and Cardiac Glycosides
Blocks influx of K
Sodium Potassium ATPase Blocking Agents
Decreases membrane potential increasing automaticity and sensitizes cells to catecholamines
EKG Findings: (Journal Emerg Med 20:2)
Since dig decreases conduction through AV and increases automaticity, findings can be predicted
1. Any T wave change 2. QT-interval shortening 3. Sagging or scooped out ST seg c depression (especially in leads c tall R) 4. Increased u wave amplitude
therapeutic levels are 0.5-2.0 ng/mL
Rapid A-Fib or Flutter and bundle branch are rare, but dysrhythmias can take any form.
PVCs are most common abnormality
Conduction block: Be concerned with a pt in baseline A-Fib now with a slow rhythm. Also any Heart Block or Sinus Brady
PAT with Block: Atrial tachycardia with Block fairly specific for Dig
Bidirectional Tachycardia-junctional tachycardia alternating between fascicles, so opposite axes
V. Tach-Especially Bigem or Trigem, Bidirectional V. Tach
Digoxin Toxicity With Normal Digoxin Levels (from EMEDHOME)
Digoxin toxicity can occur in patients with normal digoxin levels. In patients taking digoxin in recommended doses, digoxin toxicity can occur in the setting of hypokalemia or hypomagnesemia, even though the serum digoxin level is within normal limits. Digoxin directly inhibits the sodium-potassium ATPase pump in the membrane of the cardiac myocyte, causing an increase in intracellular sodium and calcium which increases myocardial contractility. Hypokalemia increases digoxin cardiac sensitivity because potassium and digoxin compete for the same ATPase-binding site. Magnesium is a cofactor of the sodium-potassium ATPase pump. Hypomagnesemia increases myocardial digoxin uptake, further inhibiting sodium-potassium ATPase pump activity. It is known that long-term digoxin users often have hypokalemia or hypomagnesemia, presumably due to diuretic usage in patients with congestive heart failure. In a suggestive clinical setting, do not exclude the possibility of digoxin toxicity simply because the digoxin level is in the therapeutic range, and be sure to check serum potassium and magnesium levels. References: (1) Raja Rao MP, et al. J Emerg Med 2013; epub, May 20, 2013. (2) Dec GW. Med Clin North Am 2003;87:317-337. (3) Chan KE, et al. J Am Soc Nephrol 2010;21:1550-1559.
Digoxin Toxicity with Normal Digoxin and Serum Potassium Levels: Beware of Magnesium, the Hidden Malefactor. Rao MPR et al. J Emerg Med 2013 May 16 [Epub ahead of print]
and he points us to this article indicating the upper limit of therapeutic may be 1.0
Bidirectional Ventricular Tachycardia (from Steve Smith’s Blog)
There are alternating ventricular beats; the frontal and transverse axes alternate because there is alternating right bundle and left bundle branch block morphologies. This is, of course, not because there is actually RBBB and LBBB, but because the origin of the ventricular beat alternates from right ventricle (LBBB) to left ventricle (RBBB).
We treated her with esmolol without any effect. No therapy helped her, but she did spontaneously convert to NSR 8 hours later. A Chinese PharmD and herbal specialist identified the root as aconitum Carmichaelii.
Bidirectional Tachycardia is rare, and usually associated with digitalis toxicity. It has been reported to be unresponsive to electrical cardioversion and lidocaine, but responsive to flecainide. Aconite (also known as monkshood, or wolfsbane) seems to trigger automaticity by direct activation of inward sodium channels during phase II of the cardiac action potential; thus, flecainide, which blocks these sodium channels appears to be effective in rats.
I had some great questions on this from Beth Bilden, toxicologist:
1. 1. In a patient with a wide comlex dysrhythmia accompanied by hypotension (both likely caused by the unidentified toxin), I would have been tempted to give sodium bicarb which probably would have made things worse. My answer: Although the QRS is wide, it is not wide because of delayed conduction; it is wide because of bundle branch blocks morphology which indicated a focus of dysrhythmia in the ventricle, not a delay in conduction. Therefore, bicarb would not be indicated and was not given. In fact, the best treatment for this (flecainide), when taken in overdose is reversed with sodium bicarb!
2. Esmolol was used for rate control, right? If so, was a calcium channel blocker considered rather than a beta blocker since a sodium channel blocking toxin/toxicant would decrease inotropy and a sodium channel blocking agent had not been excluded from the differential? My answer: Again, I don’t think the ECG is consistent with a sodium channel blocking agent. I have to admit, I had no idea what the toxin was and thus what I should do, so I tried esmolol, knowing I could shut it off if it did not work. No one else knew what to do, so she was only observed overnight and (very luckily) survived. Obviously, if I saw a case of this now, I’d know the differential and have a much better idea how to treat it. As would all of you readers!
Smith SW et al. Bidirectional Ventricular Tachycardia Resulting From Herbal Aconite Poisoning (Case Report). Annals of Emergency Medicine 2005; 45(1):100-101.
Posted by Steve Smith at 4:06 PM
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Labels: aconite, bidirectional tachycardia, digitalis, poisoning, ventricular tachycardia
Christopher said…Would a Ia like procainamide be effective, or are Ic’s required in digitalis induced bidirectional tachycardia?
August 4, 2011 4:53 PM
Steve Smith said…Little data, but a 1c (Flecainide) is a better sodium channel blocker than the 1a’s, and does not delay repolarization as the 1a’s do. Best I can tell you.
August 4, 2011 5:09 PM
looking at this particular tracing, how does one differentiate between bidirectional VT and an underlying BBB (or even an underlying non-BBB) with some sort of bigeminy?
or have we been too careless in identifying bigeminy, and instead should be more suspicious of something like bidirectional VT?
(i can’t get the question to not sound stupid.)
burnedoutmedic said…what about such things as, say, underlying junctional rhythm with bigeminy without P waves? can those occur? if so, how does one tell those apart from bi-directional VT?
Steve Smith said…Bigeminy is always irregular, with the PVC coming early, resulting in “grouped” beating. In this case, every R-R interval is exactly the same. This is also true of atrial bigeminy. If there were p-waves in front of each complex, then it would be alternating RBBB and LBBB. But there are no p-waves. This is automaticity alternating from right to left. Then the question is this: could bidirectional tachycardia be grouped, and I have to say I don’t know the answer, but I suspect that, because there could be differing rates of automaticity in the right and left ventricles, that it is likely.
To add in differentiation from bigeminy, there is not the expected compensatory pause if these were PVCs, nor is there a resetting of the sinus rate if these were PACs/PJCs conducting aberrantly. This leaves bigeminal interpolated PVCs, but that just sounds crazy (if possible at all).
Another differentiator would likely be palpable pulses with both styles of beats if this were bidirectional tachycardia versus bigeminal PVCs which wouldn’t be likely to be perfusing.
Peak dose after 2 hrs, steady state after 6-8. Unlike APAP, it is the steady state, not the peak that is fatal.
Acute: <1.6=non-toxic, >3=toxic, between=window, chronic-much lower levels can be fatal (LD50=6), common sign nausea and vomiting
Increased toxicity c-renal failure, lyte abnormalities, alkalosis
Acute=increased K (>5.5 poor prognostic sign), chronic=decreased K
N/V, anorexia, visual disturbances
Ingestion-Give AC, multi-dose?
If you are going to lavage, give atropine first
Raise K to 3.5-4
Consider Mg to terminate vent dysrhythmias (never use in bradydysrhythmias)
or use phenytoin/lidocaine/amiodarone
Atropine then Pacing for brady
Some say do not give Ca even to treat hyperkalemia, use only insulin/glucose and bicarb
though no real evidence:
Frequently-cited first report Bower JO, Mengle HAK. The additive effect of calcium and digitalis: a warning with a report of two deaths. JAMA 1936;106:1151-3. 2 pts on digitalis died shortly after Ca++ Stone Heart: Further Studies Smith et al. Calcium and digitalis synergism. Arch Intern Med 1939:64:322-9 Dog study with LD50 of digitalis, then given calcium to levels of 38.4-46.6 mg/dL At most, a partially-additive effect The danger of injecting calcium into the digitalized patient is simply that of injecting calcium into any patient with cardiac disease Certainly, this danger cannot be great in practice, considering the widespread use of calcium intravenously.
new report J Emerg Med 2011;40(1):41
no support for stone heart
FAb fragments from sheep-very EXPENSIVE, takes 19 minutes to work
Always use if hyperkalemia >5.0, uncontrollable dysrhythmias, Serum levels >10, ingestion of >10 mg or 4 mg in child
Empiric for Acute-10 vials over 30 minutes c filter
Arrest-20 by bolus
Dig Dose x Bioavailability (.8 for normal) x .5=number of vials
(dig level (Ng/ml) x wt in kg)/100
Administration of Digitalis Antibody Fragments
· Severe ventricular dysrhythmias
· Progressive and hemodynamically significant bradydysrhythmias unresponsive to atropine
· Serum potassium greater than 5 mEq/L
· Rapidly progressive rhythm disturbances or rising serum potassium
· Coingestion of cardiotoxic drug as beta blockers, calcium channel blockers, or tricyclic antidepressants
· Ingestion of plant known to contain cardiac glycosides plus severe dysrhythmias (rare)
· Acute ingestion greater than 10 mg plus any one of factors 1 through 6 above
· Steady-state serum digoxin greater than 6 Ng/ml plus any one of factors 1 through 6 above
· Ingestion of greater than 0.1 to 0.3 mg/kg or steady-state digoxin greater than 5 Ng/ml plus rapidly progressive symptoms or signs of digitalis intoxication or potentially life-threatening dysrhythmias or conductions blocks or serum potassium greater than 6 mEq/L
· Coingestion of other cardiotoxic drugs with additive or synergistic toxicity
· Ingestion of plant known to contain cardiac glycosides plus severe dysrhythmias (rare)
Can not get regular dig levels after digibind, must get free dig levels.
digibind takes 19 minutes to work
Dig Ab drip 10 vials over 4 hours
for dig-like substances
The usual oral dose is four grams of Cholestyramine in sorbitol (or water) every four-to-six hours. Consider four doses
Chan Su/Kyu Shun
Chinese aphrodisiac AKA rock hard or love stone
Get dig levels, start at 10 vials digibind
Bradycardia and vomiting
Dig assays are based on polyvalent assay, only some parts react with Chan Su, some monovalent wont react.
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Dig Ekgs from LITFL BlogBack to top
Beta Blockers & Calcium Channel Blockers
B1 Heart, Eye (stimulates humor production), Kidney (stimulate plasma rennin secretion)
B2 Smooth Muscle, Skeletal Muscle, Liver (Glucose Release), Heart (?)
B3 Adipose Tissue
Propranolol penetrates to CNS, so altered mental status
Beta blockers can give elevate potassium, while CCBs wont
Unless delayed action preparation, no symptoms in 4 hours and you are in the clear
propranolol is actually a sodium channel blocker
Calcium Channel Blockers
Verapamil has the worst toxicity
Brady + hypotension
24-36 hours maximum duration
Vomitting is a vagal stimuli so avoid it
CCBs do not cause AMS
CCBs block receptor in B-Islet cells, preventing insulin release, so can see hyperglycemia as opposed to the normal-low sugar in B-Blockers
Nifedipine and other dihydropyridines (amlodipine, felodipine, isradipine, nicardipine, nimodipine, nisoldipine) will cause profound hypotension without bradycardia, due to poor affinity for myocardial calcium channels. This selectivity is not lost in overdose. They may actually present with reflex tachycardia
Weak/Dizzy, mild confusion, bradycardia progressing to severe hypotension and shock
Selectivity is lost in overdose (except dihydropyridines)
· Activated Charcoal, pulse .5g/kg Q4 (if sustained release)
· Whole bowel-Golytely 1-2L/hour
· Frequent glucose and k checks
· Atropine (probably should avoid as it will not work but will limit gastric motility)
· Calcium, 1 amp of CaCl or 3 amps of CaGluc, may be repeated x 5 without checking Calcium. Give over 3-5 minutes. Make sure not dig toxicity. Shoot for Ca of 15-20.
· Glucagon (5 mg bolus, may be repeated x 1. Then dose originally needed for reversal/hr, use sterile water not included diluent) May need to give glucose in order for it to keep working Mix with D5W. Bolus 50-150mcg/kg Infusion 70mcg/kg/hour (put 10mg in 100cc D5W)
· Insulin/Glucose 10-20 units of RI (some suggest 1 unit/kg/hr, not .1) along with 25 grams D50 followed by .2-1 unit/kg/hr with fingersticks q30 minutes and adequate glucose replacement
· May need to use norepinephrine or alternatively isoprel/Epi/dopamine (at doses up to 200 mcg/kg/min)
· Aminophylline-releases catecholamines and in high doses, phosphodiesterase inhibitor (PDI), augments cAMP in the cell. Amrinone and milrinone are selective PDIs used in CHF that give inotropy s chronotropy, aminophylline gives both. 5.6 mg/kg over 20 minutes and maintenance infusions (0.5mg – 0.9 mg/kg/min) utilized in the treatment of bronchospastic disease have been employed successfully in these situations. Increased intra and extracellular Ca Amrinone .75mg/kg followed by infusion of 5-10 ug/kg/min
· IABP, consider dialysis, CP Bypass,
HyperInsulinemia/Euglycemia Treatment (Crit Care 2006;10:212)
toxicity causes by blockade of L-type ca channel in myocardial and vascular muscle
also impairs insulin release from b-islet cells and decreases sensitivity to insulin
lack of fuel compromises cellular metabolism
high insulin treatment attempts to combat this
benefits usually seen 30-45 minutes after starting treatment
1 unit/kg as a bolus then .5 unit/kg/hour
FS q 30 minutes
may need 20 – 30 grams/hour of glucose
most recent review of high-dose insulin (Clincal Toxicology 2011;49:277)
and hiet review
Any patient who took a regular preparation and has no sx and no pr prolongation on ekg after 6 hours may be discharged. Any sustained release prep should be admitted. Any sotalol overdose should be admitted.Back to top
Clonidine and Imidazolines
Alpha 2 agonist. Also can see the same toxicity when peds drink their grandma’s Visine.
Peripherally it acts as alpha 1 causing vasoconstriction. Centrally decreases sympathetic outflow
Initial hypertension and then lethargy, hypoventilation, Miosis, hypoxia, hypotension, decreased body temperature, and bradycardia
Think of it as a heroin wanna-be
IVF and then dopamine
Consider Nalaxone (unknown why, but may reverse altered mental status by blockade of endogenous opioids)
Consider yohimbine (5.4 mg Tab) try 1 PO
®) is an alpha-2 adrenergic agonist that is approved for the management of hypertension.
Off-label uses include heroin or nicotine withdrawal, ethanol dependence, prophylaxis of migraines, impulse
control disorder, and attention-deficit hyperactivity disorder (ADHD). Clonidine stimulates alpha
adrenoceptors in the brain stem which results in reduced sympathetic outflow from the CNS. The result is a
decrease in peripheral resistance, renal vascular resistance, heart rate, and blood pressure.
Clonidine is rapidly absorbed through the oral route, with 75-90% absorbed within 30 minutes.
Antihypertensive effects are seen within 30-60 minutes of oral administration. The transdermal formulation
yields therapeutic plasma concentrations within 2-3 days of application. The absorption when applied to the
skin of infants and children is unknown. Half-life is approximately 7.5-10.8 hours, with a longer half life of 16-
40 hours in the presence of renal dysfunction. Approximately 50% of oral drug is metabolized in the liver.
Overdoses occur as a result of unintentional oral ingestions by children, therapeutic errors, and intentional
overdoses in adolescents and adults. Transdermal patches are a danger to children as accidental application
to skin or chewing the patch can cause serious toxicity. Even discarded clonidine patches contain significant
amounts of drug. As little as one 0.1 mg tablet has caused signs and symptoms of toxicity in children. Toxic
effects usually occur within 30 minutes to 4 hours of exposure and resolve within 24-72 hours. Tachycardia
and hypertension may be present early on and progress to bradycardia and hypotension. Other clinical
effects include lethargy, coma, seizures (rare), hypotonia and hyporeflexia, miosis, respiratory depression and
apnea, and hypothermia. Cardiac dysrhythmias such as AV block may occur.
Following an overdose, activated charcoal may be administered if the patient is able to protect the airway.
Patients may require respiratory and blood pressure support. Bradycardia can be treated with atropine.
Naloxone has been used successfully to reverse clonidine-induced respiratory depression, hypotension, and
coma, but results are inconsistent.
Lisa A. Maher, PharmD
Pediatric Pharmacy Resident, Johns Hopkins Hospital
Found in eye drops such as Visine
Sx and treatment similar to above.Back to top
Block metabolism of endogenous opoids, so nalaxone can reverse AMS and hypotension.
PMID: 1928887 and PMID: 2996820
? mechanism from UMd Tox Tidbits: ACE inhibitors may also inhibit the metabolism of enkephalins and potentiate their opioid effect which includes lowering of blood pressure. Nalaxone may blunt this response.
Sodium Channel Blockers
Class Medication Extended-Release Preparations (Brands) Phenylalkylamine Verapamil Calan SR, Isoptin SR, Covera HS, Verelan PM Benzothiazepine Diltiazem Cardizem SR, Cardizem CD, Cardizem LA, Taztia XT, Cartia XT, Dilt-CD DihydropyridineNifedipine Procardia XL Nicardipine Cardene SR Isradipine DynaCirc CR Nisoldipine Sular
Route Onset of Action Time to Peak Level Time to Peak Effect Oral 1.5-6 h 2-3 h 4-6 h Intravenous 5-30 min Intermediate 1.5-3 h Table 4. Distribution Of ß-Adrenoreceptor Subtypes Within Organs ß1 Heart Increase contractility, automaticity, and conduction velocity Adipose tissue Activate lipolysis Posterior pituitary ADH secretion ß2Vascular and respiratory smooth muscle Relaxation/dilatation Skeletal muscle Relaxation Glycogenolysis Promote K+ reuptake Liver Glycogenolysis and gluconeogenesis Gallbladder and ducts Relaxation Pancreas (islets cells) Increased secretion Eye Ciliary muscle relaxation Kidney Renin secretion Bladder Detrusor muscle relaxation Uterus Muscle relaxation
Table 5. Differences In Evaluating The ECG In Patients With Acute Digoxin, ß-blocker, And CCB Toxicity
Digoxin ß-Blocker CCBAtrial tachycardia + Wide QRS + +/ High-degree AV block + + Biventricular tachycardia +
indicates absent; and + indicates present.
Table 6. Differences In Evaluating Patients With Acute Digoxin, ß-Blocker, And CCB Toxicity
Digoxin ß-Blocker CCBMental status changes + GI symptoms ++ Blood pressure Normal Decreased Decreased Heart rate Decreased Decreased Decreased Potassium Increased Mildly increased
Glucose No effect Decreased Increased
indicates absent; and + indicates present.
Table 7. Calculation Of Dose Of Digoxin-Specific Immunotherapy
Calculation or Empiric Dose Number of VialsKnown amount ingested Amount ingested (mg) x 0.8 (bioavailability of digoxin) / 0.5 mg (amount of digoxin Fab per vial) Known serum digoxin level Serum digoxin level (ng/mL) x patient’s weight (kg) / 100 Empiric, acute overdose 10 vials (adult or child) Empiric, chronic toxicity 3-6 vials (adult) Empiric, chronic toxicity 1-2 vials (child) Gallbladder and ducts Relaxation Pancreas (islets cells) Increased secretion Eye Ciliary muscle relaxation Kidney Renin secretion Bladder Detrusor muscle relaxation Uterus Muscle relaxation Specific Treatment Modalities In Digoxin, ß-Blocker, And CCB Toxicity
Digoxin ß-Blocker CCBDigoxin Fab + Atropine + + + Calcium salts + ++ Glucagon ++ + Catecholamines + + Phosphodiesterase inhibitors + + Transvenous pacing +
Intra-aortic balloon pumps + +
indicates not recommended; + indicates recommended; and ++ indicates strongly recommended.
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