Beta Blocker Toxicity and Safety

BETA-BLOCKERS

Presentation By: Christopher KhemrajMohamed MohamedProject Distribution By:Ebey P. Soman

References Marks, Jay, and Omudhome Ogbru. "Beta Blockers." MedicineNet. MedicineNet, n.d. Web. 12

Nov 2010. <http://www.medicinenet.com/beta_blockers/article.htm>.

"Beta-adrenergic Blocking Agents (Systemic)." Drugs.com. N.p., 20 OCT 2010. Web. 12 Nov 2010. <http://www.drugs.com/mmx/metoprolol-succinate.html>.

"Beta-Adrenergic Blocking Agents (Beta Blockers)." Facts and Comparisons 2010. n. pag. Wolters Kluwer Health, Inc. . Web. 12 Nov 2010. <http://online.factsandcomparisons.com>.

"Medication Package Insert Information for: TENORMIN TABLET 50MG ." MEDSort. N.p., n.d. Web. 13 Nov 2010. <http://drugs.medsort.com/Drugs/DrugPackageInsert.aspx?MedID=5811#tablist>.

Propranolol: Toxicology Data Network (TOXNET). National Library of Medicine :Hazardous Substances Data Bank (HSDA), Web. 15 Nov. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~AGpJcu:1>.

"Beta Blockers - Top 10 toxicities." University of Conneticut . Web. 14 Nov 2010. <http://www.uconnem.org/toxicologyweb/cardiovascular.jpg>.

Atenolol: Toxicology Data Network (TOXNET). National Library of Medicine :Hazardous Substances Data Bank (HSDA), Web. 15 Nov. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~SpU8BZ:1>.

Heitz, Cory et al. "BETA BLOCKER OVERDOSE." Emergency Medicine Education Online. Center for Simulation Technology and Academic Research, n.d. Web. 15 Nov 2010. <http://www.emedu.org/simlibrary/UploadFolder/152.11.191.200_-8589677563690905358Beta%20Blocker%20Overdose%20FINAL.pdf>.

Sharma, Adhi. "Beta Blocker Toxicity." Emedicine from WebMD. WebMD, 03 NOV 2010. Web. 15 Nov 2010. <http://emedicine.medscape.com/article/813342-overview>.

Rahm, Stephen. "A 4 year Old who ingested a medication." Pediatric Case Studies for the Paramedic. American Academic of Orthopaedic Surgeons, n.d. Web. 15 Nov 2010. <http://books.google.com/books?id=wO-5_8KqO94C&lpg=PP1&pg=PA65#v=onepage&q&f=false>.

Quick Facts & Figures

The 2007 Annual Report of the American Association of Poison Control Centers' (AAPCC) National Poison Data System reported 9291 single exposures to beta-blockers.

In 2007, the AAPCC reported 413 minor outcomes, 631 moderate outcomes, 61 major outcomes, and 3 fatalities for beta-blocker exposure

According to the 2004 AAPCC toxic exposure review, 51% of all exposures and 47.6% of all overdose fatalities are in women

Of the fatalities reported to the AAPCC, 68% were associated with individuals younger than 50 years. Forty-three percent of all fatalities reported to the AAPCC in 2004 were associated with children younger than 6 years.

Propranolol is the most toxic beta-blocker because it is non-selective and the most frequently used in suicide attempts worldwide.

Source: Sharma, Adhi. "Beta Blocker Toxicity." Emedicine from WebMD. WebMD, 03 NOV 2010. Web. 15 Nov 2010. <http://emedicine.medscape.com/article/813342-overview>.

So what are Beta-Blockers? Beta blockers are known as beta-adrenergic blocking

agents and they block norepinephrine and epinephrine from binding to receptors on nerve cells.

When norepinephrine and epinephrine are blocked, this reduces heart rate and lowers blood pressure by dilating the blood vessels.

Beta blockers work mainly by blocking Beta 1 (heart, kidney, eyes) and Beta 2 receptors (lungs, liver, muscles etc.).

Beta 3 is mostly in Adiposities and is blocked by nonselective beta blockers like propanolol

There are tons of beta-blockers on the market and majority of these drugs used to treat cardiovascular diseases and glaucoma.Source: Marks, Jay, and Omudhome Ogbru. "Beta Blockers." MedicineNet. MedicineNet, n.d.

Web. 12 Nov 2010. <http://www.medicinenet.com/beta_blockers/article.htm>.

Examples of Beta-Blockers (US) ACEBUTOLOL

HYDROCHLORIDE ATENOLOL BETAXOLOL HYDROCHLORIDE BISOPROLOL FUMARATE LABETALOLCARTEOLOL

HYDROCHLORIDE CARVEDILOL ESMOLOL HYDROCHLORIDE METOPROLOL

METOPROLOL SUCCINATE ORAL METOPROLOL TARTRATE

INJECTION METOPROLOL TARTRATE ORAL

NADOLOL

NEBIVOLOL OXPRENOLOL PENBUTOLOL SULFATE PINDOLOL PROPRANOLOL HYDROCHLORIDE

PROPRANOLOL HYDROCHLORIDE INJECTION

PROPRANOLOL HYDROCHLORIDE ORAL

SOTALOL HYDROCHLORIDE SOTALOL HYDROCHLORIDE

INJECTION SOTALOL HYDROCHLORIDE ORAL

TIMOLOL MALEATE And many more exist,

especially in foreign marketsSource: "Beta-adrenergic Blocking Agents (Systemic)." Drugs.com. N.p., 20 OCT 2010. Web. 12 Nov 2010. <http://www.drugs.com/mmx/metoprolol-succinate.html>.

FDA Approved Indications Hypertension Pediatric hypertensive emergency Angina pectoris Cardiac arrhythmias/tachycardias MI CHF Pheochromocytoma Migraine prevention Hypertrophic subaortic stenosis Parkinsonian tremors Akathisia Bleeding in portal hypertension Atrial fibrillation Generalized anxiety disorder Angina Thyrotoxicosis Fibromyalgia

- Image Source: "Atenolol." 1aMeds. Web. 12 Nov 2010. <http://www.1ameds.net/images/Atenolol.jpg>. - Source: "Beta-Adrenergic Blocking Agents (Beta Blockers)." Facts and Comparisons 2010. n. pag. Wolters Kluwer Health, Inc. . Web. 12 Nov 2010. <http://online.factsandcomparisons.com>.

How do they Work?

Beta-adrenergic receptor blocking agents compete with beta-adrenergic agonists for available beta receptor sites.

Propranolol, nadolol, timolol, penbutolol, sotalol, and pindolol inhibit both the beta 1 receptors and the beta 2receptors

Metoprolol, acebutolol, bisoprolol, esmolol, betaxolol, and atenolol are more selective and inhibit beta -1 receptors (heart mostly)

Above: Propranolol

The 2 Enantiomers of Atenolol

Sources: "Beta-Adrenergic Blocking Agents (Beta Blockers)." Facts and Comparisons 2010. n. pag. Wolters Kluwer Health, Inc. . Web. 12 Nov 2010. <http://online.factsandcomparisons.com>."Atenolol Enantiomers Structural Formula." Wikipedia. Web. 12 Nov 2010. <http://en.wikipedia.org/wiki/File:%28%C2%B1%29-Atenolol_Enantiomers_Structural_Formulae.png>."Propranolol-2D-skeletal." Wikipedia. Web. 12 Nov 2010. <http://en.wikipedia.org/wiki/File:Propranolol-2D-skeletal.png>.

Pharmacokinetics

Absorption Distribution

Many beta blockers undergo first pass metabolism upon ingestion.

Only Pindolol and Sotalol have no first pass effect

Having food in the stomach decreases the absorption of most beta blockers but increases absorption of metoprolol and propranolol.

There is no simple relationship between dose given, drug plasma levels and resulting therapeutic effect since response to a beta blocker is individual based

Metoprolol and propranolol can cross the blood brain barrier so they can produce CNS effects in overdose. Atenolol does not cross BBB so less chances of CNS effectsSource: "Beta-Adrenergic Blocking Agents (Beta Blockers)."

Facts and Comparisons 2010. n. pag. Wolters Kluwer Health, Inc. . Web. 12 Nov 2010. <http://online.factsandcomparisons.com>.

Pharmacokinetics (Con’t)

Metabolism Excretion

Majority of beta blockers are metabolized in the liver

Sotalol is not metabolized but no data exists for the extend of Sotalol absorption

As mentioned before, many beta blockers undergo first pass metabolism

Atenolol is 50% excreted unchanged in feces

Majority of beta blockers are excreted through urine

Sotalol is excreted unchanged into the urine

Only 30-40% of Acebutolol is excreted via renal tubules, the rest are excreted in the bile and other routes

Source: "Beta-Adrenergic Blocking Agents (Beta Blockers)." Facts and Comparisons 2010. n. pag. Wolters Kluwer Health, Inc. . Web. 12 Nov 2010. <http://online.factsandcomparisons.com>.

Black Box Warnings (BBW)

For atenolol, metoprolol, nadolol, propranolol & timolol

For sotalol

Abrupt stop in beta-blocker treatment may worsen angina, give myocardial infarction and ventricular arrythmias

If you are going to stop the treatment, then taper the dose

If angina occurs, restart beta blocker therapy

Do not substitute sotalol for sotalol AF

If patient has drug induced arrhythmia then monitor patient for 3 days in health care facility when starting sotalol or sotalol AF regimen

Cardiac resuscitation, ECG monitoring and renal monitoring is neededSource: "Beta-Adrenergic Blocking Agents (Beta Blockers)." Facts

and Comparisons 2010. n. pag. Wolters Kluwer Health, Inc. . Web. 12 Nov 2010. <http://online.factsandcomparisons.com>.

Pregnancy & Beta BlockersMostly Category C but…

So talk to your doctor if you have a little one on the way before taking beta blockers!

Atenolol is category D Atenolol crosses the placental

barrier Studies show mothers taking

Atenolol from 2nd trimester had babies that were too small

No studies on 1st trimester or any other fetal harm

Only Category B drugs are acebutolol, pindolol & sotalol

Most beta blockers are excreted in breast milk Sources: "Beta-Adrenergic Blocking Agents (Beta Blockers)." Facts and Comparisons 2010. n. pag.

Wolters Kluwer Health, Inc. . Web. 12 Nov 2010. <http://online.factsandcomparisons.com>."Pregnancy & Chiropractic." chiropracticatthecomo. Web. 13 Nov 2010. <http://www.chiropracticatthecomo.com/Images/Pregnant.jpg>.

Signs & Symptoms of OverdoseCardiac Issues GI & Metabolic issues

Asystole Tachycardia prolonged QT interval

(sotalol) prolonged QRS complex ventricular dysrhythmias Hypotension hypertension (partial

agonists) Bradycardia AV block

Mesenteric ischemia esophageal spasms Hyperkalemia hypoglycemia

Source: "Beta-Adrenergic Blocking Agents (Beta Blockers)." Facts and Comparisons 2010. n. pag. Wolters Kluwer Health, Inc. . Web. 12 Nov 2010. <http://online.factsandcomparisons.com>."Prolonged QRS Complex." natomy & Physiology Note Summaries. Web. 13 Nov 2010. <http://legacy.owensboro.kctcs.edu/gcaplan/anat2/notes/Image347.gif>.

Signs & Symptoms (Con’t)

CNS & Renal Issues Respiratory Issues

Seizures Coma or depressed

level of consciousness Renal failure

Apnea Cyanosis respiratory depression bronchospasm

Source: Atenolol: Toxicology Data Network (TOXNET). National Library of Medicine :Hazardous Substances Data Bank (HSDA), Web. 15 Nov. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~SpU8BZ:1>."Beta-Adrenergic Blocking Agents (Beta Blockers)." Facts and Comparisons 2010. n. pag. Wolters Kluwer Health, Inc. . Web. 12 Nov 2010. <http://online.factsandcomparisons.com>.

Exposure Risk Assessment

Before treating patient , try to determine the following:

Patient's age Past medical history or condition Name of product and strength (if

possible) Time of overdose How much or what amount they

swallowed Was it prescribed to the patient?Source: Atenolol: Toxicology Data Network (TOXNET). National Library of

Medicine :Hazardous Substances Data Bank (HSDA), Web. 15 Nov. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~SpU8BZ:1>.

Time Frame of Exposure

Symptoms may occur within 6 hours after ingestion and can be as quick as 20 minutes

Onset of detectable symptoms will depend on formulations. Extended release formulations will take longer to manifest

Source: Propranolol: Toxicology Data Network (TOXNET). National Library of Medicine :Hazardous Substances Data Bank (HSDA), Web. 15 Nov. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~AGpJcu:1>."Beta Blockers - Top 10 toxicities." University of Conneticut . Web. 14 Nov 2010. <http://www.uconnem.org/toxicologyweb/cardiovascular.jpg>.

Laboratory: What to monitor

Vital Signs such Blood Pressure

Mental Status: is the patient alert?

ECG – Important to monitor for bradycardia, heart failure or other severe cardiac issues

Serum electrolyte levels will be low

Renal failure can occur Blood glucose levels will

drop significantly

Source: Propranolol: Toxicology Data Network (TOXNET). National Library of Medicine :Hazardous Substances Data Bank (HSDA), Web. 15 Nov. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~AGpJcu:1>."Vital Signs Cartoons and Comics." CartoonStock. Web. 14 Nov 2010. <http://www.cartoonstock.com/lowres/hsc0561l.jpg>.

Suggested Treatments

1-2 Hours after Ingestion Perform assessment of

patient condition Determine serum glucose

levels – if hypoglycemic, treat with IV glucagon

Give activated charcoal to all patients and gastric lavage if still within the 2 hour period

If is ER tablets they ingested, then do whole bowel irrigation with polyethylene glycol (PEG)

Source: "Beta-Adrenergic Blocking Agents (Beta Blockers)." Facts and Comparisons 2010. n. pag. Wolters Kluwer Health, Inc. . Web. 12 Nov 2010. <http://online.factsandcomparisons.com>. "Polyethylene Glycol." Drugs.com. Web. 13 Nov 2010. <http://www.drugs.com/pro/polyethylene-glycol.html>.

Treatments (Con’t)

Supportive Treatments

Benzodiazepines for Seizures!

chest radiography to prevent cardiac failure

serum electrolytes to prevent potassium buildup

Treat seizures with benzodiazepines, if they are not working, then treat with barbiturates

Make sure activated charcoal is given

Source: "Beta-Adrenergic Blocking Agents (Beta Blockers)." Facts and Comparisons 2010. n. pag. Wolters Kluwer Health, Inc. . Web. 12 Nov 2010. <http://online.factsandcomparisons.com>."Valium." Imageshack. Web. 13 Nov 2010. <http://img31.imageshack.us/img31/2313/valium2.jpg>.

Treatments (Con’t)

Last step therapy

Atenolol, acebutolol, sotalol, and nadolol are the only beta blockers that can be removed by hemodialysis

Treat bronchospasm with beta agonists like albuterol

In patients who are still not responding to treatments mentioned above, epinephrine (parenteral) may be needed

Source: "Beta-Adrenergic Blocking Agents (Beta Blockers)." Facts and Comparisons 2010. n. pag. Wolters Kluwer Health, Inc. . Web. 12 Nov 2010. <http://online.factsandcomparisons.com>."Epinephrine." MaineVille. Web. 13 Nov 2010. <http://bdnimages.sprintout.com/uploads/large/1276912473_8d68.jpg>.

Other Treatment Options

Catecholamine agents – Epinephrine is most commonly used. However isoproterenol and dopamine can be used as well

Phosphodiesterase inhibitors - Milrinone, aminophylline and theophylline. Amrinone has been shown to be good in dog trials

Insulin – High doses Lipid Emulsion – IV, for

propanolol overdose

Atropine – Most commonly used alternative agent but least effective. If patient does not respond to a 1mg dose of atropine, you verify beta blocker toxicity (diagnosis tool)

Pacemakers – Control cardiac pace in severe beta blocker induced bradycardia

intra-aortic balloon pump – to restore perfusion and blood flow

Source: "Beta-Adrenergic Blocking Agents (Beta Blockers)." Facts and Comparisons 2010. n. pag. Wolters Kluwer Health, Inc. . Web. 12 Nov 2010. <http://online.factsandcomparisons.com>. Atenolol: Toxicology Data Network (TOXNET). National Library of Medicine :Hazardous Substances Data Bank (HSDA), Web. 15 Nov. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~SpU8BZ:1>.

Treatment Dosages

IV fluids 500 mL boluses up to 2L to raise blood pressure if the patient is hypotensive

1 to 2 mg lorazepam IV or another benzodiazepine for seizures

Propofol can be used along with the lorazepam

If patient has QRS widening and ventricular dysrhythmias, then treat with IV sodium bicarbonate 1 to 2 mEq/kg IV bolus starting dose, titrate to blood pH 7.45 to 7.55

Use lidocaine if sodium bicarb is not working

Liquid Activated Charcoal: 1 g/kg PO up to 50-100 grams. For children up to 15-30 grams

Source: Propranolol: Toxicology Data Network (TOXNET). National Library of Medicine :Hazardous Substances Data Bank (HSDA), Web. 15 Nov. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~AGpJcu:1>.Sharma, Adhi. "Beta Blocker Toxicity." Emedicine from WebMD. WebMD, 03 NOV 2010. Web. 15 Nov 2010. <http://emedicine.medscape.com/article/813342-overview>.

Treatment Dosages (Con’t)

Glucagon: Initial dosing is 5 to 15 mg slow IV push with an infusion rate of 5 to 15 mg/hour.

Phosphodiesterase inhibitor (Inamrinone) - 1 mg/kg bolus then 3 to 6 mcg/kg/minute

Calcium for beta blocker (propranolol or atenolol) & verapamil overdose - calcium chloride 0.2 mL/kg or calcium gluconate 0.6 mL/kg intravenously

Dextrose bolus is another option. Give to patient with blood glucose of less than 250 mg/dL

- Adults: 25 to 50 mL dextrose 50% - Children: 0.25 g/kg dextrose 25%

Source: Propranolol: Toxicology Data Network (TOXNET). National Library of Medicine :Hazardous Substances Data Bank (HSDA), Web. 15 Nov. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~AGpJcu:1>."Dextrose." Vetone Pharmaceuticals . Web. 15 Nov 2010. <http://www.vetone.net/images/pharmaceuticals/dextrose.jpg>.

Case Study 1

Chief Complaint: “weak and tired” Patient is a 65 year old previously healthy Caucasian male, who came to

the ED today because he feels “weak all over”. Symptoms began 2 days ago.

Vital Signs: Heart rate 49, Blood Pressure 90/60, Respiratory Rate 12, Pulse Oximetry 95% on room air, Temperature 96.9 degrees Fahrenheit

Past Medical History: He has had two previous myocardial infarctions (with a stent placed in his right coronary artery 2 years ago), congestive heart failure with an ejection fraction of 40%, hypertension, hyperlipidemia, diabetes mellitus type II, osteoarthritis, depression.

Medications and Allergies: Only provide medication list if specifically requested. Medications include aspirin, glipizide, furosemide, metoprolol, clopidogrel, simvastatin, sertraline. Allergy to penicillin (rash)

Family and Social History: 40 pack-year history of smoking, occasional alcohol use, denies illicit drug use. His mother died of a stroke at 82.

Source: Heitz, Cory. "BETA BLOCKER OVERDOSE." Emergency Medicine Education Online. Center for Simulation Technology and Academic Research, n.d. Web. 15 Nov 2010. <http://www.emedu.org/simlibrary/UploadFolder/152.11.191.200_-8589677563690905358Beta%20Blocker%20Overdose%20FINAL.pdf>.

Cast Study 1 (Con’t)

History given by patient: The patient reports that symptoms began 2 days ago and have worsened.

He feels dizzy and as if he’s going to pass out. He has had no syncope. The dizziness is worse when he goes from a sitting to standing position.

Associated symptoms: The patient has intermittent chest pains, which are described as sharp, fleeting, substernal, and without radiation. He has no chest pain currently. He has had mild dyspnea on exertion, a persistent dry cough, and mild nausea. He denies vomiting, diaphoresis, and hemoptysis. He has had a decreased appetite for one week. He has had no recent surgery, and no history of cancer, deep venous thrombosis, or pulmonary embolism. He denies headache, neck pain, visual changes, abdominal pain, fevers, rashes, or change in his bowel movements.


Case Study 1 (Con’t)

Initial Exam: Patient is a healthy appearing male. Patient

is awake, alert, and oriented. Comfortable without distress. Appears slightly fatigued.

Cardiovascular: Bradycardia with regular rhythm.

Lungs: Scattered rhonchi and end-expiratory wheezes bilaterally, with no rales.

All other physical examination results were normal however the patient got worse during the physical exam and condition deterioratedSource: Heitz, Cory. "BETA BLOCKER OVERDOSE." Emergency Medicine Education Online. Center for

Simulation Technology and Academic Research, n.d. Web. 15 Nov 2010. <http://www.emedu.org/simlibrary/UploadFolder/152.11.191.200_-8589677563690905358Beta%20Blocker%20Overdose%20FINAL.pdf>.


Lab Results: Sodium: 144, Chloride: 98, BUN: 36,

Potassium 4.5, Bicarb: 18, Creatinine 1.7, glucose 138

Urinalysis: NormalINR: 1.0Plateletes 383, WBC 8.4, Hemoglobin

11.1, Hematocrit 34.0Source: Heitz, Cory. "BETA BLOCKER OVERDOSE." Emergency Medicine Education Online. Center for Simulation Technology and Academic Research, n.d. Web. 15 Nov 2010. <http://www.emedu.org/simlibrary/UploadFolder/152.11.191.200_-8589677563690905358Beta%20Blocker%20Overdose%20FINAL.pdf>.


ECG Shows Bradycardia



IV fluids can be administered in response to his worsening hypotension, but IV fluid alone will not correct his low blood pressure.

None of the lab results are helpful in identifying beta blocker toxicity

Atropine was given, but did not resolve the patient’s bradycardia due to severe toxicity

Physician suspected beta blocker toxicity so administered glucagon which brought BP and heart rate back to normal – without continuous glucagon infusion, the BP and heart rate will began to fail againSource: Heitz, Cory. "BETA BLOCKER OVERDOSE." Emergency Medicine Education Online. Center for

Simulation Technology and Academic Research, n.d. Web. 15 Nov 2010. <http://www.emedu.org/simlibrary/UploadFolder/152.11.191.200_-8589677563690905358Beta%20Blocker%20Overdose%20FINAL.pdf>.


After multiple doses of glucagon failed to maintain the patient’s vital signs, vasopressors were initiated.

Dopamine or norephinephrine was okay to use

Glucagon infusion helped resolve bradycardia

The patient was stabilized and given under the care of a cardiologist. Source: Heitz, Cory, et al. "BETA BLOCKER OVERDOSE." Emergency Medicine Education Online.

Center for Simulation Technology and Academic Research, n.d. Web. 15 Nov 2010. <http://www.emedu.org/simlibrary/UploadFolder/152.11.191.200_-8589677563690905358Beta%20Blocker%20Overdose%20FINAL.pdf>.

Case Study 2

EMS was called after a 4 year old female child was found unconscious by her mother

Child’s mother says the child accidently ingested her husband’s blood pressure medication and she does not know how many the child took

EMS identified the medication as Sectral SR which is a extended release beta blocker

Source: Rahm, Stephen. "A 4 year Old who ingested a medication." Pediatric Case Studies for the Paramedic. American Academic of Orthopaedic Surgeons, n.d. Web. 15 Nov 2010. <http://books.google.com/books?id=wO-5_8KqO94C&lpg=PP1&pg=PA65#v=onepage&q&f=false>. "BabyTemperament." BabySleepSite. Web. 15 Nov 2010. <http://www.babysleepsite.com/wp-content/uploads/2009/06/BabyTemperament.jpg>.


Initial Assessment: Child is 35 pounds or 16kg The Child is unconscious and unresponsive Rapid shallow respiratory rate Slow and weak pulse Skin is cool and cyanosis is noted Capillary refill time was 3 seconds Bilateral wheezing is heard in the lungs No trauma or injury or bleeding found

Source: Rahm, Stephen. "A 4 year Old who ingested a medication." Pediatric Case Studies for the Paramedic. American Academic of Orthopaedic Surgeons, n.d. Web. 15 Nov 2010. <http://books.google.com/books?id=wO-5_8KqO94C&lpg=PP1&pg=PA65#v=onepage&q&f=false>.


Assessment Values: Blood glucose reading says her glucose level is

40mg/dl Blood Pressure: 70/40 mm Hg Pulse: 66 beats/min Respiratory Rate: 48 breaths/min

Source: Rahm, Stephen. "A 4 year Old who ingested a medication." Pediatric Case Studies for the Paramedic. American Academic of Orthopaedic Surgeons, n.d. Web. 15 Nov 2010. <http://books.google.com/books?id=wO-5_8KqO94C&lpg=PP1&pg=PA65#v=onepage&q&f=false>. "bradycardiac." Emedicine. Web. 15 Nov 2010. <http://img.medscape.com/pi/emed/ckb/emergency_medicine/756148-812410-813342-1371539.jpg>.

Child’s ECG reading shows bradycardia


Opened the child’s airway and intubated the child

Ventilate with 100% oxygen since RR is too low

Agonize beta 2 receptor sites via nebulizer solution of albuterol – this will cause broncodilation

Albuterol dose was 10mg (2ml) diluted in 3ml of normal saline

Glucagon 0.05-0.1 mg/kg IV up to 1mg dose. 1mg dose is repeated every 20 minutes to raise BP and heart rate

Monitored child to make sure child was responsive to the glucagon.

Source: Rahm, Stephen. "A 4 year Old who ingested a medication." Pediatric Case Studies for the Paramedic. American Academic of Orthopaedic Surgeons, n.d. Web. 15 Nov 2010. <http://books.google.com/books?id=wO-5_8KqO94C&lpg=PP1&pg=PA65#v=onepage&q&f=false>.

Case Study 3

39-year-old man was found unresponsive with empty bottle of atenolol, and some empty beer bottles

Patient’s color was pale and dusky

EMS personnel initiated an intravenous line and administered 2 mg of naloxone, 100 mg of thiamine, and one ampule of d-glucose (D50W) intravenously without effect

Source: Slater, T. (2001). A 39-year-old man with an overdose of beta-blockers. Journal Of Emergency Nursing: JEN: Official Publication Of The Emergency Department Nurses Association, 27(4), 323-326. Retrieved from MEDLINE database.Image Source: "Beta Blocker Overdose." Buzzle. Web. 15 Nov 2010. <http://www.buzzle.com/img/articleImages/438293-2623-34.jpg>.


Assessment: respiratory rate was only 8 breaths

per minute Pulse: 20 beats per minute Blood pressure: 74 mm Hg systolic Glasgow Coma Score was 7 EKG showed underlying rhythm of

sinus arrestSource: Slater, T. (2001). A 39-year-old man with an overdose of beta-blockers. Journal Of Emergency Nursing: JEN: Official Publication Of The Emergency Department Nurses Association, 27(4), 323-326. Retrieved from MEDLINE database.


Patient put on ventilator with 100% oxygen 14 breaths per minute

One mg of IV atropine was administered without effect

Patient put on external cardiac pacing of 70 beats per minute

50g of activated charcoal were administered via the nasogastric tube

Gastric lavage showed no pill fragments

Poison control center was contacted for further instructions

Source: Slater, T. (2001). A 39-year-old man with an overdose of beta-blockers. Journal Of Emergency Nursing: JEN: Official Publication Of The Emergency Department Nurses Association, 27(4), 323-326. Retrieved from MEDLINE database.


Poison control advised 12 mg of glucagon was given by IV bolus which raised BP to 80 mm Hg but heart rate was still low at 30 beats/min

3 gm of calcium chloride were administered via Iv boluses

An isoproterenol infusion was initiated at 5 μg per minute

Patient’s BP and heart rate began to go down more, Poison Control was contact and told hospital to discontinue Isoproterenol infusionSource: Slater, T. (2001). A 39-year-old man with an overdose of beta-

blockers. Journal Of Emergency Nursing: JEN: Official Publication Of The Emergency Department Nurses Association, 27(4), 323-326. Retrieved from MEDLINE database.


After initial treatment

After lab work

Since the patient was getting worse, a complete blood and toxicology workup was ordered.

Everything was negative except for exception of a blood glucose level of 211 mg/dL and a blood alcohol level of 318 mg/dL.

Metabolic acidosis was discovered during the blood test as well

Dopamine infusion was titrated up to 20 μg/kg/minute

simultaneous infusion of norepinephrine was added to try to keep the patient’s systolic blood pressure greater than 90mm Hg

A glucagon infusion was also added at a rate of 10 mg/h. The patient’s blood sugar level was checked every 4 hours

insulin was administered as needed to treat the hyperglycemia caused by the glucagon.

Source: Slater, T. (2001). A 39-year-old man with an overdose of beta-blockers. Journal Of Emergency Nursing: JEN: Official Publication Of The Emergency Department Nurses Association, 27(4), 323-326. Retrieved from MEDLINE database.


Investigation revealed the patient ingested 1500 to 2000 mg of sustained-release atenolol

Supportive care with continuous infusions of dopamine, norepinephrine, and glucagon, along with cardiac pacing, sustained the patient until the effects of the atenolol subsided.

Approximately 26 hours after his overdose, this patient’s blood pressure and heart rate stabilized and he was released

Source: Slater, T. (2001). A 39-year-old man with an overdose of beta-blockers. Journal Of Emergency Nursing: JEN: Official Publication Of The Emergency Department Nurses Association, 27(4), 323-326. Retrieved from MEDLINE database."Discharge From Hospital." Imagine.com. Web. 15 Nov 2010. <http://images.inmagine.com/img/hana/hana023/hana023175.jpg>.

Case Study 4

16-year-old female presented to the ED approximately 1.5 h after ingesting 6.0 g of acebutolol (brand name Sectral) in a suicide attempt

Patient was sleepy with “shallow respirations” and was complaining of nausea.

She had pale and cool skin with low pulse

Source: Love, J. (2000). Acebutolol overdose resulting in fatalities. The Journal Of Emergency Medicine, 18(3), 341-344. Retrieved from MEDLINE database."Coma Picture." Getty Images. Web. 15 Nov 2010. <http://images.mirror.co.uk/upl/m4/nov2009/9/3/coma-pic-getty-51293773.jpg>.


Assessment Values Treatment

No cyanosis and the lungs were clear

Heart rate was 70 beats per minute

Blood pressure was 114/87 mmHg

Within 10 min of arrival to ED, blood pressure dropped to 55/45 mmHg while the pulse remained 70 bpm

Dopamine was begun at 5 mg/kg/min and titrated up to 30 mg/kg/min with no effect

glucagon (two 10-mg boluses), isoproterenol (titrated to 9.0 mg/min), and calcium chloride (10 mL of a 10% solution) were added without success

Source: Source: Love, J. (2000). Acebutolol overdose resulting in fatalities. The Journal Of Emergency Medicine, 18(3), 341-344. Retrieved from MEDLINE database.


Initial ECG showed PR = 0.200 seconds, QRS = 0.167 seconds, QTc = 0.574 seconds with 70 bpm for heart rate

1 Hour later, ECG showed heart rates at 120 bpm with no P waves.

QRS waves widened to 0.200 seconds with bizarre variability

Whenever ventricular tachycardia occurred due to QRS waves widening, defibrillation and lidocaine was used to treat it with no effect

The patient had one seizure during this time to defibrillations but not reoccurring seizures



Since the patient was not responding, epinephrine was given - 9 boluses of 1.0 mg followed by a infusion titrated to 25 mg/min

Sodium bicarbonate given - 3 boluses at 1 meq/kg)

Charcoal was recommended by the Poison Control Center but never given

Suddenly the patient with into bradycardia – she did not respond to atropine 3.0 mg and external cardiac pacing

She was pronounced dead in the ED within 4 h of her ingestion.Source: Source: Love, J. (2000). Acebutolol overdose resulting in

fatalities. The Journal Of Emergency Medicine, 18(3), 341-344. Retrieved from MEDLINE database.


What went wrong?So what does that all mean?

The patient did not respond to a number of therapies

Acebutolol is a partial agonist and membrane-stabilizing activity

This agent blocked sodium channels which prolonged PR and QRS intervals

In addition to this, Acebutolol blocks potassium channels so ventricular repolarization time increases

Acetbutolol blocked beta receptors while blocking the sodium and potassium channels in the heart leading to ventricular dysrhythmias being developed

Due to significant ion imbalances in the heart, this is a complex tachycardia which lead to ventricular fibrillation – so the patient crashed.

Acebutolol is one of the most toxic beta blockers when taken in an overdose and has highest fatality in beta blocker overdoses


Summary Propranolol is the most common beta-blocker involved in severe

beta-blocker poisoning. It is nonselective and can lead to CNS depression, seizures, and prolongation of the QRS complex.

Beta blocker toxicity is notably distinguished by bradycardia, low respiratory rate and hypoglycemia

Seizures and other CNS effects can occur with beta blockers that can cross the blood brain barrier (more rarely with the other beta blockers)

Overdoses of beta blockers with a combination of other drugs can have wide ranging systemic effects

If within a short time after ingestion, give activated charcoal Treat with glucagon to raise blood glucose levels Widely used treatment is currently Atropine though it is

considered less effective Treat bronchospasm with beta agonists like Albuterol Treat Seizures with Benzodiazepines like Valium If the patient is still unresponsive or the condition is still

deteriorating, treat with epinephrine

Source: "Infant Feeding Myths." Mohav County WIC. Web. 15 Nov 2010. <http://legacy.co.mohave.az.us/WIC/images/theEnd.gif>.

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Beta Blocker Toxicity and Safety