Cardiology Flashcards

Question

Digoxin: -Brand -MOA -ROA -Therapeutic Range -Dosing

Answer 1

Brand: Digitek, Lanoxin MOA: inhibits Na-K-ATPase pump, causing positive inotrope effects (increase contraction) and exerting parasympathetic effects that enhance vagal tone to slow conduction through AV node (negative chronotropy - decrease HR) ROA: PO or injection Therapeutic Range: 0.8-2 ng/mL (NTI drug) -Lower range used for HF Dosing: -Typically: 0.125-0.25mg PO QD -CrCl <60mL/min: decrease dose or frequency (hold in acute renal failure) -Decrease dose by 20-25% when converting from PO to IV -With amiodarone or dronedarone, decrease dose by 50%

Answer 2

TX: used in combination usually w/ beta-blocker or non-DHP for rate control S/Sx of Toxicity: -Initial Symptoms: N/V, LOSS OF APPETITE, BRADYCARDIA (ENCOURAGE PT TO MONITOR THEIR OWN HR) -Severe Symptoms: abdominal pain, BLURRED/DOUBLE VISION, GREENISH-YELLOWISH HALOS (or altered color percepton), confusion, delirium, LIFE-THREATENING ARRHYTHMIAS -Increased risk with: hypokalemia, hypomagnesemia, hypercalcemia, hypothyroidism -AVOID dehydration which can increase risk of toxicity

Answer 3

Reversal agent: DigiFab Monitoring: electrolytes, renal function (about 85% renally cleared), HR, ECG, BP, digoxin levels (drawn 12-24 hours after dose) DDIs: substate of P-gp and CYP3A4 (minor) -Higher levels w/: AMIODARONE, dronedarone, NON-DHP CCBS, clarithromycin, itraconazole, etc. -Additive effects on decreased HR w/: amidarone, non-DHP CCBs, beta-blockers, clonidine, dexmedtomidine

Answer 4

Pre-AF: exidence of structural or electrical findings that predispose a pt to AF (ex. atrial flutter) AF: -Paroxysmal: intermittent AF taht terminates within 7 days of onset -Persisent: continuous AF sustained for >7 days -Long-standing persisent: AF substainted for >12 months Permanent AF: NO further attempts at rhythm control

Answer 5

Rate Control: typically MORE benefit than rhythm control --> pt will remain in AF and takes medications to control ventricular rate (HR) -Goal resting HR: <80 bpm in symptomatic AFib; <110 bpm in asymptomatic and reserved left ventricular function -Medications Used: beta-blockers, non-DHP CCBs, sometimes digoxin -HFrEF: avoid non-DHP CCBs Rhythm Control: goal to restore and maintain normal sinus rhythm (avoid in permanent AFib) -Electrical cardioversion can be used which is typically most effective -Medication used: class Ia, Ic, or III antiarrhythmics BOTH: stroke prophylaxis

Answer 6

Cholesterol role: structural component of cell wall, precursor in hormone synthesis, and to produce bile acids -Elminated in body as either free cholesterol or bile acids Bile acids role: needed to absorb lipids and fat-soluble vitamins -Made in liver --> bile ducts --> small intestine --> converted to bile salts and returned to liver Atherosclerosis: elevated cholesterol can form plaque on inner walls of arteries; asymptomatic, but can lead to atherosclerotic cardiovascular disease (ASCVD) including MI, stroke/TIA, stable angina, and peripheral arterial disease

Answer 7

Total cholesterol (TC): low-density lipoprotein (LDL) + high-density lipoprotein (HDL) + very-low density lipoprotein (VLDL) HDL: "good cholesterol" that takes cholesterol from the blood and delivers it to liver for removal; >/=40 (men) or >/=50 (women) Non-HDL: LDL + VLDL + lipoproteins (calculation: non-HDL = TC - HDL); <130 (desirable) -VLDL: carries TGs LDL: <100 (desirable), <70 (high risk pt goal), >/=190 (very high) -LDL = TC - HDL - (TG/5) --> cannot use if TG >400mg/dL Trigylcerides (TG): <150 (desirable), >/=500 (very high, more likelihood of pancreatitis)

Answer 8

1. 1% 2. Calculation for primary prevention -Pt: sex, age (20-79 yo), race, smoking status -Labs: TC, HDL, LDL, BP -PMH/TX hx: DM, aspirin use, anti-hypertensive use **Assess Q4-6 years if low risk 3. *Clinical ASCVD, DM, or LDL >/=190 4. Family hx of premature ASCVD, metabolic syndrome, CKD, hx of preclampsia or preamature menopause, chronic inflammatory disorders, high CRP, high coronary artery calcium score (CAC), and abnormal ankle brachial index -ASCVD risk of 7.5-19.9% and CAC score >/=100: statin is indicated*

Answer 9

*LDL and TG: diuretics, efavirenz, immunosuppressants (ex. cyclosporine, tacrolimus), atypical antipsychotics, protease inhibitors, steroids LDL: fibrates, fish oils (except Vascepa), SGLT2is, TZDs TG: IV lipid emulsions, propfol, clevidipine, bile acid sequestrants (5%), alcohol* Conditions: obesity, por diet, alcohol use disorder, hypothyroidism, smoking, DM, renal/liver disease, nephrotic syndrome -Familial (primary dyslipidemia): inherited, severe elevations

Answer 10

Non-pharm: -Diet: rich in vegetables, fruits, whole grains, and high-fiber; healthy protein sources (low-fat dairy, poultry, fish, nuts) -Limit intake of saturated fat, trans fat, sweets, sugar-sweetened beverages, and red meat -Aerobic physical activity 3-4 times/week lasting 40 minutes/session -Tobacco cessation and reduce alcohol intake Natural Products: -Can lower LDL: red yeast rices (contains naturally occurring HMG-CoA reductase inhibitors - NOT recommended since not regulated like drugs. may get variable amount), plant stanols, sterols and fibrous foods (psyllium, barley, and oat bran) -Can lower TG: OTC fish oils -Garlic: NOT considered effective for dyslipidemia

Answer 11

Clinical ASCVD (CHD, stroke/TIA, or PAD): high intensity Primary severe dyslipidemia (LDL >/=190): high intensity DM and age 40-75 yo + multiple ASCVD risk factors: high intensity DM and age 40-75 yo + any ASCVD risk: moderate intensity Age 40-75 yo with LDL 70-189 + ASCVD risk of >/=20%: high intensity Age 40-75 yo with LDL 70-189 + AASCVD risk of 7.5-19.9% + risk factors: moderate intensity

Answer 12

1. 50%; 30-49%; 30% 2. -High intensity: atorvastatin 40-80mg, rosuvastatin 20-40mg -Moderate intensity: atorvastatin 10-20mg, rosuvastatin 5-10mg, simvastatin 20-40mg, pravstatin 40-80mg, lovastatin 40mg, fluvastatin 40mg BID or 80mg XL, pitavastatin 1-4mg -Low intensity: simvastatin 10mg, pravastatin 10-20mg, lovastatin 20mg, fluvastatin 20-40mg 3. Equivalent dosing: "Pharmacists Rock at Saving Lives and Preventing Fatty Deposits" Pitavstatin 2mg = Rosuvastatin 5mg = Atorvastatin 10mg = Simvastatin 20mg = Lovastatin 40mg = Pravastatin 40mg = Fluvastatin 80mg -Pitavastatin: most potent on mg basis -Rosuvastatin: most potent agent to lower LDL (less dose than atorvastatin) 4. -Reduce dose when CrCl <30mL/min except Lipitor -CrCl <60mL/min: reduce Livalo dose (pitavastatin)

Answer 13

Muscle damage (soreness, tiredness, or weakness that is SYMMETRICAL in LARGE muscle groups in legs, back, or arms) usually within 6 weeks of TX -Myalgia: muscle soreness, tenderness -Myopathy: muscle weakness +/- CPK elevations -Myositis: muscle inflammation -Rhabdomyolysis: severe CPK (>10,000 IU/L) with myoglobinuria (muscle in urine) that can lead to acute renal failure Management: -Reduce risk: avoid DDIs (including OTCs), do NOT use simvastatin 80mg/day, and do NOT use gemfibrozil with a statin -Myalgia occurance: hold statin, check CPK, and investigate other causes; after 2-4 weeks, re-challenge w/ same statin at same or lowered dose (most tolerate) -Non-statin if pt unable to tolerate re-challenge -Coenzyme Q10 may provide benefit for mild muscle symptoms (sometimes people try vitamin D - not harmful, but may not benefit) "HMG" CoA reductase: -H: Hepatotoxicity -M: Myalgia, Myositis -G: Glucose changes

Answer 14

G = Grapefruit, P = PIs, A =Azole Antifungals, C =cyclosporine/cobicistat, M= macrolides (except azithromycin), A = Amiodarone, N = Non-DHP CCBs G-M: -do NOT use with simvastatin or lovastatin -Cyclosporine only: rosuvastatin 5mg/day -Cobicistat only: atorvastatin: 20mg/day Amiodarone: simvastatin 20mg/day or lovastatin 40mg/day Non-DHP CCBs: simvastatin 10mg/day or lovastatin 20mg/day **In general, lovastatin and simvastatin are major CYP3A4 substrates followed then by atorvastatin.

Answer 15

Drugs: atorvastatin (Lipitor), lovastatin (Altoprev), pravastatin (Pravachol), rosuvastatin (Crestor), simvastatin (Zocor), fluvastatin, pitavastatin MOA: inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, preventing conversion of HMG-CoA to mevalonate (rate-limiting step in cholesterol synthesis) ROA: PO Administration: -Take in evening: fluvastatin, lovastatin (w/ evening meal), simvastatin --> cholesterol production more at night (shorter T1/2) -Take any time due to longer T1/2: atorvastatin, rosuvastatin, pitavastatin, Lescol XL (fluvastatin), pravastatin Effects: -LDL: decrease by 20-55% -HDL: increase by 5-15% -TG: decrease by 10-30%

Answer 16

Warnings: -*Muscle damage: myopathy/rhabdomyolsis and elevated CPK w/ acute renal failure (higher risk in higher doses, advanced age, concurrent use of naicin/gemfibrozil, uncontrolled hypothyroidism, renal impairment) -Do NOT use in pregnancy (consider if at high risk for CV events)* -DM: increases A1c/FBG, BUT benefit of statin outweighs risk -Hepatoxicity with increased LFTs (rare) -Rosuvastatin: proteinuria, hematuria (usually transient) -Atorvastatin: hemorrhagic stroke (if recent stroke or TIA) --> benefit outweighs risk CI: *breastfeeding, liver disease (including unexplained LFT increase), concurrent use of strong CYP3A4 inhibitors with simvastatin and lovastastin*, concurrent use of cyclosporine with pitavastatin *Monitoring:* -Lipid panel: baseline, 4-12 weeks after start or adjustment, then 3-12 months (usually annually) -LFTs at baseline and then if symptoms of hepatotoxicity (jaundice, abdominla pain) -Myalgia, myopathy, rhabdomylosis: check CPK if symptoms of muscle damage and SCr/BUN if decreased urine output

Answer 17

Brand: *Zetia* (+simvastatin = Vytorin, +bempedoic acid = Nexlizet) MOA: *inhibits absorption of cholesterol in small intestine* ROA: PO TX: in addition to moderate-intensity statin in stable pt that are at risk for CV events (IMPROVE-IT study) Effects: lowers *LDL by 18-23%* and TG by 5-10%; increases HDL by 1-3% AVEs: *myalgia*, arthralgia, pain in extremeties, diarrhea, URTIs, sinusitis Warnings: *avoid in moderate/severe hepatic impairment*, skeletal muscle effects when combined with statin, unknown risks to fetus, NOT recommended in breastfeeding Monitoring: *LFTS at baseline and as clinically indicated therafter* DDIs: -Increases levels of cyclosporine -Concurrent bile acid sequestrans decrease ezetimibe: take ezetimibe 2 hours before or 4 hours after -*Concurrent gemfibrozil: increased risk of cholethiasis*

Answer 18

Drugs: *alirocumab (Praluent), evolocumab (Repatha)* MOA: *PCSK9 is an enzyme that increase LDL receptor degradation; PSCK9is block ability of PSCK9 to bind to LDL receptors that degrade LDL* ROA: *SQ injection* Administration considerations: -Store in fridge, can be kept at room temperature for up to 30 days -Allow prefilled pen to warm to room temperature (about 30-45 minutes for Pushtronex - evolocumab) and inspect for particulate matter and discoloration TX: clinical ASCVD, heterozygous familial hypercholesterolemia (Praluent), homozgous familial hypercholesteremia (Repatha), primary hyperlipidemia Effects: lowers *LDL by about 60%*, non-HDL by 35%, apoB by 50%, and TC by 36% AVEs: *injection site rxns*, nasopharyngitis, influenza, URTIs, UTI, back pain (evolocumab), increased LFTs (alirocumab) Warnings: allergic rxns Monitoring: LDL at baseline then at 4-8 weeks to assess response

Answer 19

Drugs: *colesevelam (Welchol)*, cholestyramine (Prevalite, Questran, Questran Light), colestipol (Colestid) MOA: *bind to bile acids in intestine, forming complex that is excreted in the feces* ROA: PO Administration: -Coleveselam: *take with meal and liquid* (empty packet into 8oz glass of water, fruit juice, or diet soft drink and mix well) -Cholestryamine packet: mix in 2-6oz water or non-carbonated beverage; *sipping for a prolonged periods can lead to changes in teeth surface, resulting in discoloration, erosion of enamel or decay*; keep good oral hygiene TX: dyslipidemia -*Colesevelam: glycemia control in T2DM (lowers A1c by 0.5%); can be used in pregnancy* -Cholestyramine: pruritus due to increases levels of bile acids Effects: decreases LDL by 10-30%; increases HDL by 3-5%; *no change or increases TG by 5%* -NOT recommended to take when TG >/=300mg/dL

Answer 20

AVEs: *constipation (may need dose reduction or laxative), abdominal pain, cramping, bloating, gas, increased TGs*, dyspepsia, nausea, esophageal obstruction Warnings: -Some formulations contain phenylalanine and should NOT be used in pts w/ PKU -Increased bleeding tendency due to vitamin K deficiency CIs: -Cholestryamine: complete biliary obstruction -Colesevelam: *bowel obstruction*, TG >500 mg/dL, hx of hypertriglyceridema-induced pancreatitis DDIs: -*Colesevelam has fewer DDIs than the others*; can increase metformin ER levels -*Cholestryamine or colestipol: take ALL other drugs at least 1-4 hours before or 4-6 hours after* -Colesevelam: take cyclosporine, sulfononylureas, levothyroxine, olmesartan, phenytoin, or OCs containing EE and norethindrone four hours before -*Decreased absorption of fat-solublue vitamins (A, D, E, K), folate, and iron --> multivitamin may be needed, but seperate from bile acid sequestrant* -Monitor INR more frequently when on warfarin

Answer 21

Drugs: *fenofibrate/fenofibric acid (Tricor, Trillipix), gemfibrozil (Lopid)* MOA: peroxisome proliferator-activated receptor alpha (PRAPalpha) agonists that upregulate expression of apolipoprotein C2 (apoC-II) and apoliporotein A1 (apoA-I) -*Apoc-II increases lipoprotein lipase activity, leading to increased catabolism of VLDL particles and decrease TG* ROA: PO Effects: *decreased TG* by 20-50% and LDL by 5-20% *(can increase when TG are high)*; increases HDL by 15% AVEs: *dyspepsia (gemfibrozil), increased LFTs* (dose-related), abdominal pain, increased CPK, URTIs Warnings: *myopathy (increased w/ statin* particularly in older adults, DM, renal failure, hypothyroidism, cholethiasis), reversible increased SCr >2 mg/dL CI: *severe liver disease (including primarily biliary cirrhosis)*, sevre renal disease (CrCl <30), *gallbladder disease*, breastfeeding, concurrent use w/ repaglinide or simvastatin (gemfibrozil only) Monitoring: LFTs, renal fxn DDIs: -*Gemfibrozil should NOT be used w/ ezetimibe or statins (increased myopathy and rhabdomylosis risk)* or repaglinide (increased hypoglycemia) -*Can increase effects of sulfonylureas and warfarin* -Colchicine can increase risk of myopathy w/ fenofibrate

Answer 22

Brand: *Niacor (IR), Slo-Niacin (SR) -Also known as nicotinic acid or vitamin B3 (OTC)* MOA: *decreases rate of hepatic synthesis of VLDL, which decreases TG and LDL* and can increase rate of chylomicron TG removal from plasma -Alters binding of HDL to scavenger receptor beta-1 in liver, which removes cholesterol inside ROA: PO Administration Considerations: -*ER formulation preferred due to less flushing and hepatotoxicity*, but more expensive; take at bedtime after low-fat snack -Niacin CR most hepatotoxicity risk -*Take ASA 325mg or ibuprofen 200mg 30-60 minutes before dose; take with food; and avoid extra spicy food, alcohol, and hot beverages to prevent flushing* -Flush-free niacins (inositol hexaniacinate or hexxanicotinate), niacinamide, or nicotinamide are NOT effective Effects: decreases LDL by 5-25% and TG by 20-50%; *increase HDL* by 15-35%

Answer 23

AVEs: *flushing, pruritus, N/V/D, increased BG, hyperuricemia (or gout)*, cough, orthostatic hypotension, hypophosphatemia, decreased PLTs Warnings: *rhabdomylosis with doses >/=1 gram/day when combined with statins, hepatotoxicity*, increased BG and uric acid, decreased phosphorus, caution in unstable angina or acute phase of MI CIs: active liver disease, active PUD or arterial bleeding Monitoring: *LFTs* at baseline then Q6-12 weeks for first year then Q6 months; BG if DM; uric acid if gout hx; INR if on warfarin; lipid panel DDIs: *take 4-6 hours after bile acid sequestrants*

Answer 24

Drugs: *omega-3 Acid Ethyl Esters (Lovaza), icoscapent ethyl (Vascepa)* -Omega-3 acid ethyl esters: EPA and DHA -Icoscapent ethyl: pure EPA MOA: NOT fully understood --> may reduce hepatic synthesis of TGs ROA: PO Administration considerations: -Many OTC products marketed as dietary supplements, but ONLY RX meds are approved for TG-lowering -Stop prior to elective surgery due to increased risk of bleeding Indicated: *adjunct to diet when TG >/=500mg/dL* -Vascepa: ASCVD risk reduction when TG are 135-499 mg/dL despite maximally tolerated statin Effects: *decrease TG* up to 45%; increased HDL by 9% and *can increase LDL (Lovaza: up to 44%, NOT seen in Vascepa)* AVEs: *eructation (burping), dyspepsia, taste perversions* (Lovaza), asthralgia (Vascepa) Warnings: -*Caution with known hypersensitivity to fish and/or shellfish* -Monitor LFTs in pt w/ hepatic impairment and LDL periodically -Lovaza: can increase LDL; possible association w/ more symptomatic atrial fibrillation or flutter in pts w/ AFib particularly after first few months of initiation\ DDIs: *can prolong bleeding time (caution in meds that increase bleed risk and monitor INR w/ pt on warfarin)*

Answer 25

1. -MOA: *inhibits cholesterol synthesis in liver* via inhibition of adenosine triphosphate-citrate lyase (ACL), an enzyme upstream of HMG-CoA reducatase in cholesterol synthesis pathway -Indication: *add on therapy with statin for further LDL lowering* 2. -*MOA: inhibits intracellular production of PCSK9 via ribonucleic acid (RNA) interference, resulting in increased activity of LDL receptor -ROA: SQ injection* 3. -Approved for primarily hyperlipidemia or familial in combo with a statin -*Do NOT use with PCSK9 mAb due to overlapping MOA* 4. lomitapide (Juxatipid), mipomersen (Kynamro)

Answer 26

Etiology: typically primary HTN -Unknown cause; *risk factors*: obesity, sedentary lifestyle, excessive salt intake, smoking, family hx, DM, dyslipidemia -Secondary HTN: *renal disease*, adrenal disease (excessive aldosterone secretion), obstructive sleep apnea, or drugs Pathophysiology: *activation of sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS)*

Answer 27

-Increased sympathoimemetic activity: ADHD drugs (ex. amphetamine), decongestants (ex. pseudophedrine, phenylephrine), recreational substances (ex. cocaine, caffeine), antidepressants (ex. TCAs, SNRIs, MAOIs) -Increased Na and H20 retention: NSAIDs, immunosuppressants (ex. cyclosporine), systemic steroids -Increased blood viscosity: erythyropoesis stimulating agents -Others: oral contraceptives (especially higher estrogen content), VEGF inhibitors (ex. bevacizumab, sunitinib)

Answer 28

Diagnosis: based on average of *at least two readings on two seperate occassions* (preferred: out-of-office monitoring since it can be falsely elevated in office "white coat HTN") *Per American College of Cardiology and American Heart Association (ACC/AHA): -Normal: SBP <120mmHg and DBP <80mmHg -Elevated: SBP 120-129 and DBP <80 -HTN Stage 1: SBP 130-139 OR DBP 80-90 -HTN Stage 2: SBP >/=140 OR DBP >/=90* **If any readings fall into two categories, work with higher category *Using BP monitoring device:* -DON'T: talk; lie down or sit w/o back supported; drink caffeine, exercise, or smoke for 30 minutes prior; use finger monitor or wrist monitor -DO: go to restroom and empty bladder; sti in chair with both feet on floor and relax for at least 5 minutes; use correct cuff size; support arm at heart level (ex. resting on desk); wait 1-2 minutes in between measurements Self-monitoring: -Ambulatory monitoring device: typically warn continuously for 24 hours -Home device: ideally take 2 measurements in AM and PM before eating and taking any medications

Answer 29

Lifestyle: -*Weight loss* (1 kg of weight loss = decrease in SBP by 1mmHg) -Heart-healthy diet (DASH: Dietary Approaches to Stop HTN): high in fruits, vegetables, fiber, and low-fat and sugar) -Adequate dietary potassium intake or supplementation unless CI (CKD) -*Reduced sodium intake (<1,500mg/day which is about 1/3 of a tsp)* -Routine physical activity -Limited alcohol consumpations Natural Products: -May help: garlic, fish oil -Can increase bleeding risk *Start pharmacotherapy: stage 1 HTN (SBP 130-139 or DBP 80-89) AND one of the following: -Clinical CVD (stroke, HF, or coronary heart disease) -10-year ASCVD risk of 10% or greater -does NOT meet BP goal after 6 months of lifestyle modifications OR start when stage 2 HTN (SBP >/=140 or DBP >/=90) BP goal: <130/80mmHg Monitor and titrate if needed: Qmonth*

Answer 30

-Preferred drug classes: ACEs or ARBs, thiazide diuretics (may be preferred in African Americans), DHP CCB (may be preferred in African Americans) -Start with one drug, most pts will need two or more drugs (adding a second drug when BP above >20/10 mmHg above goal as combo first-line) before titrating up to maximum dose on first drug can be more effective and fewer side effects) -do NOT use ACEis and ARBs together --> similar MOA and AVEs -CKD: ACEI or ARB (regardless of race)

Answer 31

-Chronic HTN: occurring before pregnancy or before 20 weeks of gestation -Gestational HTN: new onset at 20 weeks or greater gestation -Preclampsia: gestational HTN + proteinuria or end-organ damage -Preferred: labetalol, nifedipine XR, and methyldopa (methodopa: least effective) --> IR nifedipine may ONLY be used if IV unavailable -Tertogenic (BBW): ACEIs, ARBs, aliskiren -Initiate drug treatment in SBP >/=140 or DBP >/=90 or continue in chronic HTN -Low-dose ASA in high risk pts for preclampsia (ex. chronic HTN, previous preclampsia, renal disease, DM)

Answer 32

1. Zestoretic 2. Hyzaar 3. Benicar HCT 4. Diovan HCT

Answer 33

1. Lotrel 2. Exforge 3. Temoretic 4. Ziac 5. Maxzide, Maxzide-25

Answer 34

Drugs: *chlorthalidone (Hygroton), hydrochlorothiazide (Microzide)*, chlorthiazide (Diuril), indapamide, metolazone MOA: *inhibit Na reabsorption in distal convoluted tubule, causing increased excretion of Na, Cl, K, and water -Only small percentage of Na is absorbed in DCT --> NOT as potent for diuresis as loop diuretics* ROA: PO, injection (chlorothiazide) TX: *preferred initial TX in HTN*

Answer 35

Chlorthalidone: *12.5-25mg daily* Hydrochlorothiazide: *12.5-50 mg daily* *In practice, may see higher doses for other indications, but these are maximum doses with benefit for HTN Most potent: chlorthalidone (and longer duration of action) Available IV: *chlorothiazide* Administration/counseling considerations: -*Effect diminished when CrCl <30mL/min* (except metazolone which is indicated in volume overload in combo w/ loop diuretic - retains diuretic effect regardless of CKD) -*Take early in day to avoid nocturia* -Hypokalemia can be avoided w/ regular intake of K-rich foods, supplements, or concurrent using of K-sparing diuretic

Answer 36

*AVEs:* -Decreased electrolytes (K, Mg, Na) -Increased Ca, UA (uric acid), LDL, TG, and BG -Photosensitivity including small increased risk of non-melanoma skin cancer, impotence (HTN itself can also be a risk), dizziness, rash Warnings: -Severe renal disease (can precipitate azotemia) -Progressive liver disease (fluid and electrolyte changes can precipitate hepatic coma) -Transient myopia or acute angle-closure glaucoma -Can precipitate or exacerbate conditions such as SLE, *gout, dyslipdemia, and DM* CIs: *hypersensitivity to sulfonamide-derived drugs (not likely to cross-react)* Monitoring: *electrolytes, renal fxn*, BP, fluid status (input/output, weight), BG (in DM) DDIs: -Hypotension caution with other BP-lowering drugs -*Drugs that cause Na and water retention (ex. NSAIDs) can decrease effectiveness -Thiazides can decrease lithium renal clearance and increase toxicity risk* -Thiaizides can increase dofetillide serum concentrations, increasing QT porlongation risk --> avoid combo

Answer 37

Drugs: *amlodipine (Norvasc), nicardipine (Cardene IV), nifedipine (Procardia XL)*, felodipine, isradipine, nisoldipine, clevidipine MOA: *inhibit Ca++ from entering vascular smooth muscle and myocardial cells (DHP CCBs: more selective for vascular smooth muscle that causes peripheral arterial vasodilation which decreases SVR and BP and coronary artery vasodilation)* ROA: PO, injection (nicardipine, clevidipine) Administration Considerations: -*Amlodipine: considered safe if DHP CCB must be used to lower BP in pt w/ HFrEF -Nifedipine ER: DOC in pregnancy* -Procardia XL: OROS/gel matrix formulation, can leave ghost tablet in stool -*Clevidipine: lipid emulsion provides 2kcal/mL (milky-white color); strict asepetic technique due to infection risk; max time of use after vial puncture is 12 hours* TX: *HTN (preferred option), chronic stable and vasospastic angina, Raynaud's phenomenon*

Answer 38

AVEs: generally well tolerated --> *peripheral edema, HA, flushing, palpitations*, reflex tachycardia, fatigue, nausea, *gingival hyperplasia (or overgrowth)* Warnings: -*Hypotension: espeically w/ severe aortic stenosis* -Worsening agina and/or MI, severe hepatic impairment, caution in HF -*Nifedipine IR: do NOT use for chronic HTN or acute BP reduction in non-pregnant adults (significant hypotension), MI, and/or death has occurred)* CIs (nicardipine IR): do NOT use in advanced aortic stenosis Monitoring: *peripheral edema*, BP, HR *Clevidipine specific considerations:* -AVEs: hypertriglyceridema (due to lipid emulsion) -Warnings: hypotension (quick onset), reflex tachycardia, infections -CIs: allergy to soybeans, soy products, or egg; defective lipid metabolism ex. lipoid nephrosis, hyperlipidemia w/ acute pancreatitis); severe aortic stenosis DDIs: -*ALL CCBs (except clevidipine): major CYP3A4 substrate* --> check for DDIs, do NOT use w/ grapefruit juice

Answer 39

Drugs: *diltiazem (Cardizem, Tiazac), verapamil (Calan SR) MOA: inhibits Ca++ from entering vascular smooth muscle and myocardial cells (non-DHP CCBs: more selective for myocardium --> less potent vasodilators, negative inotrope and chronotrope)* ROA: PO, injection (diltiazem) -IV:PO ratio is NOT 1:1 TX: *rate-control in atrial fibrillation*, chronic stable and vasospastic angina, sometimes HTN

Answer 40

AVEs: *constipation (more w/ verapamil), gingival hyperplasia*, edema (more w/ diltiazem), HA, dizziness, cutaneous hypersensitivity rxns (diltiazem) Warnings: *HF (may worsen), bradycardia,* hypotension, acute liver injury/increased LFTs, cardiac conduction abnormalties (diltiazem), hypertrophic cardiomyopathy (verapamil) CIs: hypotension (SBP <90), cardiogenic shock, 2nd or 3rd degree AV block or sick sinus syndrome (unless functioning artifical ventricular pacemaker), atrial flutter or Afib and an accessory bypass tract, concurrent use w/ IV beta-blockers (IV CCBs only) -Diltiazem: acute MI and pulmonary congestion -Verapamil: severe left ventricular dysfunction Monitoring: BP, HR, ECG, LFTs *DDIs:* -ALL CCBs (except clevidipine): major CYP3A4 substrate --> check for DDIs, do NOT use w/ grapefruit juice -Caution in other drugs that lower HR (beta-blockers, digoxin, clonidine, amiodarone, dexmedtomidine) -Non-DHP CCBs are substrates and inhibitors of P-gp and moderate inhibitors of CYP3A4 (lower dose of simvastatin or lovastatin or use statin NOT metabolized by 3A4)

Answer 41

1. Liver; Kidney 2. Angiotension-converting enzyme (ACE); ACEIs (ACE inhibitors); angiotensin receptor blockers (ARBs) 3. Aldosterone secretion which leads to increased Na and water retention AND vasoconstriction which increases systemic vascular resistance (SVR), both increasing BP 4. -CKD: ACEis and ARBs slow progression of kidney damage via inhibiting vasoconstriction effects on efferent arteriole in nephron, resulting in decreased filtration pressure and workload in glomerulus -HF: protection of myocardium from remodeling effects and improve survival especially in reduced EF

Answer 42

Drugs: *benazepril (Lotensin), enalapril (Vasotec), enalaprilat (Vasotec IV), lisinopril (Zestril), quinapril (Acupril), ramipril (Altace),* captopril, fosinopril, moexipril, perindopril, trandolapril MOA: *inhibits conversion of angiotensin I to II; also blocks degradation of bradykinin (thought to contribute to vasodilatory side effects - dry, hacking cough and angioedema)* ROA: PO, *IV (enalaprilat)* TX: HTN (preferred agent), slowing of CKD progression AVEs/Warnings: *cough, HA, angioedema, hyperkalemia, renal impairment (increased risk in bilateral renal artery stenosis -avoid use since pt needs contristriction on efferent arteriole of glomerulus), hypotension/dizziness (increased risk in volume depletion - ex. diuretic)* CIs: *hx of angioedema, use within 36 hours of sacubitril/valsartan (Entresto)*, use with aliskiren in DM BBW: *injury and death to fetus in 2nd and 3rd trimesters (D/C as soon as pregnancy detected) - can impair fetal kidney Monitoring: BP, K, renal function (increased SCr)*, s/sx of angioedema

Answer 43

Drugs: *irbesartan (Avapro), losartan (Cozaar), olmesartan (Benicar), valsartan (Diovan),* azilsartan (Edarbi), candesartan (Atacandi), telmisartan (Micardis) MOA: *prevents angiotensin II from binding to angiotensin II-type 1 (AT1) receptor on vascular smooth muscle, preventing vasoconstriction and aldosterone secretion* ROA: PO TX: HTN (preferred agent), slowing of CKD progression AVEs/Warnings: *cough, HA, angioedema, hyperkalemia, renal impairment (increased risk in bilateral renal artery stenosis -avoid use), hypotension/dizziness (increased risk in volume depletion - ex. diuretic) -Same as ACEIs, but LESS: cough, angioedema, and no washout period with Entresto -Olmesartan: sprue-like entropathy (severe, chronic diarrhea w/ substantial weight loss which can occur after months to years after initiation)* CIs: *hx of angioedema*, do NOT use with aliskiren in DM BBW: *injury and death to fetus in 2nd and 3rd trimesters (D/C as soon as pregnancy detected) Monitoring: BP, K, renal function (increased SCr)*, s/sx of angioedema

Answer 44

directly inhibits renin, preventing conversion of angiotensinogen to angiotensin I

Answer 45

ALL: 1. hyperkalemia --> caution with other medications that increase K; avoid salt substitutes containing K 2. do NOT use any RAAS inhibitor together -> increased risk of renal impairment, hypotension, and hyperkalemia ACEIs/ARBs: 1. NSAIDs - use cautiously due to risk of renal impairment and diministered anti-HTN effects 2. Entresto - do NOT use in combo (ACEIs: need 36 hour washout period) 3. Lithium - ACEIs/ARBs can decrease lithium renal clearance, increasing toxicity risk

Answer 46

Drugs: *spironolactone (Aldactone*, CaroSpir suspension), *trimaterene* (Dyrenium, *+ HCTZ = Maxzide*), amiloride, eplerenone MOA: -*Triamterene, amiloride: inhibit Na channels in late distal convoluted tubule and collecting duct of nephron, increasing Na and water excretion, but preserving K -Spirinolactone, epleronone: aldosterone receptor antagonists that indirectly inhibit Na channels (spirinolactone: non-selective and blocks androgen)* ROA: PO TX: -*Trimaterene, amiloride (NOT very potent): hypokalemia associated w/ diuretics -Spironolactone, eplerenone: HF, preferred for resistant HTN -CoSpir: HF, edema due to cirrhosis (NOT therapeutically equivalent to Aldactone)* AVEs: *hyperkalemia, increased SCr, dizziness,* hyperchloremic metabolic acidosis (rare) -*Spironolactone: gynecomastia, breast tenderness, impotence*, irregular menses, amenorrhea CIs: *hyperkelamia, severe renal impairment, Addison's disease (spironolactone),* use with strong CYP3A4 inhbitors (eplerenone) BBW *(amiloride, triamterene): hyperkalemia (K > 5.5 mEq/mL)* - more likely in DM, renal impairment, or elderly pts DDIs: -*Hyperkalemia additive risk* -Eplerenone: major CYP3A4 substrate --> avoid strong inhibitors

Answer 47

*MOA:* -Beta-1: located in heart muscle; inhibition decreass HR and myocardial contractility, decreasing BP -Beta-2: located in lungs; inhibition causes bronchoconstrictoin (beta-1 selective preferred in asthma/COPD) -Alpha-1: located in peripheral vasculature; inhibition decreases vasoconstrictoin, decreasing BP, HR, contractility, and SVR Beta-1 selective blockers: "AMEBBA" -*atenolol (Tenormin), esmolol (Brevibloc), metoprolol tartrate (Lopressor), metoprolol succinate (Toprol XL),* acebutolol, betaxolol, bisprolol Beta-1 selective blocker w/ nitric oxide-dependent vasodilation: *nebivolol (Bystolic)* Beta-1 and Beta-2 blockers (non-selective): *propranolol (Inderal LA, Inderal XL), nadolol (Corgard)*, pindolol, timolol (Timoptic - opthalamic) Non-selective beta-blocker and alpha-1 blockers: *carvedilol (Coreg, Coreg CR), labetalol* Beta-blocks with partial ISA and block catecholamines: *acebutolol*, pindolol --> may be helpful in pts with bradycardia at rest (NOT recommended post-MI or HF since do NOT adequately decrease HR) TX: *post-MI, IHD, stable angina, HF, HTN (NOT first-line), arrhythmias*

Answer 48

ROA: PO, *injection (metoprolol tartrate, esmolol)* *With food or immediately following food: Lopressor (metoprolol tartrate), Toprol XL (metoprolol succinate)* *Metoprolol tartrate: IV:PO ratio of 1:2.5* Converting metoprolol tartrate--> succinate: same TDD should be used Kapsargo Sprinkle (metoprolol succinate): swallow whole; capsule can be opened and contents sprinkled on 1 tsp of soft food (applesauce, yogurt, pudding); swallow within 60 minutes *Toprol XL (metoprolol succinate): can be cut in half, BUT do NOT crush or chew*

Answer 49

AVEs: *bradycardia, hypotension, CNS effects (fatigue, dizziness, depression), impotence (less than thiazides), cold extremeties (can exacerbate Raynaud's)* *Warnings:* -Caution in DM: can worsen hypoglycemia and mask hypoglycemia symptoms (thought to inhibit hepatic glucagon release) -Caution in bornchospastic diseases (COPD, asthma) -Caution with Raynaud's/other peripheral vascular diseases (slow titration) and pheochromocytoma (requires adequate alpha blockage first) -Can mask signs of hyperthyroidism (tachycardia) CI: severe bradycardia, 2nd or 3rd degree AV block or sick sinus syndrome (unless permanent pacemaker is in place), overt cardiac failure or cardiogenic shock -Esmolol: pulmonary HTN; use of non-DHP CCBs BBW: *do NOT D/C abruptly (particularly in pt w/CAD/IHD) --> gradually taper over 1-2 weeks to avoid acute tachycardia, HTN, and/or ischemia* Monitoring: HR (if symptomatic bradycardia), BP Nebivolol consideratoins: CI in liver impairment (Pugh Class B or C)

Answer 50

1. CI in bronchial asthma 2. Can prevent variceal hemorrhage in pts w/ portal HTN 3. Propranolol: high lipid solubility (lipophilic) and crosses BBB --> can be helpful in non-cardiac conditions (migraine prophylaxis, essential tremor), but MORE CNS side effects

Answer 51

1. *CI: severe hepatic impairment 2. Warnings: intraoperative floppy iris syndrome (IFIS) has occurred in cataract surgery 3. AVEs: weight gain, edema* 4. Carvedilol: *take ALL forms with food to decrease rate of absorption and reduce risk of orthostatic hypotension* (Carvedilol CR has lower F than IR: dosing conversions are NOT 1:1 --> ex. Coreg 3.125mg BID = Coreg CR 10mg QD) 5. Labetalol: *DOC in pregnancy*, injection common in hospital setting and can be administered as IVP or CIV

Answer 52

1. *Caution with other drugs that lower HR* 2. *Can enhance hypoglycemic effects of insulin and sulfonylureas and mask symptoms (except sweating and possibly hunger)* 3. Can decrease insulin secretion, causing hyperglycemia 4. Carvedilol, propranolol, metoprolol, nebivolol: major substrate of CYP2D6 5. Carvedilol, propranolol: inhibitors of P-gp and can increase P-gp substrates (cyclosporine, dabigatran, digoxin, ranolazine)

Answer 53

Brands: *clonidine (Catapres-TTS, Kapvay, Duraclon), guanfacine IR, guanfacine ER (Intuniv)* MOA: *centrally-acting alpha-2 adrenergic agonists; stimulation of alpha-2 decreases sympathetic outflow of NE, leading to reduction in SVR and BP* ROA: PO, patch, injection (Duraclon) TX: resistant HTN (clonidine ER or IR; clonidine IR only) especially those who cannot swallow (patch), ADHD (Intuniv, Kapvay), epidural (Duraclon) AVEs: *dry mouth, somnolence, fatigue, dizziness, constipation, decreased HR, hypotension, impotence*, HA, behavioral changes (irritability, confusion, anxiety, nightmares) -*Clonidine patch: skin rash, pruritus, erythema* Warnings: *do NOT D/C abruptly (rebound HTN, sweating, anxiety, tremor)* --> gradually taper over 2-4 days Monitoring: BP, HR, mental status

Answer 54

-*Apply Qweek to clean, dry, hairless area of skin on upper outer arm or upper chest -Remove before MRI* -Can apply adhesive cover over patch if it loosens, do NOT cut patch -Takes 2-3 days to reach therapeutic effect -Overlap is needed when transitioning from PO clonidine

Answer 55

MOA: *centrally-acting alpha-2 adrenergic agonists; stimulation of alpha-2 decreases sympathetic outflow of NE, leading to reduction in SVR and BP* ROA: PO TX:* resistant HTN (DOC in pregnancy, but less efficacy in lowering BP)* AVEs: *drug-induced lupus erythematous (DILE)*, edema or weight gain (control w/ diuretics), increased prolactin levels, transient sedation, HA Warnings: *risk of hemolytic anemia (positive Coombs test),* hepatic necrosis CI: *concurrent use w/ MAOIs*, active liver disease

Answer 56

Drugs: *hydralazine, minoxidil (Rogaine)* MOA: *direct vasodilation of arterioles (little effect on veins), decreasing SVR and BP* ROA: PO, *injection (hydralazine), topical (minoxidil)* TX: resistant HTN, *hair growth (Rogaine)* *AVEs:* -Hydralazine: peripheral edema, HA, flushing, palpitations, reflex tachycardia, N/V, peripheral neurtisi, blood dycrasias, hypotension -Minoxidil: hair growth, tachycardia, fluid retention (caution in HF or recent MI) Warnings (hydralazine - dose and duration dependent): *drug-induced lupus erythematosus (DILE)* CIs: -Hydralazine: mitral valvular rheumatic heart disease, CAD -Minoxidil: pheochromocytoma BBW (minodixil): *potent vasodilator* that can cause pericardial effusion and agina exacerbations from reflex tachycardia --> administer w/ beta-blocker and loop diuretic Monitoring: HR, BP, ANA titer (hydralazine)

Answer 57

Hypertensive crisis: severe BP elevation of >/=180/120mmHg Emergency: acute target organ damage that may be life-threatening (encephalopathy, stroke, AKI, acute coronary syndrome, aortic dissection, acute pulmonary edema) -TX with IV medications (clevidipine, enalaprilat, esmolol, hydralazine, labetalol, nicardipine, nitroglycerin, nitroprusside) -Decrease BP by no more than 25% within the first hour, then if stable decrease to 160/100mmHg in next 2-6 hours Urgency: severe asymptomatic HTN (no evidence of organ damage) -TX with short-acting PO medications (captopril, clonidine) or restart chronic HTN TX -Decrease BP gradually over 24-48 hours

Answer 58

Angina: chest pain, pressure, tightness or discomfort usually from ischemia of heart muscle or spasm of coronary arteries (in females, older adults, or w/ comorbid DM: may present as dyspnea, back pain, or pain that mimics indigestion or GERD) Stable angina: chronic coronary disease (CCD) associated with predicted chest pain BROUGHT ON BY EXERTION or EMOTIONAL STRESS and relieved WITHIN MINUTES BY REST or short-acting nitroglycerin Unstable angina (UA): type of acute coronary snydrome (ACS) that is a medical emergency where chest pain increases in frequency, intensity, or duration and NOT RELIEVED with nitroglycerin or rest Vasospastic angina (prinzmetal): occurs at rest and can be triggered (often from illicit drugs, particularly cocaine) caused by coronary artery vasospasm

Answer 59

Pathophysiology: *imbalance between myocardial oxygen demand (workload) and supply (blood flow)* -Myocardial demand increases with: increased HR, contractility, or left ventricular wall tension from increased preload and/or afterload (in stable angina: often DECREASED due to atherosclerosis, causing narrowing of blood flow to heart = CAD) Risk factors: heart disease, vascular disease/stroke, HTN, smoking, dyslipidemia, DM, obesity, physical inactivity Diagnosis: *cardiac stress test either w/ exercise or IV medications* (dobutamine, regadenoson) while monitoring for sympotoms, changes in HR and BP, or other abnormalities (ex. ST segments), no changes in troponin (chest pain caused by imbalance of oxygen supply and demand rather than thromobosis that damages cardiac tissue) -*After diagnosis, a coronary angiography can be used to assess extent of atheroscelorosis and need for revascularization*

Answer 60

Non-pharm: heart healthy diet, Na: <2300mg/day, weight loss (assess BMI and waist), aerobic activity, cardiac rehabilitation, smoking cessation, reduction of alcohol, *D/C of chronic NSAID use* General TX: -Manage comorbid conditions (ex. dyslipidemia, HTN, and DM) -Admnister vaccines per guidelines with heart disease -*ASA or clopidogrel* (dual antiplatelet therapy = DAPT: NOT useful in secondary prevention in stable agina and recommended only after recent ACS or precutaneous coronary intervention = PCI) -Rivaroxaban low-dose with ASA: indicated in select pts with CAD or PAD -*Reduction of CV events:* ACEis/ARBs + high-intensity statin -Anti-anginal TX (beta-blockers, CCBs, nitrates): decreases myocardial oxygen deman or increases myocardial oxygen supply to prevent symptoms (if remains symptomatic with one, add a second drug from these options, *ranolazine: considered after these therapies added*) -*Nitroglycerin (SL or translingual =TL spray): immediate relief of symptoms for ALL pts -Vasospatic angina: avoid beta-blockers, DHP CCBs preferred* TX approach: *ABCDE = Antiplatet/antiangina, BP, cholestrol/cigarretes cessation, diet/DM, exercise/education*

Answer 61

Brands: *Bayer, Bufferin, Ecotrin* MOA: *irreversibly inhibits cyclooxygenase-1 and 2 (COX-1 and -2) enyzmes, which results in decreased prostaglandin (PG) and thromboxane A2 (TXA2) production -TXA2 = potent vasoconstrictor and inducer of PLT aggregation* ROA: PO, ER capsule (Durlaza) Administration considerations: -*Used indefinitely in stable angina (decreased incidence of CV events/death) -Non-enteric coated, chewable ASA is preferred in ACS (if only enteric ASA available: chew 325mg) -ER products (ex. Durlaza) should NOT be used when rapid onset needed (ex. ACS, pre-PCI)* -To decrease nausea, EC or buffered product or take with food -*PPIs may be used to protect GI tract from chronic ASA use (consider risks from PPIs: decreased bone density, infection risk) Stable angina: 75-100mg QD*

Answer 62

AVEs: *dyspepsia, heartburn, bleeding*, nausea Warnings: *bleeding (including GI bleed/ulceration - increased w/ heavy alcohol use or when use w/ other drugs that have bleeding risk), tinnitus (sign of salicylate overdose)* CIs: *NSAID or salicyclate allergy*; children and teenagers w/ viral infection (risk of Reye's syndrome - somnolence, N/V, confusion), rhinitis, nasal polyps, asthma (urticaria, angioedema, or bronchospasms) DDIs: -*Additive bleed risk* -Caution in combo w/ other ototoxic drug

Answer 63

Brand: *Plavix* MOA: *prodrug that irreversibly inhibits P2Y12 ADP-mediated PLT activation and aggregation* ROA: PO Dosing for stable angina: *75mg QD (when ASA CI)*

Answer 64

AVEs: generally well tolerated *unless bleeding occurs* Warnings: *bleeding risk (stop 5 days prior to surgery), do NOT use w/ omeprazole or esomeprazole*, premature D/C increases risk of thrombosis, *thrombotic thrombocytopenia purpura (TTP)* CIs: *active serious bleed* BBW: *prodrug that needs converstion to active metabolite via CYP2C19 (poor metabolizer: higher CV events --> consider alternative)* Monitoring: bleeding, Hgb/Hct as necessary *DDIs:* -Additive bleed risk -Avoid moderate or strong CYP2C19 inhibitors (omeprazole, esomeprazole)

Answer 65

Beta-blockers: reduce myocardial oxygen demand to decrease HR, contractility, and left ventricular wall tension (decreases afterload) -Avoid in vasospatic angina (can exacerbate vasospasms) CCBs: preferred for vasospastic angina 1. Reduce myocardial oxygen demand by decreasing HR and contractility (non-DHP CCBs) or decrease SVR/afterload (DHP CCBs) 2. Increase myocardial oxygen supply by increasing blood flow to coronary arteries

Answer 66

Drugs: -Short acting: *nitroglycerin SL tablet (Nitrostat), nitroglycerin TL spray (NitroMist, Nitrolingual)* -Long acting: *nitroglycerin ointment 2% (Nitro-BID)*, nitroglycerin transdermal patch (Nitro-Dur), nitroglycerin ER capsule (Nitro-Time), *isosrbide mononitrate*, isosorbide dinitrate IR (Isordil) MOA: -*Reduce myocardial oxygen demand: decreases preload (free radical nitric oxide vasodilates veins more than arteries)* -Increase myocardial oxygen supply: increases blood flow through collateral (non-atherosclerotic) arteries ROA: PO, topical, translingual spray, transdermal patch Short-acting dosing: *0.4mg/SL tablet or TL spray (for ALL pts for fast relief of anginal episode)* BiDil (isosorbide dinitrate/hydralazine): *HFrEF*. especially in African Americans

Answer 67

AVEs: *HA, flushing, syncope*, dizziness Warnings: *hypotension, tachyphylaxis*, can aggregate angina caused by hypertrophic cardiomyopathy CIs: -Hypersensitivity to organic nitrates -*Use with PDE-5is* or soluble guanylate cyclase stimulators - riociguat) -Short-acting nitrates: increased IOP, severe anemia, circulatory failure and shock Monitoring: BP, HR, chest pain DDIs: -*do NOT use long-acting nitrates in combo w/ PDE5is* or soluble guanylate cyclase stimulators -*Caution w/ other drugs that lower BP and alcohol* -Short-acting nitrates should NOT be used if PDE5i recently taken (avanafil: 12 hours, sildenafil/vardenafil: 24 hours, tadalafil: 48 hours) --> occassionally in emergencies

Answer 68

*ALL Short Acting Nitrates*: -Take one dose at first sign of chest pain -Call 911 immediately if chest pain persists after first dose, continue to take two additional doses at 5 minute intervals while waiting for ambulance -> do NOT take more than 3 doses/15 minutes *Nitroglycerin SL tablets (Nitrostat):* -Keep SL tablets in orginial container in orgininal amber glass bottle and keep tightly capped, store at room temperature and avoid moisture -Place tablet under tongue and let dissolve (do NOT chew, crush, or shallow) -Slight burning or tingling sensation is NOT a sign of how well medication is working Nitroglycerin TL Spray: -Prime before first use and if NOT used within six weeks -*do NOT shake -Press button firmly to release spray onto or under tongue, close mouth after spray* -do NOT inhale spray and try NOT to swallow quickly afterward -do NOT spit or rinse mouth for 5-10 minutes after dose

Answer 69

Long-acting nitrates: *require a 10-12 hour nitrate-free interval to decrease tolerance (longer for some products)* -Isosorbide mononitrate, IR: BID 7 hours apart; ER dosed Qam -Isosorbide dinitrate (IR): BID 7 hours apart or TID at 8am, 12pm, and 4pm for a 14-hour nitrate-free interval Nitroglycerin Patch (Nitro-Dur): *wear on for 12-14 hours, off for 10-12 hours; rotate sites (preferred: chest, but other sites except kness or elbows); dispose of safely* Nitroglycerin Ointment (NitroBID): *dosed BID 6 hours apart with a 10-12 hour free interval -Measure with dose-measuring applicator provided.* Place applicator on flat surface, squeeze ointment onto applicator, and place applicator (ointment side down) on chest or other area of skin -Spread ointment using dose-measuring applicator lightly onto skin, do NOT rub. Tape applicator into place -Can stain clothing --> cover applicator completely

Answer 70

Brand: Aspruzyo Skinkle, Ranexa MOA: selectively inhibits late phase Na current and decreases intracellular Ca; can decrease myocardial oxygen demand by decreasing ventricular tension and oxygen consumption ROA: PO TX: *add-on treatment in stable angina -NOT to be used for acute TX of chest pain* AVEs: dizziness, HA, constipation, nausea -*Little to no effects on HR or BP* Warnings: *QT prolongation*, acute ran failure in CrCl <30mL/min CIs: liver cirrhosis, *use with strong CYP3A4 inhibitor or inducer* Monitoring: ECG, K, renal fxn DDIs: *major substrate of CYP3A4 --> avoid strong inhibitors or inducers*

Answer 71

1. *Atherosclerosis in coronary arteries*, causing arteries to narrow and making blood flow more difficult. *Plaques can rupture leading to thrombosis and causing sudden reduced blood flow (ischemia) which can lead to myocardial necrosis* 2. *Age (men >45, women > 55 or early hysterectomy), family hx (first-degree relative w/ onst before 55 yo in men or 65 yo in women), smoking, HTN, known CAD, dyslipidemia, DM, chronic stable angina, lack of exercise, excessive alcohol* 3. -*Symptoms*: chest pain (discomfort, squeezing, or pressure) lasting >/=10 minutes, severe dyspnea, diaphoresis, syncope/presyncope, palpitationsm, pain that radiates (arms, back, neck, jaw, or epigastric region) -Females, elderly, and pts with DM less likely to present with classic symptoms

Answer 72

12-lead ECG within 10 minutes of first medical contact, troponins I and T (TnI or TnT) - cardiac enzymes that should be measured within 3-6 hours after symptoms onset in pts with all ACS symptoms, creatinine kinase myocardial isoenzyme (CK-MB) and myoglobulin (less sensitive measure) -*ST-segment elevation myocardial infarction (STEMI): positive cardiac enzymes , ST segment elevation, complete blockage -NSTE-ACS (non-ST elevation acute coronary syndromes) = unstable angina (UA) or NSTEMI (non-STEMI) -UA: negative cardiac enzymes, no ECG changes, partial blockage -NSTEMI: positive cardiac enzymes, no ECG changes, partial blockage*

Answer 73

Goals: immediate relief of ischemia and preventing MI expansion and death PCI: coronary revascularization that involves inflating a small balloon inside coronary artery to widen it and improve blood flow and usually stent placed to keep artery open NSTE-ACS: can be treated with medications alone OR PCI (early invasive strategy) STEMI: requires blocked arteries to be opened as quickly as possibly with PCI or fibrinolytics -PCI preferred if it can be done within 90 minutes of hospital arrival (optimal door-to-balloon time) OR within 120 minutes of first medical contact (usually ambulance) -IF NOT possible, fibrinolytics and should NOT be given within 30 minutes of hospital arrival (door-to-needle time) Drug TX: MONO-GAP-BA -MONO = Morphine, Oxygen, Nitrates, ASA -GAP = GPIIb/IIa antagonists, anticoagulants, P2Y12 inhibitors -BA = beta-blockers, ACEIs Overview: -NSTEM-ACS: MON-GAP-BA +/- PCI -STEMI: MONA-GAP-BA + PCI or fibrinolytic

Answer 74

*Given IMMEDIATELY PRN* -M: Morphine sulfate: *pain relief* and ease anxiety --> NOT routine, but reserved for unacceptable chest discomfort despite other TX (vasodilatory effect of cardiology vessels) -O: Oxygen: when arterial oxygen saturation <90% (SaO2 <90%) or those in respiratory destress -N: Nitrates: for *dilation of coronary arteries to improve blood flow, reduction of preload and afterload (modestly), and decrease chest pain --> SL 0.4mg Q5 minutes x 3 doses*; if NOT administered and persistent HTN, chest pain, or HF, IV NTG can be considered (*do NOT use if SBP <90* HR <50, or right ventricular infarction) -A: ASA:*non-enteric coated chewable ASA (162-325mg) to ALL immediately (do NOT use XR) and continue maintenance of 75-100mg QD indefinitely (alternatively: clopidogrel or ticagrelor)*

Answer 75

GAP: Give these medications next -G: GPIIb/IIIa receptor antagonists (abciximab, *eptifibatide*, tirofiban) - for PCI -A: Anticoagulants: inhibit clotting factors and can reduce infarct size (*LMWHs: enoxparin, dalteparin; UFH; or bivalirudin)* -P: P2Y12 inhibitors *(clopidogrel, prasugrel, ticagrelor*) - prasugrel only for PCI *AVOID in acute setting:* -NSAIDs (except ASA): can increase risk of moratlity, reinfarction, HTN, cardiac rupture, renal insufficiency, and HF -IR nifedipine: increases risk of moratlity

Answer 76

BA: *Give these medications within 24 hours and continue outpatient* -B: Beta-blockers: antianginal (decrease BP, HR, and contractility, decreasing ischemia, reinfarction, and arrhythmias; prevent cardiac remodeling and *increase long-term survival) --> PO low dose beta-1 selective without ISA activity unless CI* (decompensated HF, cardiogenic shock, HR <45); concomitant HFrEF: bisoprolol, metoprolol succinate, or carvedilol); IV can be used in some scenarios -A: ACEIs: prevent cardiac remodeling and decrease preload/afterload --> *PO ACEi indefinitely in all pts with LVEF <40%*, HTN, DM, or stable CKD unless CI; do NOT use IV ACEI due to hypotension risk

Answer 77

*Aspirin (ASA = Bayer, Bufferin, Ecotrin): irreversibly inhibits COX-1 and COX-2 decreasing production of thromboxane A2 (TXA2), an inducer of PLT activation and aggregation* P2Y12 inhibitors*: clopidogrel (Plavix), prasugrel (Effient), ticagrelor (Brillinta),* cangrelor (Kengreal) --> *bind to PLT adenosine diphosphate (ADP) P2Y12 receptor, preventing ADP-mediatedactivation of GPIIb/IIIa receptor complex* GPIIb/IIIa receptor antagonists: *eptifibatide* (Integrillin), tirofiban (Aggrastat), abciximab --> *block PLT glycoprotein IIb/IIIa receptor, which is the binding site for fibrinogen, von Willebrand factor, and other ligans to induce PLT aggregation* Protease-activated receptor-1 antagonist: *vorapaxar* (Zontivity) --> *binds to PAR-1 receptor, preventing thrombin and thrombin receptor agonist peptide-induced PLT aggregation*

Answer 78

1. *Clopidogrel, Prasugrel* 2. -*Clopidogrel: 75mg PO QD -Ticagrelor: 90mg PO BID x1 year then 60mg BID* 3. *Cangrelor: only indicated as adjunct to PCI* in pts who are P2Y12 inhibitor naive and NOT receiving GPIIb/IIIa inhibitor --> *transition to PO inhibitor after PCI* 4. *Prasugrel* 5. DDIs: -*Additive bleed risk* (if ACS pt experiences bleeding, manage w/o D/C especially after first few months when pt has increased risk of subsequent CV events) -*Clopidogrel: avoid in combo w/ CYP2C19 inhibitors (esomeprazole, omeprazole)*; increases effects of repaglinidine (hypoglycemia risk) -Ticagrelor: major CYP3A4 substrate - avoid with strong inhibitors or inducers; avoid simvastatin and lovastatin doses greater than 40mg/day; monitor digoxin levels

Answer 79

AVEs: *bleeding -Clopidogrel, prasugrel: generally well tolerated unless bleeding occurs (clopidgrel even less risk) -Ticagrelor: dsypnea (>10%)*, increased SCr and uric acid Warnings: *premature D/C increases risk of thrombosis, thrombotic thombocytoepnia purpura (TTP)* -Ticagrelor: severe hepatic impairment, bradyarrhythmias CIs: *active serious bleed (GI bleed, intracranial hemorrhage) -Prasugrel: hx of TIA/stroke* *BBW:* -Clopidogrel: prodrug needing conversion with CYP2C19 (consider alternative in poor metabolizer) -Prasugrel, Ticagrelor: someimes significant fatal bleeding; avoid use when CABG likely -Prasugrel: NOT recommended in pt >75 yo due to high bleed risk unless pt considered very high risk (DM or prior MI) -Ticagrelor: after initial ASA dose of 162-325mg, do NOT exceed maintenance of 100mg/day because higher daily doses reduce effectiveness *Stop ___ days prior to elective surgery:* -Clopidgrel, ticagrelor: 5 days -Prasugrel: 7 days

Answer 80

Drugs: *eptifabatide* (Integrillin), tirofiban (Aggrastat), abciximab ROA: *injections (IV)* TX: *medical intervention in ACS or receiving PCI +/- stent* -Abciximab (NOT currently available): only irreversible inhibitor indicated for ONLY PCI +/- stent -If used in PCI, given w/ heparin AVEs: *bleeding, thrombocytopenia* CI: -Thrombocytopenia (PLT <100,000) -Hx of bleeding diathesis -Severe uncontrolled HTN -Recent major surgery or trauma within past 4 weeks for tirofiban and 6 weeks for eptifabatide -Hx of stroke within 30 days or any hx of hemorrhagic stroke (eptifabatide) Monitoring: Hgb, Hct, PLTs, s/sx of bleeding, renal fxn

Answer 81

Brand: Zontivity MOA: *protease-activated receptor-1 antagonist, preventing thrombin and thrombin receptor agonist peptide-induced PLT aggregation* ROA: *PO* TX: *hx of MI or PAD to reduce CV events (CV death, MI, stroke, urgent coronary revascularization)* -Used with ASA and/or clopidogrel in clinical trials AVEs: bleeding, anemia Warnings: do NOT use in severe liver impairment BBW: bleed risk (including ICH and fatal bleeding), do NOT use in hx of stroke/TIA/ICH/active serious bleed DDIs: substrate of CYP3A4 and inhibitor of P-gp --> avoid w/ strong 3A4 inhibitors or inducers

Answer 82

Drugs: *alteplase (Activase, Cathflo Activase - single-use vial), tenecteplase (TNKase)*, reteplase (Retavase) MOA: *bind to fibrin and convert plasminogen to plasmin to breakdown clots -Alteplase: recombinant tissue plasminogen actiator (tPA, rtPA)* ROA: *injections (IV)* TX: *ONLY for STEMI within 30 minutes of hospital arrival (door-to-needle time) when PCI is NOT available* AVEs: *bleeding (including ICH)* CIs: *differ when alteplase is used for ischemic stroke -Active internal bleed or bleeding diathesis -Hx of recent stroke -Severe uncontrolled HTN (unresponsive to emergency therapy)* -Any prior intracranial hemorrhage (ICH) -Recent intracranial or intraspinal surgery or trauma is past 2-3 months -Intracranial neoplasm, arteriovenous malformation, or aneurysm Monitoring: *Hgb, Hct, s/sx of bleeding*

Answer 83

Lifestyle: smoking cessation, management of chronic conditions, avoid excessive alcohol intake, physical activity, heart healthy diet *Drugs for secondary prevention:* -Aspirin (ASA): 81mg QD indefinitely unless CI -P2Y12 inhibitor (DAPT: ticagelor or clopidogrel + ASA in medical management x1 year at least OR clopidogrel, prasugrel, or ticagrelor + ASA x1 in PCI x1 year and continue if tolerating and NOT high risk of bleeding) -Nitroglycerin: SL or spray PRN indefinitely -Beta-blocker: 3 years with target HR 50-60bpm; continue indefinitely in HF or need for management of HTN -ACEI: indefinitely in LVEF <40%, CKD, or DM unless CI -Aldosterone antagonist: indefinitely in LVEF <40% and symptomatic HF or DM (CI: significant renal impairment of SCr >2.5 in men or >2 in women OR hyperkalemia K >5) -Statin: high-intensity statin indefinitely for most (>/= 75 yo: consider moderate or high intensity)

Answer 84

OTC for pain relief: APAP, non-acetylated salicylates, or tramadol or small doses of narcotics before using NSAIDs *(if insufficient: naproxen is lowest risk --> COX-2 inhibitors AVOID with highest CV risk)* Triple anti-platelet therapy: *use for shortest time possible* -Clopidogrel preferred P2Y12 + ASA + anicoagulant for about 4-6 weeks -*PPIs shuold be prescribed in any pt w/ hx of GI bleed during therapy*

Answer 85

HF: heart is NOT able to supply sufficient oxygen-rich blood to body due to impaired ability of left ventricle to fill (diastolic dysfunction) or eject blood (systolic dysfunction) Ischemic: *from decreased blood flow to heart (ex. MI)* Non-ischemic: ex. long-standing uncontrolled HTN (other causes: valvular disease, excessive alcohol intake, illicit drug use, congenital hear defects, viral infections, DM, and cardiotoxic drugs/chest radiation) Cardiac output (CO): *volume of blood pumped out by heart in one minute = HR x SV (stroke volume: volume ejected from left ventricle)* Cardiac index (CI): relates CO to size of pt and BSA

Answer 86

Compensatory Mechanisms: -In HFrEF, there is low CO, and body will compensate w/ neurohormonal pathways to increase blood volume or force/speed of contractions to temproraily elevate, BUT can lead to myocyte damage and cardiac remodeling (hypertrophy, dilated cardiomyopathy) -*Compensatory methods: upregulating RAAS to increase blood volme and vasoconstriction; SNS activation to release NE and EPI to increase HR, contractility (positive inotrope), and vasoconstriction; and vasopression which increases vasoconstriction and fluid retention* S/Sx: -Symptoms: *dyspnea (SOB at rest or upon exertion), cough, fatigue, weakness, reduced exercise capacity* -Labs/biomarkers: *increased B-type natriuretic peptide (BNP - from strech of fluid overload in heart, signals for Na excretion; normal <100pg/mL); increased NT--proBNP (N-terminal proBNP; normal <300pg/mL)* --> used to distinguish between cardiac and non-cardiac causes -Left-sided: orthopnea (SOB when lying flat), paroxysmal nocturnal dyspnea (PND), bibasiliar rales (crackling lungs); S3 gallop; hypoperfrusion (renal impairment, cool extremeties) -Right-sided: peripheral edema, ascites, jugular venous distension (JVD), hepatojugular reflux (HJR; neck vein distention from pressure placed on abdomen), hepatomegaly (enlarged liver due to fluid congestion)

Answer 87

Diagnosis: echocardiography (echo) to estimate left ventricular ejection fractoin (LVEF) -EF: 50% or greater: HF with preserved EF (HFpEF), diastolic dysfunction --> impaired ventricular relxaation and filling during diastole -EF 41-49%: HF with mildly reduced EF (HFmrEF) --> mixed systolic and diastolic dysfunction -*EF 40% or less: HF with reduced EF (HFrEF), systolic dysfunction --> impaired ability to eject blood during systole* -EF 40% or less at baseline, but improves to EF >40%: HF with improved EF (HFimpEF) --> EF improved with TX, treatments with HFrEF should be continued despite higher EF ACC/AHA Staging: -Stage A: at risk for HF, but w/o symptom, structural heart disease, or elevated biomarkers (ex. HTN, ASCVD, DM) -Stage B: pre-HF: structural heart disease, abnormal cardiac function, or elevated biomarkers w/o symptoms (ex. LVH, low EF, valvular disease) -*Stage C: structure and/or functional cardiac abnormalities w/ prior to current symptoms of HF -Stage D: advanced (refractory HF) w/ severe or recurrent hospitalizations despite maximal TX* New York Heart Association (NYHA) Functional Class: -I: no limitations of physical activity -II: slight limitation of physical activity (ex. comfortable at rest, *but ordinary activities result in symptoms)* -III: marked limitation of physical activity (ex. comfortable at rest, but *minimal exertion such as bathing/dressing causes symptoms) -IV: Unable to carry on physical activity w/o symptoms or symptoms at rest*

Answer 88

"Drug Informatoin NATION" D: Dipeptidyl peptidase 4 inhibitors (alogliptin, saxagliptin) I: Immunosuppressants (TNF inhibitors: adaliumumab, etanercept; interferons) N: Non-DHP CCBs (if LVEF amiodarone and dofetllide are preferred in HF) T: Thiaziolidinediones I: Itraconazole O: Oncology drugs (anthracyclines - doxorubicin, daunorubicin) N: NSAIDs

Answer 89

Lifestyle: 1. *Monitor and document body weight daily* in AM after voiding and before eating --> *notify provider if weight increases* by 2-4 lbs in one day or >/=5 lbs in one week or if symptoms worsen 2. *Avoid excessive sodium intake* (restrict to <1500mg/day in those w/ HTN) 3. Restrict fluds in stage D HF (1.5-2L/day) 4. Smoking cessation and stop use of illicit drugs 5. Reduce alcohol intake 6. Obtain recommended vaccines: influenza, pneumococcal 7. Reduce weight 8. Physical activitiy Natural products: -*Omega-3 fatty acids: reasonable to decrease mortality and CV hospitalizations when in COMBO with drug therpay -Hawthorn and coenzyme Q10: may improve symptoms (coeznyme: antioxidant, hawthorn: vasodilative w/ positive inotrope effects)* -Avoid use of products containing ephedra (ma huang) or ephedrine

Answer 90

*Guideline-Directed Medical Therapy (GDMT): ALL pts w/o CIs* 1. ARNI, ACEI, or ARB: decreases mortality and morbidity; ARNI preferred over ACEIs and ARBs to further reduce mortality 2. Beta-blockers: metoprolol succinate, carvedilol, bisprolol reduce moratlity and hospitalizations 3. Aldosterone receptor antagonists (ARA): spironolactone or eplerenone to reduce mortality and morbidity in NYHA Class II-IV HF 4. Sodium-glucose cotransporter 2 (SGLT2) inhibitors: decreases hospitalizations and mortality in pts w/ or w/o DM Potential Add-Ons: 1. Loop diuretics - reduce blood volume to reduce edema and congestion *for symptoms relief* 2. Hydralazine and nitrate (BiDil) - *decreases morbidity and mortality in Black pts* w/ NYHA class III-IV HF; can be considered for pts who cannot receive RAAS inhibitor 3. Ivabradine - decreases risk of hospitalization and CV death in stable NYHA class II-III HF *w/ resting HR >/=70bpm in normal sinus rhythm on maximially tolerated dose of beta-blocker* 4. Digoxin - provides small increase in CO, improves symptoms, and decreases cardiac hospitalizations (NO mortality benefit); *considered in pts who cannot tolerate first-lines or remain symptomatic on first lines* 5. Vericiguat - decreases risk of hospitalizations and CV death *after recent hospitalization or need for IV diuretics* (worsening pt on first-line therapies)

Answer 91

Brand: *Entresto* MOA: *valsartan (ARB) + sacubitril, a neprilysin inhibitor (enzyme responsible for degradation of several beneficial vasodilatory peptides including natriuretic peptides, adrenomedullin, substance P, and bradykinin)* ROA: PO TX: *NYHA Class II-IV HFrEF (first-line over ACEI or ARB) to reduce mortality, morbidity, and hospitalizations; HFpEF* AVEs/Warnings: *cough, angioedema, hyperkalemia, renal impairment (increased risk w/ bilateral renal artery stenosis -avoid use), hypotension/dizziness (increased risk if volume-depleted - diuretic use)* CIs: *use of ACEI within 36 hours (none for ARBs - since lower risk of angioedema)*, hx of angiodema*, use with alkiskiren in DM BBW: *injury and death to developing fetus when used in 2nd or 3rd trimester (D/C as soon as pregnancy detected)* Monitoring: *BP, K, renal fxn (increased SCr), s/sx of HF* and angioedema DDIs: -*Additive hyperkalemia* or hypotension risk -*do NOT use with another RAAS inhibitor (36 hour washout period with ACEIs)* -Use with NSAIDs increases risk of renal impairment -*Can decrease lithium renal clearance, increasing risk of toxicity*

Answer 92

1. Entresto: 97/103mg PO BID 2. Enalapril: 10-20 mg PO BID 3. Lisinopril: 20-40mg PO QD 4. Quinapril: 20mg PO BID 5. Ramipril: 10mg PO QD **Most ACEIs target is 40mg/day

Answer 93

1. Losartan: 50-150mg PO QD 2. Valsartan: 160mg PO BID 3. Metoprolol succinate: 200mg PO QD 4. Carvedilol: -IR: 25mg PO BID (if 85kg or less) or 50mg BID (if >85kg) -CR: 80mg PO QD 5. Spironolactone: 25-50mg PO QD

Answer 94

1. DURING acute decompensated HF if hypotension or hypoperfusion present --> taper over 1-2 weeks to avoid acute tachycardia, HTN, and/or ischemia 2. K > 5mEq/L, CrCl (eGFR) 2 mg/dL in women, >2.5mg/dL in men) 3. -dapagliflozin (Farxiga): 10mg PO QD, cutoff: eGFR <25mL/min -empagliflozin (Jardiance): 10mg PO QD, cutoff: eGFR <20mL/min **If pt on med and then eGFR falls bellow cutoff, can continue

Answer 95

1. sotagliflozin (Jardiance) 2. *False* 3. *metoprolol succinate, bisoprolol, carvedilol*

Answer 96

Drugs: *furosemide (Lasix), bumetanide (Bumex), torsemide* (Soaanz), ethacrynic acid MOA: *inhibit Na and Cl reabsorption in the thick ascending limb of the loop of Henle, increasing excretion of Na, K, Cl, Mg, Ca, and H20 and decreasing fluid volume and preload* Oral equivalent dosing: *furosemide 40mg = torsemide 20mg = bumetanide 1mg = ethacrynic acid 50mg* IV:PO ratos: -*Furosemide: 1:2 -Bumetanide, ethacrynic acid: 1:1* Administration considerations: -Take early in day to avoid nocturia (no later than 4pm) -*Furosemide injection: store at room temperature* (fridge causes crystals to form that may dissolve w/ warming; solution should be clear - do NOT use if yelllow) -Furoscix (furosemide): single-dose prefilled cartridge for on-body infusor (administere SQ infusion) -Bumetanide and furosemide injections: light-sensitive, store in amble bottles, IV admixtures do NOT require light protection

Answer 97

AVEs: -*Decreased electrolytes: Na, Cl, Mg, K, Ca (thiazides: increase Ca) -Increased: HCO3 (metabolic acidosis), UA, BG, TGs, total cholesterol -Orthostatic hypotension, photosensitivity, myalgias* Warnings: *sulfa allergy (likely to not cross-react - does NOT apply to ethacrynic acid), ototoxicity (more e/ ethacrynic acid or IV: hearing loss, tinnitus, vertigo), AKI (due to excessive fluid loss)* CIs: anuria, hepatic coma (bumetanide and torsemide only) BBW: profound diuresis resulting in fluid and electrolyte depletion Monitoring: *renal function, fluid status (input/output, weight), BP, electrolytes, s/sx of HF* DDIs: -*Avoid NSAIDs (renal impairment) -Can alter lithium levels, leading to toxicity or inadequate treatment* -Caution w/ other drugs that lower BP -Additive diuresis and electrolyte abnormalities w/ thiazide diuretics -Additive ototoxicity risk

Answer 98

Brand: Corlanor MOA: hyperpolarization-activated cyclic nucleotide-gated channel blockers; disrupts "funny" current I in the SA node, decreasing HR ROA: PO TX: *add-on therapy in HFrEF in pt reciving GDMT in sinus rhythm and resting HR >/=70bpm to decrease hospitalizations for worsening HF* AVEs: *bradycardia, HTN*, luminous phenomena (phosphenes - seeing flashes of lights) Warnings: *bradycardia* that can increase risk of QT prolongation and ventricular arrhythmias (not recommended in 2nd degree AV block), increased risk of Afib, fetal toxicity (contraception should be used) CIs: ADHF; sick sinus syndrome, SA block, or 3rd degree AV block unless permanent pacemaker in place; clinically significant hypotension or bradycardia; HR maintained exclusively by pacemaker; severe hepatic impairment with strong CYP3A4 inhibitor Monitoring: HR, ECG, BP -*Target HR: 50-60 bpm* DDIs: -do NOT use with moderate or strong CYP3A4 inhibitors or strong inducers -Cuation with other drugs that lower HR

Answer 99

Brand: *Digitek, Lanoxin* MOA: *inhibits the Na-K-ATPase pump* in myocardial cells, increasing intracellular Ca and increasing CO (positive inotrope) and exerting parasympthatetic effects that slow AV nodal conduction *lowering HR (negative chronotrope)* ROA: PO, injection TX: *add-on in HFrEF pt on GDMT to improve symptoms, exercise tolerance, and QOL and reduce hospitalizations -Usually added for ventricular rate control in AFib, HFrER, and low BP* Typical dose: *0.125-0.25mg PO QD* *Dose Adjustments:* -CrCl <60mL/min: lower dose or frequency, hold in AKI -Decrease dose by 25-50% when swtiching from PO to IV Therapeutic range: *0.5-0.9 ng/mL* (higher range for Afib) -Narrow therapeutic index drug

Answer 100

AVEs: dizziness, visual/mental disturbances, HA, N/V/D Warnings: 2nd/3rd degree heart block w/o pacemaker, Wolff-Parkinson-White syndrome w/ AF, vesicant (avoid extravasation) CIs: ventricular fibrillation Monitoring: electrolytes, renal fxn, HR, ECG, BP, digoxin levels (drawn 12-24 hours after dose) Signs of toxicitY: -Symptoms: *N/V, loss of appetite*, abdominal pain, *blurred/double vision, greenish-yellow halos* (or altered color perception), confusion, delirium, *bradycardia, life-threatening arrhythmias* -*Increased risk w/ hypo-k, hypo-Mg, and hyper-Ca; avoid dehydration* -Hypothyroidism can increase digoxin levels Antidote: *DigiFab* DDIs: substrate of *P-gp* and CYP3A4 (minor) -*Reduce digoxin dose by 50% when starting amiodarone* or dronedarone -Caution in concurrent administration of verapamil, cyclosporine, itraconazole, erythromycin, clarithromycin, quinidine, propafenone, and others -*Caution with other drugs that lower HR*

Answer 101

Brand: Verquvo MOA: *soluble cyclase stimulator, increasing cyclic GMP and causing smooth muscle relaxation and vasodilation* ROA: PO TX: reduction of CV death and hospitalizations *following hospitalization for HF or need for IV diuretics in chronic symptomatic HF pt on GDMT* AVEs: *hypotension*, anemia, dyspepsia CI: *do NOT use with riociguat* BBW: do NOT use in pregnancy (contraception required during use and for one month post-TX) DDIs: -May enhance hypotensive effects of PDE5is --> avoid combo -Pts taking long-acting nitrates excluded from study due to potential hypotension

Answer 102

Brands: *K-Tab, Klor-Con, Klor-Con 10, Klor-Con M10/M15/M20* TX: *hypokalemia (often in HF)* AVEs: abdominal pain/cramping, diarrhea, nausea, flatulence Warnings: *risk of hyperkalemia* (caution in renal impairment, disorders that alter K (untreated Addison's disease), or medications that increase K) CIs: hyperkalemia, solid oral formulations (delayed or obstructed passage through GI tract)

Answer 103

-ER capsules: contents can be sprinkled on small amount of applesauce or pudding -K-Tab, Klor-Con (ER tablets - "Non-M tablets"): swallow whole --> do NOT crush, chew, cut, or suck -Klor-Con M (ER tablet, M = microencapsulated): if difficult to swallow whole, can cut in half or dissolve in water (stir for 2 minutes and drink immediately) -Oral packet: dissolve contents in water and drink immediately -Oral solution: 10% (20mEq/15mL) or 20% (40mEq/15mL); mix each 15 mL with 6oz of water

Answer 104

Stroke: a cerebrovascular accident (CVA) *when blood flow to area of brain is interrupted* *Ischemic stroke causes* -Thrombosis during cerebral atherosclerotic infarction (similar to MI, but in brain) --> "non-cardioembolic" stroke -Emobolus that forms in heart and travels to brain --> "cardioembolic" stroke (common cause: Afib) Hemorrhagic stroke: *bleeding in brain* often from intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH) -*ICH causes: trauma (ex. motor vehicle collision) or use of antithrombotics -SAH causes: cerebral aneurysm rupture, resulting in severe HA* Transient ischemic attack (TIA): temporary clot or block of blood flow in brain ("mini stroke") that can be a precursor to stroke

Answer 105

Risk factors: -Modifiable: *HTN (most important), Afib*, dyslipidemia, DM, physical inactivity, smoking -Non-modifiable: *prior stroke/TIA*, advanced age (>/=80 yo), race (higher in African Americans), genetic disease (ex. sickle cell disease), females Presentation: *ACT F.A.S.T.* -F: Face dropping -A: Arm weakness -S: Speech difficulty -T: Time to call 911 Diagnosis: *brain imaging through CT* ideally within 20 minutes of arrival *to identify ischemic vs. hemorrhage stroke* -National Institutes of Health Stroke Scale (NIHSS): visual fields, sensory/motor, etc. --> helps determine severity of stroke

Answer 106

Monitor: intracranial pressure (ICP), cerebral perfusion pressure (CPP), and BP Alteplase: *ONLY fibrinolytic FDA-approved to treat ischemic stroke and must meet criteria of -CT rules out NO bleeding on brain imaging -Stroke symptom onset ("last known well") if 4.5 hours or less per guidelines (FDA-approved: 3 hours or less) -Alteplase can be administered within 60 minutes of hospital arrival (door-to-needle time) -NO CIs* *CIs to Alteplase* -Active internal bleeding -Hx of recent stroke within past 3 months (following a stroke, tissue is fragile and more prone to bleeding) -Severe uncontrolled HTN (BP >185/110mmHg) -Labs that increase bleeding risk: INR >1.7, aPTT >40 seconds, PLT <100,000 -Treatment-dose LWMH within previous 24 hours, use of direct thrombin inhibitor, or direct factor Xa inhibitor within previous 48 hours or taking warfarin with INR >1.7 -BG < 50mg/dL (could be a stroke mimic) Alteplase dose: *0.9mg/kg (max: 90mg)* -10% given as a bolus -Remainder given over an hour Other TXs: -*ASA: 81-325mg PO ASAP within 48 hours after stroke onset --> should NOT be given within 24 hours of fibrinolytic* -DVT prophylaxis with intermittent pneumatic compression (ICP) devices recommended; if SQ UFH or LMWH started, do NOT start within 24 hours of receiving alteplase -HTN management: *if alteplase NOT administered, IV anti-HTNs may NOT be required* unless severely elevated (BP >/=220/120mmHg); 15% reduction of BP within first 24 hours of stroke is considered safe (maintain BP <180/105mmHg after) -Hyperglycemia management: maintain in range of 140-180 mg/dL to prevent hypoglycemia

Answer 107

1. HTN management - *BP goal of <130/80mmHg*; BP mediation may be often initiated after first several days following a stroke 2. Dyslipidemia - *high-intensity statin*, adding ezetimibe or PCSK9i if LDL goal not met 3. DM - GLP-1 agonist or SGLT2i can help with ASCVD risk 4. *Afib - cardioembolic stroke due to Afib requires anticoagulation* 5. Antiplatelet TX -*Non-cardioembolic stroke or TIA: ASA, ASA/ER dipyridamole, or clopidogrel recommended to rpevent recurence; prasugrel CI in hx of TIA or stroke from intracranial bleed risk -Minor ischemic stroke: clopidogrel + low dose ASA* within 24 hours and continued 21-90 days, then *monotherapy antiplatelet therapy indefinitely* -Minor/moderate stroke (NIHSS Score alternative often considered -*ASA dose in ischemic stroke: 50-325mg QD*

Answer 108

Brand: *Aggrenox* MOA *(dipyridamole): inhibits uptake of adenosine into PLTs and increases cAMP levels, inhibiting PLT aggregation* ROA: PO Administration considerations: -*NOT interchangeable with individual componenets of ASA and dipyridamole* -Amount of ASA provided NOT adequate for prevention of cardiac events AVes: *HA (vasodilatory effects from dipyridamole)* Warnings: *hypotension and chest pain in CAD can occur due to vasodilatory effects of dipyridamole*

Answer 109

General TX: mainly supportive -D/C anticoagulants and use reversal agents -If evidence of seizure, anticonvulsant, BUT no prophylaxis indication -ICP devices for DVT prophylaxis -IV osmotic therapy (hypertonic saline or mannitol): increase plasma osmolarity to draw water out of brain and into intravascular space to be renally excreted to reduce intracranial pressure (ICP) Mannitol injection: -Inspect for crystals before administering (if present, warm solution to resolve) -Use filter for adminstration with concentrations >/=20% -Maintain serum osmolarity <300-320 mOsm/kg -Warnings: CNS toxicity, extravasation, nephrotoxicity -CI: severe renal disease (anuria, severe hypovolemia, pulmonary edema or congestion, active intracranial bleeding (except during craniotomy)

Answer 110

SAH: often from cerebral aneurysm rupute which vasospasms can occur even 3-21 days after bleed General TX: mainly supportive, surgery -Oral nimodipine: shown to improve outcomes in SAH -Prophylatic anticonvulsants can be considered in immediate post-hemorrhagic period to prevent seizures (long-term use NOT recommended, but may be considered for pts w/ risk factors - prior seizure, intracranial hematoma) Nidopine: non-DHP more selective for cerebral arteries due to increased lipophilicity, ONLY indicated for SA -PO taken for 21 days -If capsules cannot be swallowed and oral solution unavailable, capsule contents may be withdrawn with parenteral syringe then transferred to oral syringe -Label oral syringes: "For Oral Use Only" or "Not for IV Use" including commercially available solution -AVEs: hypotension -CI: use with strony CYP3A4 inhibitors -BBW: do NOT administer IV or by other parenteral routes --> death and serious life-threatening AVEs (cardiac arrest, CV collapse, hypotension, bradycardia) -DDIs: major substrate of CYP3A4