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Pet Poison Helpline ©20173 6 0 0 Amer i c an B l v d . W . , # 7 2 5 B looming ton , MN 55431www.petpo i sonhe lp l i ne . com

Clear Eyes, Dry Nose, No Problem? Wrong!Intoxications due to Eye Drops and Nasal Sprays

Colleen Almgren, DVM, PhD, DABT, DABVTSenior Veterinary ToxicologistPet Poison Helplinecalmgren@petpoisonhelpline.com

November 14, 2017

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Speaker Introduction

Colleen Almgren, DVM, PhD, DABT, DABVT

Senior Consulting Veterinarian, Clinical Toxicology

Veterinary Toxicologist

Pet Poison Helpline

•Commonly found in nasal sprays and eye drops used to relieve redness and congestion• Cause vasoconstriction with topical/nasal application•Common active ingredients: oxymetazoline, naphazoline, tetrahydrozoline, xylometazoline

Eye drops and nasal sprays:(imidazolines, imidazoline decongestants)

Oxymetazoline nasal:Afrin, Afrin Sinus, Nostrilla, Zicam Sinus Relief

Oxymetazoline ophthalmic:Visine L.R. Long Acting Redness Relief, OcuClear

Oxymetazoline:

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Naphazoline nasal:Privine

Naphazoline ophthalmic:AK-Con, Clear Eyes Redness Relief, Clear Eyes Maximum Redness Relief, Naphcon

Naphazoline:

Antazoline/Naphazoline ophthalmic:Vasocon-A

Naphazoline/Pheniramine ophthalmic:Naphcon-A, Opcon-A, Visine-A, Eye Allergy Relief

Naphazoline/Zinc sulfate ophthalmic:Clear Eyes Maximum Strength Itchy Eye Relief, Clear Eyes

Naphazoline Multi-ingredient medications:

Tetrahydrozoline nasal:Tyzine Nasal, Tyzine Pediatric Nasal, Tyzine

Tetrahydrozoline ophthalmic:Clarine, Tetrasine, Visine Original, Eye Moisturizing Relief

Tetrahydrozoline Multi-ingredient medications:

Povidone/tetrahydrozoline ophthalmic: Clear Eyes Triple Action Relief, Clear Eyes Traveler’s Eye Relief, Murine Tears Plus, Visine Advanced Relief

Tetrahydrozoline/zinc sulfate ophthalmic:Visine A.C, Visine Totality Multi-Symptom Relief

Tetrahydrozoline:

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Xylometazoline nasal:Otrivin, Balminil Nasal Decongestant, Triaminic Decongestant Spray

Xylometazoline:

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Lopidine (Alcon) - Apraclonidine 5 mg/ml; sympathomimetic; alpha-2 adrenergic receptor agonist , weak alpha-1 adrenergic receptor agonist

Alphagan (Allergan) - brimonidine tartrate ophthalmic solution; 0.2%, relatively selective alpha-2 adrenergic receptor agonist

Alphagan-P (Allergan) - (brimonidine tartrate ophthalmic solution) 0.1% or 0.15%, alpha-adrenergic receptor agonist

Other Alpha Adrenergic Agonists:

Topical Ointments for Rosacea:

Oxymetazoline topical:Rhofade 1%

Brimonidine topical:Mirvaso 0.33% (each gram of gel contains 5mg of brimonidine tartrate equivalent to 3.3mg of brimonidine free base)

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Alpha-1 agonist

Alpha-2 agonist

Beta H1

H2

Oxymetazoline x X

Naphazoline X

Tetrahydrozoline X X

Xylometazoline X

Brimonidine X

Apraclonidine x X

• Narrow Margin of Safety – Medical Emergency!

• Small bottles - pack a big punch

• Owners often find the pet collapsed next to the bottle

• Rapid Onset – approx. 15-30min

• Duration 12-36hrs

Imidazoline DecongestantsAlpha-2 Receptor Agonists:

• Sympathomimetic compounds with alpha-agonist activity, primarily on alpha-2 adrenoreceptors

• Little or no effect on beta receptors

• Binding to central receptors causes hypotension, bradycardia, and sedation

• Binding to peripheral receptors causes vasoconstriction and hypertension

Mechanism of Action

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• Vomiting

• Weakness

• Arrhythmias, usually bradycardia

• Hypotension (may see hypertension early in syndrome)

• Delayed CRT

• Collapse

• CNS: drowsiness, coma, muscle tremors

Clinical Signs

• Do not induce vomiting (due to rapid onset of signs) – exception ointments

• Blood pressure and ECG monitoring

• Monitor electrolytes and BG in symptomatic patients

• Monitor for CNS signs and treat symptomatically

• IV Fluid Therapy – standard crystalloids, 1.5-2X maint

• If patient is hypotensive (systolic BP < 90 or MAP < 60), bradycardic or depressed

• Reversal agents• Atipamezole (Antisedan) 50 mcg/kg (give ¼ dose IV and remainder

IM)• Yohimbine (alpha 2 antagonist) 0.1 mg/kg IV

Treatment

• Always Use Specific Antagonists if Available

• Naloxone – 0.02 mg/kg IV or IM PRN (only use if reversals are not available)

• Bradycardia: Atropine IV 0.01 – 0.02 mg/kg as needed (if HR < 50 bpm dog; < 120 cat)

• Vasopressors for significant hypotension not responding to fluid therapy alone

• For Agitation: Butorphanol 0.1-0.5 mg/kg IV, IM, SQ q2-4 hrs prn

• For Tremors/Seizures: Diazepam 0.5 – 1 mg/kg IV prn

• Vomiting: Maropitant – 1 mg/kg IV or SQ q 24 hours

Treatment

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Water (purified),

Xylitol, Saline,

Grapefruit Seed Extract

Alpha-adrenergic agonists

Beta-blockers

Combination glaucoma drugs

Carbonic anhydrase inhibitors

Parasympathomimetics

Epinephrine

Prostaglandins

Hyperosmotic agents

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Timoptic XE (Merck) - timolol maleate; non-selective beta-adrenergic receptor blocking agent)0.25% contains 2.5 mg/ml of timolol (3.4 mg of timolol 0.5% contains 5 mg/ml of timolol (6.8 mg of timolol maleate). Inactive ingredients: gellan gum, tromethamine, mannitol, and water for injection. Preservative: benzododecinium bromide 0.012%.

Istalol (ISTA) - timolol maleate ophthalmic solution 0.5%

Betoptic S (Alcon) - 0.25% betaxolol hydrochloride, a cardioselective beta-adrenergic receptor blocking agent

Beta Blockers:

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Combigan (Allergan) - brimonidine tartrate 0.2%, timolol maleate 0.5%

Cosopt (Akorn) – dorzolamide 2% ( carbonic anhydrase inhibitor), timolol 0.5% (beta blocker)

DuoTrav (Alcon) - travoprost 0.004% (prostaglandin F2α analog, timolol maleate 0.5% ophthalmic

Combination Ophthalmics:

• Bradycardia• Hypotension • Decreased cardiac contractility• Decreased cardiac output• Hypoglycemia• Hyperkalemia • Less Common: bronchospasm, respiratory depression, apnea, delirium, seizures,

coma, renal failure secondary to hypoperfusion• Possible ECG findings: sinus bradycardia, prolonged PR and QRS intervals,

asystole, junctional arrhythmias, V-tach or V-fib• Dose >2-3X high end of a therapeutic poses toxicity concern

Combigan (Allergan) - brimonidine tartrate 0.2%, timolol maleate 0.5%

Clinical Signs:

• Continuous ECG or frequent heart rate monitoring. • Blood pressure q. 2-4 hours; more frequent if patient is symptomatic,

bradycardic, or hypotensive. • IV crystalloid therapy to help maintain blood pressure• Bradycardia: Atropine 0.02 - 0.04 mg/kg IV• Hypoglycemia: bolus 50% dextrose (0.5-1 ml/kg) diluted with additional saline

(1:2 ratio), then follow with 2.5-5% CRI of dextrose supplementation in IV crystalloids

• Hyperkalemia: dextrose, insulin, or calcium gluconate• Bradycardia and/or hypotension unresponsive to fluids and atropine: Intralipid

or High Dose Insulin/Dextrose

Treatment:

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Trusopt (Merck) - 20 mg/mL dorzolamide (22.3 mg of dorzolamide hydrochloride)

Azopt (Alcon)- brinzolamide 1%

CAI causes diuresis and bicarbonate loss and can result in electrolyte, metabolic, and renal disturbances. CAI rarely result in serious toxicity

Lethargy, confusion, metabolic acidosis, tachycardia, tachypnea electrolyte abnormalities (hyperkalemia and hyperchloremia) can develop.

Carbonic Anhydrase Inhibitors:

Xalatan (Pfizer)- latanoprost 0.005%

Lumigan (Allergan)- bimatoprost 0.03%

Travatan Z (Alcon)- travoprost 0.004%

Rescula (Novartis)- unoprostone isopropyl 0.15%, synthetic docosanoid

Prostaglandins:

• Xiidra - lifitegrast 5% • Binds to the integrin lymphocyte function-associated antigen-1 (LFA-1), a cell

surface protein found on leukocytes • Blocks interaction of LFA-1 with its cognate ligand intercellular adhesion molecule-1

(ICAM-1).• May inhibit T-cell adhesion to ICAM-1 • Inhibit T-cell activation• Inhibit secretion of inflammatory cytokines in human peripheral blood

mononuclear cells• Treatment of dry eye disease (DED)

Lymphocyte function-associated antigen-1 (LFA-1) Antagonist:

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Blackwell’s Five-Minute Veterinary Consult Clinical Companion:

Small Animal Toxicology 2nd Edition

Drs. Lynn Hovda, Ahna Brutlag, Robert Poppenga, Katherine Peterson

www.wiley.com/go/vet

Paperback | May 2016 | 960 pages | 978-1-119-03654-8 | $109.99 · CAN $120.99

• Provides concise, bulleted information focused on the most important facts needed when treating a poisoned cat or dog

• Carefully organized for ease of use in an emergency, with important toxicants arranged alphabetically within categories

• Details clinically relevant information on the most common toxicants encountered by small animals

• Presents a wealth of color photographs to aid in plant identification

• Includes 14 new topics to this edition covering cyclosporine A, sleep aids, tacrolimus, bath salts, synthetic marijuana, poisonous lizards, imidacloprid, spring bulbs, and sodium monofluoroacetate

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Thank you for attending!

CE credit FAQs

1. When will I get my CE certificate? We’ll email it to you by the end of the day tomorrow.

2. I attended the webinar but wasn’t the person who logged in. Can I still get interactive CE credit? Yes. Send your name and email address to info@petpoisonhelpline.com by 1pm central time on November 15, 2017 (strict deadline).

3. Can I watch the recorded webinar online for CE credit? Yes. You can receive non-interactive CE credit. Go to the “For Vets” page on our website, www.petpoisonhelpline.comfor more info.

Comments? Questions? Email us! info@petpoisonhelpline.com

References:

• Cote E. Over the counter human medications in small animals. Part 1, Gastrointestinal, urinary and ophthalmic drugs. Comp Cont Ed Prac Vet 1998; 20:603-605. .

• Daggy A, Kaplan R, Roberg Rm et al. Pediatric Visine (tetrahydrozoline) ingestion: case report and review of Imidazoline toxicity Vet Hum Tox 2003; 45(4): 210-212.

• Fitzgerald KT, Bronstein AC, Flood AA. Over the counter toxicities in companion animals. Clin Tech Small Anim Prac 2006; 21:215-216.

• Volmer P. Oral toxicity of skin and eye products. In: ACVIM 18th Proceedings, Seattle, WA. 2000;: 45: 47,

• Waratuke KE. Imidazoline decongestants. In: Hovda LR, Brutlag AG, Osweiler G, Peterson K. The 5 Minute Veterinary Clinical Companion Consult: Small Animal Toxicology, 2nd ed. Ames, Iowa. Wiley-Blackwell. 2016:pp. 333-338.

• Welch SL. Imidazoline decongestants. In: Vet Clin Small Anim 2002; 32: 447.

References:

• Doepker B, Healy M, Cortez E, et.al. High dose insulin and ILE therapy for cardiogenic shock induced by intentional calcium channel blocker and beta blocker overdose: A case series. J Emerg Med. 2014 Apr;46(4):486-9.

• Engebretsen, KM, Kaczmarek KM, Morgan J, et al. High-dose insulin therapy for beta-blocker and calcium channel blocker poisoning. Clin Tox, 2011 49 277-283.

• lger JS, Engebretsen KM, Obetz CL, Kleven TL, Harris CR. A comparison of vasopressin and glucagon in beta-blocker induced toxicity. Clin Tox. 2006; 44:45-51.

• Kerns W, Schroeder D, Williams C, Tomaszewski C, Raymond R. Insulin improves survival in a canine model of acute beta-blocker toxicity. Annals of Emergency Medicine. 1997; 29:748-757.

• Kline JA, Tomaszewski CA, Schroeder JD, Raymond RM. Insulin is a superior antidote for cardiovascular toxicity induced by verapamil in the anesthetized canine. The Journal of Pharmacology and Experimental Therapeutics . 1993; 267:744-750.

• Kline JA, Raymond RM, Leonova ED, Williams TC, Watts JA. Insulin improves heart function and metabolism during non-ischemic cardiogenic shock in awake canines. Cardiovascular Research. 1997; 34:289-298.

• Love JN. The effect of propranolol intoxication on QTc interval in a canine model. The Journal of Emergency Medicine. 1998; 16:1-4.

• Love JN, Hanfling D, Howell JM. Hemodynamic effects of calcium chloride in a canine model of acute propranolol intoxication. Annals of Emergency Medicine. 1996; 28:1-6.