CATEGORIES, TYPES, INCREASES, AND DECREASES

Primary and secondary

What two categories of conditions are included in disorders of lipoprotein metabolism (dyslipidemia)?

Acute pancreatitis and atherosclerosis

What are the two major clinical sequelae of dyslipidemia?

Lipids and proteins

What two components form the large macromolecular complex known as lipoproteins?

Triglycerides and cholesteryl esters

What two components form the hydrophobic core of lipoproteins?

Phospholipids, unesterified cholesterol, and apolipoproteins

What three components surround the hydrophobic core of lipoproteins?

Five or six

How many major classes of lipoproteins are there?

Inverse

What is the relationship between the relative density and size of lipoprotein classes?

Bigger, more buoyant, and less dense

What three physical characteristics increase as the triglyceride content of a lipoprotein increases?

Denser and smaller in size

What two physical characteristics result when a lipoprotein particle is stripped of triglycerides and has more proteins?

Pro-atherogenic

What category describes all lipoprotein classes except HDL?

Anti-atherogenic

What category describes HDL lipoprotein?

Endogenous, exogenous, and reverse cholesterol transport

What are the three pathways involved in lipoprotein metabolism?

Chylomicron remnants

What is the end product of the exogenous pathway?

LDL

What is the final product of the endogenous pathway?

Reverse cholesterol transport pathway

What pathway transports peripheral cholesterol stores back to the liver for excretion to the bile?

Lipid-lowering agents

What category of drugs inhibits the HMG CoA reductase pathway?

Reductase inhibitors, fibric acid derivatives, niacin, bile acid-binding resins, and sterol absorption inhibitors

What five categories of conventional drugs are used for dyslipidemia?

PCSK9 inhibitor, MTP inhibitor, antisense oligonucleotide, and omega fatty acids

What four categories of other agents are used for dyslipidemia?

Class I, Class II, Class III, and Class IV

What are the four classes in the Vaughan Williams classification of antiarrhythmic drugs?

Class IA, Class IB, and Class IC

What are the three subclasses of Class I sodium channel blocking drugs?

Disturbance in impulse formation, disturbance in impulse conduction, and re-entry of circus movement

What are the three mechanisms that cause arrhythmia (or dysrhythmia)?

Supraventricular and ventricular

What two categories are used to classify arrhythmias according to their location?

Primary arrhythmias and secondary arrhythmias

What two categories are used to classify arrhythmias based on underlying cause?

Beta blockade

What is the mechanism of action for Class II antiarrhythmics?

Potassium channel blockade

What is the mechanism of action for Class III antiarrhythmics?

Calcium channel blockade

What is the mechanism of action for Class IV antiarrhythmics?

Moderate reduction in phase zero, increase in APD and ERP

What are the three effects of Class IA sodium channel blockade?

Weak reduction in phase zero, decrease in APD and ERP

What are the three effects of Class IB sodium channel blockade?

Strong reduction in phase zero, no effect on APD and ERP

What are the three effects of Class IC sodium channel blockade?

Phase zero, one, two, three, and four

What are the five phases in the action potential of cardiac muscle cells?

Phase zero, three, and four

What are the three phases in the action potential of specialized conducting cells (pacemaker cells)?

Rapid sodium influx

What ion movement causes Phase zero (rapid depolarization) in cardiac muscle action potential?

Potassium efflux and calcium influx

What two ion movements occur during Phase two (plateau stage) in cardiac muscle action potential?

Potassium efflux

What ion movement causes Phase three (rapid repolarization) in cardiac muscle action potential?

Rapid calcium influx

What ion movement causes Phase zero (depolarization) in pacemaker cell action potential?

Slow sodium influx

What ion movement causes Phase four (pre-potential) in pacemaker cell action potential, which confers automaticity?

Decrease

What is the primary effect of statins on LDL cholesterol?

Minimal reduction

What is the effect of statins on triglycerides?

Slight increase

What is the effect of statins on HDL cholesterol?

Lower LDL

What is the principal effect of reductase inhibitors (statins)?

Decrease triglycerides and slightly increase HDL

What are the two main effects of fibric acid derivatives (fibrates)?

Increase HDL and decrease triglycerides, LDL, and Lipoprotein A

What are the four effects of Niacin on lipid profile?

Decrease LDL

What is the primary effect of cholesterol absorption inhibitors (Ezetimibe)?

Decrease LDL, increase triglycerides, and small increase in HDL

What are the three main effects of bile acid-binding resins?

Reduction of serum triglyceride levels

What is the primary effect of n-3/Omega Fatty Acids?

Massive reduction in LDL, increase in HDL, and decrease in TG and Lp(a)

What are the four effects of PCSK9 inhibitors on lipid profile?

Reduction of LDL cholesterol

What is the primary effect of MTP inhibitors (Lomitapide)?

Reduction in the production of atherogenic lipids (LDL and lipoprotein A)

What is the net result of Mipomersen's mechanism of action?

Reduction in LDL

What is the primary effect of Inclisiran (RNAi Inhibitor of PCSK9)?

Reduction in LDL

What is the primary effect of Bempedoic Acid (ATP Citrate Lyase Inhibitor)?

White clot

What type of clot forms inside arteries, consisting mostly of platelets?

Red clot

What type of clot forms inside veins, characterized by fibrin trapping red blood cells?

High pressure and high velocity

What two blood flow characteristics are seen in the arterial system, promoting white clot formation?

Low pressure and low velocity

What two blood flow characteristics are seen in the venous system, allowing time for fibrin clot formation (secondary hemostasis)?

Artery

Which type of thrombosis problem suggests giving agents to address platelets?

Vein

Which type of thrombosis problem suggests giving agents directed at secondary hemostasis?

Inhibition of aggregation of platelets

What is the general mechanism of action of antiplatelet drugs?

Inhibition of conversion of arachidonic acid to TXA2

What is the mechanism of action of Aspirin and NSAIDs?

Inhibition of ADP-induced platelet aggregation

What is the mechanism of action of Thienopyridines?

Inhibition of the crosslinking by fibrinogen between different platelets

What is the mechanism of action of Glycoprotein IIB/IIIA Inhibitors?

Irreversible inhibition of COX-1 and COX-2

What is the specific mechanism of action of Aspirin?

Inhibition of phosphodiesterase (PDE)

What is the primary mechanism of PDE and Adenosine Uptake Inhibitors?

Increases cAMP and reduces calcium

What is the effect of PDE inhibition?

Inhibition of the synthesis of protein C and clotting factors X, IX, VII, and II

What is the mechanism of action of Vitamin K antagonists (Warfarin)?

Depletion of protein C

What specific effect of Warfarin causes an initial prothrombotic effect?

Activation of antithrombin III

What is the mechanism of action of Heparin and Low Molecular Weight Heparin (LMWH)?

Mostly in inhibition of Factor X, not much to thrombin

What is the primary action of LMWH after activating Antithrombin III?

Mostly inhibits Factor X and partly inhibits thrombin

What is the primary action of Antithrombin III after activation by Heparin?

Direct thrombin inhibition

What is the mechanism of action of Argatroban, Bivalirudin, and Dabigatran?

Direct inhibition of Factor Xa

What is the mechanism of action of Rivaroxaban, Apixaban, and Edoxaban?

Competitive inhibition of plasminogen activation

What is the mechanism of action of epsilon Aminocaproic Acid and Tranexamic Acid?

Binding with plasminogen to become plasmin

What is the mechanism of fibrinolytic agents (e.g., Streptokinase, Alteplase)?

Fibrin degradation

What is the primary effect of Plasmin in clot dissolution?

Factor VIII release from the endothelium

What is the mechanism of action of Desmopressin?

Thrombin burst provision

What is the mechanism of action of Recombinant Factor VIIA (rFVIIa)?

Provision of activated clotting factors II, V, and X

What is the mechanism of action of FEIBA and aPCC?

Increases in serum aminotransferase activity

What adverse effect is occasionally seen in patients on statin therapy, often intermittent?

More than three times the upper limit of normal (ULN)

At what level of liver function test elevation should statin discontinuation be considered?

Myalgia, myopathy, myositis, and rhabdomyolysis

What are the four classifications of statin-induced muscle disorders?

Rhabdomyolysis

What is the most severe form of statin myopathy?

Increased risk of myopathy

What is the consequence of Gemfibrozil inhibiting the uptake of active hydroxy forms of statins?

Vasodilation

What side effect can result from PDE and Adenosine Uptake Inhibitors?

Bleeding

What is the primary side effect of all anti-clotting drugs (antiplatelets, anticoagulants, and fibrinolytics)?

Thrombosis

What is a side effect associated with the use of rFVIIa, epsilon Aminocaproic Acid, Tranexamic Acid, FEIBA, and aPCC?

Flushing and dyspepsia

What are the two most common side effects that limit patient compliance to Niacin therapy?

Prostaglandin effect

What is the cause of flushing, the common side effect of Niacin?

Minimal adverse effects

What is the general profile of adverse effects for Ezetimibe?

Constipation and bloating

What are the two most common adverse effects of bile acid-binding resins?

Malabsorption of Vitamin K and Folic Acid

What are two specific nutrient deficiencies that can be caused by bile acid-binding resins?

GI disturbance and anti-thrombotic effect

What are the two main side effects of n-3/Omega Fatty Acids?

Local injection reactions and flu-like symptoms

What are two common side effects of PCSK9 inhibitors and Mipomersen?

Liver toxicity (or hepatic steatosis)

What is the main concern or side effect associated with Mipomersen?

Hyperuricemia and tendon rupture

What are the two side effects of Bempedoic Acid?

Sinus arrest

What is a result of a disturbance in impulse formation?

AV block

What is an example of a disturbance in impulse conduction?

Ventricular tachycardia and supraventricular tachycardias

What two types of arrhythmias often involve re-entry of circus movement?

Ischemia and excessive myocardial fiber stretch

What are two physical factors that precipitate cardiac arrhythmias?

Excessive discharge or sensitivity to autonomic transmitters and excessive exposure to foreign chemicals

What are two chemical factors that precipitate cardiac arrhythmias?

Bradycardia

What condition is primarily treated with an implanted pacemaker?

Ventricular tachycardia and ventricular fibrillation

What two conditions are the primary indications for an Implantable Cardioverter Defibrillator (ICD)?