Congestive Heart Failure Flashcards
What is Cardiac Failure
Failure of cardiac function to deliver oxygenated blood to tissue and the function defined as Cardiac Output
What is the aim of drug therapy in CHF
To relieve symptoms
To improve quality of life
To improve survival
Determinants of Stroke Volume
Afterload
Preload
Contractility
Strategies to treat CHF
- Reduce Afterload-Artery dilators
- Reduce Preload-Remove water and Vein Dilators
- Increase contractility-Inotropes
- Inhibit RAAS system
- Inhibit Sympathetic NS activation
Drugs used for the treatment of CHF
Artery Dilators: ACEI, Hydralazine and Minoxidil
Inotropes: Digoxin, Dobutamine and Milrinone
Diuretics: Furosemide
Vein Dilator: Nitrate(NTG) and ACEI-Captopril
ACEI
B-blocker
Drugs proven to improve Survival
Aspirin
B-blockers
ACE inhibitors
Classes of Drugs for CHF
- Inotropics
- Vasodilators
- Neurohormonal antagonists
- Diuretics
Inotropes:
Examples
Digoxin
Catecholamines
Phosphodiesterase III inhibitor
_NEUROHORMONAL EFFECTS
Decreases Plasma Noradrenalin (Reduced Sympathetic tone)
Decreases Peripheral nervous system activity
Decreases RAAS activity (switches off)
Decreases Vagal tone or
Normalizes arterial baroreceptors
_EFFECTs (SUMMARY)
Positive inotropia: Na K-ATPase inhibition
Negative chronotropia
Negative dromotropia
Increased Parasympathetic tone: Decreased AV conduction & heart rate
Decreased Sympathetic tone
A dromotropic agent affects the conduction speed in the AV node, and subsequently the rate of electrical impulses in the heart.
Digoxin:
Long Term Effects
Survival similar to placebo
Fewer hospital admissions
More serious arrhythmias
More myocardial infarctions
Digoxin:
Clinical Uses
Atrial Fibrillation with rapid ventricular response.
Congestive Cardiac Failure refractory to other drugs
Digoxin:
Contraindications
- Digoxin toxicity• RELATIVE- Advanced A-V block withoutpacemaker- Bradycardia or sick sinus without PM- Extrasystoles- Marked hypokalemia- W-P-W with atrial fibrillation
Digoxin Side Effects/Toxicity:
Cardiac Manifestations
Arrhythmias:
Ventricular
Supraventricular
Blocks:
SA and AV blocks
Exacerbates cardiac failure
Digoxin Side Effects/Toxicity:
Extracardiac
Gastrointestinal:
- Nausea, vomiting, diarrhea
Nervous System:
- Depression, disorientation, paresthesias
Visual:
- Blurred vision, scotomas and yellow-green vision
Hypoestrogenism:
- Gynecomastia, galactorrhea
Digoxin:
Drug Interactions
Antacids and Cholesteramine:
=> to reduced absorption of digoxin
Calcium Channel Blocker:
- Oppose the effect of digoxin on the heart
Drugs that cause Hypokalemia: Diuretics
- Cause digoxin arrhythmias
Drugs that block AV node: Quinidine
- worsen digoxin toxicity (bradycardia)
Catecholamines:
B-adrenergic stimulants classification:
B1 Stimulants which Increase contractility:
Dobutamine
Mixed DA, B1 & B2: Dopamine DOPAMINE AND DOBUTAMINE EFFECTS Dopamine μg/kg/ml Dobutamine <2 2-5 >5 Receptors DA1/DA2 β1 β1+α β1 Contractility ± ++ ++ ++ Heart rate ± + ++ ± Arterial pressure ± + ++ ++ Renal perfusion \++ + ± + Arrhythmia - ± ++ ± POSITIVE INOTROPES: CONCLUSIONS • May increase mortality • Safer in lower doses • Use only in cardiogenic shock • NOT for use as chronic therapy
Conclusion of Positive Inotropes
May increase mortality
Safe in lower doses
Use only in cardiogenic shock
Not for us as chronic therapy
Vasodilators:
Drugs
ACE Inhibitors & AT-1 blockers
Nitrates
ACEI:
Advantages
Inhibit left ventricular remodeling post-myocardial infarction
Modify the progression of chronic congestive heart failure -Increases Survival - Decreases Hospitalizations -Improve the quality of life
In contrast to others vasodilators, do not produce neurohormonal activation or reflex tachycardia
Tolerance to its effects does not develop
ACEI:
Side Effects
Inherent in their mechanism of action
- Hypotension
- Hyperkalemia
- Angioneurotic edema
Due to their chemical structure:
- Cutaneous eruptions
- Neutropenia, thrombocytopenia
- Digestive upset
ACEI:
Contraindications
Renal artery stenosis
Renal insufficiency
Hyperkalemia
Arterial hypotension
Intolerance (due to side effects
AT1 Receptor Blockers:
Drugs
Losartan
Valsartan
Ibersartan
Competitive and selective
Inhibition of AT1 receptors
Nitrates: Hemodynamic Effects
Types
Venous Vasodilation
Arterial Vasodilation
Coronary Vasodilation
Venous Dilation:
Decrease Preload: When that happens:
It also decreases the following:
- Pulmonary congestion
- Ventricular size
- Vent. Wall stress
- MVO2
Arterial Vasodilation
Decreases Afterload:
Thus decreasing:
- Cardiac Output and
- Blood Pressure
Coronary Vasodilation
Increases myocardial perfusion:
Nitrates:
Tolerance
” Decrease in the effect of a drug
when administered in a long-acting form”
Develops with all nitrates
Is dose-dependent
Disappears in 24 h. after stopping the drug
Can be avoided or minimized
- Intermittent administration
- Use the lowest possible dose
- Intersperse a nitrate-free interval
Allow peaks and valleys in plasma levels
- Vascular smooth muscle recovers its nitrate sensitivity during the nadirs
- Patches: remove after 8-10 h
Nitrates:
Contraindications
Previous hypersensitivity
Hypotension (< 80 mmHg)
1st trimester of pregnancy
WITH CAUTION in:
- Constrictive pericarditis
- Intracranial hypertension
- Hypertrophic cardiomyopathy
Nitrates:
Clinical Uses
Pulmonary congestion
Orthopnea and paroxysmal nocturnal
dyspnea
Congestive cardiac failure with myocardial
ischemia
Acute congestive cardiac failure and pulmonary
edema: TNT SL or IVI.
Neurohormonal Antagonists:
B-blockers
Inhibit cardiotoxicity of catecholamines
Decreases Neurohormonal activation
Decreases Heart rate
B-Blockers:
Clinical Uses
Suspected adrenergic activation
Arrhythmias
Hypertension
Angina
ß-Adrenergic Blockers:
Contraindications
Hypotension: BP < 100 mmHg
Bradycardia: Heart rate < 50 bpm
Clinical instability
Chronic bronchitis, ASTHMA
Severe chronic renal insufficiency
Diuretics:
Drugs
Thiazides
Loop diuretics
Potassium Sparing Diuretics
Thiazides
Inhibit active exchange of Na-Cl in
cortical diluting segment of
ascending loop of Henle.
Loop diuretics
Inhibit exchange of Na-Cl-K
in thick segment (ascending
loop of Henle)
K- sparing
Inhibit reabsorption of
Na in distal convoluted
& collecting tubule
Thiazides:
Mechanism of Action
Excrete 5 - 10% of filtered Na+
Increases Elimination of K+
Decreases Excretion of uric acid and Ca
Minimal dose - effect relationship
Some inhibit carbonic anhydrase: increase elimination of HCO3
Loop Diuretics:
Mechanism of Action
Excrete 15 - 20% of filtered Na+
Increases Elimination of K+, Ca+ and Mg++
Decreases Resistance of afferent arterioles
– Increases Release renal PGs
– NSAIDs may antagonize diuresis
K-Sparing:
Mechanism of Action
Eliminate < 5% of filtered Na+
Inhibit exchange of Na+ for K+ or H+
Spironolactone = competitive antagonist for the aldosterone receptor
Amiloride and triamterene block Na+ channels controlled by aldosterone
Diuretic Effects
Volume and preload
– Improve symptoms of congestion
No direct effect on cardiac output, but excessive preload reduction may improve arterial distension.
Neurohormonal activation:
– Increased levels of renin and Angiotensin II
– Exception: Reduced with spironolactone
Diuretics: Adverse Reactions:
Thiazides and Loop Diuretics
Changes in fluid balance and electrolytes:
– Reduce Volume
– Reduce Na+, K+, Mg++
– Metabolic alkalosis
Other changes:
– Increase blood glucose and uric acid
– Increase LDL cholesterol & Trigliserides
Cutaneous allergic reactions
Idiosyncratic effects:
– Blood dyscrasia, cholestatic jaundice and acute pancreatitis
Gastrointestinal effects
Genitourinary effects:
– Impotence and menstrual cramps
Deafness, nephrotoxicity
(Loop diuretics)
Diuretics: Adverse Reactions:
K-Sparing
Changes in electrolytes:
– ↑ Na+, ↑ K+, acidosis
Musculoskeletal:
– Cramps, weakness
Cutaneous allergic reactions :
– Rash, pruritis
Drugs used for Acute Heart Failure
In hospital: intravenous
Diuretics: Furosemide
Nitrates:
Inotropic agents: Dopamine/ dobutamine
Oxygen
Drugs used for Chronic Heart Failure
Systolic dysfunction:
Diuretic + ACEI / ARB
Beta blocker
Spironolactone or eplerenone if needed
Digoxin if AF
Hydrallazine + nitrate
Anticoagulant/ antiplatelet drugs
Drugs which may aggravate or induce Heart Failure
Drugs that increase fluid retention
– NSAIDs
– Rosiglitazone/ Pioglitazone
– High salt content: Fleet enema
Drugs with negative inotropic effect
– Betablocker
– Calcium channel blocker
Direct cardiotoxicity
– Cancer chemotherapy
