Cardiac Drugs Flashcards

Question

What is the MOA of b-adrenoreceptor blocking agents?

Answer 1

MOA: antagonists to βreceptors. Some are “selective” for β1 others are “non-selective” and antagonize both β1 and β2. * Function of B receptors: * •β1– heart (HR and contractility) slowing down HR * •JG cells (renin) targetting these only decreasing it and the SNS impact on its release \>decreasing ventricular remodeling * •β2– smooth muscle in vasculature and pulmonary airways. * Fx of drug: Decrease RAAS and heart work and AV conduction across the node; decreasing remodeling, hypertrophy, and cell death post-MI * **propanolol**- nonselective (cardiac affects w/out bronchospacsti coutput. Lipid soluble entering brain and affecting autonomic impacts resulting in fatigue, insomnia, and sexual dysfunction * **metoprolol-** popular beta 1 selective long term oral strategy w/ liver metabolism. can be used to treat sinus tach. * **nebivolol**- B1 selective interact w/ B3 trigger NO release * •**Esmololas-** β1 selective, but very short-acting, so useful for IV administration in acute situations * Treats: * CAD * HF (w/ decreased EF decreases in mortality) stable * Atrial fibrillation-caused by distention of atria blockade at AV node following atrial distension and prevents SVT * Sx: hypotension, bradycardia, fatigue, insomnia, sexual dysfunction- suggestthat factors such as fatigue, insomnia, sexual dysfunction not consistent; arrhythmias involving the AV node; and post-MI ventricular arrhythmias * Interactions: Impacts: P450 system breaksdown these drugs w/ inhibitors of this pathway affecting the efficacy of these drugs and w/ variations so works for some people but not for others. not to be used w/ drugs that slow AV conduction ex. amiodarone, verapamil, and diltiazem * Delivery: treatment started at low doses and titrated to target doses based on tolerance and vitals * Contraindication: Not to be used for hypertension, decrease cardiac demand.

Answer 2

* ACEi/ARB Indication: first-line treatment for hypertension, particularly in patients with DM, HF, renal disease take pressure of nephrons decreasing volume and vasoconstriction * ACEi/ARB Fx: Decrease both preload (decreased blood volume) and afterload (decreased vasoconstriction) àdecreased cardiac workload * Interactions: Avoid use of aliskiren(affects renin- first line) with ARBs or ACEIs; its blockade of renin and decrease of renal filtration makes it a lesser choice for renal patients. Less controllable profile and have more unexpected side effects like renal function. * ACEI- april showers casino used in HF given in all stagees of CHF, 1st line hypertension, and MI. start at low dose titrate to maximal target * HFrEF block ACE from converting angiotensin II and diminish inactivation of bradykinin (which is why a cough develops) * ACEi: risk of angioedema and bronchiole constriction (dry cough) due to prevention of the metabolism of bradykinin; ARBs less so. Due to protein kinase, * Sx: TERATOGENIC, hyperkalemia (decreased RAAS- MUST CHECK), dry cough and hypotension (particularly if taken w/ diurhetic), altered taste ACE as zinc dependent enzyme altering zinc levels, hypotension, skin rash 1) angioedema rare from too many bradykinin (ARBS take instead) -fat pregnant lady2) eczematous rash * **•Lisinopril:** can be used with hepatic impairment * **•Enalapril:** more cough and side effects; can be given IV * **•Ramipril:** lowest all-cause mortality in HF * •ARBS MOA: block (sartan-sorry taken seat) competitive antagonist of angiotensin II T1 receptors, leading to (potentially) more complete blockage because of AT2 receptor activity, which may account for the slightly different profile seen with ARB use, e.g., potential cognitive protection and no afffect on bradykinin. * ARBs- carginogen (nitrosamine) contamination during their manufacture * **Losartan:** enhanced uric acid excretion; first-pass metabolism * **Valsartan:** BID dosing; benefit in HF for those not tolerating ACEi * **•Irbesartan:** additional benefit with diabetic nephropathy compared to valsartan

Answer 3

* Indications: for angina, decreases cardiac work * Non-dihydropyrides: * * **Verapamil**: (vanilla) affinity for both cardiac and vascular channels. More for contractility * **Diltiazem:** (chocolate) affinity for both cardiac and vascular channels, not as much inotropydepression. Or contractility decrease cardiac work ad coronary spasm * Dihydropyridines: vascular * **Amlodipine:** affinity for vascular channels; long half-life * **Nifedipine:** affinity for vascular channels help w/ coronary spasm Sx: flushing, dizziness (dilating arteriles w/ vasodilating and less perfusion) headache, hypotension, and peripheral edema

Answer 4

* Alpha-1 antagonism (L) (vasodilateby blocking smooth muscle constriction from sympathetic tone) * Prazosinas α1 antagonist- more for refractory cases as add-on medication * Sx: orthostatic hypotension, tachycardia, dizziness and headache, sexual dysfunction * alpha-2 agonism (central nervous system effects of decrease norepinepherineand decreased sympathetic tone) (R). * Sx: constipation, dry mouth, drowsiness, hypotension, and confusion * Clonidineand methyldopaas α2 agonists * •Central acting to decrease sympathetic outflow * •Methyldopa as prodrug needing multiple dosing and used in pregnancy * •Clonidine as second-line HTN med Beta-2decrerasein tone Combined alpha/beta blockers: * **labetelol-** * More for gestational HTN and HTN emergencies (rapid-acting) * nonselective Beta- blocker decreased contractility * Alpha blocker- drop rate * **carvedilol-** Useful for patients with HTN and HF. P-glycoprotein substrate (alpha and beta blocker) and CP450 * Metabolism concerns: a drug may not work because of the p-glycoprotein- avoid uptake of toxic alcolatenot allowing other drugs to establish therapeuticalssuch as this.

Answer 5

MOA: Dilates arterioles over veins (selectively- alternative to ACE and ARBS), through a number of mechanisms that include K channel hyperpolarization, inhibition of Ca release from smooth muscle vascular cell SR, and stimulation of NO formation. * Fx: Decreased total peripheral resistance particularly arteriolar resistance and decrease afterload. Does not dilate coronary arteries (induces angina) * Sx. Causes reflex tachycardia, and stimulation of RAAS, and are therefore taken in combination with other meds (βblockers, diuretics) or as an add on . can cause lupus like condition headache, tachycardia, palpitations, angina, nausea * I**sosorbide dinitrate-** to venodilate-storing blood in veins rather than heart * two combined improve symptoms and survival in black patients w/ HFrEF on standard therapies * adverse efects of this is headache, dizzines,s ypotension

Answer 6

MOA: •L-Arginine metabolized to produce nitrous oxide (NO) which stimulates smooth muscle relaxation (vasodilation) mostly venodilation and Decreases total peripheral resistance * Fx: •Dilates peripheral and coronary arteries (relieves angina) * delivery: increases in GMP leads to myosin light chain dephosphorylation vino dilates reducing preload and arterial dilates coronary vasculature increasing blood supply to the heart ( * Indications: angina, hypertensive emergency, MI * Sx: •Vasodilation and subsequent headache, flushing, reflex tachycardia, postural hypotension give w/ beta blocker to prevent * develop tolerance to the vasodilation, so nitrate-free intervals if chronic dosing occurring. •Need nitrate-free intervals during the day to avoid desensitization to the vasodilation. 12 on, 12 off at night * •Significant first-pass effect, so typically sublingual or patch/ointment (transdermal) * Nitroglycerin for rapid relief * isosorbide dinitrate(mono nitrate longer lived longer acting) with longer half-life. venodilate stroing fluid in veins rather than heart.

Answer 7

* insufficient cardiac output •Preload (EDV), afterload (aortic pressure), Frank-Starling relationship Overstrip w/ diminishing returns * **Left-sided failure** (pulmonary impact) * **Right-sided failure** (typically from L-sided failure; peripheral impact) * **Systolic failure** (decreased ejection fraction); heart failure due to reducedejection fraction (HFrEF)- ventricle not pumping effectively * **Diastolic failure** (decreased ventricular filling); heart failure with preservedejection fraction (HFpEF) due to hypertrophy causing decrease cardiac output. * **Acute,** decompensated failure (myocardial illness or MI). symptoms include (dyspnea on exertion, ortopnea, paroxysmal nocturnal dyspnea, fatigue, and peripheral edema): can aggressively address congestive features such as pulmonary edema with diuresis or acute loss of cardiac output with short-term inotropic agents-contractility. Causes LV failure (using loop). Constant diurhesismight effect electrolyte balance. RAAS inhibitors are important targets * **Chronic**, compensated failure: **cardiac remodeling**- body is able to restore cardiac output compensating but damaging slowly over time. Loss of cells from ischemic damage. differential levels of electrical activity (no longer as a smooth contraction) due to altered levels of motility. consider fluid and sodium restrictions; treatment of comorbidities, some diuresis as needed; avoidance of triggers. Controlling RAAS. only give inotropic agents for acute signs. DO NOT GIVE NSAID, alcohol, nondi- CCB, antiarrhtymics * **Natriuretic peptid**e (stretch receptors in chamber of heart from salt water loss)- counteract salt water retention from RAAS retention. results in vasodilation, natriuresis, inhibition of renin and aldosterone release, reduction in myocardial fibrosis improving cardiac function and Hf symptoms.

Answer 8

Drives myocytes to contract: action potential, calcium comes in, induces release from SR, troponin, eneratestension. Calcium must leave to relieve it. L type- long acting will let calcium into cell triggering additional release from sarcoplasmic reticulum as well as binding. This allows cardiac muscle to successful contract SERCA pump- gets rid of calcium at the end of contraction Another way to pump out is use sodium gradient to pump Ca2+ out of the cell

Answer 9

* Digoxin ♣ Dobutamine ♣ Dopamine ♣ Milrinone • Antiarrhythmics fx is to want to increase contractility * digoxin- * MOA: •poison the Na+/K+ ATPaase pump, decreases ability of myocyte to pump sodium from the cell, decrease transport and counterexchangeof calcium increasing calcium in the cytoplasm to enhance binding to troponin. Maximizing further release. Prolonging refractory period and decreasing conduction velocity * Fx: •Enhances vagal tone, so slower AV nodal conduction * Sx: •Long half life and narrow therapeutic index for digoxin. Because it binds to the K site of the sodium pump, hypokalemia. (affecting membrane potential) if combined w/ diurhesishypokalemic can increase poisoning and arrhythmias. Substrate of P-gp inhibitors: verapamil, amiodarone will increase it making it toxic * Indicated: stage 3 HF because increasing contractility over the long term is dangerous; think of atrial fibrillation from atrial distension in HF because of backup from ventricles); Controls ventricular response rate in a fib and flutter. * •**Dobutamine- Positive inotropic**as pure β1 agonist(turning on cAMP, enhancing increased input of calcium through L-type calcium channels; with increasing calcium into myocardial cells. IV * **Dopamine-**•B-receptor with D receptor activity as well (affecting renal and causing vasodilation in kidney) increasing dose increases B function * **•Milrinone** as a Phophodiasterase PD3 inhibitor can also trigger vasodilation, IV form, inhibit breakdwonof cAMP- increasing B1 activity on the heart. (affecting EDV and SVR) * •**Sedenophile-** PD3 inhibitor smooth muscle to fill genitalia

Answer 10

see picture... •AV nodal effects, so third-line agent for atrial fibrillation/flutter

Answer 11

Essential hypertension- baseline condition have to be taken 2 times on two seperate occasions, or look at it for other factors. 130 As it drops below 120 again becomes dangerous again because of problems getting blood to brain and kidneys etc. * Diagnosed HTN with known CVD or 10 year risk of ASCVD ≥ 10%: * ◦Goal: SBP \< 130, DBP \< 80 * threshold for pharmacology (140/90\>130/70 or 160/100\>140/90) * Diagnosed HTN with no known CVD or 10 year risk of ASCVD ≥ 10%: * ◦Goal: SBP \< 130, DBP \< 80 * Threshold: \>130/80 or 140/90 still have same goal * Yes, it’s the same, but the strength of the evidence/recommendation is different between these two. * Adults with CKD: * ◦Goal: \<130/\<80 * Adults with diabetes: * ◦Goal: \<130/\<80 * Older adults: * ◦Goal: SBP \< 130, no diastolic recommendations * Makes the numbers easy to remember!. Treatment Goals- all goals under 130 diastolic- \<80 unless geriatric \>65 with more orthostatic hypotension

Answer 12

* •First thing you need to diagnose someone w/ HBP * •First intervene Activity, nutrition. * Weight loss if obese/overweight ex. 10% decrease in body weight can have massive improvement of BG, BP, and lipid control * Heart Healthy/DASH diet- helps stop hypertension with beneficial effects in cardiovascular made up of high magnesium low sodium * Potassium supplementation (esp. dietary)- be careful w/ kidney disease because they cant filter it out ex. Loop diurheticcan become hypokalemic can do calcium supplementation * Increase physical activity, pref. structured 30 min/day most days of the week * EtOH abstinence or moderate use only no more than 7-women, 14-men drinks in a week and 3-women, 4-men drinks in a day * •If go into stage 1 must do pharmacologic if greater than 10% risk of cardiovascular disease * •Stage 2- start medications no matter the risk

Answer 13

* First line agents: * ◦CCB, ACEI, or ARBs (ACE and ARB ceiling affect because working in the same area avoiding duplication) and thiazides * ◦Thiazides or CCB can be used in elderly and black patients including diabetics effective w/out much of the risk (ACEI and ARB less effective) * ◦Higher endogenous renin levels make ACEiand ARBs more effective in younger, white patients * any patient w/ chronic kidney disease ACEiand ARB helpful in diabetes - renal protective * Stage I HTN: * ◦Initial therapy with one of the above agents * Stage II HTN: * ◦Initial therapy should be two of the above agents that work in different ways

Answer 14

Three different schools of thought: * ◦1. Push dose of the first drug to its max prior to adding a second (JNC-8) * ◦2. Add a new drug to a moderate dose of the initial drug. * Higher doses do not produce a proportional response and lead to higher side effects * ◦If 25 mg of HCTZ causes a 15-point drop in systolic, 50 mg will not guarantee a 30-point drop, but do increase the risk of side effects * ◦3. “Sequential monotherapy” – If one drug is ineffective, change to another class for monotherapy. (UpToDate) * Each different drug has a 30-50% chance of producing an antihypertensive response

Answer 15

ACE inhibitors for conditions including: ## Footnote ◦Heart Failure ◦Asymptomatic LV dysfunction ◦History of STEMI- due to damage of the heart ◦History of Non-STEMI anterior infarct ◦Diabetes- renal protectivity ◦Systolic Dysfunction ◦ProteinuricCKD ARBS first line in patients w/ same as ACEI but who cannot tolerate their side effects (cough and angioedema)

Answer 16

◦Osteoporosis (increase calcium reabsorption in distal tubule)

Answer 17

* Chlorthalidone, HCTZ: * ◦Okay to use until CrCl(until the creatinine clearance or glomerular filtration rate) \< 10 mL/min, then not recommended * Furosemide:- lasiksloop diurhetics * ◦In acute renal failure, increase dose to a max of 1-3 g to get adequate response. * Avoid use in oliguric states * ◦If on dialysis, supplemental dose not needed after dialysis as drug is not removed * Spironolactone: * Contraindicated in anuria, acute renal impairment, or decreased renal excretory function. Potassium sparing drugs, major kidney issues do not use this drug making hyperkalemia (muscle flacidity) * If you arentmaking urine you arentgetting clearance of the medication

Answer 18

◦Atrial fibrillation ◦Angina ◦Obstructive airway disease

Answer 19

◦Not to be used as a first-line drug ◦Can be helpful in patients with: Atrial fibrillation Stable heart failure Asymptomatic LV dysfunction ANGINA

Answer 20

Initiate treatment with combination therapy when BP is \> 20/10 above goal. Be sure to use a drug that works in a different pathway (for example, ACEiand ARB both work in RAA system)

Answer 21

* •Stage a- Asymptomatic, no structural changes, treat other medical conditions, •Manage:Hypertension, lipid, weight, and diabetes management, risk reduction. prevention mode maybe- ACE, ARB, and statin for cholesterol * •Stage B- due to structural heart disease no active HF present but structural predisposition for it, **MI**. Chronic heart disease, valvularheart disease. * •History of MI with reduced ejection fraction: Prevention with ACEior ARBs * Acute MI and reduced ejection fraction:Prevention with beta blockers * if reduced left ventricular ejection fraction avoid CCBS * Control BP (diurhetics to control fluid overload) * Coronary revascularization- angina or cardiac ischemia can prevent w/ angioplasty or bypass * Afib management- hypertension management * Risk factor control (lipids, BP) * * Goals: prevent symptomalogyslow or stop cardiac remodeling, ARB&ACE- BP and fluid levels. B-blocker- rate control to decrease- rate issue CABBAGE (ischemic heart disease) or defibrilator * •Stage C- symptoms of heart failure SOB- pitting edema developing crackles or ralesin the bases in the lungs * make sure to get echo and measure how well it is functioning in order to guide your decision making * •Preserved ejection fraction- reduce symptoms improving overall patient quality of life, use diurheticfor extra fluid loop (keep an eye on the electrolyte) and thiazide * •Reduced ejection fraction- trying to keep patient from needing to go inpatient. DiurhesACEs ARBS, beta blocker, aldosterone antagonist. Stop the body from holding onto fluid or sodium and chloride. May need bypass graft or pacemakers. * •ACEior ARB plus BB * •Loop diuretics if there is volume overload (Class II-IV) * •For persistently symptomatic black patients (class III-IV): add hydralazine and isosorbide dinitrate * •Class II-IV with normal renal function, can consider adding an aldosterone agonist * •Stage D- HF not going away struggling to control , circulatory impairment (venous stasis and renal damage depending upon perfusion), need oxygenation, cardiology- need list for transplant, experimental, inotropic agents, may need to go onto hospice or pallativecare

Answer 22

* •Heart failure that has not responded to any of the Guideline-Driven Medical Therapy (GDMT) * •Only remaining options are: * •Procedures to drain excess fluid-dialysis,pericentesis, * •Continuous inotrope infusion * •Cardiac transplant * •Experimental therapies

Answer 23

BP indicates blood pressure; CI, contraindication; CO, cardiac output; F, fever; H, hepatic; HA, headache; HF, heart failure; HR, heart rate; LFT, liver function test; MAO-I, monoamine oxidase inhibitor; N, nausea; N/A, not applicable; N/R, not recommended; P, plasma; PDE, phosphodiesterase; PVR, pulmonary vascular resistance; R, renal; SVR, systemic vascular resistance; T, tachyarrhythmias; and t ½, elimination half-life.

Answer 24

A and B Plateau- calcium comes in, extend refractory to avoid tetany. 0- sodium runs into the cell quickly. 3- massive repolarization potassium Atrial- shorter SA/AV node- phase 0 calcium slower T type then L type. 4-cAMP sodium channel faster than the others rapidly depolarizing Everything has an intrinsic funny current: increasing depolarization from normal graual increase in sodium permeabiility due to intrinsic firing rate

Answer 25

Absolute refractory period- Inactivation gate shut Phase 3- relative refractory channel some of them are reconfigured w/ greater than normal force can fire off Supranormalperiod- -70 sodium cannels reconfigured activation gate ready, inactivation gate out of the way making it a vulnerability. When prolonging phase 3 prolong supranormalperiod and increased vulnerability being able to set up arrhythmia

Answer 26

Normal heart contains waves ofsynctiumwhere depolarization and repolarization occurs at the same time and in the same orientation. Ifthis synctiumis interupptedcan develop dysrhythmia ex. Automaticity in atria or reentry loop. Reentry loops- ex. Necrotic, MI, have differential activity going slower through these damaged tissue while everything goes around normal can come back around the reentry loop. class i drugs prevent by slowiing conduction or increasing refractory class III

Answer 27

drugs aim at blocking sodium or calcium to reduce ration of ions to potassium. decreasing slop of phase 4 and/or raises threshold of discharge to a less negative voltage decreasing frequency of discharge usually affecting misbehaving cells more than normal Atrial- beta blocker and calcium channel blocker. Trying to slow things across the AV node for adequate ventricular filling. Can form thrombi and need anticoagulants Must impact action potential using amiodaronewhen its down in the ventricle

Answer 28

MOA: binding to open/inactivated Na channel (use dependence) block abnormal firing not normal dont use for afib- can be ineffective and lead to 1:1 ventricular response rate and ventricular rate above 200bpm

Answer 29

* MOA: Class IA: slow phase 0 depolarization, affecting phases 1 and 3 (similar to class III activity). intermediate slow rate of association w/ sodium channels. Slow down phase 1 and phase 3 increasing refractory (K blockade as well) * Fx: prolong action potential and repolarization can increase risk of inducing arrhythmia ventricular fibrillation). Less popular because when play with action potential can develop longer supernormal period at phase three and can trigger off arrhythmia Torsades * Indicated for: WPW * **Procainamide**: IV for variety of arrhythmias (third-line choice) * Sx: Sodium channels can also affect tone of vessels triggering hypotension; lupus

Answer 30

* MOA: shorten Phase 3 repolarization decreasing during of action potential. rapid association/dissociation low affinity from NA channels. * Meds: * Lidocaine: IV treat ischemia induced ventricular arrhythmias (second-line choice) or use with amiodarone ( first line ) * Fx: . •Interfere with the active channels and inactive sodium channels benefiting, shortening active potential and decreasing refractory. •Does not impact conduction, and so not useful for AV junction arrhythmias * Sx: CNS toxicity, altered mentation with nystagmus, tremor, paresthesia, convulsions as a visible sign if dose high * Interactions: Impactedby cytochrome P450 (CYP) isoenzymesimpacted by P glycoprotein system make individuals more senstivefor some over others

Answer 31

* MOA: hold strongly to sodium channels slow dissociation from Na, slow phase 0 depolarization; . Also blocks K channels to prolong AP * Meds: * Flecainide: slows conduction in tissues; impacts threshold making it harder to achieve and be higher higher threshold decreasing automaticity, * •Propafenone: slows conduction, with some beta blocking effects, so can cause bronchospasm, * Indications: atrial (afib) and refractory ventricular arrhythmias for long-term without structural heart disease * Avoided in: people with LVHHFCAD * sx: blurred vision, dizziness, and Nausea * •Interactions: cytochrome P450 CYP issues for both; FDA-approved testing for CYP variations for propafenone metabolism; more with warnings about concurrent meds that affect the particular CYPs (propafenone also inhibits P-glycoprotein)

Answer 32

* MOA: impact SA, AV nodes; contractility. Diminish face for deep polarization and depressed automaticity, prolong AV conduction, and decreased heart rate and contractility. * Fx: For increased sympathetic activity arrhythmias; arrhythmias involving the AV node (stable a-fib, SVT); and post-MI ventricular arrhythmias (vtach); angina, Impact cardiac remodeling post-MI * •Metoprololas B1 selective, long term oral; given to stable a-fib and sinus tach, reduces the risk of bronchospasm * •Esmololas β1 selective, but very short-acting, so useful for IV administration in acute situations * Sx: bronchospasm not given to patients w/ COPD or asthma, or WPW and AVRT. Bradycardia and hypotension and fatigue

Answer 33

* MOA: prolong Phase 3: longer AP blocking potassium channels prolonging refractory period * Fx: Long-half life Beta block and affect AV node for atrial and supraventricular; Drug of choice for ventricular arrhythmias. •In effect, class I-IV-type functions (sloping of phase 1, plateau, * Meds: * •Amiodarone- has components of all four classes, treats pre-excitation AFib and those who are critically ill w/ it, severe refractory super ventricular and ventricular arrhythmias. Least pro arithmetic * •Dronedarone: shorter half-life than amiodarone, without the iodine can’t call center brain.. Less adverse affects items; second line to amiodarone. Sulfa group * •Sotalol: also with beta blocking effects (catecholamine), so can impact atrial and ventricular arrhythmias, particularly in those with CAD * Ibutilide- Conversion (atrial flutter), iv AVRT AND WPW * Sx: longer supranormal but also risk of arrhythmia. can impact thyroid function developing hypothyroid situations and bluish skin discoloration also affecting eyes nerves and liver * •Inhibitor to many CYPs and P-glycoprotein impact other meds

Answer 34

* Fx: non-dihydropyridine •Impact atrial arrhythmias with their AV nodal slowing calcium channel blockers. Decreasing the rate of pay is 40 polarization slowing AVN as a no currents * Indications: better for atrial arrhythmias, reentrant SVT and decreasing ventricular rate in a flutter and fib * Meds: * Verapamil (heart-vanilla- show up AV node being slowed down) and * Diltiazem(dual function heart and vessel) (the “not dihydropyridines”) * •Inhibitor to CYP (3A4) and P-glycoprotein

Answer 35

digoxin mag sulate adenosine ranolzaine

Answer 36

* •MOA: Necessary to transport sodium, calcium, and potassium across the membrane. bivalent cation nature helps to stabilize excitable membranes (involved in ATP synthesis impact sodium pump activity or ATPases can interact with phospholipids can stabilize membranes); * Fx: slows SA node and myocardial conduction time; first-line for torsadesde pointes

Answer 37

•Adenosine: natural nucleoside signaling agent; drug of choice to stop acute supraventricular tachycardia with short (10 second) activity to quickly slow AV nodal conduction. Decreases conduction velocity, prolongs refractory period and decreases automaticity. Flushing chest pain and hypertension

Answer 38

•Ranolazine: shortens phase III and hence AP; for refractory atrial and ventricular arrhythmias (as add-on agent). Inhibits the late sodium current improving oxygen supply and demand. Second anginal Dizziness and constipation

Answer 39

* Stable angina * Unstable angina * Prinzmetal, variant- can have nothing show up when evaluated for obstructive , vasospasticangina * (acute coronary syndrome as unstable angina, NSTEMI, or STEMI) * Decrease coronary work and increase coronary delivery * Stable angina- Smaller fixed lesion, only felt during exercise can get worse * Unstable angina- progression rapidly rupture of plaque more likely to trigger thrombus and stenosis * NSTEMI- initial insult endocardialtissue impacted compared to elsewhere ischemic on the inside, ischemic vector gives overall impression of ST depression * STEMI-transmuralSTEMI tombstone more dramatic appearance

Answer 40

B-blockers, calcium channel blockers both di and nondi, nitrates, and sodium channel blockers Beta blockers – decrease the oxygen Amanda, decreased heart rate, contractility, cardiac output, and blood pressure. Reducing frequency and severity of angina. Initial antianginal therapy in all patients unless vasospastic. Metoprolol. Should be avoided in severe bradycardia, given to patient with diabetes, PVD, and COPD Calcium channel blocker‘s gas protect by inhibiting entrance of extra calcium into cardiac and smooth muscle cells which would have depleted energy stores and worse in the ischemia. Arteriolar vasodilators decreasing vascular resistance which decreases oxygen consumption. Used in vasospastic angina due to this relaxation. Amlodipine/diltiazepam vasospastic angina. acute-acceleratingex. Esmolol chronic- control ex. metoprolol

Answer 41

* Treatment depends on presentation * Hemodynamically unstable patients: * §Inpatient management, IV BB (esmolol/quick turnaround-not on the list, propranolol, metoprolol(tartrate-(lopressor) short acting BB and succinate(toprolXL)-long acting)) or CCB (diltiazem, verapamil) * §If patient in shock or with severe hypotension (Poor perfusion, not awake, not appropriate oxygen), pulmonary edema, or ongoing MI/ischemia, if medication cant be transported to the heart to work cardioversion may be indicated * §Hemodynamically stable patients: symptoms but awake and moving * §Preferred strategy: rate control and anticoagulation * §Beta blocker or CCB first line- slow down nodal contraction for BB contraindications w/ anticoagulation * §In MI/Ischemia: Beta blockers (metoprolol if stable, esmolol if unstable not used in COPD pt.), preffered over calchannel blockers (diltiazem preferred over verapamil). * Maintenance management- need anticoagulation * For paroxysmal, persistent, or permanent AF: BB (diltiazem or verapamil) , CCB (nondyhydropidine), or sometimes digoxin * Acute AF w/out preexcitation: IV BB or nondyhydropidine CCB * Pre-excitation AF: not digosin, nondyhydropidine CCB, and amiodarone * §Monotherapy usually effective in older patients with limited physical exertion and higher likelihood of AV nodal dysfunction * §Combination therapy usually needed in younger patients or those more physically active. * §Hypertensive patients: BB (diltiazem or verapamil) or CCB * §CAD: Beta blocker don’t use CCB for this or CHF * §Heart failure: BB +/- Digoxin * §Severe COPD or Asthma: Avoid BBs; diltiazem or verampil * criiticall ill w/out pre-excitation or (normal w/ pre-excitation)- IV amiodarone

Answer 42

* ¡If no contraindications, can use Ibutilide (1st) flecanide, dofetalide, and propafenone for pharmacologic cardioversion * ¡If stable, Amiodarone or digoxin can be used for atrial fibrillation, but the comparatively slow onset of action makes it inappropriate for unstable patients * ¡Recurrent episodes of afib and flutter you should admit and make sure to watch them as you give them the meds because of the adverse affects. * §Oncesafety is established by administration under observation, patients may take (class III antiarrhythmics) propafenone or flecanide outside the hospital to terminate A fib or A flutter when they determine the episode * Dofetilidecan not be used outside the hospital * ¡Electrical synchronized cardioversion also can be effective * ¡Forprevention (unstable and not controlled by meds), ablation is preferred, but dofetilide (often given with an AV node blocker with the exception of verapamil-nondyhydropyride) or amiodarone (class III drugs) can be used until definitive treatment. * ¡Anticoagulation is needed for patients in sustained A Flutter

Answer 43

* ¡Sinus bradycardia, sick sinus syndrome: Implantable pacemaker. Heart rate lower than it should be should needing to place a pacemaker to get heart going where it should * ¡Sinus tachycardia: Treat underlying cause (hypotensive); if electrial- IV metoprolol to stabilize, oral metoprolol to maintain if symptomatic. * ¡Pre SVT: Vagal maneuvers first (bear down, cough hard), then adenosine, then verapamil, or maybe beta blockers. Prevention with BB or non-dihydropyridine CCBs. If not helpful, class Ic agents (propafenone, flecanide) * Amiodarone can be used in patients with no cardiac structural heart disease (post-MI, congenitol)and sotalol in those with structural heart disease * Atrial Tachycardia: If hemodynamically unstable, cardioversion immediately; if stable with symptoms, use oral or IV BB or CCB

Answer 44

* ¡AV Reentrant Tachycardia (AVRT), Wolff-Parkinson-White (WPW): * §Narrow-Complex (Orthodromic AVRT): similar to PVST * §Vagal maneuvers, IV adenosine, verapamil * §Wide-complex (Antidromic AVRT or A fib with antegrade conduction down the bypass tract (bypass fast but still screwing around w/ the AV node)): * §Avoid BB and CCB due to high likelihood of increased risk of V fib (block the AV node, but not the accessory pathway, meaning the ventricular response rate will be very high because the blockade will not be able to work on the other track * §Bypass tract- IV procainamide and ibutilideare preferred * §Cardioversion,valsalva, carotid massage, adenosine. If asymptomatic or mildly symptomatic, vagal maneuvers first, then adenosine, then non-dihydropyridine CCB (verapamil) or BB IV.

Answer 45

* ¡Ventricular Tachycardia * §Ideally synchronized external cardioversion * §If wide-complex tachycardia, consider IV administration of class I or III antiarrhythmic drugs (amiodarone, lidocaine, procainamide) * §For maintenance, cardiologist can consider using BB or CCB * ¡Polymorphic V-Tach with normal QT interval * §Unstable rhythm – Defibrillate! * §Isoproterenol can be used in increase heart rate if bradycardia is causing the V-Tach * §True-v-tach: Beta blockers, possibly amiodarone if defibrillation ineffective, candidate for pacemaker * ¡Torsadesde Pointes: * §Polymorphic V-Tach with prolonged QT interval * §Defibrillate! If hemodynamicallyunstable * §Magnesium can both treat and suppress Torsadesde Pointes.

Answer 46

there is an additive risk to drive lipid-lowering choices also controlling BP and sugar

Answer 47

* Drive a lot of our decision making (high and moderate intensity) * Add onshelp w/ lipid profile but not mortality * Backing off if older or have bad disease * glucose- increases arthroscleroticprocesses either * High risk of CAD in next 10 years- moderate

Answer 48

* MOA: inhibit HMG coAreductase early stage to making cholesterol. with not much cholesterol increase LDL recpetorsleading to increases LCL uptake from the blood and w/ the cleansing of the blood stream less LDL circulating, clearing the LDL not making LDL in the first place. indirectly decreasing inflammation * Timeline Days-years: Lower LDL-C, endothelial function restored, inflammation reduced of endothelial cells , ischemic episodes reduced, vulnerable plaques stabilized, and cardiac events reduced * Adverse effects: liver failure (LFT), myopathy (chicken wing). teratogenic * •Statin impacts on liver enzymes increasing them, (HMC CoA) affecting other liver issues requiring liver monitoring * •The loss of the cholesterol (necessary for cell membrane) and mevalonyl precursors (sarcolemma-plasma of skeletal muscle) can occasionally generate muscle issues may generate myopathy complaining of muscle pain especially when taking niacin, need to measure creatinine * •New study: did not recognize formal pattern of congenital abnormalities, but until consensus, pregnancy contraindication remains (similar to Beta blocker discussion) not a consistent genital abnormality that appears, * increases the effect of warfarin

Answer 49

Lower plasma cholesterol levels via synthesis inhibition and internalizing circulating LDL-C (cholesterol); note how atorvastatin and rosuvastatin have higher maximal LDL lowering, so can be used in high-intensity situations (improve endothelial function, plaque stabilization, anti-inflammatory effects)

Answer 50

* statins- greatly decrease LDL, mily increase HDL and mildly decrease triglycerides * Niacin- Greatly increases HDL, decrease triglyceride, mildly decrease LDL * •Bile sequestrants- decrease LDL, barely increase HDL and decrease triglycerides * •Fibrates- greatll decrease triglycerides, mildly increase HDL * Antibodies-greatly drop LDL more, as an add on to max out someone on statin therapy; mildly increase HDL

Answer 51

* MOA: inhibits lipolysis in adipose tissue reducing production of free fatty acids. a precursor for triglyceride synthesis * Fx: •Preferentially impact triglyceride activities that are coming out of adipose cells supply it and impacting production of triglyceride going into LDL. Lessening LDL and upgrade and picture of HDL. Decreases hepatic production of TryGlyceride, VLDL and apo B (receptor on liver for VLDL), with indirect triggering of increased HDL levels by decreasing its liver degradation * Use: •Used in combination with other meds, but has not shown increased benefit over statins * Vitamin B3, NAD (nicotinamide adenine dinucleotide) precursor * •Adverse effects: * –flushing from prostaglandin and itching- reduced by aspirin * decreases levels of secretion of uric acid –hyperuricemia and gout * –hepatotoxicity * hyperglycemia

Answer 52

* MOA: PPARs proliferator-activated receptors when Binding to fatty acids or eicosanoids and fibrates becoming activated when activated, and bind to peroxisome that breakdown lipid organelles. decreasing tryglyceride concentration through increase expression of lipoprotein lipase, and increasing apoplipoproteins (which increases HDL) enhancing breakdown oftriglycerides leaving cholesterol behind. * Indictation: hypertriglyceridemias. * Adverse effects: GI disturbances, including increased gallstone risk from cholesterol bile excretion (altering lipid circulation sending out more for excretion) * DO NOT USE IN RENAL FAILURE-as excreted as a glucuronideconjugate-phase 2 reaction for liphophilizingdrug

Answer 53

* MOA: •Prevent bile acid reabsorption by binding bile acids in intestine leading to excretion w/ less recycled bile salt material, forcing the liver to not synthesize cholesterol for LDL but instead bile (•Promote conversion of cholesterol to bile acids/salts in hepatocytes). this then leads Hepatocytes upregulate LDL receptors. * Promoting efficacy: •Compensatory response can limit efficacy; Combination therapy with statins can increase efficacy * Adverse affects * •GI side effects including constipation and nuasea. including impairment of absorption of fat-soluble vitamins * •Decreased efficacy of other drugs given that liver overdoing trying to make cholesterol, * •Enterohepaticrecirculation- bile is not chemically taken up when involving w/ fat but acting as emulsification agent to make them smaller (allowing pancreatic lipases to break it down) * –Steatorhea, fat soluble items not reabsorbed

Answer 54

* MOA: blockade of•cholesterol transporter and is an absorption inhibitor in the small itnestine decreasing dlivery of it to the liver via chylomicrons . decreasing liver stores and increase clearance of it from the blood. * adverse effects: •Adjunctive use, with some liver and gut issues (and the same renal excretion caution as fibrates)

Answer 55

* MOA: •PCSK9 (proprotein convertase subtilisinkexintype 9) binds to LDL receptors and degrades them, so that PCSK9 inhibitors will allow for more liver uptake of LDL-C. breaks down receptors. If you leave more receptors out there develop more endocytosis take up more LDL getting it out of circulation * Indications: •For those maxed on statins * Meds: similar outcomes * alirocumab * evolocumab * Delivery: given via injections of •Monoclonal antibodies every 2-4 weeks w/ expensive agents w/ injection * •Sx: SQ injection of these monoclonal antibodies, with possible allergic or injection site responses

Answer 56

* MOA: Polyunsaturated fatty acids at higher doses (4 gram level) will inhibit VLDL and TriGlyceride liver synthesis, •w/ high enough dose and chronic diet, fatty acid become incorporated into cells moderating cellular features: cell membrane lipids and subsequent membrane protein-mediated responses and lipid-mediator interactions. Think of them competing for enzyme spotsas for arachidonic acid andinflammationpathways, or for **TG** synthesis enzymes (competitive antagonism). As a result, triglycerides can be lowered by 25%, although clinical impact data do not necessarily show a benefit. * Examples: Particular ones of interest from marine fish are EPA: eicosapentaenoicacid and DHA: docosahexaenoic acid. * Adverse effects: •GI effects, fishy taste (from consumption of the fish oil pills), and possible bleeding risks for those on anticoagulation.v

Answer 57

* •Primary prevention- preventing a disease from happening. * •Individuals without diabetes with LDL-C of 70-189 mg/dL * •Use pooled cohort equations to estimate 10-year ASCVD risk and plug into Non-ASCVD risk algorithm (Slides 3 and 5) * Adults ≥ 21 y.o. with LDL-C ≥ 190 mg/dL * •Treat all patients in this group with high-intensity statin unless contraindicated * •Goal of 50% LDL-C reduction, if LDL responds HDL crappy can add * •Additional therapy can be added with non-statin medication if goal not reached on maximal statin monotherapy * Diabetes: * Moderate-Intensity statin should be initiated or continued at the time of DM diagnosis regardless of lipid levels * If 10-year risk of ASCVD risk is ≥ 7.5%, high-intensity statin therapy advised * If patient \< 40 y.o., \> 75 y.o., or LDL-C \<70 mg/dL, provider should present risk-benefit profile to patient and statin therapy can be a patient decision * Once conversation happened put down risks and benefits in writing * •Secondary prevention- early identification of disease through things like screening. * High-intensity statin therapy first-line in all patients ≤75 y.o. with clinical ASCVD unless contraindicated * If high-intensity not tolerated or contraindicated, use moderate-intensity therapy in addition to conjunctive agents * Risk-benefit analysis and patient preference should guide decision making in patients \>75 y.o. * •Tertiary- there and our main goal is to try and stop or slow the progression of the disease and complications that arise thereafter * •Do they have any confirmed atherosclerotic disease if not don’t unless have high LDL \>190- starting them on high intensity statins. * •LDL \<190 but if diabetic intermediate statin w/ 10 year risk bumped to high intensity * •LDL and diabetic go together a lot * •Normal \< 130; if other risk factors number drops down lower * •HDL- \>40 * •Requiring liver capability in order to take it * •Lipids don’t necessarily indicate atherosclerotic disease they are a marker and risk factor but doesn’t indicate

Answer 58

see picture * •LDL-C: Does not exist- want to get it down 70-90 w/ concominantcardiovascular disease but below 130 * •Non-LDL-C: Does not exist * •HDL: No specific goal, but higher is considered better to a certain point level of all cause mortality increases once HDL passes 80mg/dL. * •Goals are to treat based on risks

Answer 59

* 1) Prostacyclin secreted by intact healthy endothelium and increased cAMP keeps platelet inactivated (low calcium). Stabilizing platelets and inhibiting release of granules * 2) injury-1b-vonwildebrandfactor exposed when damage endothelial cells. Platelet-grab on site of injury, other platelets, and fibrin net having a * 3) variety of proteins released in response to decreased cAMP causing calcium release including ADP, serotonin, thromboxane, and PAF, which lead to calcium increase in the cell and granule release; (Release calcium into cytoplasm or cell fragment developing variety of events ex. Exocytosis of granule, ADP spewed, thrombin activated) and enhance expresssion of glycoprotein IB and II to form hemostasis plug recruting more platelets on the surface * stimulation of platelet by ADP, thrombin, and collagen results in activation of phospholipases liverating (**Arachachothronicacid**- Thromboxina2 potent stimulator of platelet) from phospholipid converted to prostaglandin by COX-1 then thomboxane. (aggregation progress0 * 4) fGlycoprotein/fibrinogen holds onto two sepearate platelet cross-linking and leading to platelet aggregation. tissue factors lead to formation of prothrombin to thrombin which converts fibrinogen to fibrin forming plug * 5) plasminogen deactivates the clotsand dissolves fibrin network as it heals

Answer 60

* MOA: inhibits thromboxane A2 synthesis by irreversibly binding and inhibitting COX-1 inactivating it. Facoring antiaggregraotry effects of pratacyclin preventing platelet aggregation irreversibility inhibiting platelet function. * Indications: cerebral ischemia, MI (primary and secondary) * Adverse effects: hemorrhagic stroke, GI bleeding Aspirin shutting down prostaglandin nonsteroidaldrugs impact prostaglandin formation lessening blood flow through kidneys leading to varieties of toxicities

Answer 61

* Aspirin- Shutting down cyclooxegenaseirreversible shutting down inflammation * Reye syndrome- hepatic encephalitic syndrome viral cannot take it * Stephenjohnsonsyndrome. Interaction w/ antiviral * Other drugs: Shutting down ADP and longer term inactivation of the platelets * DP- signaling diphosphate strategy to interfere. Interfere w/ receptor activity acting on ADP ex. Anti-platelyagents

Answer 62

Platelet * No nucleus * No protein synthesis * Forms thromboxane A2 * Aspirin inhibits COX-1 permanently * Platelet must be replaced Endothelial * Nucleated * Active protein synthesis * Forms prostacyclin A2 * Aspirin inhibits COX-2 non-competitively * Enzyme re-synthesis after ~6 h

Answer 63

* MOA: inhibit binding of ADP to P2Y12 on platelets inhibitting activation of glycoprotein * Use: is more efficacious than aspirin, for acute coronary syndrome (ACS), post-PCI (percutaneous coronary intervention) post-MI, post-stroke, * Meds: • * Clopidogrel: Prevent atherosclerotic events in patients w/ recent MI or stroke or w/ peripheral artery disease, and percutaneous coronary intervention. maximum inhibtion of platelet aggregation: 3-5 day. * Prasugrel: decrease thrombotic cardiovascular events in patients w/ ACS (unstable angina, nonstemi, stemi, MI) maximum inhibtion of platelet aggregation: 2-4 hours * Ticagrelor: reversible, arterial thromboembolism (PCI or MI and unstable angina) . maximum inhibittion of platelet aggregation in 1-3 hours the binding at the receptor is not permanent, and so is taken with ASA (up to a point) * Adverse effects: •More serious/frequent bleeding * •No effect on prostaglandin metabolism, therefore no change in vasoconstriction

Answer 64

* MOA: Inhibiting phosphodiasterase increasing intracellular levels of cAMp decreasing calcium and thromboxane synthhesis decrease platelet adhesion to thrombogenic surfaces. producing vasodilation * Use: stroke prevention in conjunction w/ asprinin dont use for unstable angina (because of vasodilator) * •Note the dual action, so that there is not only platelet aggregation inhibition by decreasing thromboxane A2 synthesis, there is also vasodilating. * adverse affects- headache and dizziness lead to orthostatic hypotension

Answer 65

* Intrinsic pathway- inside the vessel * Factor 12\>11\>9\>10 * •aPTTevaluation of intrinsic pathway * •Heparin- interact w/ antithrombin3 in intrinsic pathway modified by the PTT. (protein C, protein S, and antithrombin III) * higher number of agents to stabilize and form clot * Extrinsic Pathway * Factor 7\>10 * •Factor 7 major interacting as it is released from damaged endothelial (von wildebrandfactor)• * PT evaluation of extrinsic pathway * •Warfarin- impact synthesis of 7 and 10 and modify keeping track w/ prothrombin tyime * 10\>2 (prothrombin) to thrombin leading fibrinogen to fibrin * •Factor 10- from both intrinsic and extrinsic more from the 7 side * •Coagulation factors- circulating activated factors work on the next step

Answer 66

* MOA: Allosterically interact w/ antithrombin III to enhance counterregulatory to shut down coagulation cascade (factor II and 10). accelerates binding of anti-thrombin inhibitting thrombin by 1000X. * Fx: •Heparins: prevent fibrin formation, lessen thrombi, as in PE. interfere w/ the formation of thrombi, surgery and acute MI, Can be used in pregnancy not crossing placenta * Kinds: Heparin very large; low molecular weight heparin about 1/3 the size. Sulfatedmucopolysaccharides, with a wide range of molecular weights (bioavailability make it difficult); use IV or SQ, as does not cross cell membranes. * LMWH: Less monitoring for LMWH (contraindicated in renal disease w/ bioaccumulation. * **•Reversible: with protamine** (positive charges-large molecule interacting w/ negatively charged sulfide groups neutralizing heparin so not interacting w/ thrombin 3 * Adverse affection: Concerns with bleeding, and HIT (heparin-induced thrombocytopenia-type II more common fractioned heparin, as well as hypersensitivity, heparin as a haptenfor platelet factor 4 generating autoantibody against); Long-term use can trigger **osteoporosis** (osteoclast stimulation)

Answer 67

* •MOA: inhibiting factor Xadirectly, selectively binds to antithrombin III. * Use: Similar indications as to heparin, but less risk of HIT and less monitoring. * Adverse affects: With renal excretion, not for patients with renal impairment. bleeding w/ no reversal,

Answer 68

* •MOA: parenteral anticoagulatants. reversibility inhibic site of free and clot-bound thrombin. * Use: in those w/ PCI, those at risk for HIT (heparin), unstable angina with angioplasty * adverse: bleeding

Answer 69

* MOA: Warfarn produces clotting factors w/ diminshed activity. slowly after drug administration. 72-96 hours. INvolving factors 2, 7, 9, and 10, which are all made from vitamin K. •Prevent prothrombin 7 (kicks off 10), 10 gets everything going * reversal w/ vitamin K after 24 hours and fresh frozen plasma * Use: DVT, PE, stroke in afib, prostethic heart valves; VTE prevention following orthopedic surgery; mechanicalaorticvalve; rheumatic mitral valve disease; following stent placement; atrial fib/flutter; elective cardioversion; mitral stenosis; active cancer and PE * Adverse effects: bleeding; teratogenic * Monitoring: Warfarin needs monitoring as items such as concurrent medications, diet, genetics (CYP status, especially for CYP2C9) can all impact on its function for a given individual. Monitor by INR (international normalized ratio; PT) prothrombin time of 2-3 times normal. How to dose warfarin individualized to target INR * •Remember delayed onset (lag time) – need to bridge of dosing change and INR. 2 days to change, 1 week for it to stabilize making small doses to adapt * •INRGoals:▫2-3 (twice as long in time to clot) * Mechanical mitral valve: 2.5-3.5 * Advantages: * ▫Cheap * ▫Oral * ▫Keep track of INR keeping dose if something else changes have to keep truck of INR * ▫Long half-life (missed dose little hiccup) * •Disadvantages: * ▫Monitoring * ▫Drug Interactions * ▫Food Interactions (consistent diet of greens and its okay, but random leafy greens INR will exhibit due to vitamin K) * ▫Long half-life- for surgery lovenoxbridge (low molecular weight bridge a week before surgery taking off of coumadin). If trauma plasma and vitamin K to reverse * Ex. Traveling patients not a good idea changing

Answer 70

* NOACs: the novel oral anticoagulants (-xaban) * MOA: only targettingactivated factor 10 * Use: •All useful for stroke prevention in patients with nonvalvular atrial fibrillation; prophylaxid treatment of DVT and PE * Adverse effects: Premature discontinuation increases risk of thromboembolic event. Allergy, active pathologic bleeding, mechanical heart valves or TVR. CYP and P-glycoprotein impacts, as well as renal excretion * Idarucimub reversal for dabigatran * Meds: * Dabigatran: direct thrombin inhibitor affecting both (clotted and free); metabolized by esterases thrombin activated and clumped into somewhere. * •Apixaban: targets factor Xa reducing production of thrombin from prothrombin no reversal * •Rivaroxaban: targets factor Xa, shorter half-life * •Advantages: * ▫No monitoring * ▫Short half-life (in case of emergency) * •Disadvantages * ▫Short half life (requires diligence with dosing to maintain antithrombotic effect) * ▫Not all meds have reversal agents, though the most common do

Answer 71

* •(tPA): short half-life with targeting of bound plasminogen-alteplase. tenecteplase- longer-half life and greater bdinging affinity but isnt selective in its targets of thrombolytics. * •MOA: Targets plasminogen and breaks down fibrin and hemostasis plugs lysing thrombi * Use: DVT, PE, MI restoring catheter and shunt function, and strokes. * •Window of usefulness: think of stroke protocol window in 1-3 hr range (up to 4.5 hrsin selected pts) or 12 hr window for acute MI. Windows of use in MI before risk of bleeding outweightbenefit of breaking the clot * •adverse affects: Alteplasecan trigger angioedema, as well as the bleeding demonstrated aka gastric ulcer and w/ any head traumas

Answer 72

* •Tranexamic acid: inhibit plasminogen activation; more potent; counterregaltorything and clot stays in place, natural bleeding; can create thrombosis * •Idarucizumab:antibody to reverse dabagatran. Novel oral anticoagulatint, expensive, IV * •Protamine: lots of (+) charge to interact vs. heparin; creating dyspnea, flushing, bradycardia, and hypotension * •Vitamin K: for warfarin resupplying the ingredient vs. FFP (warfarin). 24 hours vs. * (Andexanetalfa as an expensive biological F Xadecoy for apixaban and rivoroxaban, approved by FDA in 2018) detect the meds that bind. * FactprXadrugs like this need BID dosing.

Answer 73

* •Initiate anticoagulation immediately upon diagnosis to prevent complications * ▫Injectable (fondaparinux) or oral (apixaban, rivaroxaban) Factor Xainhibitors –OR – * Low molecular weight heparin (enoxaparin) – OR * ▫Unfractionated heparin * •Long-term anticoagulation usually carried out with oral Factor Xaor direct thrombin inhibitors or with warfarin * •Anticoagulation should last for 3-6 months unless this is a recurrent problem or permanent physiology in which case it would last longer (potentially lifelong) VTE Prohylaxis postoperatively: * •Very low risk: Early and frequent ambulation * •Low risk or patients with contraindications to pharmacologic therapy: Mechanical-compression devices because of lying down to reduce clots * •Moderate to high risk: Pharmacologic therapy * •Very high risk: Mechanical and pharmacologic PE- No longer treated with fibrinolysis unless: * Persistent hypotension or shock0 you must break it break it * Severe or worsening right ventricular dysfunction ("submassivePE") * Cardiopulmonary arrest due to PE * Extensive clot burden (eg, large perfusion defects on ventilation/perfusion [V:Q] scan or extensive embolic burden on computed tomography) * Free-floating right atrial or ventricular thrombus * •DVT- Very rarely treated * Systemic thrombolyticsare associated with decreased risk of post-thrombotic syndrome, increased risk of bleeding complications, and increased rate of complete clot lysis * Only widely-accepted indication is for extensive ilio-femoral thrombosis with associated severely symptomatic limb swelling or limb-threatening ischemia

Answer 74

Pharmacological agents postoperatively * •LMWH and injectiblefactor Xainhibitor for high-risk surgical patients (such as TKA, THA) * •Low-Dose heparin: used with contraindication to LMWH (i.e. renal disease) * •Warfarin used in a delayed setting unless bridging with enoxaparin carried out for immediate anticoagulation * •ASA for orthopatients (THA, TKA) ineligible for other anticoagulation * •Direct thrombin inhibitor, factor Xainhibitors not well studied, but rivaroxaban(following after knee and hip replacement) indicated following THA/TKA

Answer 75

* •Used in acute MI or CVA (ischemic stroke) * •Must be administered within a certain window * ▫Most effective when within 3 hours of CVA, but can be given up to 4.5 hours of onset of symptoms of embolic (non-hemorrhagic)stroke (Per CMDT 2019) * Alteplase * * ▫Within 12 hours of acute MI at which point there is a 10% reduction in mortality (some guidelines say 24, but use 12 as the accepted value at this time). * Best results within 3 hours (per CMDT 2019) * Catheterization is preferred * Tenecteplace, Alteplace, Reteplace

Answer 76

use NOAC or warfarin * •Atrial fibrillation * •**Prosthetic heart valves/signififanct mitral stenosis should be given warfarin** * •History or risk of stroke, TIA, or MI * •Recent surgery * •Prolonged immobilization * •Peripheral arterial disease * •AcuteVTE (ventousthromboembolism- DVT * •Clotting disorders, including: * ▫Protein S deficiency * ▫Protein C deficiency * ▫Antiphospholipidsyndrome * Risk factors: * age- asyou get older bleed more \>65 or 75. wont have vasopressiveresponse * previous bleeding (ex. Stroke) * cancer- because of hypo and hypercoagulability * renal and liver failure (at risk for developing more bleeding no factors) * thrombocytopenia/anemia * antiplatelet therapy * poor anticoagulant control * comorbidity and reduced functional capacity * recent surgery * frequent fall * alcohol abuse