Intensive Care of Acute Poisoning - A. V. Hovenko 2010

Main types of acute poisoning and their treatment
Drug poisoning
Amitriptyline poisoning

Amitriptyline is a tricyclic antidepressant with thymoleptic, antidepressant, anxiolytic, sedative, and antidysuric properties. It inhibits the reuptake of Neurotransmitters (such as adrenaline, dopamine, and serotonin) by presynaptic nerve terminals, leading to the accumulation of monoamines in the synaptic cleft and enhanced postsynaptic signaling. Prolonged use reduces the functional activity (desensitization) of Brain beta-adrenergic and serotonin receptors, normalizes adrenergic and serotonergic transmission, and restores the balance between these systems, which is disrupted in depressive states. It also blocks Central Nervous system M-cholinergic and histamine receptors.

Tricyclic antidepressants (such as amitriptyline, azafen, imipramine, and fthoracizine) are widely used in psychiatric practice and frequently become the cause of Acute Poisoning.

Acute amitriptyline poisoning is life-threatening, even when the patient's general condition appears satisfactory and respiratory function is preserved. Seizures and severe Impairment of Vital body Functions can occur unexpectedly. A key indicator of severe cardiotoxicity—prolongation of the QRS complex on the ECG—may appear only 3–5 days (the latent period) after ingestion of a toxic dose of the drug.

In high doses, drugs of this group exert a stimulating effect on the brain, and patients may experience epileptiform seizures. Their effect on the Peripheral Nervous System is twofold: on the one hand, they exhibit pronounced adrenergic activity by increasing the release of adrenaline and dopamine; on the other hand, they show anticholinergic effects, resulting in symptoms similar to those observed in cholinergic poisoning.

Furthermore, the Toxic Effect of tricyclic antidepressants extends to the myocardium, causing Heart block (atrioventricular or intraventricular), ventricular fibrillation, and cardiac arrest. The lethal dose of amitriptyline exceeds 1 g.

Detoxification of antidepressants occurs primarily in the Liver, with only about 15% of the total amount excreted by the Kidneys.

Symptoms of poisoning. Even after the ingestion of therapeutic doses, toxic manifestations such as tachycardia, tremor, insomnia, and hallucinations may occur. Mild poisoning is characterized by a parasympatholytic syndrome resembling atropine poisoning, which manifests as dry oral mucosa, generalized vasodilation, Skin flushing, tachycardia, mydriasis, ataxia, and stupor. In severe poisoning, symptoms of central nervous system damage rapidly progress to include hallucinations, delirium, and epileptiform seizures.

Severe poisoning presents with high body fever and cardiac disturbances, including tachycardia and intraventricular block that frequently progresses to atrioventricular block and extrasystoles, potentially leading to ventricular fibrillation. Intraventricular blocks with a prolonged QRS complex are characteristic of these poisonings.

Treatment.

1. Gastric lavage.

2. Specific therapy involves cholinesterase inhibitors (physostigmine, aminostigmine, galantamine, proserine), which inhibit cholinesterase and promote the release of large amounts of acetylcholine, thereby neutralizing the pathological effects of poisoning. Aminostigmine or physostigmine is preferred, as proserine (neostigmine) practically does not cross the Blood-brain barrier.

Aminostigmine is administered intramuscularly at a dose of 1–2 ml of a 0.1% solution every 30–40 min. The total dose should not exceed 6 ml.

Physostigmine (eserine) is administered subcutaneously at 0.01 mg/kg of body weight. This dose is repeated in 1–2 hours until the desired effect is achieved.

Galantamine is administered subcutaneously at 0.1 mg/kg of body weight and repeated after 12 hours.

3. Correction of fluid volume disorders using crystalloids and HES preparations.

4. Hemisorption.

5. A characteristic feature of amitriptyline is its ability to bind rapidly and tightly to blood Proteins, as its chemical Structure is similar to Vit B6. Due to this and to normalize tissue Respiration, elevated doses of Vit B₆ must be regularly administered during intensive therapy.

6. Suppression of Lipid Peroxidation processes (programmed administration every 6–8 hours), Vit C (up to 10 ml/day), Vit E, and riboxin.

7. Control of psychosomatic agitation with benzodiazepines.

8. Correction of arrhythmias: tachyarrhythmia (cordarone, anaprilin, atenolol, lidocaine if BP>90 mm Hg); bradyarrhythmia (atropine, isadrin, isoproterenol). In complete AV block, The Use of an external pacemaker is indicated.

The following are strictly contraindicated:

- quinidine (due to cardiotoxic effects);

- cardiac Glycosides (increases myocardial oxygen debt);

- neuroleptics.

Forced diuresis is impractical because amitriptyline forms hydrophobic compounds within the body.