Module 10 Data: HF & HTN Flashcards
1
Q
Please take special notice of the terms that are used. They will be critical to understanding this condition and ensure the patient is on all appropriate medications.
Heart Failure (Note the term congestive heart failure is not used because not all heart failure is associated with congestive symptoms and thus the need for diuretics is only where congestive symptoms are present)
- Left sided vs Right sided
- NYHA functional classification
- Class I No limitation of physical activity
- Class II Slight limitation of physical activity
- Class III Marked limitation of physical activity
- Class IV Unable to carry on any physical activity w/o discomfort
- As you can see from the descriptions, this classification system is highly subjective .. with a patient able to move back and forth between stages based on degree of limitations (and how well they are being managed).
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2
Q
ACC/AHA classification
- Stage A –High risk; no structural abnormalities
- Stage B –Structural abnormalities; no symptoms
- Stage C –Structural abnormalities; current or previous symptoms
- Stage D –End stage symptoms refractory to treatment
- Unlike NYHA’s classification, a patient can NOT move back to an earlier stage. You can also see that this system promotes identification and screening of individuals at risk.
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3
Q
Please note medications that prevent or improve clinical symptoms (morbidity) vs those that slow progression and improve survival (mortality / outcomes)
o When considering certain classes of medication, select agents are approved OR are dosed to a specific target dose
Examples
Beta blockers - All patients with stable NYHA Class II or III HF due to LV dysfunction OR ACC/AHA Stage B if s/p MI or asymptomatic LVH or EF < 40%) should receive a beta-blocker (unless not tolerated).. carvedilol, metoprolol extended/controlled release and bisoprolol are the only beta blockers that should be used in HF (CIBIS II, MERIT HF trial, COPERNICUS trial) …titrated to “target doses” if possible
Beta blockers may reduce mortality in stable patients with class II and III heart failure and possibly class IV heart failure
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4
Q
- Please note medications that prevent or improve clinical symptoms (morbidity) vs those that slow progression and improve survival (mortality / outcomes)
o When considering certain classes of medication, select agents are approved OR are dosed to a specific target dose
Examples
ACEIs /ARBs - ALL patients with left ventricular dysfunction (HFrEF) and current or prior symptoms should receive an ACEI (unless contraindicated or patient is intolerant) .. titrated to “target doses” if possible
slow progression, decrease mortality as well as the combined risk of death and hospitalizations
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5
Q
- Please note medications that prevent or improve clinical symptoms (morbidity) vs those that slow progression and improve survival (mortality / outcomes)
o When considering certain classes of medication, select agents are approved OR are dosed to a specific target dose
Examples
Diuretics - for patients with congestive symptoms .. they DO NOT provide any mortality benefit
NOTE term: Diuretic resistance- described below
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6
Q
Other interventions to review for HF include ARNIs, MRAs, ISDN/Hydralazine, Digoxin, SGLT2Is
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7
Q
- –2/3 of cases of HF attributable to CHD -Reduction in muscle mass - ♯1 cause, s/p MI where heart tissue dies (hypokinetic). The › the infarcted, area the › degree of HF (Table 6-1, 6-3)
o Although statins can not be recommended on the diagnosis of HF alone, ASCVD is typically part of the clinical picture …. Thus virtually ALL patients with HF should be on a statin 2/2 to ASCVD
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8
Q
- Definition of HF: structural or functional change that impairs the hearts ability to provide enough CO to support metabolic function
o o Congestion is not a necessary component of HF
o o Left-sided failure - Blood not effectively pumped from the left ventricle to the peripheral circulation
o o Right-sided failure - Blood not effectively pumped from the right ventricle into the lungs
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9
Q
- Each of the classification schemes are used in various clinical venues. Each have their own unique advantages and disadvantages
o o NYHA
o o ACA/AHA
See Above
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10
Q
- Diuretics - Reduce symptoms associated with fluid retention (pulmonary / peripheral edema), improve exercise tolerance.
o No Fluid overload, NO need for additional or aggressive diuresis. Note, that in some patients the initiation of beta-blockers can result in edema, thus those with current or recent history of edema should have a diuretic on board
o Caution: CO output is partially being maintained by volume and high filling pressures. Excessive diuresis may compromise CO
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11
Q
- Loop diuretics (eg. torsemide, furosemide) DOC in HF.
o § ADR’s –electrolytes (Na, K, Mg, Ca wasting), ototoxicity
Hypokalemia augmented by ↑ [aldosterone] in HF as part of a compensatory mechanism
This (hypokalemia) may increase the potential for digoxin toxicity (if used)
Watch your labs
Additional potassium supplementation may be necessary
Recall that MRAs should not be thought of as a potassium sparing diuretic in the context of heart failure and thiazide are generally not effective in hear failure (and CrCl < 30ml /min) and are more suited for use in HTN.
What agents used in HF may offset the need for K replacement and is a reason monitoring is so important?
ACEI/ARB, ARNIs, aldosterone antagonists (all of these increase [K]
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12
Q
o Goals of reducing edema and improving symptoms can be generally be achieved with a loop diuretic alone.
o Greater diuretic capabilities and they retain their efficacy with decreased renal function
o Appropriate use of diuretics is key to the success of other drugs used for HF
too little diuretic: diminish patients response to ACEI’s
too much diuretic: volume contraction, increases risk of hypotension and renal insufficiency
o These agents have no effect on disease progression or mortality
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13
Q
o Thiazides - Utilization in HF less than loops as a single agent, but as combination therapy with loops for synergistic effect with demonstrated diuretic resistance
§ Note: Thiazides are usually insufficient in dealing with edema and volume overload in patients with HF (except in maybe very early disease). In fact, even increasing doses has little benefit in improving diuresis . In addition, they are NOT effective with a CrCl < 30ml/min. Discontinue and replace with a loop diuretic in symptoms of edema volume overload in HF
§ Note: Ocassionally, some thiazides (metolazone) may be used in combination with loops for their [K] sparing properties
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14
Q
o § Diuretic Resistance - poor response to a diuretic (loop) / edema refractory to loop diuretics that have been optomized
Overcoming diuretic resistance
increase CO to increase RBF and delivery of drug to nephron
vasodilators – reverse the widespread vasoconstriction in HF, including that of the renal vasculature which is restricting GFR
if on a loop, increase freq. / dose
if insufficient response – additional agents added on to get sequential response (ex optomized loop + metolazone or thiazide)
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15
Q
- Mineralocorticoid antagonists (MRAs) - in one respect, they can be thought of a potassium sparing diuretic, however in HF the non-renal effects (↑ BR sensitivity ,↓ LVH, ↓/stop myocardial / vascular fibrosis) may outweigh the renal effects of these agents and play an important role in decrease morbidity and mortality
o spironolactone, eplerenone
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16
Q
- Positive (+) inotropes improve the symptoms of HF by moving patients to a higher ventricular function curve, that is, greater CO for a given filling pressure (or preload or PCWP)because of greater contractile force
o o Digoxin
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17
Q
- Vasodilators - improve the symptoms of HF by moving patients to a higher ventricular function curve and by reducing filling pressures
o o ACEI / ARB/ ARNI
o o ISDN / NTG – (venodilators )Reduces filling pressures and pulmonary congestion
o o Hydralazine - arterial dilator
§ Use combination regimen w/ ISDN in certain populations
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18
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- Impact of dilators on survival / mortality
o ACEIs / ARBs – improve survival, decrease mortality - neprilysin inhibitor - (aka ARNI - angiotensin receptor neprilysin inhibitor)
o o Neprilysin is a neutral endopeptidase that degrades several endogenous vasoactive peptides including natriuretic peptides, bradykinin, and adrenomedullin
o o Inhibition of neprilysin increases levels of these peptides and counters neurohormonal over activation that contributes to vasoconstriction, sodium retention, and maladaptive remodeling
o o In combination with valsartan - Chronic HF class II-IV
§ Clinical benefits: Decrease mortality, heart failure hospitalization, and risk for worsening heart failure compared to enalapril in patients with symptomatic heart failure and ejection fraction ≤ 40%.
§ For patients with NYHA class II to IV HFrEF (LVEF ≤40 percent) with no improvement in NYHA functional class or worsening symptoms on optimally titrated ACE inhibitor (or ARB), beta blocker, mineralocorticoid receptor blocker, and diuretics
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19
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o o Guidelines - In patients with chronic symptomatic HFr EF NYHA class II or III who tolerate an ACE inhibitor or ARB, replacement by an ARNI is recommended to further reduce morbidity and mortality
Note: this is a strong recommendation, but based on moderate (vs high) level of evidence
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20
Q
- Hydralazine + ISDN – improve survival, decrease mortality
- Alpa-1 antagonist – no effect
- CCB (verapamil, diltiazem) - increase mortality ( amlodipine, felodipine) - no change
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21
Q
Beta blockers - use may seem contradictory. Why ?
* Beneficial effects in stable angina:
o Block the effects of high [NEPI] and other sympathetic NT
o Decrease ventricular arrhythmias (sudden cardiac death)
o Decrease cardiac hypertrophy (remodeling) and cardiac cell death (apoptosis)
o Decrease vasoconstriction and heart rate
o Decrease mortality
* o Start very low, titrated very slow (too fast = decompensation)
* o Caution NYHA III IV – may further impair contractility
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22
Q
Emerging therapies:
* HCN channel blocker (Ivabradine)- Indicated to decrease risk of hospitalization for worsening HF in patients with stable, symptomatic (NYHA class II-III) chronic heart failure with EF ≤ 35%, who are in sinus rhythm with resting heart rate ≥ 70 BPM and either are on guideline directed evidence based therapy, including maximally tolerated doses of beta blockers or have a contraindication to beta-blocker use.
* SGLT2Is reduces risk of worsening heart failure, cardiovascular death, and all-cause death in adults with heart failure with reduced ejection fraction, regardless of presence of diabetes
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23
Q
- Vericiguat - is indicated to reduce the risk of cardiovascular death and heart failure (HF) hospitalization following a hospitalization for HF or need for outpatient IV diuretics, in adults with symptomatic chronic HF and ejection fraction less than 45%.
o Patients with age less than 75 years, chronic renal insufficiency, LV ejection fraction <45%, and NYHA functional class III or IV appear to receive further benefit. Further investigation is needed to elucidate the role of vericiguat amongst available evidence-based therapies and target populations.
o Achieving the “quintuple therapy” of RAAS inhibition (ACEi/ARB/ARNI and MRA), beta blocker, SGLTi, and an sGC modulator could be the ideal regimen, but it remains to be seen how one accomplishes this through the ritual of outpatient medication titration and adherence. - Consider goals of therapy including prevention and management of underlying disorders
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24
Q
- ACE (or ARB) - By blocking ACE, we are decreasing production of ANG II and aldosterone and attenuating the deleterious effects of neurohormones
o Decreased hospitalization (approximately 30%), Symptom improvement (↓ morbidity), Improved clinical status (Improved EF), Less diuretic required, Improve exercise tolerance AND decrease mortality regardless of race, age or gender.
All patients with LV dysfunction (regardless of NYHA classification) should receive an ACE I (unless intolerant) - Benefits are observed in mild, moderate or severe HF with benefits in days and symptomatic improvement after several weeks
Who should NOT receive an ACEI
Patients who have experienced angioedema (allergic reaction)
Pregnant or planning to become pregnant
Bilateral renal arterial stenosis
Caution in : SBP < 80 mmHg ; SCr > 3mg/dl ; K > 5 mEq/L
Note: renal dysfunction should not be a contraindication to ACE I use in these patients. These patients should just be monitored closely for development of ARF and/or hyperkalemia
o These agents are doses to a “target dose” if possible. Start low, go slow titrating every few weeks to decrease the risk of orthostasis (“first dose phenomenon”)
o Monitoring should include K, SCr, BUN, BP, dry cough
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o Although you do not need to memorize doses, you must know that they are dosed to a target dose (if possible)
ACEi and ARBs
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* ARBs are considered a reasonable alternative to a patient intolerant of ACEI or if they are already taking an ARB it is reasonable to continue
o There is NO reason to choose and ARB over an ACEI in the absence of ACEI intolerances (listed below)
E.g. Dry Cough
E.g. Angioedema
o Dosing is to a TARGET DOSE if possible. Start low, go slow titrating every few weeks because ... same reason as ACEIs
o Monitoring should include K, SCr, BUN, BP
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o Routine combined use of an ACE inhibitor ARB is potentially harmful
o Although you do not need to memorize doses, you must know that they are dosed to a target dose (if possible)
* ARNIs - Sacubitril /Valsartan - Neprilysin is a neutral endopeptidase that degrades several endogenous vasoactive peptides including natriuretic peptides, bradykinin, and adrenomedullin. Inhibition of neprilysin (Sacubitril) increases levels of these peptides and counters neurohormonal over activation that contributes to vasoconstriction, sodium retention, and maladaptive remodeling
o Although you do not need to memorize doses, you must know that they are dosed to a target dose (if possible)
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o ACC /AHA 2016: In patients with chronic symptomatic HFrEF NYHA class II or III who tolerate an ACE inhibitor or ARB, replacement by an ARNI is recommended to further reduce morbidity and mortality
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o ESC / SIGN: sacubitril/valsartan recommended instead of ACE inhibitor or angiotensin receptor blocker (unless contraindicated) in patients with New York Heart Association class II-III heart failure and left ventricular ejection fraction ≤ 40% with ongoing symptoms of heart failure despite optimal treatment
o Starting dose is 49/51 mg twice daily. After two to four weeks, the dose is doubled to the target maintenance dose of 97/103 twice daily, as tolerated by the patient.
o Monitoring similar to ACEI / ARB
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* Beta blockers
o Best studied beta blockers in HF (and only ones approved) are carvedilol, metoprolol succinate extended/controlled release (NOT metoprolol tartarate) and bisoprolol. If a patient is on another BB, it must be changed (gradually) to one of the three with evidence in HF
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o Benefits are in addition to those achieved with ACEIs - Decrease mortality ( 35% decrease), Decrease hospitalizations, Symptom improvement (decrease morbidity), Improved clinical status ( ↑EF, ↓tachyarrhythmias), Slowed disease progression (, ↓ remodeling, ↓ apoptosis) regardless of race, age or gender.
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o All patients with (hemodynamically) stable NYHA Class II or III (and possibly Class IV) HF due to LV dysfunction should receive a beta-blocker (unless not tolerated) OR ACC/AHA stage B if s/p MI or asymptomatic LVH or EF < 40%
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o o Who should not receive a BB
§ Volume overload
§ Symptomatic bradycardia
§ ACTIVE NYHA II or III (or IV) until stable
§ Acute decompensation
§ Advanced heart block
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o Initiation can begin when patient is stable / euvolemic. Dosing is to a TARGET DOSE if possible. Start low, go slow . Too aggressive increase may result in decompensation. Should not be prescribed without a diuretic in patients with current or recent history of fluid retention
Initial doses - bisoprolol 1.25 mg qd, carvedilol 3.125 bid, carvedilol CR 10mg qd, metoprolol succinate CR/XL 12.5 -25 mg qd
Target doses (if you can get there) - Bisoprolol 10 mg qd, carvedilol 25 mg bid, carvedilol CR 80mg qd, metoprolol XL 200 mg qd
Although you do not need to memorize doses, you must know that they are dosed to a target dose (if possible)
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Monitoring should include HR, BP
§ If hypotension alone is problematic, decrease dose of ACEI ARB / ARNI. Higher BB doses are associated with greater mortality reductions
§ If Edema is problematic - increase the diuretic
§ Fatigue / weakness - should resolve spontaneously in a few weeks
patients need to be aware of the benefits of beta blockers and that beta blocker therapy may make them feel worse during initiation of therapy. Symptom improvement may not be apparent for several months
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* Beta blockers
o Best studied beta blockers in HF (and only ones approved) are carvedilol, metoprolol succinate extended/controlled release (NOT metoprolol tartarate) and bisoprolol. If a patient is on another BB, it must be changed (gradually) to one of the three with evidence in HF
*
o Benefits are in addition to those achieved with ACEIs - Decrease mortality ( 35% decrease), Decrease hospitalizations, Symptom improvement (decrease morbidity), Improved clinical status ( ↑EF, ↓tachyarrhythmias), Slowed disease progression (, ↓ remodeling, ↓ apoptosis) regardless of race, age or gender.
o All patients with (hemodynamically) stable NYHA Class II or III (and possibly Class IV) HF due to LV dysfunction should receive a beta-blocker (unless not tolerated) OR ACC/AHA stage B if s/p MI or asymptomatic LVH or EF < 40%
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o o Who should not receive a BB
§ Volume overload
§ Symptomatic bradycardia
§ ACTIVE NYHA II or III (or IV) until stable
§ Acute decompensation
§ Advanced heart block
*
o Initiation can begin when patient is stable / euvolemic. Dosing is to a TARGET DOSE if possible. Start low, go slow . Too aggressive increase may result in decompensation. Should not be prescribed without a diuretic in patients with current or recent history of fluid retention
Initial doses - bisoprolol 1.25 mg qd, carvedilol 3.125 bid, carvedilol CR 10mg qd, metoprolol succinate CR/XL 12.5 -25 mg qd
Target doses (if you can get there) - Bisoprolol 10 mg qd, carvedilol 25 mg bid, carvedilol CR 80mg qd, metoprolol XL 200 mg qd
Although you do not need to memorize doses, you must know that they are dosed to a target dose (if possible)
*
o o Monitoring should include HR, BP
§ If hypotension alone is problematic, decrease dose of ACEI ARB / ARNI. Higher BB doses are associated with greater mortality reductions
§ If Edema is problematic - increase the diuretic
§ Fatigue / weakness - should resolve spontaneously in a few weeks
patients need to be aware of the benefits of beta blockers and that beta blocker therapy may make them feel worse during initiation of therapy. Symptom improvement may not be apparent for several months
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* Diuretics
o o Indicated in patients with fluid retention / congestive signs and symptoms. No congestive symptoms, no diuretic!
§ Consider if there Are there "other" causes of edema (eg. CCBs (amlodipine), NSAIDs, corticosteroids, etc) and remove these causes first (if possible)
*
o o Benefits
§ Short term :↓JVD, ↓pulmonary congestion, ↓ peripheral edema
§ Intermediate term: Decrease daily symptoms, Increase exercise tolerance
NO MORTALITY BENEFITS... Should be combined with ACEi, BB, MRA
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o Are thiazide diuretics effective for HF? Only for early, mild HF. Higher doses are rarely effective in improving s/sx of congestion / volume overload when used as monotherapy
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o Loop diuretics are preferred in HF because of greater diuretic capabilities and they retain their efficacy with decreased renal function
Initiate therapy with low doses of diuretic (i.e. furosemide 20-40 mg/day) and increase dose until patient maintains stable dry weight without dyspnea
§ Adjustments Based on symptomatic improvements and body weights (sensitive marker or fluid retention and loss)
Monitoring - weights and electrolytes (see above)
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* Aldosterone antagonist - are used because Aldosterone is a neurohormone that plays a role in sodium and water retention and ventricular remodeling (collagen deposition and cardiac fibrosis)
o Recommended in class II-IV (Stage C) patients with LVEF ≤ 35% to reduce morbidity and mortality unless a CI exists. Patients with class II should have a history of CV hospitalization or elevated BNP levels or to reduce morbidity and mortality in patients s/p MI when they have LVEF <40% with symptoms of HF or LVEF <40% and diabetes
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o Benefits : Decrease all cause mortality (30%), Decrease hospitalization (35%), Improved symptoms
o Should be added to ACEi (or ARB) and β blocker therapy as long as:
§ SCr should be less than 2.5mg/dl ♂ , 2.0 ♀ and GFR > 30 ml/min
§ K should be < 5.0 mEq/L
o Monitoring - K, SCr, BUN, gynecomastea (w/ sprionolactone)
Aldosterone antagonist
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* Digoxin - Positive inotropic effect identified in the 1920’s
o o Digoxin produces symptomatic benefits
o o Target serum concentration when treating patients with HF
o o Place in therapy
Early in therapy for patients with HF and atrial fibrillation to help control ventricular response
For HF patients in normal sinus rhythm, used with other standard HF therapies (ACEI’s, beta-blockers, diuretics) in patients with persistant symptoms despite optimal therapy
o o Monitoring / signs of toxicity .. NTI
digoxin levels
–Visual – blurred vision, blue-green / yellow halos
GI – N/V anorexia abdominal pain
CNS - fatigue / dizziness / delirium / confusion / CTZ stimulation
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Hydralazine / ISDN
§ Recommended to reduce morbidity and mortality for patients self-described as African Americans with NYHA class III–IV HFrEF receiving optimal therapy with ACE inhibitors and beta blockers OR to reduce morbidity or mortality in patients with current or prior symptomatic HFrEF who cannot be given an ACE inhibitor or ARB because of drug intolerance, hypotension, or renal insufficiency
§ Benefits: Decreased mortality (43%), decreased hospitalization (39%)
§ Monitoring - BP, dizsiness
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o Ivabradine - Within the SA node, ivabradine selectively blocks the HCN channel, inhibits the If current, and lowers heart rate
Ivabradine can be beneficial to reduce HF hospitalization for patients with symptomatic (NYHA class II-III) stable chronic HFrEF (LVEF ≤35%) who are receiving GDEM, including a beta blocker at maximum tolerated dose, and who are in sinus rhythm with a heart rate of 70 bpm or greater at rest
Monitoring - Heart rate and cardiac rhythem
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o SGLT2Is
cardiovascular benefits in patients with HFrEF were seen in patients previously treated with current evidence‐based therapies (e.g. ACE inhibitors, β‐blockers, ARBs).
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Statins
§ Not recommended solely on the basis of HF diagnosis
2/3 of the cases of HF are caused by CHD and the #1 cause being damaged myocardium s/p MI. CHD and MI are considered to be clinical ASCVD which IS an indication for statins, regardless of baseline LDL
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Omega – 3 fatty acids
§ Reasonable adjunct therapy in NYHA II-IV symptoms and HFrEF or HFpEF to reduce mortality and cardiovascular hospitalizations
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Anticoagulation
§ For patients with established coronary artery disease, (not solely on the basis of HF), antiplatelet therapy with aspirin 75 to 100 mg daily or clopidogrel 75 mg daily.
§ Recommended in HF with permanent / persistent / paroxysmal aFib with an additional risk factor for stroke, (not solely on the basis of HF), with no preference on agent
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The following was part of a classmates post and you may find useful:
Mnemonic based on evidence-based research for treatment of systolic heart failure. B A N D A I D (2) stands for beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, nitrate-hydralazine (or potentially neprilysin inhibitor), diuretics, aldosterone antagonist, ivabradine (selective sinus node inhibitor), devices (automatic implantable cardioverter defibrillator, cardiac resynchronization therapy or both) and digoxin (Chia, Fulcher & Keech, 2016).
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Hypertension
* ACC/AHA 2017 Goals / Guidelines should be used for the purposes of this exam (See graphic below). Other sources of guidance, may have other BP goals or recommendations in specific circumstances
<150/90 mmHg general population ≥ 60years (a)
<140/90 mmHg general population < 60years (a)
<140/90 mmHg patients with diabetes ≥ 18 years (a)
*
o < 140/80 mmHg (lower SBP [<130 mmHg] may be appropriate in certain individuals, such as younger persons, if target can be achieved without treatment burden) (b)
<140/90 mmHg patients with CKD ≥ 18 years (a)
*
o ≤ 140/90 mmHg patients with CKD w/o proteinuria (c)
o ≤ 130/80 mmHg patients with CKD w/ proteinuria (c)
* < 130/80 mmHg patients with known CVD or 10-year ASCVD event risk of 10% or higher. For adults without additional markers of increased CVD risk, a BP target of less than 130/80 mm Hg may be reasonable (d)
o SBP ≤ 140 patients 55-79
o SBP 140-145 patients ≥ 80
<135/85 mmHg black patients w/o target organ damage, preclinical CHD or CHD (e)
<130/80 mmHg black patients w/ target organ damage, preclinical CHD or CHD (e)
a : JNC8 (Joint National Committee) 2014
b : ADA (American Diabetic Association)2014
c : KDIGO (Kidney Disease : Improving Global Outcomes) 2012
d : ACCF / AHA (American College of Cardiology Foundation / American Heart Association) 2013
Note - 2017 update bases goals on estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk. This updated guidance is not a globally accepted guideline because although The guideline provided more than 100 recommendations, a systematic review performed as part of the guideline's development considered only four key questions. Also, harms of treating a patient to a lower blood pressure were not assessed in the systematic review.
e : ISHB (International Society for Hypertension in Blacks) 2010
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* Compelling Indications (Text refers to Drug selection in hypertension with or without other major conditions Table 5-3, 5-7)
o Example
Diabetes - ACEI/ARB
BPH - alpha blockers
Pregnancy - methyldopa, labetolol
* Please note comments regarding various antihypertensives (Table5-7)
* ISA
* Cardioselectivity
________________________________________
[Isolated systolic hypertension and Hypertensive emergencies are not addressed in this course]
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Hypertension
* The BP relationship to risk of CVD is continuous, consistent, and independent of other risk factors. Each increment of 20/10 mm Hg doubles the risk of CVD across the entire BP range starting from 115/75 mm Hg.
* Risk factors:
o Cigarette smoking, Obesity (BMI ≥ 30), Physical inactivity, Dyslipidemia, Diabetes mellitus, Renal dysfunction, Age: men > 55 years, women > 65 years, Family history (First degree relative) of premature cardiovascular disease (age: men < 55, women < 65)
* Drugs: Steroids, NSAIDS, Amphetamines/anorexiants, Erythropoietin, Cyclosporine, tacrolimus, Decongestants, EToH
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* SBP is stronger predictor of CV disease than DBP in patients >60yo
* DBP control was more important than SBP control for reducing cardiovascular risk in patients <60 years of age
When to start therapy
* JNC8
o >/= 60 years: Initiate pharmacological treatment to lower BP at SBP 150 mm Hg or DBP 90mmHg and treat to a goal SBP <150 mm Hg and goal DBP <90 mm Hg.
o <60 years initiate pharmacological treatment to lower BP at DBP 90mmHg and treat to a goal DBP < 90mmHg
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Goals (JNC8)-
* o <150/90 mm Hg general population ≥ 60years
* o <140/90 mm Hg general population < 60years
* o <140/90 mm Hg patients with diabetes ≥ 18 years
* o <140/90 mm Hg patients with CKD ≥ 18 years
ACC/ AHA 2017
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*Recommended BP target for the vast majority of patients is less than 130/80 mm Hg - Rationale: Lowering BP to incrementally lower levels prevents CVD and death
*Benefits of aggressive BP control using pharmacotherapy remain debatable for certain patients where improved outcomes across all major endpoints for patients achieving a more intensive BP-lowering goal were not consistently observed.
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* Non-pharmacological therapies should be encourage in all patients, including normotensive patients, stage I and stage II HTN. A trial of Lifestyle modification for 6 months was appropriate in "pre-hypertensive patients"; however the designation of pre-hypertension has been removed in JNC8.
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* Lifestyle modifications for HTN: -
o o Smoking Cessation
o o Weight loss in overweight and obese (5-20mmHg reduction/10 kg of weight loss)
o o DASH
o o Physical activity
o o Limit EToH
* Patients presenting with stage I or stage II should be started on pharmacotherpy simultaneously with lifestyle modification.
* Patients presenting with stage II are started on dual therapy simultaneously with lifestyle modification.
o Note differences based on race
o JNC8
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In the absence of compelling indication in the general population,
* 1st line:
*ACE inhibitors or ARBs
*CCBs
*Thiazide diuretics
* In black adults with hypertension but without HF or CKD, including those with DM, initial antihypertensive treatment should include a thiazide-type diuretic or CCB
* Pharmacological interventions
o o Monotherapy reaches target BP of <140/90 mm Hg in only 50-60% of patients
§ Combo therapy uses lower doses and results in better BP reduction than maximizing dose of one drug. Combine drugs with different MOAs (Diuretic should usually be part of combo)
*
o
§ If goal BP is not reached within a month of treatment, maximize the dose of the initial drug OR add a second drug (thiazide-type diuretic, CCB, ACEI ,ARB) not currently employed (ie. NOT from the same class) (and before reaching the first drugs dosing limit)
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§ Stage 1 - May consider thiazide-type diuretics, ACEI, ARB, CCB, or combination.
*
o
§ Stage 2 - Two-drug combination for most (usually thiazide-type diuretic or CCB and ACEI / ARB).
*
o
§ First-line agents (Evidence for decreasing morbidity and mortality derived from ALLHAT)
Non - Blacks: Thiazide-type diuretics, CCB, ACEI / ARB
Blacks : Thiazide-type diuretics or CCB
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Compelling indications (Table 5-3)
§ Heart failure: ACE/ARB, BB (3 approved), ..in certain patients diuretics, MRAs, ISDN/hydralazine
Also discussed in heart failure discussion
§ Post-MI : BB (without ISA) plus ACEI or ARB; MRA
§ CAD/Angina: ACEI or ARB ; BB (without ISA); CCB
§ DM: ACEI/ARB; thiazide; CCB
§ CKD: ACEI / ARB
§ Stroke/TIA: ACE/ARB, CCB +/- Thiazide
§ BPH: alpha antagonist (eg terazosin) (not uroselective agents)
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* Thiazides for HTN - Hydrochlorothiazide (HCTZ) / Chlorthalidone are the prototypical thiazide diuretic. Chlorthalidone used in many large studies with results extrapolated to HCTZ
o o According to the JNC-8 guidelines thiazide diuretics are the first line treatment for hypertension. Exceptions are those patients with “compelling indications”
Note: increase doses beyond "usual" provides little additional BP lowering.
Therapy with dual thiazides is NOT recommended
If not initial choice, this is a reasonable add on for uncontrolled HTN
o o ADRs - Electrolyte abnormalities: ↓ K, ↓ Na, ↑ Ca*, ↑UA ; Photo sensitivity; ↑TC and LDL ; etc
o o Ineffective in patients with CrCl <30ml/min
NOTE: Unlike HF where loop diuretics were used, in HTN, thiazides ARE routinely used
o o Monitoring K, Mg, Na, BUN/Scr, glucose, uric acid
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* Potassium sparing diuretics often used in combination with thiazides
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* ACEIs - According to the JNC-8 guidelines ACEi are the first line treatment for hypertension in non-black population and for the following compelling indications:
o Heart failure, Post MI, High coronary disease risk, Diabetes, Chronic kidney disease, Decrease proteinuria (even in absence of HTN) , Recurrent stroke prevention
o o DO NOT FORGET TO INCLUDE IN PATIENTS THAT HAVE THESE COMPELLING INDICATIONS.
o o ADRs: Adverse Effects
§ Hypotension/Orthostatic hypotension (1st dose phenomenon .start low, go slow)
§ Dry cough (5-20% incidence)
§ Headache
§ Dizziness
§ Angioedema (0.1-0.5% incidence)
§ Renal insufficiency
§ Increased serum potassium levels
Use with caution in patients with CKD or on K-sparing diuretics, K supplements, aldosterone antagonists (MRAs)
Increasing doses may be associated with increasing [K]
o o Contraindications??
o o Monitoring K, Scr, BUN, cough
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* ARBs - When an ACE-I is not tolerated (eg Dry cough, angioedema)
o o Should NOT be considered clinically superior to ACEIs
o o Should NOT be used in combination with ACEIs
o o Monitoring K, SCr
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* Direct renin inhibitors - alternative in the treatment of hypertension, but at this time, evidence does not support a clear advantage over ACEIs and ARBs
o o Not addressed by JNC8
o o Contraindicated in patients with diabetes when used in combination with ACE inhibitors or ARBs because of increased risk of renal impairment, hyperkalemia, and hypotension
o o Many interactions
o o ADRs similar to ACEI /ARBs
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* Beta blockers - ↓ BP by ↓CO via ↓HR & cardiac contractility
* Compelling indications : Heart failure (select BBs), Post-MI, coronary artery disease / angina
* NOT considered 1st (or even 2nd) line antihypertensive in the absence of a compelling indication (above)
o Why aren’t B-blockers first-line without compelling indications anymore?
Weak evidence for cardioprotection in pts. without compelling indications (such as post-MI, CAD, angina, heart failure).
Lack of benefit on cerebrovascular and renal disease endpoints
Higher rate of primary composite outcome of CV death, MI or Stroke compared to use of an ARB
* DO NOT FORGET TO INCLUDE IN PATIENTS THAT HAVE THESE COMPELLING INDICATIONS.
*
o o Can be classified several ways
§ Cardioselective (beta 1)
Atenolol , Metoprolol tartrate / Metoprolol succinate, bisoprolol, etc
§ Non-selective (beta 1 and 2)
Propranolol, Nadolol , labetolol, etc
§ Those with ISA - these agents are actually partial agonists rather than antagonists
No clinical utility or advantage over other agents; May be useful in patients treated with other BBs that develop bradycardia
Acebutolol, carteolol, etc
§ Those with mixed actions
Carvedilol - alpha-1 blockade, prominent antioxidant activity, anti-proliferative effects
Nebivolol - stimulates NO \ vasodilation
Others...
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Relative contraindications to beta-blockers: Asthma and COPD (bronchospasm), Diabetes, Severe peripheral vascular disease (decreased output can worsen symptoms), Heart block, Severe bradycardia, Severe acute heart failure, Pregnancy category C. Can you explain each of these??
o o ADRs - Hypotension, Bradycardia, Depression , Sexual dysfunction, CNS effects (fatigue, hallucinations, dizziness), decrease HDL, increase triglycerides
§ Abrupt cessation of b - blocker treatment can lead to fatal cardiac rhythm disturbances, hypertension, and severe anginal attacks or MI
o o Monitoring HR, bronchospasm, fatigue, mental status, HF
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* CCBs - : all CCBs are equally effective when used alone in treatment of mild to moderate hypertension. Most effective in low-renin hypertensives esp. elderly & African – Americans
o o Considered to be a first line agent for general population as well as initial add on therapy if 2 (or more) agents are required. CCBs are 1 of the 2 initial choices in black population. May be used as initial therapy choice in patients with compelling indications: High CVD risk / angina, Diabetes
o o Currently there are 8 L-type calcium channel antagonists FDA indicated for the treatment of hypertension
§ DHPs (amlodipine, felodipine, etc)
§ Non-DHPs (verapamil, diltiazem)
o o ADRs
§ Peripheral and pulmonary edema (may necessitate alternate therapy rather than adding on a diuretics)
Peripheral edema caused by CCBs is a well known adverse effect, especially in women. Measures to reduce edema include decreasing the dose, foot elevations, compression stockings, changing to a non-dyhdropyridine CCB or suing the CCB in combination with a venodilator such as an ACEI. Interestingly, unless the edema is multi-factorial, adding a diuretic is often unsuccessful
eg Amlodipine
§ Get excessive bradycardia with verapamil and diltiazem. could cause AV - block (don’t give with b blocker) or use in HF patient or SA node dysfunction
§ Get reflex tachycardia with older, rapid onet DHPs (eg nifidipine)
§ Verapamil has high incidence of constipation
§ Dizziness , HA, Flushing
§ Monitoring-HR, edema, HA, dizziness, constipation
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* Alpha 1 antagonists (second generation agents; eg terazosin)
o o Minimal contribution to clinical outcomes except in men with symptomatic BPH ..
Uroselective agents (eg tamsulosin) will help with urogenetial problems, but will not help with blood pressure control
REVIEW TOPIC IN MENS HEALTH
o o 1st dose phenomenon, esp. w/ too rapid dose escalation or if used in combination
o o ADRs :orthostatic hypotension, tiredness, dizziness and headache
o o Monitoring Postural hypotension, first-dose syncope, HA, dizziness, HR
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* Alpha 2 agonist (clonidine)
o o Clinical use: HTN, addiction, pain management, menopausal symptoms, ADHD. NOT first line, but rather as 3rd or 4th agent
o o ADRs - dry mouth, sedation, bradycardia, sexual dysfunction, dizziness, edema
§ Withdrawal syndrome – following abrupt d/c – rebound hypertension because of receptor down regulation. Occurs 18-36 hours after d/c
o o Monitoring Sedation, dry mouth, HR, withdrawal HTN
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* Methyldopa
o o DOC for hypertension in pregnancyy .. recall m/w health
o o ADRs- sedation, dry mouth, hyperprolactinemia (gynecomastia/galactorrhea), hepatotoxicity
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* Hydralazine
o o Not employed as monotherapy in HTNbecause of development of tachyphylaxis
See HF for use in combination wit ISDN
o o Genetic polymorphism affecting metabolism
o o ADRs - HA, dizziness, flushing, tachycardia, palpitations, Myocardial ischemia, Pulmonary HTN, Drug-induced lupus
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* Minoxidil
o o Not used as monotherapy, HTN not responsive to other therapies
o o Other indication?
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Special populations
* women
o o Oral contraceptives may increase BP, and BP should be checked regularly. In contrast, HRT does not raise BP.
Development of HTN — consider other forms of contraception.
o o Pregnant women with HTN should be followed carefully. Methyldopa, preferred for the safety of the fetus. Can also use labetolol, CCBs, and hydralazine.
o o ACEI, ARBs, and direct renin inhibitors contraindicated in pregnancy.
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Special populations
* Minorities
o o In general, treatment similar for all demographic groups.
o o Socioeconomic factors and lifestyle important barriers to BP control.
o o Prevalence, severity of HTN increased in African Americans.
o African Americans demonstrate somewhat reduced BP responses to monotherapy with BBs, ACEIs, or ARBs compared to diuretics or CCBs.
o These differences usually eliminated by adding adequate doses of a diuretic.
o These agents should still be used if comorbid conditions dictate
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Special populations
* Elderly
o o Use caution. Patients group at higher risk of orthostasis
Are the benefits of more aggressive therapy offset by the potential for sever ADRs
o o Initiate with low dose
o o Titrate slowly
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Follow up
* Patients should return for follow-up and adjustment of medications until the BP goal is reached, beginning at 4 weeks; Sooner if BP is worrisome
* More frequent visits for stage 2 HTN or with complicating comorbid conditions.
* Serum potassium and creatinine monitored 1–2 times per year.
* After BP at goal and stable, follow-up visits at 3- to 6-month intervals.
* Comorbidities, such as heart failure, associated diseases, such as diabetes, and the need for laboratory tests influence the frequency
of visits.
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Considerations ..
* BBs useful in the treatment of atrial tachyarrhythmias / fibrillation, migraine, thyrotoxicosis (short-term), essential tremor, or perioperative HTN, stable angina and stable heart failure.
* CCBs useful in Raynaud’s syndrome, stable angina and certain arrhythmias.
* Alpha-blockers useful in BPH.
* ACEI / ARBS have demonstrated benefits in patients with diabetes and CKD
* Thiazide diuretics should be used cautiously in gout or a history of significant hyponatremia.
* BBs should be used with caution in patients with asthma and reactive airways disease and generally avoided in second- or third-degree heart block.
* BBs may mask hypoglycemic response and inhibits recovery
* ACEIs ,ARBs and direct renin inhibitors are contraindicated in pregnant women or those likely to become pregnant.
* ACEIs should not be used in individuals with a history of angioedema.
* Aldosterone antagonists and potassium-sparing diuretics can cause hyperkalemia.
* African American patients: β-blockers and ACE inhibitors are generally less effective as monotherapy than in white patients; however, combination therapy with thiazides improves effectiveness; β-blockers and ACE inhibitors should still be used if comorbid conditions dictate
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This module will focus on ACC/AHA 2017 guidance.
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Do not focus on hypertensive crisis: not on exam.
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Recommended BP goals per ACC/AHA 2017 guidance:
- General <130/80 mmHg
- Older patients <130 mmHg
- Diabetes <130/80 mmHg
- Chronic kidney disease < 130/80 mmHg
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BP
- Normal: <120/80
- Elevated: 120-129 and <80
- S1HTN: 130-139 OR 80-89
- S2HTN: >140 OR > 90
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BP Threshold and Goals of Pharmacologic Therapy in patients with HTN according to clinical conditions.
Everyone has a BP threshold for antihypertensive therapy initiation at >130/80 except those regarding secondary stroke prevention and those with No Clinical CVD and 10-year ASCVD RISK <10% (both at >140/90).
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Non-pharm approaches to HTN?
- Dietary Sodium Restriction
- Increase Potassium Intake
- Low-fat diet
- Diet high in vegetables and fruit
- Weight loss in overweight/obese
- Regular physical activity
- Moderation of alcohol consumption
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Consider rac, age, and "compelling indications" when prescribing BP meds.
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- Normal BP (<120/80): reassess yearly
- Elevated BP (120-129/<80): non-pharm therapy only. Reassess in 3-6 months.
- S1HTN (130-139/80-89): Clinical ASCVD or estimated 10-year CVD risk ≥ 10%?
- - No: Non-pharm; reasess 3-6 months.
- - Yes: non-pharm therapy and BP-lowering medication. Reassess in 1 month.
- S2HTN: (BP ≥ 140/90): Non-pharm therapy, BP-lowering meds, and reassess in 1 month.
- - - For S1HTN with ASCVD or 10-year 10% risk OR S2HTN, are BP goals met?
- - - - No: assess and optimize adherence to therapy.
- - - - Yes: Reassess in 3-6 months.
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Patient on an ACEi and an ARB is an automatice contraindication.
- Increased risk of cough and angioedema, and increased cost because there's no benefit.
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For diabetes, diuretics, CCBs, and either ACEi or ARBs are indicated.
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Patient presents with S2HTN
- BP > 140/90
- Lifestyle and medications
- Started on medications
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If patient has HTN and HF, stay away from medications that cause edema.
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How could therapy be altered if SEs are problematic? (For example CCB is causing pedal edema)
- Change to dihydropyridine CCB or add a diuretic
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If patient has edema and HTN, change them from Verapamil or Diltizaem to a dihydropyridine CCB like Amlodipine, or add a diuretic.
Make just ONE change.
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How should therapy be monitored?
- ACEIs/ARBs tend to increase potassium
- Diuretics tend to decrease potassium
- Thiazides increase uric acid
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You don't have to do labs on your patients every month regarding treatment.
At monthly intervals you would review medication and lifestyle adherence, BP measurements, adequacy of BP control, and other diagnostic tests to assess changes in clinical status and target organ damage.
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Every visit determine whether patient is experiencing any adverse reactions or drug interactions.
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Once BP is controlled, monitor patient every 3-6 months to assess BP control, electrolytes and renal function as appropriate, clinical status, and target organ damage.
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For members of black race, start on diuretic or CCB, BUT if they have diabetes, start on an ACEI first.
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If patient has HF and HTN, don't start on ACEI because ACEI causes swelling. Start on a diuretic instead.
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Heart Failure:
- Compensatory response:
- - Tachycardia and increased contractility due to SNS activation
- Beneficial Effect of Compensation:
- - Increased cardiac output
- Detrimental Effects of Compensation:
- - Increased MVO2
- - shortened diastolic filling time
- - B-receptor downregulation, decreased receptor sensitivity
- - Precipitation of ventricular arrhythmias
- - increased risk of myocardial cell death.
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Heart Failure:
- Compensatory response:
1. - - increased preload through sodium and water retention
2. - - vasoconstriction
- Beneficial Effect of Compensation:
1. - - optimizes stroke volume via Frank-Starling mechanism
2. - - Maintains BP and perfusion in the face of reduced cardiac output
- Detrimental Effects of Compensation:
1. - - pulmonary and systemic congestion and edema formation
1. - - increased MVO2
2. - - increased MVO2
2. - - increased afterload decreases stroke volume and further activates the compensatory responses
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Heart Failure:
- Compensatory response:
- - Ventricular hypertrophy and remodeling
- Beneficial Effect of Compensation:
- - Maintains cardiac output
- - Decreases myocardial wall stress
- - Decreases MVO2
- Detrimental Effects of Compensation:
- - diastolic dysfunction
- - systolic dysfunction
- - increased risk of myocardial cell death
- - increased risk of myocardial ischemia
- - increased arrhythmia risk
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Exacerbating or Precipitating Factors in Heart Failure (Cardiac):
- acute ischemia
- arrhythmia
- endocarditis
- myocarditis
- pulmonary embolus
- uncontrolled hypertension
- valvular disorders
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Exacerbating or Precipitating Factors in Heart Failure (Metabolic):
- anemia
- hyperthyroidism/thyrotoxicosis
- infection
- pregnancy
- worsening renal function
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Exacerbating or Precipitating Factors in Heart Failure (Patient-Related):
- dietary/fluid nonadherence
- HF therapy nonadherence
- use of cardiotoxins like cocaine, chronic alcohol, amphetamines, and sympathomimetics
- offending medications: NSAIDs, COX-2 inhibitors, steroids, lithium, beta blockers, CCBs, antiarrhythmics, alcohol, thiazolidinediones.
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What is the role of diuretics in HF and what is the impact on mortality?
- Diuretics are used for relief of acute symptoms of congestion and maintenance oe euvolemia. These agents interfere with sodium retention by increasing urinary sodium and free water excretion. The primary rationale for the use of diuretic therapy is to maintain euvolemia in symptomatic or stages C and D HF. Diuretic therapy is recommended for all patients with clinical evidence of fluid overload. In mild HF, diuretics may be used on an as-needed basis. However, once the development of edema is persistent, regularly scheduled doses will be required.
- Consider what symptoms would warrant use; remember no edema secondary to HF, no diuretic needed.
- Are loop diuretics or thiazides preferred?
- - Note, rarely will increasing the dose of a thiazide diuretic be sufficient to treat symptoms of volume overload in HF
- - If stage A or B (and/or has HTN), throw on a thiazide diuretic. 2 birds 1 stone.
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Loop diuretics are preferred in stages C and D.
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Stage A : address RFs, may use ACEI or ARB if compelling indication.
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Stage B HF:
- address RFs
- drugs
- - ACEI or ARB
- - beta blocker
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Stage C HF:
- tx plan: salt restriction
- drugs:
- - diuretic for edema (loop?)
- - ACEIs
- - beta blockers
- in selected patients:
- - ARBs
- - ARNIs
- - digoxin
- - aldosterone antagonists
- - hydralazine/nitrates
- - ivabradine
- - devices:
- - - biventricular pacing
- - - implantable defibrillators
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Stage D HF:
- tx plan:
- - continue interventions under stages A through C
- - end of life care/hospice
- - specialized interventions:
- - - heart transplant
- - - chronic inotropes
- - - mechanical support
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A = none, but treat their other diseases
B = both beta blockers and ACEIs
C = now adding on others
D = death, palliative care
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If AA pt gets angioedema or dry cough, the ACEI can be switched out for hydralazine/isosorbide dinitrate combination.
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What medications should be part of all regimens in patients with stable heart disease because of their long-term impact on mortality?
- especially beta blockers, ACEIs, and aldosterone antagonists.
- - note, although mineralocorticoid receptor antagonists can be considered a potassium sparing diuretic, their benefit in heart failure relates to its neurohormonal properties... NOT as a diuretic
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How are these meds dosed to a target if possible?
Beta blockers require titration up and down.
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Aldosterone antagonists are only used in stages C and D
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BB = carvedilol, metoprolol succ., and bisoprolol (cave men suck bad in HF)
Use these beta blockers in HF.
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How should these meds be monitored?
- ACEIs/aldosterone antagonists: watch potassium
- beta blockers: watch HR, BP, and signs of decompensation
- Digoxin: watch level (NTI), s/sx of toxicity and potassium
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Furosemide, bumetanide is renally dosed. Remember for exam.
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What is the role of digoxin? What is its impact on mortality and how should therapy be monitored?
- the exact role of digoxin in therapy remains controversial largely due to disagreement on the risk vs benefit of routinely using this drug in patients with systolic HF. Digoxin was shown to decrease HF-related hospitalizations but did not decrease HF progression or improve survival. Moreover, digoxin was associated with an increased risk for concentration-related toxicity and numerous adverse effects.
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Current recommendations are for the addition of digoxin for patients who remain symptomatic despite an optimal HF regimen consisting of an ACEI or an ARB, beta blocker, and diuretic. In patients with concomitant atrial fibrillation, digoxin may occasionally be added to slow ventricular rate; however, beta blockers are more effective at controlling ventricular rate, especially in the setting of exercise. Clinicians may also consider adding digoxin in patients with severe HF who have not responded symptomatically to neurohormonal blockade.
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Regarding digoxin, concentrations below 1.2 ng/mL were associated with no apparent adverse effect on survival, whereas higher concentrations increased the relative risk of mortality.
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Desired digoxin range is 0.5 to 0.9 ng/mL, with preferred concentration at or less than 0.8 ng/mL
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Digoxin toxicity:
- fatigue
- weakness
- confusion/delirium/psychosis
- N/V
- anorexia
- visual disturbances like halos, photophobia, and color-perception problems (red-green or yellow-green vision).
- many kinds of arrhythmias
- slowed/accelerated conduction
- delayed after-depolarizations
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Risk of digoxin toxicity in particular the cardiac manifestations, are increased with electrolyte disturbances like hypokalemia, hypercalcemia, and hypomagnesemia.
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