Cardio Exam 2

Quinnidine & Procainamide

Class-1A

• MOA: Na+ channel blocker, voltage-gated channel

• Binds both activated and inactivated Na+ channels

• fast-acting tissue, atria and ventricles

• ALSO Blocks K channels

• Increases ↑ QRS(slower depolarization for ventricles) and ↑ QT interval time

• prolongs AP and ERP

• K channels are the repolarizing part so blocking it will increase the duration of action potential (increase time for ventricles to repolarize = increase QT interval time)

Lidocaine and Mexiletine

Class-1B

•  MOA: Na+ channel blocker, voltage-gated channel

• only inactivated Na+ channels

• Selective for ischemic myocardium.

• Lidocaine for emergency, IV

• Decrease ↓QT prolongation

• Binds to fast-response tissue (atria, ventricles, Purkinje cells)

• prolongs APD and ERP.

Flecainide & Propafenone

Class-1C

• MOA: Na+ channel blocker, voltage-gated channel

• Increases ↑↑ QRS prolongation

• Longest duration from class 1

• Fast response phase 0 (Na)

• prolongs AP and ERP

Sotalol

Class 2

• MOA: β-blockers & K-channel blocker

• non-selective BB, also a class 3 K+ channel blocker. Can use it to control HR and control conduction velocity in the atria

• Slow response, targets SA and AV node

• Increased PR interval due to delayed conduction time through the AV node

• QT prolongation due to K-channel blockage

• Decrease HR from decreased SA node

Esmolol

Class 2

• Selective β1-blockers

• Selective B1B: only affect SA node and AV node

• Increased PR interval due to delayed conduction time through the AV node

Amiodarone

MOA: K+ channel Blockers

• Class 1, 2,3 & 4 actions

• Increases QT, QRS, and PR interval

• Prolongs AP duration and ERP

• Both in Fast cells, phase 0 (Na) and 3 (K). In slow cells, phase 0 (Ca entry).

• long half-life

Dronedarone: 

MOA: K+ channel Blockers

• Structurally related to aminodarone without the iodine

• Class 1, 2,3 & 4 actions

• Increases QT, QRS, and PR interval

Bretylium

MOA: K+ channel Blockers

IV only, class 3

Sotolal

MOA: non-selective BB, also a class 3 K+ channel blocker (Class 2 and 3)

•  Can use it to control HR and control conduction velocity in the atria

• Prolongs AP duration and ERP, QT prolongation (due to K channel blockade) and PR (slow down AV node)

Non-dhp: Verapamil and Diltiazem

Class 4: MOA: Ca2+ channel Blockers

• will affect CO and HR

• Reduce conduction velocity through AV node: Prolonged PR interval

• Useful for re-entry SVT

Magnesium

Class 4: MOA: Ca2+ channel Blockers

(Natural Ca2+ channel blocker) → will slow down SA and AV node, only slow down HR, but not affect CO

Adenosine

PR interval increase, reduce HR

• Fast-onset reducing conduction velocity through AV node

• Also acts on the SA node, decreasing HR

• Used to manage SVT, supraventricular tachycardia 

Unfractionated Heparin (UFH)

MOA: binds to ATIII (Antithrombin 3) → enhanced ATIII’s ability to inactivate 2a and 10a

• Heparin also has a long >18-saccharide chain for thrombin inhibition → long so that it can wrap around and grab thrombin (2a) and factor 10a to inhibit both

• 10a does not need the long chain of saccharide for inhibition 

• IV

• no renal/hepatic dose adjustments

• Daleparin (Fragmin)

• Tinzaparin (Inohep)

• Low Molecular Weight Heparin (LMWH)

• Chain not as long as heparin so will not be as effective as inhibiting factor 2a (Thrombin), inhibits 10a more

Enoxaparin (Lovenox)

• Inhibits factor 10a more than 2a(thromnin)

• Needs renal dose adjustment (bc renally eliminated)

• Preferred anticoag in oncology & pregnant patients

• SQ, weight-based

Fondaparinux: (Arixtra)

Factor Xa inhibitor

MOA: Synthetic pentasaccharide analog that inhibits Factor Xa

• Can use in patients with HIT

• No antidote to reverse effects

• SQ, in blood

• C/I in CrCl < 30mL/min

Rivaroxaban (Xarelto)

Apixaban (Eliquis)

Edoxaban (Savaysa)

DOACs

Direct Factor Xa Inhibitors

• Nonvalvular AF and treatment of DVT/PE

• C/I in  CrCl < 30mL/min (renal issues) 

• DDIs: CYP3A4 and p-gp

• Oral, once/twice daily, NO monitoring needed

Dabigatran (Pradaxa)

MOA: Inhibit both circulating and clot-bound thrombin

Direct Thrombin Inhibitors

• Avoid in renal impairment  CrCl < 30mL/min

• S/E: GI upset and dyspepsia → take with food

DTI IV agents

MOA: Inhibit both circulating and clot-bound thrombin

• Argatroban: only for HIT and ACS(acute Coronary syndrome) patients; reduce dose in hepatic disease

• Bivalidurin: only for HIT and ACS, reduce dose in renal disease

• Give IV bolus and IV continuous infusion

• No reversal agents

Warfarin

• Vitamin K antagonists, inhibits VKOR, reduces Vitamin K

• Works in the liver

• Delayed onset, will take 5-7 days

Protamine

MOA: chemically neutralizes heparin by binding to it so ti does not bind to AT3

• Reversal agents for UFH & LMWH

• Heparin is an acid (neg charged)

• Protamine is a base (Pos charged)

Idarucizumab (Praxbind)

Reversal for Dabigatran:

MOA: a humanized mouse monoclonal antibody

Vitamin K

Kcentra

Reversal for Warfarin

Activates vitamin K-dependent clotting factors

Clopidogrel (Plavix)

P2Y12 inhibitor

• Pro-drug → requires 2 step conversion to active metabolite → drug becomes active after metabolism in the liver

• Irreversible

• Primary PCI: to prevent platelet aggregation

• DDI: 2C19 inhibition → will decrease efficacy due to lack of conversion to active metabolite (bc 2C19 metabolizes and activates clopidogrel/P2Y12 receptor) → decrease platelet inhibition and decreased efficacy

Prasugrel (Effient)

P2Y12 inhibitor

• More potent effects compared to clopidogrel (does not need CYP2C19 for activation)

• Better efficacy but higher rates of bleeding bc of it

• No reversal

• Primary PCI for MI pts, prevent platelet aggregation for those for stent surgery

Aspirin (Salicylate)

Antithrombotic

• Irreversible inhibitor for COX-1  → inhibits thromboxane A2 synthesis

• ADRS: GI hemmorrhage, Hypersensitivity reactions, Toxicity

Ticagrelor (Brilinta)

P2Y12 inhibitor

• Reversible

• Oral

• DDI: 3A4 inhibitors and inducers

Cangrelor (Kengreal)

P2Y12 inhibitor

• Only IV

• Reversible

Abciximab (Reopro)

Eptifibatide (Integrilin)

Tirofiban (Aggrastat)

GP2b/3a inhibitors

• Blocks final common pathway of platelet aggregation

• Used in addition to anticoagulant and P2Y12 inhibitor during PCI

• DNU in combo with Bivalirudin → increased risk of bleeding

• Can induce thrombocytopenia → HIT → cause platelet activation

t-PA (Aleplase, Activase)

Tenectaplase (TNKase) (Alternative)

Fibrinolytic

MOA:  Recombinant t-Pa (alteplase) binds to fibrin in thrombus → converts entrapped plasminogen to plasmin → initiates local fibrinolysis

• Atorvastatin (Lipitor) (has high intensity → reduce LDL more and maxes HDL increase)

• Fluvastatin (Lescol)

• Lovastatin (Altoprev)

• Pitavastatin (Livalo; Zypitamag)

• Pravastatin (Pravachol)

• Rosuvastatin (Crestor) (Has high intensity reduce LDL more and maxes HDL increase)

• Simvastatin (Zocor)

HMG CoA reductase inhibitors (Statins)

• Target liver

• Inhibits enzyme HMG CoA reductase

• Decrease LDL cholesterol production & increase LDL-receptor expression at hepatocyte

• May increase HDL

• Stabilize atherosclerotic plaques

Bempedoic acid (Nexletol)

ACL inhibitor

• Target Liver

• Inhibits cholesterol synthesis in the liver upstream of HMG-CoA Reductase

• Upregulates LDL receptors → decrease in plasma LDL-C

• Prodrug: activated in the liver cells (Acyl-CoA synthetase 1 (ACSVL1)

• Selective for hepatocytes does not affect myocytes (no muscle pain)

Alirocumab (Praluent) 

Evolocumab (Repatha) 

Inclisiran (Leqvio)

PCSK9 Inhibiting agents

• Inhibits PCSK9 → prevents the formation of PCSK9/LDL-R complex → LDL-R is save, can grab more circulating LDL from the blood for faster clearance of LDL = lowering LDL

• Target liver

• Not first line bc of cost

• More efficacious than high-dose statins

• SQ

• Higher LDL reduction than statins

Colesevelam (Welchol)

Colestipol (Colestid)

Cholestyramine (Questran)

Bile Acid Sequestrants (BAS) or resins

• Target Intestine

• Moderate lowering LDL-C

• bind to negatively charged bile acids in the intestine, forming an insoluble complex that is excreted in the stool.

• May be used in statin-intolerant patients

• G.I side effects: Nausea, bloating, constipation, gas

• C/I history of bowel movement & in pancreatitis

Ezetimibe (Zetia)

Cholesterol absorption inhibitor

• Intestine

• Addon therapy

• Does not add on to muscle pain risk

• Minimal GI effects

• Reduce Triglycerid, non-HDL-C & LDL-Cholesterol

Fenofibrate, Gemfibrozil

Fibrates or fibric acids

Uses PPAR a nuclear factor will cause lipoprotein metabolism → upregulate LPL → more triglyceride hydrolysis → decrease triglyceride levels

• EPA: Eicosapentaenoic acid 

• DHA : Docosahexaenoic acid

• Icosapent ethyl

Omega-3 Fatty Acids

• Inhibit TG-Synthesizing enzymes, Increase LPL

• Reduce hepatic synthesis and secretion of VLDL particles (which mainly contain TG)

Niacin or nicotinic acid

• MOA: inhibition of FFA release from adipose tissue,  increase lipoprotein lipase activity (lowers triglycerides), & reduce rate of hepatic VLDL and LDL synthesis from liver

• Lowers triglycerides, LDL-C, TG

• Increases HDL-C

• Lots of ADRs: Flushing (Vasodilation, can cause tachycardia)