or equal to 200
triglycerides goal
less than or equal to 150
LDL cholesterol goal
less than or equal to 100
HDL cholesterol goal
greater than or equal to 60
process of atherogenesis
LDL enters the intima of endothelium which becomes oxidized into proinflammatory lipids causing adhesion and entry of monocytes and T lymphocytes. Monocytes differentiate into macrophages and consume large amounts of LDL transforming into foam cells. The foam cells release growth factors that encourage atherosclerosis and creation of lipid pools.
Statins MOA
competitive HMG CoA reductase inhibitors that prevent the synthesis of (mevalonate) cholesterol in the liver leading to a reduced intracellular supply of cholesterol which ultimately causes increased cell surface LDL receptors that bind and internalize circulating LDL-c reducing plasma cholesterol
LDL-c effect of high intensity statins
lowers LDL-c by greater than or equal to 50%
LDL-c effect of moderate intensity statins
lowers LDL-c by 30-49%
LDL-c effect of low intensity statins
lowers LDL-c by less than or equal to 30%
Statins clinical indications
used to lower the risk of atherosclerotic cardiovascular disease events by lowering plasma cholesterol levels in all types of hyperlipidemia
Statins contraindications
pregnancy, lactation, active or chronic liver disease, red yeast rice, grapefruit juice
Statins administration
administered orally usually taken at night (liver is most active at night)
Statins adverse effects
elevated liver enzymes and liver toxicity (reversible when statin stopped), myopathy and rhabdomyolysis (CK levels above 150), photosensitivity, may increase levels of warfarin (check INR prior to initiating/changing doses), GI upset
Atorvastatin and Rosuvastatin clinical indications
most potent statins used to lower triglycerides, LDL, and total cholesterol (Rosuvastatin reaches increased levels in Asians), atorvastatin metabolized by CYP
Lovastatin clinical indications
low potency statin used mostly to lower LDL, metabolized by CYP
Simvastatin clinical indications
medium potency statin used to lower triglycerides, LDL, and total cholesterol, metabolized by CYP - inhibitors may increase risk of rhabdomyolysis
Pravastatin clinical indications
low to medium-potency statin (medium only at high doses)
Statin preferred with renal impairment
Atorvastatin
Niacin MOA
inhibits lipolysis in adipose tissue reducing production of free fatty acids and triglycerides - reduces VLDL secretion from liver lowering LDL-c plasma concentrations
Niacin clinical indications
used to lower plasma levels of LDL-c, triglycerides, and lipoprotein(a), and is the most effective agent for increasing HDL-c in the treatment of familial hyperlipidemias and severe hypercholesterolemia, often used in combination with other agents
Niacin contraindications
hepatic disease, active peptic ulcer, low BP, severe gout, and individuals with high uric acid levels (diabetics)
Niacin adverse effects
intense cutaneous flush accompanied by uncomfortable feeling of warmth and pruritis, nausea, abdominal pain, hyperuricemia/gout, impaired glucose tolerance, hepatoxicity, and hypotension
Gemfibrozil MOA
a fibrate that is a peroxisome proliferator-activated receptor-alpha agonist which decreases triglycerides by lowering VLDL levels and increases HDL levels (increases lipoprotein lipase activity)
Gemfibrozil clinical indications
hypertriglyceridemia, type III hyperlipidemia, and low HDL
Gemfibrozil contraindications
coadministration with statin therapy due to risk of myopathy, renal and hepatic dysfunction, pre-existing gallbladder disease or biliary cirrhosis
Gemfibrozil adverse effects
GI upset, gallstones, myopathy, hepatic dysfunction, increased levels of warfarin
Fenofibrate MOA
a fibrate that is a peroxisome proliferator-activated receptor-alpha agonist that decreases triglycerides (more effective than Gemfibrozil) by lowering VLDL levels and increases HDL levels (increases lipoprotein lipase activity)
Fenofibrate adverse effects
GI upset, gallstones, myopathy, hepatic dysfunction, increased levels of warfarin (check INR)
Fenofibrate contraindications
renal and hepatic dysfunction, pre-existing gallbladder disease or biliary cirrhosis
Fenofibrate clinical indications
same as gemfibrozil - low HDL and hypertriglyceridemia, better than gemfibrozil when combined with statins
Bile acid sequestrates MOA
bind bile acids in gut to form an insoluble complex preventing reabsorption in small intestine increasing the levels of cholesterol taken up to make new bile resulting in decreased serum level of cholesterol, upregulating LDL receptors (decreasing LDL)
Bile acid sequestrates clinical indications
hyperlipidemias, elevated LDL, digitalis toxicity, and chronic pruritis
Bile acid sequestrates contraindications
biliary cirrhosis, biliary obstruction, gallstones, hypertriglyceridemia, GI obstruction, coagulopathy, hypothyroid patients, prolonged use in renal disease, pregnancy/lactation
Bile acid sequestrates adverse effects
constipation, bloating, nausea, flatulence, interferes with absorption of some drugs/fat-soluble vitamins (digoxin, warfarin, thyroid meds), can increase serum triglyceride concentration
Colesevelam clinical indications
bile acid sequestrate that is used to treat hyperlipidemia and elevated LDL as well as type II diabetes in lowering glucose levels (fewer side effects than other bile acid sequestrates)
Colestipol clinical indications
bile acid sequestrate that is used to treat hyperlipidemia and elevated LDL as well as adjunctive to diet and exercise in type II diabetes to improve glycemic control (do not use in type I diabetes or diabetic ketoacidosis)
Ezetimibe (Zetia) MOA
selective inhibitor of absorption of dietary and biliary cholesterol in the small intestine
Bile acid sequestrates pharmacokinetics
metabolized in small intestine and avoids the liver and kidneys
Ezetimibe clinical indications
used usually in combo with statin to modestly lower LDL and in treatment of phytosterolemia
Ezetimibe contraindications
severe hepatic insufficiency, pregnancy/lactation
Ezetimibe adverse effects
hepatic dysfunction and myositis
Ezetimibe pharmacokinetics
metabolized in the small intestine and liver with biliary and renal excretion
Omega-3 fatty acids MOA
inhibit VLDL and triglyceride synthesis in the liver
Omega-3 fatty acids clinical indications
lowering of triglycerides and used as adjunct to diet and exercise (not shown to reduce cardiovascular mortality)
Omega-3 fatty acids contraindications
patients on anticoagulants, thrombolytics, or antiplatelets due to increased risk of bleeding, patients with a history of fish hypersensitivity
Omega-3 fatty acids adverse effects
GI disturbances, increased bleeding risk
drug with the largest lowering effect on LDL
statins then bile acid sequestrates
drug with the largest increasing effect on HDL
niacin then fibrates
drug with the largest lowering effect on triglycerides
fibrates then niacin
drug to avoid in hypertriglyceridemia
bile acid sequestrates
effects of combining statins with fibrates
increased risk for rhabdomyolysis
reasons to use lipid-lowering drug combinations
significantly increased VLDL levels, both LDL and VLDL levels elevated initially, LDL or VLDL levels not normalized with single agent, elevated levels of lipo(a) or HDL deficiency coexists with other hyperlipidemia
Evolocumab MOA
inhibits PCSK9 (a protein that binds to LDL receptors in the liver) resulting in decreased levels of circulating LDL in the blood
Evolocumab clinical indications
used to decrease LDL when individuals have a genetic condition or in those with heart disease whose cholesterol has been difficult to control with other lipid-lowering medications
Evolocumab pharmacokinetics
administered SC with half-life of 11-20 days
