Cardiovascular: Palpitations, syncope, arrhythmias, bradycardia, AV node block, tachycardia
Factors increasing the possibility of digoxin toxicity
Pharmacological and toxic effects are greater in hypokalemic patients.
K + -depleting diuretics are a major contributing factor to digoxin toxicity.
Arrhythmias may be converted to normal sinus rhythm by K + . when the plasma K + conc. is low or within the normal range.
When the plasma K + conc. is high, antiarrhythmic drugs, such as lidocaine, procainamide, or propranolol, can be used.
Severe toxicity treated with Digibind , an anti-digoxin antibody.
A 96-year-old AAF was admitted from a nursing home with complaints of abdominal pain, N/V, dizziness, confusion and double vision for 5 days. She was discharged from the hospital just 4 days ago. Digoxin was started during that previous hospitalization for control of tachycardia in atrial fibrillation. One day prior to discharge, digoxin level was 1.8 mg/mL and digoxin dose was decreased to 125 mcg PO Q 48 hr. PMH Hypertension, atrial fibrillation, coronary artery disease, stroke, congestive heart failure. Medications Metoprolol, Digoxin, ASA, lisinopril, Lasix, Coumadin, Nexium
What could it be???
Dopamine acts at a variety of receptors (dose dependant)
Rapid elimination- can only be administered as a continuous infusion
Stimulates beta-adrenergic receptors and produces a positive inotropic response
Unlike the vasoconstriction seen with high doses of dopamine, dobutamine produces a mild vasodilatation
Inamrinone (amrinone) and Milrinone (bipyridines)
Acts by inhibiting the enzyme Phosphodiesterase
Thus lead to increase of intracellular concentrations of cAMP
cAMP is responsible for the conversion of inactive protein kinase to active form
Protein kinases are responsible for phosphorylation of Ca channels
Thus causing increased Ca entry into the cell.
Increase myocardial contractility by increasing the Ca influx during AP
Also have vasodilating effect
Selective for PDE isoenzyme-3 (found in cardiac and smooth muscle)
Both are orally active
Only available in parenteral forms
Clinical trials- increased mortality (oral)
Still new drugs are under trial
Inamrinone: nausea, vomiting, arrhythmias, thrombocytopenia and liver enzyme changes
Withdrawn in some countries
Milrinone: arrhythmias, less likely to cause other ADR
Brain (B-type) natriuretic peptide (BNP) is secreted constitutively by ventricular myocytes in response to stretch
BNP binds to receptors in the vasculature, kidney, and other organs, producing potent vasodilation with rapid onset and offset of action by increasing levels of cGMP
Niseritide is recombinant human BNP approved for treatment of acute decompensated CHF.
It reduces systemic and pulmonary vascular resistances, causing an indirect increase in cardiac output and diuresis.
Effective in HF because cause reduction in preload and afterload
Overwhelming evidence to support the use of β-blockers in CHF, however
Mechanism involved remain unclear
Part of their beneficial effects may derive from slowing of heart rate and decrease myocardial O 2 consumption.
This would lessen the frequency of ischemic events and potential for development of a lethal arrhythmia.
Suggested mechanisms also include reduced remodeling
β-Blockers may be beneficial through resensitization of the down-regulated receptor, improving myocardial contractility.
Recent studies with bisoprolol, carvedilol and metoprolol showed a reduction in mortality in patients with these drugs
CI in unstable cases
Management of Chronic HF (combination of drugs)
Limit physical activity
Reduce water intake
Digitalis (ther. margin, DI with quinidine)
Management of acute HF
Treating cause (surgery to correct valvular disorders)