wikitox:2.1.11.4.1_anticholinergics
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+ | Link to 2.1.11.4.1 [[: | ||
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+ | ---- | ||
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+ | ====== Anticholinergic drugs ====== | ||
+ | |||
+ | ===== DRUGS INCLUDED IN THIS CATEGORY ===== | ||
+ | |||
+ | * Orphenadrine | ||
+ | * Procyclidine | ||
+ | * Benztropine | ||
+ | * Benhexol (trihexyphenidyl) | ||
+ | * Atropine | ||
+ | * Homatropine | ||
+ | * Datura and other anticholinergic plants | ||
+ | |||
+ | ===== OVERVIEW ===== | ||
+ | |||
+ | Most anticholinergic drugs cause predominantly CNS effects ([[: | ||
+ | |||
+ | ===== MECHANISM OF TOXIC EFFECTS ===== | ||
+ | |||
+ | All these drugs block muscarinic acetylcholine receptors in the autonomic and central nervous system. In addition, they may block histamine (H1) receptors. The presumed mechanism for the cardiac effects of orphenadrine is blockade of voltage-gated ion channels. The exact type of block(s) has not been determined but the ECG changes in humans and animals suggest Ca++, Na+ and K+ channels may all be involved as there is progressive prolongation of PR, QRS, and QT intervals. | ||
+ | |||
+ | ===== KINETICS IN OVERDOSE ===== | ||
+ | |||
+ | ==== Absorption ==== | ||
+ | |||
+ | All these drugs are rapidly absorbed from the small intestine. Peak concentrations occur in therapeutic use within 4 hours. However, in overdose, the anticholinergic effect slows gastric emptying and may delay absorption. This may lead to multiple and delayed peak concentrations. | ||
+ | |||
+ | ==== Distribution ==== | ||
+ | |||
+ | These drugs are all highly lipid soluble and have large volumes of distribution. CNS penetration and clinical effects occur rapidly. | ||
+ | |||
+ | ==== Metabolism - Elimination ==== | ||
+ | |||
+ | All of these drugs are metabolised in the liver. It is likely that they all undergo some [[: | ||
+ | |||
+ | ===== CLINICAL EFFECTS ===== | ||
+ | |||
+ | ==== The anticholinergic syndrome ==== | ||
+ | |||
+ | The [[: | ||
+ | |||
+ | ==== Cardiac effects ==== | ||
+ | |||
+ | Sinus tachycardia is a usual finding and the absence of this suggests one of the following: Direct cardiotoxic effect of drug slowing cardiac conduction (e.g. with orphenadrine). Coingestion or regular treatment with negatively chronotropic drug (e.g. [[: | ||
+ | |||
+ | ==== Central nervous system effects ==== | ||
+ | |||
+ | Sedation or excitation may occur. If the patient is conscious, an anticholinergic delirium may make management difficult. | ||
+ | |||
+ | ==== Late presentation ==== | ||
+ | |||
+ | Patients presenting late, often have more marked CNS features and less autonomic effects. This may be due to both increasing CNS concentrations with time and tolerance to peripheral anticholinergic effects. | ||
+ | |||
+ | ===== INVESTIGATIONS ===== | ||
+ | |||
+ | ==== ECG ==== | ||
+ | |||
+ | This should be done routinely, though cardiac effects are uncommon with any of these drugs except orphenadrine. | ||
+ | |||
+ | ==== Blood concentrations ==== | ||
+ | |||
+ | Unhelpful as an aid to management. | ||
+ | |||
+ | ===== DIFFERENTIAL DIAGNOSIS ===== | ||
+ | |||
+ | See [[: | ||
+ | |||
+ | ===== DIFFERENCES IN TOXICITY WITHIN THIS DRUG CLASS ===== | ||
+ | |||
+ | Orphenadrine, | ||
+ | |||
+ | ===== TREATMENT ===== | ||
+ | |||
+ | ==== Supportive ==== | ||
+ | |||
+ | The usual - Maintenance of airway, ventilation, | ||
+ | |||
+ | ==== GI Decontamination ==== | ||
+ | |||
+ | Oral [[: | ||
+ | |||
+ | ==== Antidotes ==== | ||
+ | |||
+ | === Physostigmine (and other anticholinesterases) === | ||
+ | |||
+ | This can be useful to diagnose an anticholinergic drug as a cause of delirium in a patient whose history of drug ingestion is unclear. There are a number of reports of severe complications occurring related to physostigmine use in certain situations and the routine use for treatment or diagnosis is unwise. It should only be used (if at all) during cardiac monitoring. It does not differentiate between different drugs with anticholinergic effects. It does not protect against any of the more serious complications that are due to the membrane blocking, cardiac or [[: | ||
+ | |||
+ | |||
+ | ==== Treatment of specific complications ==== | ||
+ | |||
+ | === Antidotes === | ||
+ | |||
+ | [[: | ||
+ | |||
+ | === Delirium === | ||
+ | |||
+ | Physostigmine will cause a temporary (about 15-30 minutes) improvement in delirium without sedating the patient. This may be useful if the patients cooperation is required (e.g. for drinking activated charcoal). It should not be used continuously because of reported severe adverse effects and should only be used (if at all) while the patient is on a cardiac monitor. [[: | ||
+ | |||
+ | === Arrhythmias === | ||
+ | |||
+ | The mechanism for the development of arrhythmias is unknown and no animal or human studies have been done. It would be reasonable to try any of the following treatments, which have been used in other drugs with [[: | ||
+ | |||
+ | * bicarbonate or hyperventilation | ||
+ | * lignocaine | ||
+ | * [[: | ||
+ | * overdrive pacing (120-140 bpm) | ||
+ | |||
+ | === Fever === | ||
+ | |||
+ | This may respond to external cooling or [[: | ||
+ | |||
+ | |||
+ | ==== Elimination enhancement ==== | ||
+ | |||
+ | Is not indicated. | ||
+ | |||
+ | ===== LATE COMPLICATIONS, | ||
+ | |||
+ | Delirium and other signs may persist for some days. Serious late complications have not been reported and no follow up is required after resolution of the initial clinical signs - ECG findings in patients who have received [[: | ||
+ | |||
+ | ===== REFERENCES ===== | ||
+ | |||
+ | Burns MJ, Linden CH, Graudins A, Brown RM, Fletcher KE.A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning. //Ann Emerg Med// 2000; | ||
+ | |||
+ | Francis PD, Clarke CF. Angel trumpet lily poisoning in five adolescents: | ||
+ | |||
wikitox/2.1.11.4.1_anticholinergics.txt · Last modified: 2018/09/01 09:00 by 127.0.0.1