Pretty in Yellow Digoxin, Milrinone, Nesiritide

Circulatory (CV & Renal) 1. Heart Failu e Failure 2. Diuretics 3. Anti-hypertens Anti-hypertensives ives 4. Antiarrhythmi Antiarrhythmics cs 1.1 – “Pretty in Yellow”: Digoxin, milrinone, nesirit nesiritide ide • Inotropy = changes to ventricular contractility. Positive inotropy → ↑ contractility • Chronotropy = changes in HR. ⊕ inotropy = ↑ HR, ⊖ inotropy = ↓HR. • Digoxin (DJ foxglove): o Digitalis plants (foxglove) used to derive digoxin (DJ foxglove sounds like digoxin). Natural inotropic. o Indications: ▪ SSx treatment of CHF but provide no M&M benefit (lone kid with sad balloon). Narrow therapeutic index: only used when CHF is refractory of first line treatment ▪ Direct stimulation of vagus nerve (Las Vegas theme) used for treatment of some atrial arrhythmias s o Cardiac glycosides inhibit NA-K-ATPase, which is responsible for benefits & Side effects/toxicities (3Ⓟ powered Banana vending machine inhibiting supervisor from leaving the room; supervisor carrying salty peanuts). ▪ Inhibition of the NA-K-ATPase →↑intracellular Na, which stimulates Na-Ca exchanger efflux of Na & influx of calcium (student with peanuts allowing in ice-cream carrying students while the) →↑sarcoplasmic reticulum calcium stores → ↑contractility & LV systolic function (jock flexing arms) ▪ Inhibition of NA-K-ATPase → ↓K uptake and consequent serum hyperkalemia (excess bananas floating around outside). This is a sign of digoxin toxicity & correlates to ↑mortality. ▪ Can be used for symptomatic treatment of e.g. MI, although provides no M&M benefit. narrow therapeutic window; usually only used when diuretics & ACE-inhibitors have failed to control SSx. ▪ Can be to treat some arrhythmias d/t parasympathomimetic effects via vagal stimulation & M2 Receptor stimulation (“Las Vegas” dance theme; arrhythmia records; kids doing funky dances) • Affects atrial arrhythmias d/t preferential control of AV node (e.g. CHF d/t systolic dysfunction with concurrent AFib) o Toxicity is common d/t narrow therapeutic window. May include: ▪ Hyperkalemia d/t ↓K uptake. Important marker of acute toxicity; dose dependent relationship with mortality. ▪ Arrhythmias. Notorious for premature ventricular contractions, although many arrhythmias possible (variety of broken records on the floor) • Serial EKG & cardiac monitoring indicated in patients with digoxin toxicity ▪ Bradycardia d/t hindered SA & AV node d/t PNS activity at SA node (nodal notes on heart-shaped dance floor) ▪ May precipitate AV block (gal blocking inappropriate advances with heart shield pendent) • Contraindicated in patients with significant sinus or AV block • Should be used cautiously with other drugs that affect this physiology (“this door to remain un-Blocked” shield sign over door) ▪ Patients may be fine for several hours with initial administration, then present with GI symptoms including N/V, Abd pain (kid standing in spotlight looking like he’s going to be sick) ▪ Chronic toxicity: lethargy, delirium, disorientation. Alterations in color vision, especially for yellow (xanthopsia) (yellow spotlight) ▪ Increased susceptibility to or exacerbation of toxicity seen with • Hypokalemia d/t ↑binding of digoxin to Na-K-ATPase (freshman stuffed in vending machine) o Loop diuretics are the most common cause, but others (e.g. diarrhea, vomiting) may also precipitate • Renal dysfunction is often encountered in setting of chronic digoxin toxicity; increases serum half-life →↑susceptibility to toxicity (kidney shaped jukebox knocked over; vandal holding long, tapering flag for ↑half-life) o Regularly assessing renal function indicated in anyone on digoxin. o Renal clearance affected by many other drugs, including amiodarone, diltiazem, quinidine, verapamil; alter tubular transport of digoxin →↑serum transportation. ▪ Digoxin immune Fab reverses toxicity (“Fabulous Las Vegas”) o “Digitalis effect”: ECG ST-depressions with “scooped” appearance, T wave changes, QT interval shortening (scoop out of Tasty ice cream). Not related to toxicity or detrimental effects, but seen with use. Apparently benign. • Milrinone (“One in a million!” campaign poster) o Positive inotrope used to improve cardiac output in acute HF decompensation. o β1 receptor stimulation →↑cAMP →↑cardiac contractility (flexed arm) o inhibit PDE →↓cAMP breakdown (“Phoster Disinterest” campaign slogan). Causes arteriolar dilation which can help reduce afterload in AHF (big dilated ears). Need to monitor for hypotension. • Nesiritide (elephant campaign poster) o Positive inotrope used to improve cardiac output in acute HF decompensation. o Synthetic form of BNP, which stimulates ↑cGMP in smooth muscle cells (BNP & cGMP = “Bump the Grump” campaign slogan). Leads to arterial & venous dilation, decreasing afterload and preload respectively (big arterial ears, and baggy venous pants). o Sodium loss results in diuresis, which may be helpful in the setting of acute HF (water pouring out of trunk).