Lecture

• Cardiac Glycosides consists of the digitalis purpurea(common foxglove) and digitalis lanata(woolly foxglove). Digitalis refers to these drugs
• Digoxin(Lanoxin) is the only cardiac glycoside available for use
• The toxic level digoxin(lanoxin) is very close to the therapeutic level
• Digoxin(Lanoxin) primarily increases the force of myocardial contraction but doesn't affect the MVO2 of the heart. Secondarily it decreases HR and AV conduction speed by stimulating the Vagus nerve
• Digoxin(Lanoxin) increases kidney function thru improved renal bloodflow. This causes to the excretion of excess fluids and combats edema(additional help against CHF)
• Digoxin(Lanoxin) is used to treat CHF. It has positive ionotropic, negative chronotropic and negative dromotropic effects
• Therapeutic doses of Digoxin(Lanoxin) cause ST depression, T wave alteration and increased PR interval(Due to dromotropic effects at AV nodes).
• Higher doses of Digoxin(Lanoxin) can cause potential conduction blockages
• Digoxin inhibits ATPase so there's nothing to power the Na+/K+ pump. This leads to an accumulation of Na+ within the cell which slows down the activity of the Na+/Ca+ exchanger.
• Slowing down the activity of the Na+/Ca+ pump slows the loss of Ca+ from cells which causes the contractions to be more stronger and shorter. Also causes an elongation of phase 2

  
• Digoxin causes an interference with Na+/K+ pump which slows down the return of K+ back into contractile cells after an action potential. This causes a slowed repolarization and prolonged refractory period

  
• Maintenance doses of Digoxin are 0.125 to 0.5 mg PO
• Digitization is the front loading of drug to rapidly achieve therapeutic levels.
• Adverse effects of Digoxin: ectopic beats leading to PVCs (aren't associated with cardiac ischemia) and arrhythmias(PVC induced V fib or V tac)
• Treatment for digoxin toxicity: Digoxin Immune Fab(Digibind, DigiFab) and activated charcoal(absorbs meds from the stomach but can't do shit past 30 minutes as its already in the bloodstream)
• If PT is hypokalemic, they are sensitized to the toxic effects of Digoxin which increases the chance of arrhythmias.
• If PT is hyperkalemic, it antagonizes the therapeutic effect of digoxin
• Hypercalcemia enhances the action of digoxin as there's more Ca+ ions in the intracellular space. This increases the chance of arrhythmias
• Hypocalcemia causes a protective effect against digoxin toxicity.
• Diuretic therapy eliminates excess Na+ and water thru urination.
• Diuretic therapy is often used with cardiac glycosides to rapidly decrease congestion and decrease MVO2.
• Thiazide diuretics are milder and typically for long term usage. They fxn by blocking reabsorption of Na+ in the distal tubules
• Organic acids or loop diuretics are potent and used in severe CHF or PTs with impaired renal fxn. They function in the loop of henle
• Aldosterone antagonists are weak diuretics and one of them is spironolactone(Aldactazide and Aldactone)
• An example of loop diuretics is furosemide(Lasix)
• Vasodilators dilate arteries and veins to reduce PVR, decrease MVO2/cardiac workload. Decreases BP and heart is able to pump more blood with less effort. It decreases both preload and afterload of the heart
• Vasodilators are the preferred treatment for CHF due to their limited adverse effects
• Arterial vasodilators decrease afterload while venous vasodilators decrease preload
• Hydralazine is an arterial dilator that decreases BP and decreases afterload.
• ACEIs inhibit formation of angiotensin 2 which dilates arteries/veins and promotes excretion of Na+ and H2O. It secondarily decreases inactivation of bradykinin which increases vasodilation
• ACEIs are Captopril(Capoten, Captoril), Enalapril(Vasotec), Lisinopril(Prinivil, Zestril) and Perindopril(Coversyl) and Ramipril(Altace)
• ARBs(Angiotensin Receptor Blockers) block angiotensin 2 receptors(AT1) which stops it from taking effect. It dilates arteries/veins and promotes excretion of Na+ and H2O but doesn't affect Bradykinens
• ARBs are: candesartan(Atacand), Irbesartan(Avapro), Losartan(Cozaar), Valsartan(diovan/entresto) and telmisartan(Micardis).
• ACEIs work high up in the CNS while ARBs work a bit lower

  
• The adverse effects ACEIs/ARBs are: headaches, dizziness, hyperkalemia(excess K+ retention) and hypotension.
• Adverse effects of ACEIs specifically are: a dry cough and angioedema due to the bradykinins(do not use EPI to treat this)
• Treatment for the adverse effects of ACEIs is fresh frozen plasma given in hospitals
• NTG is a potent veno dilator and dilates the coronary arteries as well. It decreases venous return by containing nitrite ions that are converted to NO in the blood.
• NTG has these adverse affects: headaches, dizziness, postural hypotension, tachycardia and vasomotor flushing
• NTG is very potent but its effects are short lived