Prolonged coma due to amitriptyline overdose and genetic polymorphism: a case report. 2022

Tijs van de Wint, and Aurelia H M de Vries Schultink, and Arend Jan Meinders, and Ankie Harmsze, and Peter Bruins
Department of Anesthesiology, Intensive Care and Pain Management, St. Antonius Hospital, Amsterdam, The Netherlands. t.van.de.wint@antoniusziekenhuis.nl.

BACKGROUND Reduced consciousness has a wide variety of possible causes, not infrequently being toxic in nature. An intoxication might be obvious, but in this paper an unexpected case with a tricyclic antidepressant is presented. METHODS A 76-year-old caucasian female was found unconscious. Primary diagnostic evaluation, including a negative drugs of abuse test, did not give direction to any clear cause. Yet an intraventricular conductive disorder with widening of the QRS complex and electroencephalogram abnormalities did suggest a possible drug effect. Heteroanamnestic information led to the suspicion of an amitriptyline intoxication, which was confirmed by further laboratory analysis. The patient remained comatose for several days. High concentrations of amitriptyline indicated a large overdose of amitriptyline and, in combination with a cytochrome P450 2D6 poor metabolizer status, could explain the long persistence of her comatose state. CONCLUSIONS We present a tricyclic antidepressant intoxication, where the patient is thought to have taken a large amount of amitriptyline at once, which, in combination with a cytochrome P450 2D6 poor metabolizer status, led to an unusual long persistence of her coma.

UI MeSH Term Description Entries
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D003128 Coma A profound state of unconsciousness associated with depressed cerebral activity from which the individual cannot be aroused. Coma generally occurs when there is dysfunction or injury involving both cerebral hemispheres or the brain stem RETICULAR FORMATION. Comatose,Pseudocoma,Comas,Pseudocomas
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D000639 Amitriptyline Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antagonize cholinergic and alpha-1 adrenergic responses to bioactive amines. Amineurin,Amitrip,Amitriptylin Beta,Amitriptylin Desitin,Amitriptylin RPh,Amitriptylin-Neuraxpharm,Amitriptyline Hydrochloride,Amitrol,Anapsique,Apo-Amitriptyline,Damilen,Domical,Elavil,Endep,Laroxyl,Lentizol,Novoprotect,Saroten,Sarotex,Syneudon,Triptafen,Tryptanol,Tryptine,Tryptizol,Amitriptylin Neuraxpharm,Apo Amitriptyline,Desitin, Amitriptylin,RPh, Amitriptylin
D000929 Antidepressive Agents, Tricyclic Substances that contain a fused three-ring moiety and are used in the treatment of depression. These drugs block the uptake of norepinephrine and serotonin into axon terminals and may block some subtypes of serotonin, adrenergic, and histamine receptors. However, the mechanism of their antidepressant effects is not clear because the therapeutic effects usually take weeks to develop and may reflect compensatory changes in the central nervous system. Antidepressants, Tricyclic,Tricyclic Antidepressant,Tricyclic Antidepressant Drug,Tricyclic Antidepressive Agent,Tricyclic Antidepressive Agents,Antidepressant Drugs, Tricyclic,Agent, Tricyclic Antidepressive,Agents, Tricyclic Antidepressive,Antidepressant Drug, Tricyclic,Antidepressant, Tricyclic,Antidepressive Agent, Tricyclic,Drug, Tricyclic Antidepressant,Drugs, Tricyclic Antidepressant,Tricyclic Antidepressant Drugs,Tricyclic Antidepressants
D019389 Cytochrome P-450 CYP2D6 A cytochrome P450 enzyme that catalyzes the hydroxylation of many drugs and environmental chemicals, such as DEBRISOQUINE; ADRENERGIC RECEPTOR ANTAGONISTS; and TRICYCLIC ANTIDEPRESSANTS. This enzyme is deficient in up to 10 percent of the Caucasian population. CYP2D6,Debrisoquine 4-Hydroxylase,Debrisoquine Hydroxylase,CYP 2D6,Cytochrome P450 2D6,Debrisoquine 4-Monooxygenase,Imipramine 2-Hydroxylase,Sparteine Monooxygenase,2-Hydroxylase, Imipramine,4-Hydroxylase, Debrisoquine,4-Monooxygenase, Debrisoquine,CYP2D6, Cytochrome P-450,Cytochrome P 450 CYP2D6,Debrisoquine 4 Hydroxylase,Debrisoquine 4 Monooxygenase,Hydroxylase, Debrisoquine,Imipramine 2 Hydroxylase,Monooxygenase, Sparteine,P-450 CYP2D6, Cytochrome,P450 2D6, Cytochrome
D062787 Drug Overdose Accidental or deliberate use of a medication or street drug in excess of normal dosage. Drug Overdoses,Overdose, Drug,Overdoses, Drug

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