Cardiology Flashcards
Rhythm of the Heart: Describe the electrical pathway of the heart
- Electrical impulse begins with the sinoatrial (SA) node in the right atrium (heart’s natural pacemaker)
- Impulse travels from right atrium to left atrium, causing atria to contract (normal HR: 60-100bpm
- Signal reaches the atrioventricular (AV) node and begins to slow down
- Impulse travels to Bundle of His which splits into left and right branches for the signal to spread through the ventricles via Purjkinje fibers
Arrythmias:
-What is used to diagnosis?
-S/Sx of arrythmias
-Causes
-Types
Diagnosis: electrocardiogram (ECG)
-Holter Monitor: amulator ECG that records electrical activity continuously for 24-48 hours which can detect arryhthmias that are INTERMITTENT (heart going in and out of normal sinus rhythm)
S/Sx: some asymptomatic
-Heart flutter (beating too fast) or skipping a beat
-Dizziness, fatigue, and SOB (from not having enough circulation)
-Chest pain, lightheadedeness, syncope
Causes: myocardial ischemia or infarction MOST COMMON
-Damage to cardiac tissue (HTN, HF, heart valve disorders)
-Others: electrolyte imbalances (especially K, Mg, Na, and Ca), elevated sympathetic startes (hyperthyroidism, infection), drugs (illicit drugs, drugs that prolong QT interval, ANTIARRHYTHMICS)
Types:
-Supraventricular arrhythmias: atrial fibrillation (AF), atrial flutter, supraventricular reentrant tachycardias (paroxysmal supraventricular tachycardias or PSVTs)
-Ventricular arrhythmias: premature ventricular contractions (PVCs), ventricular tachycardia, ventricular fibrillation
Cardiac Action Potential: Ventricular
-Explain phase 0-4 that causes ions to move through channels and cause the electrical impulse of ther heart
Action potential: SA node (pacemaker) has AUTOMATICITY, other mycoytes: rely on threshold voltage
Phase 0: influx of sodium (Na) causes rapid ventricular depolarization, causing ventricular contraction (QRS Complex)
Phase 1: Na channels close; early rapid repolarization
Phase 2: influx of Ca and efflux of K causes a plateau in response
Phase 3: efflux of K causes rapid ventricular repolarization, causing ventricular relaxation
Phase 4: resting membrane potential is established; atrial deplorization occurs (P wave on ECG)
QT Intervals:
-What does the QT interval represent?
-What is considered a prolonged QT and the main risk associated with it?
-Causes of QT prolongation
QT Interval: ventricular depolarization and repolarization
Prolonged QT interval: >440-460 milliseconds (msec), but more worrisome when >500 msec
-Main risk: Torsade de Pointes, a lethal ventricular tachyarrhythmia that can cause sudden cardiac death
Causes of QT prolongation:
-Multiple QT prolonging drugs taken at the same time
-Higher doses of QT-prolonging drugs
-Reduced drug clearance due to renal disease, liver disease, or drug interactions
-Electrolyte abnormalities (hypokalemia, hypomagnesemia, hypocalcemia)
-HF or bradycardia
-Female
Drugs that cause QT prolongation
Antiarrhythmics: Class Ia (HIGHEST risk), Ic, and III
Anti-infectives: antimalarials, azole antifungals, MACROLIDES, QUINOLONES (including azithromycin - Zithromax has less DDIs, but NOT in regards to QT prolongation), lefamulin
Antidepressants: SSRIs (citalopram/escitalopram highest risk; sertaline is most preferred), TRICYCLIC ANTIDEPRESSANTS, mirtazapine, trazodone, venlafaxine
-Citalopram max dosing: 40mg (elderly, high risk: 20mg); escitalopram: max dosing 20mg (elderly, high risk: 10mg)
Antiemetics: 5-HT3 antagonists (-setrons), droperidol (one of WORST QT prolongers and NOT IN CHEMO GUIDELINES), metoclopramide, promethazine
Antiarrhythmic Drug Classifications: Class I-IV (Vaughan-Williams Classification)
Class I: Na Channel Blockers
-Ia: disopyramide, quinidine, procainamide
-Ib: lidocaine, mexiletine
-Ic: flecainide, propafenone
Class II: Beta-blockers
Class III: K Channel Blockers - dronedarone, dofetillide, sotalol, ibutilide, amiodarone
Class IV: Non-dihydropyridine CCBs - verapamil, diltiazem
Disopyramidine
-Brand
-MOA
-ROA
-AVEs
-Warnings/CIs
-BBW
Brand: Norpace, Norpace CR
MOA: class Ia antiarrhythmic - blocks Na channels (negative inotrope)
ROA: PO
AVEs: ANTICHOLINERGIC (ex. dry mouth, constipation, urinary retention)
Warnings/CIs:
-Warnings: PROARRHYTHMIC, hypotension, exacerbation of HF, worsening of BPH/urinary retention, narrow-angle glaucoma, MYASTHENIA GRAVIS (from anticholinergic effects)
-CI: 2nd/3rd degree heart block (unless functional artifical pacemaker present), cardiogenic shock, congeintal QT syndrome, sick sinus snydrome
BBW: reserve use for pts with LIFE-THREATENING ventricular arrhythmias
Quinidine:
-MOA
-ROA
-AVEs
-Warnings
-CIs
-BBW
MOA: class Ia antiarrhythmic - blocks Na channels (negative inotrope)
ROA: PO
AVEs: DRUG-INDUCED LUPUS ERTHEMATOSUS (DILE) - stop if buterfly rash occurs; DIARRHEA/STOMACH CRAMPING, rash, lightheadedness
Warnings: PROARRYHTMIC, HEMOLYSIS RISK (G6PD deficiency or positive Coombs test), hepatotoxicity
CIs: concurrent use w/ quinolones that prolong QT interval or ritonavir; 2nd/3rd heart block or idioventricular conduction delays (unless pt has functional artifical pacemaker), thrombocytopenia, thrombotic thrombocytopenic purpura (TTP), myasthenia gravis
BBW: may increase mortality risk in TX of AFib/A flutter and non-life threatening ventricular arrhythmias
Quinidine Counseling Points
- Take with food or milk to decrease GI upset (lots of potential diarrhea/stomach cramping side effects)
- CINCOHONISM (quinidine toxicity: tinnitus, hearing loss, blurred vision, HA, delirium)
-Avoid changes in Na intake: decreased Na can increase quinidine levels
-Alkaline foods/alkaline urine can increase quinidine levels
Procainamide:
-MOA
-ROA
-TX
-AVEs
-Warnings/CIs
-BBW
-Therapeutic levels and risks for toxicity
MOA: Class 1a antiarrhythmic - Na channel blocker (negative inotrope)
ROA: injection
TX: DOC for Wolff-Parkinson-White Syndrome
AVEs: hypotension, rash
Warnings/CIs: PROARRHYTHMIC
-Cis: heart block, systemic lupus erythematosus, TdP
BBW:
-Reserve for pts w/ life-threatening ventricular arrhythmias
-Potentially fatal blood dyscrasia (agranulocytosis): monitor in first 3 months and periodically thereafter
-Long-term use: positive antinuclear antibody (ANA) which can result in DILE (drug-induced lupus erythematosus)
Therapeutic levels: 4-10mcg/mL (combined w/ procainamide and NAPA)
-Metabolized to active metabolite, N-acetyl procainamide (NAPA) which is RENALLY cleared –> decrease dose when CrCl <50mL/min; slow acetlyators at risk for drug accumulation
Class Ib Antiarrhythmics
-Drugs/Brands
-MOA
-ROA
-TX
-Warnings
-CIs
-BBW
Drugs: lidocaine (Xylocaine), mexiletine
MOA: block Na channels (negative inotrope)
ROA: lidocaine (injection), mexiletine (PO)
TX: ventricular arrhythmias ONLY (no use in AF)
-IV lidocaine: refractory VT or cardiac arrest
Warnings: caution in elderly, hepatic impairment, and HF
-Mexiletine: blood dyscrasias, severe skin rxns (DRESS), proarrhythmic)
CIs: 2nd/3rd degree heart block (unless pt has functional artifical pacemaker)
-Mexiletine: cardiogenic shock
-Lidocaine: Wolff-Parkinson-White syndrome, Adam-Strokes syndrome, allergy to corn or corn-related products or amide-type anesthetics
BBW (mexiletine): reserve use for pts w/ life-threatening ventricular arrhythmias; abnormal liver fxn seen in pts w/ CHF or ischemia
Flecanide:
-MOA
-ROA
-AVEs
-Warnings/CIs
-BBW
MOA: class Ic antiarrythmic - blocks Na channels (negative inotrope)
ROA: PO
AVEs: dizziness, visual disturbances, dyspnea
Warnings/CIs:
-Warnings: avoid in severe hepatic and renal impairment
-CI: 2nd/3rd degree heart block (unless pt has functional artificial pacemaker), cardiogenic shock, structural heart disease (MI, HF), concurrent use of ritonavir
BBW: PROARRHYTHMIC especially if AF (DO NOT USE in chronic AF), resreve for life-threatening ventricular arrhythmias
-When treating atrial flutter, 1:1 atrioventricular conduction may occur (rapid ventricular rate), pre-emptive negative chrontropic therapy (digoxin, beta-blockers) can decrease the risk
Propafenone:
-Brand
-MOA
-ROA
-AVEs
-Warning/CIs
-BBW
Brand: Rythmol SR
MOA: Class Ic antiarrhythmic - Na channel blocker
-has significant beta-blocking effects, negative inotropic and proarrhythmic properties
ROA: PO
AVEs: taste disturbance (metallic), dizziness, visual disturbances, N/V
Warnings/Cis:
-PROARRHYTHMIC
-CIs: sinoatrial and atrioventricular disorders (unless pt has functional artificial pacemaker), sinus bradycardia, cardiogenic shock, hypotension, structural heart disease (HF, MI), bronchospastic disorders, marked electrolyte imbalances
BBW: reserve for pt w/ life-threatening ventricular arrhythmias
Amiodarone:
-Brand
-MOA
-ROA
-TX
-T/2
Brand: Nexterone, Pacerone
MOA: Class III antiarrhythmic - K+ channel blocker
-ALSO: blocks Na and Ca channels and alpha/beta adrenergic receptors
ROA: PO or injection
TX: preferred antiarrhythmic in HF
-Pulseless VT/VF, VT w/ pulse, secondary prevention of ventricular arrhythmias
-Off-label: AF/atrial flutter
T1/2: 40-60 DAYS
Amiodarone: IV preparation/considerations
- Infuse in NON-PVC container (polyolefin or glass) when >2 hours –> PVC tubing is okay
- Premixed IV bags: longer stability (Nexterone: comes in non-PVC and non-DEHP GALAXY plastic container)
- Use 0.22 micron filter
- Central line preferred
- Incompatible w/ heparin –> flush w/ saline instead
- Many Y-site additive incompatibilities
- Slow or decrease infusion rate if hypotension or bradycardia occurs
Amiodarone:
-AVEs
-Warnings
-CIs
AVEs: HYPOTENSION, BRADYCARDIA, dizziness, tremor/ataxia, malaise/fatigue, nausea, drug-induced lupus erythematosus (DILE), severe skin rxns (SJS/TEN)
Warnings (KNOW ALL):
-Molecule contains iodine: can induce an AUTOIMMUNE hyper- (Graves) or hypothyroidism (hypo more common = Hoshimotos as drug also partially inhibits peripheral conversion of T4 to T3)
-Visual impairment: optic neuropathy, corneal microdeposits (most pts get, but usually do NOT cover pupil and are not bothersome)
-Photosensitivity: blue-gray skin discoloration (sun protection required)
-Nephrotoxicity: peripheral neuropathy
-Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to use
-AVOID in pregnancy (teratogenic) and when breastfeeding if possible
CIs: IODINE HYPERSENSITIVITY, sick sinus syndrome, 2nd/3rd degree heart block, bradycardia causing syncope *unless using artificial pacemaker), cardiogenic shock
Amiodarone:
-BBW
-Monitoring
-DDIs/Drug adjustments needed when amiodarone is started
BBW:
-Pulmonary toxicity: check baseline chest X-ray, PFTs
-Hepatotoxicity: check baseline LFTs
-USE FOR life-threatening arrhythmias only, PROARRHYTHMIC –> continuous ECG monitoring and cardiac resuscitation should be available for initiation
Monitoring: ECG, BP, HR, ELECTROLYTES
-Q3-6 months: thyroid function, chest X-ray
-Q6 months: LFTs
-Regular eye exams
DDIs:
-Amiodarone can increase the levels of other drugs: inhibitor of CYP2C9 (moderate), 2D6 (moderate), 3A4 (weak), and P-gp
-Additive effects w/ drugs that decrease HR: non-DHP CCBs, digoxin, beta-blockers, clonidine, demedetomidine
-do NOT use sofosbuvir together: enhanced bradycardia effect of amiodarone
-When starting amiodarone, decrease digoxin by 50%, decrease warfarin by 30-50%, and do NOT exceed 20mg/day of simvastatin or 40mg/day of lovastatin
Dronedarone
-Brand
-MOA
-ROA
-AVEs
-Warnings
-CIs
-BBW
Brand: Multaq
MOA: Class III antiarrhythmic - primarily blocks K channels
ROA: PO
AVEs: PROARRHYTHMIC, diarrhea, bradycardia, asthenia
Warnings: HEPATIC FAILURE, PULMONARY TOXICITY (including fibrosis, pneumonitis), marked increased SCr, prerenal azotemia and acute renal failure (ususally during hypovelemia)
-Avoid in pregnancy and nursing mothers
CIs:
-Concurrent use of erythyromycin or strong CYP3A4 INHIBITORS and QT-PROLONGING drugs
-2nd/3rd degree heart block (unless pt has functional artificial pacemaker), HR <50bpm, QTc>500 msec, PR interval > 280 msec
-Lung or liver toxicity from previous amiodarone use
-Hepatic impairment
BBW: decpmpensated HF (NYHA Class IV or any class w/ recent hospitalization) or permanent AF (from increased risk of death, stroke, and HF)
How does dronedarone differ from amiodarone?
Dronedarone is a synthetic version of amiodarone does NOT contain iodine and has little effect on thyroid function, BUT the drug has further increased risk of heaptic failure and death/stroke and HF in pts w/ decompensated HF or permanent Afib
Sotalol
-Brand
-MOA
-ROA
-AVEs
-Warnings/CIs
-BBW
Brand: Betapace AF, Betapace, Sotylize, Sorine
-Betapace should NOT be substituted with Betaface AF (distributed w/ educaitonal info specific to AF/atrial flutter pts)
MOA: Class III antiarrhythmic - K= channel blocker
-ALSO: non-selective beta-blocker
ROA: PO or injection
AVEs: BRADYCARDIA, palpitations, chest pain, dizzinesss, fatgiue, dyspnea, N/V
Warnings/CIs:
-Warnings: PROARRHYTHMIC (increased risk of TdP w/ QT prolongation), worsening of HF, bronchoconstriction
-CIs: 2nd/3rd degree heart block (unless functional artificial pacemaker), congeintial or aquired long QT syndrome, sinus bradycardia, uncontrolled HF, cardiogenic shock, asthma
BBW: initiation and dose increases should be done in hospital w/ continuous ECG monitoring and experienced staff due to risk of VT and QT prolongation
-Adjust dosing interval on CrCl (<60mL/min) to decrease proarryhtmia
-QT prolongation directly related to CONCENTRATION
Ibutilide
-Brand
-MOA
-ROA
-TX
-AVEs
-BBW
Brand: Corvert
MOA: Class III antiarrhythmic - K channel blocker
ROA: injection
TX: cardioversion ONLY
AVEs: ventricular tachycardias (TdP), hypotension, QT prolongation
BBW: VERY PROARRHYTHMIC - aminister w/ continious ECG monitoring and experienced staff, confirm benefits outweight risks
-CORRECT HYPOKALEMIA and HYPOMAGENESMIA PRIOR TO USE AND DURING
Dofetilide
-Brand
-MOA
-ROA
-TX
-AVEs
-CIs
-BBW
Brand: Tikosyn
MOA: Class III antiarrhythmic - K channel blocker
ROA: PO
TX: preferred antiarrhythmic in HF
AVEs: ventricular tachycardias (TdP)
CIs: congenital or aquired long QT snydromes, QTc >440 msec at baseline
-do NOT use with: cimeditine, dolutegravir, itraconazole, ketoconazole, megestrol, prochlorperazine, trimethoprim, verapamil, Biktarvy –> inhibit renal tubular secretion of dofetilide
BBW: must be initiated w/ continous ECG monitoring and experienced staff to assess CrCl for A MINIMUM OF THREE DAYS, VERY PROARRHYTHMIC
Adenosine:
-Brand
-MOA
-ROA
-T1/2
-TX
AVEs
-CIs
Brand: Adenocard
MOA: activates adenosine receptors to decrease AV node contraction
ROA: injection
T1/2: <10 SECONDS
TX: SUPRAVENTRICULAR RE-ENTRANT TACHYCARDIAS (Paroxysmal suprventricular tachycardias - PSVTs)
AVEs: transient new arrhythmia, facial flushing, chest pain/pressure, GI distress, transient decrease in BP, dyspnea
CIs:
-DO NOT USE for ventricular tachycardia or for converting AF/A flutter
-2nd/3rd degree heart block, sick sinus syndrome or symptomatic bradycardia (except in functional pacemaker), bronchospastic lung disease
Class IV Anitarrhythmics:
-Drugs/Brands
-MOA
-ROA
-AVEs
-Warnings/CIs
-DDIs
Drugs: diltiazem (Cardizem, Cartia XT, Dilt XR, Diltzac, Tiazac, Taztia XT), verapamil (Calan, Convera, Verelan)
MOA: calcium channel blocker that slows HR and has negative intropic effects (decreased contraction)
ROA: PO or injection
AVEs: EDEMA, HA, DIZZINESS, HYPOTENSION, ARRYHTMIAS, HF, CONSTIPATION (especially verapamil), GINGIVAL HYPERPLASIA
Warnings/CIs:
-Warnings: 1st degree heart block w/ sinus bradycardia, increased LFTs
-CIs: severe hypotension (SBP <90mmHg), 2nd/3rd degree heart block/sick sinus syndrome (unless functional pacemaker), cardiogenic shock, systolic HF, Wolff-Parkinson’White Syndrome w/ Afib, HFrEF
DDIs: CYP3A4 substrate and inhibitors; P-gp subsrates
-Avoid grapefruit juice
-Use statins NOT metabolized by CYP3A4 (pravastatin, rosuvastatin, pitavastatin) or lower doses of statins
-Additive effects w/ amiodarone, digoxin, beta-blockers, dexmedetomidine (decrease HR)
Digoxin:
-Brand
-MOA
-ROA
-Therapeutic Range
-Dosing
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%
Digoxin:
-TX
-S/Sx of Toxicity
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
Digoxin:
-Reversal Agent
-Monitoring
-DDIs
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
Define the definitions of atrial fibrillation (AF):
-Pre-AF
-AF: paroxysmal, persistent, long-standing persistant
-Permanent AF
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
Rate versus Rhythm Control in AFib
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
Cholesterol:
-Role in body
-Role of bile acids
-What is atherosclerosis?
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
Define the types of cholesterol and their desirable/high levels. What are the calculations for non-HDL, LDL, and total cholesterol (TC)?
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)
Dyslipidemia:
1. Lowering LDL by 1% reduces ASCVD risk by ___% (the likelihood a pt having teir first CV event in the next 10 years).
- What factors do the ASCVD risk score consider?
- What are the scenarios a pt will get put on a statin without needing their ASCVD risk score calculated?
- If a pt’s risk is uncertain, what other factors can be considered?
- 1%
- 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
- *Clinical ASCVD, DM, or LDL >/=190
- 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*
Drugs that can raise:
-LDL and TG
-LDL only
-TG only
Conditions that can increase cholesterol
*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
Dyslipidemia: TX
-Non-pharm
-Natural products
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
Determine statin intensity ot put pt on in the following:
-Clinical ASCVD (CHD, stroke/TIA, or PAD)
-Primary severe dyslipidemia (LDL >/=190)
-DM and age 40-75 yo + multiple ASCVD risk factors
-DM and age 40-75 yo + any ASCVD risk
-Age 40-75 yo with LDL 70-189 + ASCVD risk of >/=20%
-Age 40-75 yo with LDL 70-189 + AASCVD risk of 7.5-19.9% + risk factors
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
Statins: Intensity / Dosing
1. High intensity statins are intended to lower LDL by about _____% or more from baseline. Moderate intensity will lower by ____-____%, and low intensity will lower by ____% or less.
- Statins and doses of low, moderate, and high intensity statins.
- Statin equivalency dosing
- When to dose adjust?
- 50%; 30-49%; 30%
- -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
- 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)
*Statins: What are the most common side effects among the drug class and management? *
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
Statins: What is the maximum daily dose with DDIs (G-PACMAN)?
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.
Statins:
-Drugs/Brands
-MOA
-ROA
-Which ones should be taken in the PM and why?
-Effects on cholesterol
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%
Statins:
-Warnings
-CIs
-Monitoring
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
Ezetimibe:
-Brand
-MOA
-ROA
-TX
-Effects on cholesterol
-AVEs
-Warnings
-Monitoring
-DDIs
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
Proprotein Convertase Subtilisn/Kexin Type 9 Monoclonal Antibodies (PCSK9is):
-Drugs/Brand
-MOA
-ROA
-Adminsitration considerations
-TX
-Effects on cholesterol
-AVEs
-Warnings
-Monitoring
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
Bile Acid Sequestrants / BIle Acid Binding Resins:
-Drugs/Brands
-MOA
-ROA
-Administration considerations
-TX
-Effects on cholesterol
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
Bile Acid Sequestrants / BIle Acid Binding Resins:
-AVEs
-Warnings
-CI
-DDIs
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
Fibrates:
-Drugs/Brand
-MOA
-ROA
-Effects on cholesterol
-AVEs
-Warnings
-CI
-Monitoring
-DDIs
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
Niacin:
-Brand
-MOA
-ROA
-Administration considerations
-Effects on cholesterol
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%
Niacin:
-AVEs
-Warnings
-CIs
-Monitoring
-DDIs
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
Fish oils:
-Drugs/Brands
-MOA
-ROA
-Administration considerations
-When are fish oils indicated?
-Effects on cholesterol
-AVEs
-Warnings
-DDis
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)
Miscellaneous drugs for cholesterol:
1. What is the MOA of bempedoic acid, and when would it be indicated?
- What is the MOA of inclisiran and its ROA?
- When should and shouldn’t inclisiran be added?
- Which specialty drugs are approved for homozygous familial hypercholesterolemia with a REMS progrm for hepatotoxicity?
- -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 - -MOA: inhibits intracellular production of PCSK9 via ribonucleic acid (RNA) interference, resulting in increased activity of LDL receptor
-ROA: SQ injection - -Approved for primarily hyperlipidemia or familial in combo with a statin
-Do NOT use with PCSK9 mAb due to overlapping MOA - lomitapide (Juxatipid), mipomersen (Kynamro)
Hypertension (HTN):
-Etiology
-Pathophysiology
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)
Drugs that increase BP
-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)
Hypertension:
-Diagnosis
-How to properly take BP
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
Hypertension:
-Lifestyle management
-Natural products
-When to start pharmacotherapy
-BP goal
-How often to check BP and titrate medication if NOT at goal
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*
Hypertension: General TX with pharmacotherapy
-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)
Hypertension: TX in pregnancy
-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)
Brand names for combination HTN medications:
1. lisinopril / HCTZ = __________
- losartan / HCTZ = __________
- olmesartan / HCTZ = _________
- valsartan / HCTZ = __________
- Zestoretic
- Hyzaar
- Benicar HCT
- Diovan HCT
Brand names for combination HTN medications:
1. benazepril / amlodipine = __________
- valsartan / amloidpine = ___________
- atenolol / chlorthalidone = ___________
- bisoprolol / HCTZ = ___________
- triamterene / HCTZ = ___________
- Lotrel
- Exforge
- Temoretic
- Ziac
- Maxzide, Maxzide-25
Thiazide diuretics:
-Drugs/Brands
-MOA
-ROA
-TX
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
Thiazide Diuretics:
-Chlorthalidone dosing
-Hydrochlorothiazide dosing
-Which thiazide is the most potent?
-Which thiazide is available as IV?
-Administration/counseling considerations
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
Thiazide diuretics:
-AVEs
-Warnings
-CIs
-Monitoring
-DDIs
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
Dihydropyridine CCBs (DHP CCBs):
-Drugs/Brands
-MOA
-ROA
-Administration considerations
-TX
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
Dihydropyridine CCBs (DHP CCBs):
-AVEs
-Warnings
-CIs
-Monitoring
-Specific considerations in clevidipine
-DDIs
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
Non-DHP CCBs:
-Drugs/Brands
-MOA
-ROA
-TX
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
Non-DHP CCBs:
-AVEs
-Warnings
-CIs
-Monitoring
-DDIs
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)
Renin-Angiotensin-Aldosterone System (RAAS):
1. Angiotensinogen is released from the _________. Renin released from the ________ converts angiotensinogen to angiotensin I.
- Angiotensin I is converted to angiotensin II via ____________release from the lungs which can be inhibited by _________. Angiotensin II can be inhibited by __________.
- What are the effects of angiontensin II?
- What is the benefit of using drugs that inhibit RAAS in CKD and HF?
- What are black patients more at risk for when using medications that inhibit RAAS?
- Liver; Kidney
- Angiotension-converting enzyme (ACE); ACEIs (ACE inhibitors); angiotensin receptor blockers (ARBs)
- Aldosterone secretion which leads to increased Na and water retention AND vasoconstriction which increases systemic vascular resistance (SVR), both increasing BP
- -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 </=40%
- Angioedema
Angiotensin-Converting Enzyme Inhibitors (ACEIs):
-Drugs/Brands
-MOA
-ROA
-TX
-AVEs
-Warnings
-CIs
-BBW
-Monitoring
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
Angiotensin Receptor Blockers (ARBs):
-Drugs/Brands
-MOA
-ROA
-AVEs/Warnings
-CI
-BBW
-Monitoring
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
Aliskiren: MOA
directly inhibits renin, preventing conversion of angiotensinogen to angiotensin I
What are DDIs with RAAS inhibitors (ACEIs, ARBs, aliskiren)?
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
- Entresto - do NOT use in combo (ACEIs: need 36 hour washout period)
- Lithium - ACEIs/ARBs can decrease lithium renal clearance, increasing toxicity risk
Potassium-sparing Diuretics:
-Drugs/Brands
-MOA
-ROA
-TX
-AVEs
-CIs
-BBW
-Monitoring
-DDIs
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
Beta-blockers:
-MOA
-Beta-1 selective blockers
-Beta-1 selective blockers w/ nitric oxide-dependent vasodilation
-Non-selective beta blockers (beta 1 and 2)
-Non-selective beta blockers and alpha-1 blockers
-Beta blockers with partial intrinsic sympthomimetic activity (ISA) that partially simulate beta receptors while blocking catecholamines (NE)
-TX
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
Beta-1 selective blockers:
-ROA
-Drugs that must be taken with food
-Metoprolol tartrate: IV: PO ratio
-Converting from metoprolol tartrate to metoprolol succinate
-Administration directions for Kapsargo Sprinkle
-Administration directions for Toprol XL
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
Beta-1 Selective Blockers:
-AVEs
-Warnings
-CI
-BBW
-Monitoring
-Nebivolol specific considerations
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)
Beta-1 and Beta-2 Blockers (Non-selective beta-blockers): what are some other considerations beyond those for beta-1 blockers?
- CI in bronchial asthma
- Can prevent variceal hemorrhage in pts w/ portal HTN
- Propranolol: high lipid solubility (lipophilic) and crosses BBB –> can be helpful in non-cardiac conditions (migraine prophylaxis, essential tremor), but MORE CNS side effects
Non-selective beta-blockers with also alpha-1 inhibition: what are some other considerations beyond those for beta-1 blockers and non-selective beta-blockers?
- *CI: severe hepatic impairment
- Warnings: intraoperative floppy iris syndrome (IFIS) has occurred in cataract surgery
- AVEs: weight gain, edema*
- 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)
- Labetalol: DOC in pregnancy, injection common in hospital setting and can be administered as IVP or CIV
Beta-blocker DDIs
- Caution with other drugs that lower HR
- Can enhance hypoglycemic effects of insulin and sulfonylureas and mask symptoms (except sweating and possibly hunger)
- Can decrease insulin secretion, causing hyperglycemia
- Carvedilol, propranolol, metoprolol, nebivolol: major substrate of CYP2D6
- Carvedilol, propranolol: inhibitors of P-gp and can increase P-gp substrates (cyclosporine, dabigatran, digoxin, ranolazine)
Clonidine, guanfacine:
-Brands
-MOA
-ROA
-TX
-AVEs
-Warnings
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
Dosing frequency of clonidine patches and administration considerations
-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
Methyldopa:
-MOA
-ROA
-TX
-AVEs
-Warnings
-CIs
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
Direct Vasodilators:
-Drugs/Brands
-MOA
-ROA
-TX
-AVEs
-Warnings
-CIs
-Monitoring
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)
Hypertensive Crisis: define emergency versus urgency and general TX
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
Stable Angina:
-Define: angina, stable angina, unstable angina, and vasospastic angina
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
Stable Angina:
-Pathophysiology
-Risk factors
-Diagosis
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
Stable angina:
-Non-pharmacotherapy TX
-General drug TX
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
Aspirin (ASA):
-Brands
-MOA
-ROA
-Administration considerations
-Dosing for stable angina
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*
Aspirin (ASA):
-AVEs
-Warnings
-CIs
-DDIs
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
Clopidogrel:
-Brand
-MOA
-ROA
-Dosing for stable angina
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)
Clopidogrel:
-AVEs
-Warnings
-CI
-BBW
-Monitoring
-DDIs
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)
Explain why beta-blockers and CCBs can work on the heart as antianginals for stable angina
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)
- Increase myocardial oxygen supply by increasing blood flow to coronary arteries
Nitrates:
-Drugs/Brands (list short acting versus long-acting)
-MOA
-ROA
-Short-acting nitrate dosing
-BiDil indication
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
Nitrates:
-AVEs
-Warnings
-CIs
-Monitoring
-DDIs
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
Nitrates Counseling:
-SL nitroglycerin
-TL spray nitroglycerin
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
Nitrates Counseling:
-Long-acting nitrates
-Nitroglycerin patch
-Nitroglycerin ointment
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
Ranolazine:
-Brand
-MOA
-ROA
-TX
-AVEs
-Warnings
-CI
-Monitoring
-DDIs
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
Acute Coronary Syndrome (ACS):
1. What does ACS result from?
2. Risk factors
3. S/Sx
4. Diagnosis
- 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
- 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
- -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
Acute Coronary Syndrome (ACS): Diagnosis
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*
Acute Coronary Syndrome (ACS): General TX
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
ACS: MONA
-Explain the purpose of the medications
-Explain timing of medications
-Discuss administration considerations/doses
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)
ACS: GAP
-Explain the purpose of the medications
-Explain timing of medications
-Discuss administration considerations/doses
-What medications to avoid in acute setting?
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
ACS: BA
-Explain the purpose of the medications
-Explain timing of medications
-Discuss administration considerations/doses
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
Antiplatelet drugs/Brands and MOAs:
-ASA
-P2Y12 inhibitors
-GPIIb/IIIa receptor antagonists
-Protease-activated receptor-1 antagonists
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
P2Y12 Inhibitors:
1. Which drugs are prodrugs that irreversibly bind to the receptor classifed as thienopyridines?
- Maintenance dose for clopidogrel and ticagrelor
- Which one comes as an injection, and when is it indicated?
- Which one is sensitive to moisture and needs to be dispensed in original container?
- DDIs
- Clopidogrel, Prasugrel
- -Clopidogrel: 75mg PO QD
-Ticagrelor: 90mg PO BID x1 year then 60mg BID - 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
- Prasugrel
- 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
P2Y12 Inhibitors:
-AVEs
-Warnings
-CI
-BBW
-When to stop before elective surgery
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
Glycoprotein IIb/IIIa Receptor Antagonists:
-Drugs/Brands
-ROA
-TX
-AVes
-CI
-Monitoring
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
Vorapaxar:
-Brand
-MOA
-ROA
-TX
-AVEs
-Warnings
-BBW
-DDIs
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
Fibrinolytics:
-Drugs/Brands
-MOA
-ROA
-TX
-AVes
-CIs
-Monitoring
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
Secondary Prevention after ACS:
-Lifestyle
-Drugs for secondary prevention
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)
Secondary Prevention after ACS:
-OTC choices for pain
-Considerations if pt undergoes triple antiplatelet therapy
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
Chronic Heart Failure (CHF):
-Define
-Ischemic versus non-ischemic HF
-Define cardiac output (CO) and cardiac index (CI)
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
Chronic Heart Failure (CHF):
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)
Chronic Heart Failure (CHF):
-Diagnosis and types of HF
-ACC/AHA Staging
-NYHA Functional Class
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
Drugs that worsen or cause heart failure (HF)
“Drug Informatoin NATION”
D: Dipeptidyl peptidase 4 inhibitors (alogliptin, saxagliptin)
I: Immunosuppressants (TNF inhibitors: adaliumumab, etanercept; interferons)
N: Non-DHP CCBs (if LVEF </=50%)
A: Antiarrhythmics (class I agents - quinidine, flecainide; dronedarone –> amiodarone and dofetllide are preferred in HF)
T: Thiaziolidinediones
I: Itraconazole
O: Oncology drugs (anthracyclines - doxorubicin, daunorubicin)
N: NSAIDs
Chronic Heart Failure (CHF):
-Lifestyle Management
-Natural Products
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
- Avoid excessive sodium intake (restrict to <1500mg/day in those w/ HTN)
- Restrict fluds in stage D HF (1.5-2L/day)
- Smoking cessation and stop use of illicit drugs
- Reduce alcohol intake
- Obtain recommended vaccines: influenza, pneumococcal
- Reduce weight
- 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
HFrEF: General TX
-Explain why certain drugs may be added
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
- 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
- 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
- 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
- Vericiguat - decreases risk of hospitalizations and CV death after recent hospitalization or need for IV diuretics (worsening pt on first-line therapies)
Sacubitril/Valsartan:
-Brand
-MOA
-ROA
-TX
-AVEs/warnings
-CIs
-BBW
-Monitoring
-DDIs
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
HFrEF targeted doses for:
1. Entresto
- Enalapril
- Lisinopril
- Quinapril
- Ramipirl
- Entresto: 97/103mg PO BID
- Enalapril: 10-20 mg PO BID
- Lisinopril: 20-40mg PO QD
- Quinapril: 20mg PO BID
- Ramipril: 10mg PO QD
**Most ACEIs target is 40mg/day
HFrEF targeted doses for:
1. Losartan
- Valsartan
- Metoprolol succinate
- Carvedilol
- Spironolactone
- Losartan: 50-150mg PO QD
- Valsartan: 160mg PO BID
- Metoprolol succinate: 200mg PO QD
- Carvedilol:
-IR: 25mg PO BID (if 85kg or less) or 50mg BID (if >85kg)
-CR: 80mg PO QD - Spironolactone: 25-50mg PO QD
HFrEF TX:
1. When should beta-blockers be D/C in HF?
- When should spironolactone or eplerenone NOT be initiated in HF?
- Which SGLT2is are approved for HFrEF and their doses?
- DURING acute decompensated HF if hypotension or hypoperfusion present –> taper over 1-2 weeks to avoid acute tachycardia, HTN, and/or ischemia
- 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
HFrEF TX:
1. What is a dual SGLTi that inhibits 1 and 2 that is approved to decrease CV death, hospitalization, and urgent visits for HF?
- True or False: hydralazine/isosoribide dinitrate (BiDil) can cause nitrate tolerance overtime.
- What beta-blockers are only indicated in HFrEF?
- sotagliflozin (Jardiance)
- False
- metoprolol succinate, bisoprolol, carvedilol
Loop Diuretics:
-Drugs/Brands
-MOA
-Oral equivalent dosing
-IV:PO ratio
-Administration considerations
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
Loop Diuretics:
-AVEs
-Warnings
-CIs
-BBW
-Monitoring
-DDIs
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
Ivabradine:
-Brand
-MOA
-ROA
-TX
-AVEs
-Warnings
-CI
-Monitoring
-DDIs
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
Digoxin:
-Brand
-MOA
-ROA
-TX
-Typical dose, when to dose adjust, and therapeutic range
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
Digoxin:
-AVEs
-Warnings
-CIs
-Monitoring
-Signs of toxicity
-Antidote
-DDIs
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
Vericiguat:
-Brand
-MOA
-ROA
-TX
-AVEs
-CI
-BBW
-DDIs
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
Potassium chloride:
-Brands
-TX
-AVEs
-Warnings
-CIs
-Monitoring
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)
Potassium chloride: Administartion considerations in ER capsules, ER tablets, oral packet, and oral solution
-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
Strokes:
-Define stroke
-Causes of ischemic vs. hemorrhagic stroke
-Define transient ischemic attack (TIA)
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
Strokes:
-Risk Factors
-Presentation
-Diagnosis
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
Ischemic Stroke: Acute Management
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
Ischemic Stroke: Secondary Prevention
- HTN management - BP goal of <130/80mmHg; BP mediation may be often initiated after first several days following a stroke
- Dyslipidemia - high-intensity statin, adding ezetimibe or PCSK9i if LDL goal not met
- DM - GLP-1 agonist or SGLT2i can help with ASCVD risk
- Afib - cardioembolic stroke due to Afib requires anticoagulation
- 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 </=5): ticagrelor + ASA up to 30 days
-*NO added benefit in increasing ASA dose in pts already have taken who had stroke or TIA *–> alternative often considered
-ASA dose in ischemic stroke: 50-325mg QD
Extended-release dipyridamole/aspirin:
-Brand
-MOA
-ROA
-Administration considerations
-AVEs beyond ASA warnings
-Warnings beyond ASA warnings
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
Intracranial Hemorrhage (ICH): General TX and main drug considerations
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)
Subarachnoid Hemorrhage (SAH): General TX and main drug considerations
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
