MDR1 Mutation

TL;DR. Častá genová mutace u pasteveckých plemen vypíná ochranný protein a běžné léky činí toxickými nebo smrtelnými.

Shetland Sheepdogs are among the herding breeds highly predisposed to the MDR1 mutation.

Co to je?

The MDR1 (ABCB1) mutation is a hereditary defect that impairs P-glycoprotein, an efflux pump concentrated at the blood-brain barrier and in liver, kidney, and gut. Without a working pump, many drugs accumulate in sensitive tissues and cause neurologic or organ toxicity at ordinary doses.

Příčiny a rizikové faktory

Autosomal incomplete dominant inheritance. Homozygous mutants lack functional P-glycoprotein; heterozygous carriers have reduced capacity and can still react at higher doses. Risk is breed-linked: Collie, Shetland Sheepdog, Australian Shepherd, Miniature American Shepherd, German Shepherd, Old English Sheepdog, Border Collie, English Shepherd, Whippet, Longhaired Whippet, Silken Windhound, and mixes with herding ancestry.

Příznaky

• Vomiting, ataxia, lethargy, tremors, hypersalivation
• Depression, anorexia, mydriasis, diarrhea
• Bone marrow suppression (chemo substrates)
• Occasional: tachycardia, dehydration, seizures

"Common findings in dogs recorded in decreasing frequency included vomiting, ataxia, lethargy, tachycardia, hypersalivation, mydriasis, and seizures." - Plumb's Veterinary Drug Handbook, p.1982

Dilated pupils and severe lethargy are common clinical signs of drug toxicity in MDR1-affected dogs.

Jak diagnostikují veterináři

One-time MDR1 genetic testing (cheek swab or blood) classifies clear, carrier, or affected. In acute toxicity: history of drug exposure, neurologic exam, CBC/chemistry for organ support and marrow effects.

Intravenous fat emulsion (lipid rescue therapy) is used to reverse severe lipophilic drug toxicities.

Možnosti léčby

No cure for the genotype. Acute exposure: decontamination if recent; Activated Charcoal; Intravenous Fat Emulsion for severe lipophilic toxicity (e.g. ivermectin); IV fluids, seizure control, intensive support. Lifelong: avoid or dose-adjust high-risk drugs (loperamide, high-dose ivermectin, some chemotherapeutics, acepromazine, butorphanol).

Prognóza

Excellent if never exposed to problem drugs. Guarded after high-dose toxicity depending on drug, dose, speed of care, and access to lipid rescue.

Prevence

Test at-risk breeds and mixes before routine meds or chemo. Keep a contraindicated-drug list for every caretaker. Prefer MDR1-safe heartworm preventives when indicated.

Kdy volat veterináře

Emergency now: seizures, severe ataxia or inability to stand, stupor, non-reactive dilated pupils, uncontrolled drooling with vomiting after a suspect drug.

Pro konkrétní plemena

Highest prevalence reported in Collies; also common in Shelties, Australian Shepherds, and Miniature American Shepherds. Appearance alone does not predict status; DNA test once.

Zdroje

• Plumb's Veterinary Drug Handbook, pages 1280, 1982, 2140.
• Small Animal Internal Medicine (5th Edition), page 1178.
• Small Animal Critical Care Medicine (2nd Edition), page 993.

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