Why this poison is interesting

This library already has two entries defined by a lesion rather than a molecule — sodium-channel blockade, defined by a channel, and methaemoglobin inducers, defined by an oxidation state. The methaemoglobin inducers page already names sodium-channel blockade as the library's other class-defined entry. This is the third, and it extends a grouping the library already makes about itself. Antihistamines, tricyclics, antipsychotics, antiparkinsonian agents, antispasmodics and the antimuscarinic plants are chemically unrelated and produce one recognisable syndrome, which is exactly the shape those two pages use.

It also completes a different pair. The library covers the poisoning in which acetylcholine accumulates — organophosphates and carbamates, both facetted Cholinergic — and until now had no entry for the one in which its receptor is blocked. The two are not opposites in a trivial sense: they are opposites with a shared antidote logic running in both directions. Atropine treats one. Physostigmine — itself a carbamate — is the contested treatment for the other. The carbamates page already notices this in passing, describing the same chemistry used deliberately; this is the page where that observation belongs.

The mechanistic hook that makes the syndrome worth explaining rather than merely listing is smaller than either of those. It is a single positive charge. Hyoscine hydrobromide and hyoscine butylbromide are the same alkaloid; one is a tertiary amine, the other a quaternary ammonium compound. The Buscopan label states the consequence flatly: as a quaternary ammonium derivative, hyoscine butylbromide does not enter the central nervous system. Therefore, anticholinergic side effects at the central nervous system do not occur.³ Two versions of one drug, and the charged one produces only half of this page's syndrome.

A poison is a drug whose kinetics have escaped its pharmacology.

The toxic principle

Muscarinic acetylcholine receptors carry the whole of parasympathetic postganglionic transmission and a substantial part of central cholinergic signalling. Blocking them competitively removes both. The peripheral half of the syndrome is a catalogue of parasympathetic tone being withdrawn, organ by organ, and it is entirely predictable from knowing which organs are parasympathetically driven.

The eye: Loss of parasympathetic drive to the iris sphincter and the ciliary muscle. Pupils widely dilated and unreactive to light¹, with blurring of vision and photophobia². The unreactivity matters: it is a pharmacological block of the effector, not a defect of the afferent or efferent pathway. Established
The heart: Loss of vagal tone at the sinoatrial node. Tachycardia, reported in association with overdose on both labels.¹² It is a release phenomenon rather than a stimulant one — nothing is being driven, something is being removed. Established
Sweat glands: The anomaly that identifies the syndrome. Sweat glands are sympathetically innervated but use acetylcholine as their transmitter, so an antimuscarinic dries the skin while everything else about the patient looks sympathomimetic. This is the single most useful discriminator at the bedside and it is why the sympathomimetic differential separates on the feel of the skin rather than on the pupils, the pulse or the mental state. Established
Bladder and gut: Detrusor relaxation with urinary retention², and reduced gastrointestinal motility. The gut effect is the therapeutic action of the antispasmodics in this group and, in overdose, the reason absorption is prolonged and charcoal's window is widened.¹ Established
The brain: Central muscarinic blockade produces the delirium — agitation, restlessness and confusion with severe sleeplessness lasting up to 24 hours or more, visual and auditory hallucinations, and, distinctively, that most subjects are euphoric but the occasional patient may be anxious and aggressive.¹ Only the molecules that can cross reach this half. Established

One charge, two syndromes — the cleanest natural experiment in the library

Hyoscine is sold in the UK in two forms. Hyoscine hydrobromide, a tertiary amine, is a travel-sickness tablet whose overdose section lists tachycardia, arrhythmia, blurring of vision and photophobia, urinary retention, with drowsiness... usual but paradoxical stimulation with hallucinations may occur.² Hyoscine butylbromide, the quaternary salt, has a label stating that it does not enter the central nervous system and therefore central anticholinergic side effects do not occur, its peripheral action arising from a ganglion-blocking action within the visceral wall as well as from an anti-muscarinic activity.³ Same alkaloid, same receptor, one permanent positive charge, and only one of them produces a delirium. The charge is doing something no amount of receptor pharmacology can explain — it is a distribution property, not a binding property. Established

The same logic explains why the syndrome varies so much between causative drugs. A pure antimuscarinic that crosses freely, such as procyclidine or hyoscine hydrobromide, produces this page's syndrome and nothing else. A drug that is antimuscarinic among several other actions produces this syndrome plus its own, which is why the tricyclic, antipsychotic and antihistamine pages each describe the toxidrome as one component of something larger. The antipsychotics page puts it most directly: muscarinic blockade gives the anticholinergic picture that quetiapine's label names explicitly.

Toxicokinetics

Procyclidine is used as the reference molecule because it is a pure central antimuscarinic with a UK label that describes both the syndrome and its duration, and because its overdose section takes an explicit position on the antidote.

Procyclidine — and the two kinetic features that belong to the syndrome rather than to any molecule
Parameter	Therapeutic	In overdose	Why it changes
Absorption	Adequately absorbed from the gastro-intestinal tract with a bioavailability of 75%; small first-pass effect¹	Prolonged by the poisoning itself — the label extends the charcoal window possibly longer in view of its likely effects on gastric motility¹	The one genuinely kinetic feature of this syndrome, and it is self-inflicted. An antimuscarinic slows the stomach that is delivering it, so absorption continues past the point at which decontamination is usually abandoned. This applies to co-ingestants too, which matters more than it does for the antimuscarinic itself.
Distribution	Disappears rapidly from the tissues¹. For the class, distribution is what decides the syndrome: a quaternary compound does not enter the central nervous system³	Unchanged in kind	Distribution is the mechanism on this page, not a footnote to it. Everything that separates a peripheral antimuscarinic poisoning from a delirium happens at the blood-brain barrier, and nothing about the receptor differs between them.
Quaternary comparison	Hyoscine butylbromide: only partially absorbed following oral (8%) or rectal (3%) administration; absolute bioavailability of 100 mg dosage forms less than 1%; plasma protein binding approximately 4.4%³	A very large ingestion still delivers very little systemically	A charge costs absorption as well as brain entry. The same property that keeps the molecule out of the central nervous system keeps most of it out of the circulation. The label notes high affinity for muscarinic and nicotinic receptors with distribution to abdominal and pelvic muscle and intramural ganglia³ — a drug that stays where it was swallowed.
Metabolism	Procyclidine: about one fifth of an oral dose metabolised in the liver, principally by cytochrome P450 and then glucuronidated; very little of the parent compound is excreted in the urine unchanged¹	No bioactivation described	The label states that no detailed information is available on the metabolic fate of procyclidine¹ — an unusual admission, and a reason not to build any argument about accumulation or interaction on this molecule.
Half-life and clearance	Procyclidine: mean plasma elimination half-life approximately 12 hours after both oral and intravenous administration; clearance 68 mL/min¹	Prolonged relative to the drug's clinical half-life	The half-life does not explain the duration of the syndrome, and this is the most striking mismatch on the page. Twelve hours against disorientation... lasted 1 to 4 days¹ — the delirium outlasts several half-lives of the drug that caused it.
Dialysability	—	No, and the label says so unusually directly: other active measures such as the use of cholinergic agents or haemodialysis are extremely unlikely to be of clinical value¹	EXTRIP has addressed no antimuscarinic; its published recommendations index covers 22 poisons and contains none of them.⁷ That is an absence of assessment rather than a recommendation against — but here, unusually, a UK label supplies the recommendation against directly, and in the same clause it dismisses the antidote.

Metabolism and the metabolites

There is no bioactivation anywhere in this syndrome. Every molecule that reaches the receptor arrives already able to block it, and metabolism removes the effect rather than creating it. What metabolism contributes is only variability, and for the reference molecule even that is poorly characterised — procyclidine's label states that no detailed information on its metabolic fate is available.¹

One receptor, reached from two directions — and the barrier that decides which syndrome appears

An antimuscarinic, swallowedAlready the toxic species. Antihistamine, tricyclic, antipsychotic, antiparkinsonian agent, antispasmodic or plant alkaloid
Tertiary amine — uncharged at physiological pHCrosses into the brain. Both halves of the syndrome: delirium and the peripheral signs¹²
Quaternary ammonium — permanently chargedDoes not enter the central nervous system, so anticholinergic side effects at the central nervous system do not occur³
Parasympathetic effector organs, and central cholinergic pathwaysDilated unreactive pupils, tachycardia, dry skin, retention, ileus; and, if the drug crossed, hallucinations and delirium¹²
The gut slowsA feedback loop onto absorption — the syndrome prolongs the delivery of the drug producing it¹
Physostigmine — a carbamate that also crossesRaises acetylcholine at the blocked receptor. The competition is reversed by adding transmitter, not by removing drug

Elimination and accumulation

The elimination story of this syndrome is unusual in that the drug's kinetics and the syndrome's duration do not match, and nobody on this page can fully explain why. Procyclidine's half-life is about 12 hours¹, and its label reports that in recorded cases, the disorientation has lasted 1 to 4 days and ended in a recuperative sleep, with severe sleeplessness lasting up to 24 hours or more.¹

A delirium that outlasts its cause

Four days of disorientation from a drug with a twelve-hour half-life is between six and eight half-lives — by which point conventional pharmacokinetics predicts essentially none of the drug remains. Three explanations are available and this page endorses none of them: that receptor occupancy at the relevant central sites persists beyond measurable plasma concentrations; that the delirium, once established, has its own course independent of the drug that started it; or that the recorded cases involved continuing absorption from a gut the drug itself had stopped.¹ The label reports the observation and offers no mechanism, and this page follows it. The clinical consequence is the same whichever is true: plasma kinetics are a poor guide to when this patient will be better. Inferred

The self-slowed gut deserves its own note, because it inverts a rule this library states elsewhere. Charcoal is conventionally considered within an hour, and the antihistamine page quotes a label saying exactly that. Here the label deliberately extends the window: charcoal should be used if the drug was ingested within the previous hour or two (or possibly longer in view of its likely effects on gastric motility).¹ The more important version of this is not about the antimuscarinic at all — it is about whatever else was swallowed with it, which is also still sitting in a stationary stomach.

Target organs — and why those

Brain

TargetCentral muscarinic acetylcholine receptors

Why hereCentral cholinergic transmission is heavily involved in attention, memory and the maintenance of an ordered conscious state, and blocking it produces a hyperactive delirium rather than sedation. The organ is targeted only by molecules that can reach it, which is the argument of the whole page — the quaternary compounds produce no central effect at all.³ Note that this makes the brain the one organ on this page whose involvement is decided by physical chemistry rather than by receptor distribution. Established

At the bedsideAgitation, restlessness, confusion, visual and auditory hallucinations, severe sleeplessness up to 24 hours or more, and disorientation lasting 1 to 4 days.¹ Most subjects are euphoric.¹ Signs of CNS depression including somnolence and coma follow very large overdoses.¹

Eye

TargetIris sphincter and ciliary muscle, both parasympathetically driven

Why hereThese muscles have no significant sympathetic constrictor input, so removing the muscarinic drive leaves them unopposed and unable to respond. The pupil is targeted because pupillary constriction is a purely cholinergic act — which is why the sign is so specific and so useless as a measure of severity. Established

At the bedsideThe pupils are widely dilated and unreactive to light¹; blurring of vision and photophobia.² A fixed dilated pupil here is pharmacological and reversible — the same warning the baclofen page makes for a completely different mechanism.

Skin and thermoregulation

TargetEccrine sweat glands — sympathetically innervated, cholinergically transmitted

Why hereThe anatomical oddity that makes the toxidrome identifiable. Sweat glands sit on sympathetic nerves but respond to acetylcholine, so an antimuscarinic abolishes sweating in a patient who otherwise looks sympathomimetic. This is the only organ on the page where the syndrome's identity, rather than its severity, is decided — and in an agitated, hallucinating patient it is also the route of heat loss that has been removed. Established

At the bedsideDry, flushed skin against the wet skin of a sympathomimetic. Hyperthermia in a struggling patient is a foreseeable consequence rather than a separate complication.

Bladder and gastrointestinal tract

TargetDetrusor muscle and gastrointestinal smooth muscle

Why hereBoth are driven by parasympathetic muscarinic input, and both stop when it is blocked — which is the therapeutic action of the antispasmodics in this group and the toxic action of everything else. The gut is the only organ here that feeds back onto the poisoning itself, by slowing the absorption of the drug and of everything taken with it.¹ Established

At the bedsideUrinary retention² — worth actively looking for in an agitated patient who cannot report it — and ileus, which prolongs absorption and widens the decontamination window.¹

Heart — and what is not on this page

TargetSinoatrial node vagal tone. Not the fast sodium channel

Why hereMuscarinic blockade at the sinus node produces tachycardia and nothing more; it does not widen the QRS and does not prolong the QT. This card exists to draw a boundary rather than to describe a lesion. Several drugs that cause this toxidrome — tricyclics, some antihistamines, some antipsychotics — cause those abnormalities too, by entirely separate mechanisms, and attributing them to the anticholinergic action is the commonest conceptual error about this syndrome. Established

At the bedsideSinus tachycardia. A wide QRS in a patient with an anticholinergic toxidrome is not an anticholinergic finding — it belongs to sodium-channel blockade, it is treated with bicarbonate aimed at the channel, and it is the finding that changes the argument about physostigmine below.

Timeline of effects

A tertiary antimuscarinic — fast to arrive and remarkably slow to leave

Time

What you seeWhat is happening

0–2 hAbsorption
What you seeDry mouth, blurred vision, tachycardia. Often attributed to anxiety.
What is happeningAbsorption underway; procyclidine bioavailability about 75% with a small first-pass effect.¹ No latent phase — the swallowed molecule is the toxic species and needs no transformation.
1–6 hThe syndrome is complete
What you seeWidely dilated unreactive pupils, dry flushed skin, tachycardia, urinary retention — and, if the drug crossed, agitation and hallucinations.¹²
What is happeningPeak receptor occupancy. The peripheral and central halves appear together or the central half does not appear at all, depending on whether the molecule is charged.³ The gut has now slowed, so anything co-ingested is still being absorbed.¹
6–24 hSleeplessness
What you seeSevere sleeplessness lasting up to 24 hours or more.¹ Most patients euphoric; some anxious and aggressive.¹
What is happeningPlasma concentrations are already falling — procyclidine's half-life is about 12 hours¹ — while the central syndrome is not. This is where the mismatch between the drug's kinetics and the syndrome's duration becomes obvious.
1–4 daysThe delirium
What you seeDisorientation lasting 1 to 4 days, ending in a recuperative sleep.¹
What is happeningSix to eight half-lives after the peak. The label reports the duration and offers no mechanism for it.¹ A poisoning whose clinical course cannot be predicted from its pharmacokinetics — which is why observation rather than calculation decides disposition.
After the sleepResolution
What you seeRecovery, typically complete.
What is happeningNothing has been damaged. A competitive block leaves no lesion behind — unlike the cholinergic poisonings this page pairs with, where the enzyme must be regenerated or resynthesised.

What the mechanism predicts at the bedside

Feel the skin. Dry identifies this syndrome and wet argues against it. Every other feature — dilated pupils, tachycardia, agitation — is shared with the sympathomimetic differential; sweating is not.
Ask whether the preparation was the charged one. Hyoscine butylbromide does not enter the central nervous system³; hyoscine hydrobromide does.² Same alkaloid, different tablet, different syndrome.
Examine the bladder. Urinary retention is on the label² and an agitated, hallucinating patient will not report it. It is also a reversible cause of worsening agitation.
Do an ECG, and treat a wide QRS as belonging to a different mechanism. Muscarinic blockade produces sinus tachycardia and nothing else; the QRS belongs to sodium-channel blockade and to bicarbonate.
Expect days, not hours. The label records disorientation lasting 1 to 4 days from a drug with a 12-hour half-life¹. Planning for an overnight stay will be wrong more often than it is right.
Extend the charcoal window, and think about the co-ingestant rather than the antimuscarinic. The label itself extends it in view of its likely effects on gastric motility¹ — and a stationary stomach is holding everything else that was swallowed.
Watch the temperature. Sweating is abolished at the same time the patient becomes agitated, which removes the main route of heat loss precisely when heat production rises.
Dialysis has no role, and one UK label states it directly rather than by inference.¹ EXTRIP has assessed no antimuscarinic.⁷
Benzodiazepines are the default and are not obviously the right answer. In the one study comparing them directly, benzodiazepines controlled agitation in 24% of patients and were ineffective in reversing delirium.⁴ That is a reason to know the physostigmine argument, not a reason to act on a retrospective comparison.

The antidote, from the poison's side

This syndrome has something most pages in this library do not: an antidote with a coherent mechanism, direct comparative human data, and a well-known prohibition — where the mechanism, the data and the prohibition do not agree with one another. Setting out all three is the point of this section.

The comparative evidence is a retrospective study of 52 consecutive patients referred to a university toxicology service. Physostigmine controlled agitation in 96% and reversed delirium in 87%; benzodiazepines controlled agitation in 24% and were ineffective in reversing delirium. Initial treatment with physostigmine (n = 30) significantly reduced agitation and the level of CNS stimulation where initial benzodiazepine treatment (n = 22) did not. Patients treated initially with physostigmine had fewer complications (7% versus 46%, P < .002) and a shorter time to recovery (median 12 versus 24 hours, P = .004), with no significant difference in side effects (7% versus 14%, P = 0.6) or length of stay. The authors' own conclusion includes the necessary caveat: a prospective controlled study is necessary to confirm such findings.⁴

The complication rate points the opposite way to the reputation

The number that deserves attention is 7% versus 46% — the complication rate was lower in the physostigmine group.⁴ Physostigmine's reputation is of a dangerous drug; in the only direct comparison cited here, the patients who did not receive it did worse on complications, on delirium and on time to recovery. A treatment can be genuinely hazardous in a defined subgroup and still be safer overall than the alternative, and conflating those two statements is how a prohibition outgrows its evidence. The claim that physostigmine is too dangerous to use for anticholinergic delirium is downgraded here to traditional teaching, on the citation for the doubt above and the registry data below. This is the same structure as the digoxin-and-calcium badge already carried in this library: investigators looked for the harm and measured less of it than the teaching predicts. Traditional teaching

A registry study reinforces the gap between the evidence and the practice. Among 815 consecutive patients with anticholinergic toxidromes in the ToxIC registry, benzodiazepines alone were given in 28.7%, physostigmine alone in 12.4%, both in 8.8%, antipsychotics in 2.7%, and 47.4% received no definitive treatment at all. Patients who received only physostigmine had a significantly lower rate of intubation — 1.9% versus 8.4%, OR 0.21 (95% CI 0.05–0.87). The authors note that physostigmine was used more often for agents with primarily anticholinergic effects (26.6%) than for those with mixed or unknown effects (15.1%, P < 0.001).⁵ Toxicologists themselves, who know this evidence best, gave it to one patient in eight.

Where the prohibition is real, and what it actually rests on

The origin of the contraindication is a 1980 report of two patients with tricyclic antidepressant toxicity who developed asystole after physostigmine — given to treat seizures, not delirium.⁶ Two cases, in a poisoning with a second and independently lethal cardiac mechanism, for an indication nobody now proposes. That is a genuine warning and a thin evidence base at the same time, and the honest reading is that it identifies a subgroup rather than condemning the drug: the patient with a wide QRS, a conduction abnormality or a tricyclic ingestion. Two UK labels point the same way from different directions. Quetiapine's supplies a physostigmine dose, then states it is not recommended as standard treatment and contraindicates it in dysrhythmias, any degree of heart block or QRS widening — the abnormalities a severe quetiapine overdose produces, as the antipsychotics page sets out. Procyclidine's is blunter and applies to a pure antimuscarinic with no cardiac mechanism at all: other active measures such as the use of cholinergic agents or haemodialysis are extremely unlikely to be of clinical value.¹

A disagreement recorded rather than resolved

The procyclidine label and Burns' data genuinely conflict, and this page does not adjudicate between them. One is a UK regulatory document asserting that cholinergic agents are extremely unlikely to help in overdose of a pure central antimuscarinic¹; the other is a retrospective comparison in which they helped in 87–96% of patients.⁴ Both are cited in full above. They differ in design, in date, in jurisdiction and in the populations they describe, and a reader who concludes from this page that the question is settled has read it wrongly. The reason to record the disagreement rather than pick a winner is that a recommendation whose reasoning cannot be reconstructed is indistinguishable from an invented one — the lesson this library took from the ketamine badge in Band C.

Physostigmine: The mechanism-appropriate antidote, contested in both directions, and not stocked by most UK departments. It has no monograph on the sibling drug site, which is a gap this page makes visible rather than fills.
Benzodiazepines: The default. Controlled agitation in 24% and reversed delirium in none, in the one direct comparison.⁴ Still the right first move when physostigmine is unavailable, unsafe or unfamiliar — which in the UK is usually.
Sodium bicarbonate: Not for this syndrome. For the QRS that some of the causative drugs produce by a separate mechanism — see sodium-channel blockade. Its presence in the assessment is what determines whether physostigmine is even a question.
Activated charcoal: With a wider window than usual, because the syndrome slows the gut.¹ Aim it at the co-ingestant.
Cooling and catheterisation: Not antidotes, but the two mechanistically predictable interventions: sweating is abolished, and the bladder is not emptying.
Neostigmine, pyridostigmine, glycopyrronium: Wrong molecules for this job. All quaternary, none crosses into the brain, none reaches the delirium — the same charge argument that separates the two hyoscine salts.³

Critical appraisal

The quaternary-versus-tertiary argument is the page's organising claim and its human evidence is absent. Buscopan's label states in 5.1 that hyoscine butylbromide does not enter the central nervous system and in 5.2 that animal studies demonstrate it does not pass the blood-brain barrier but no clinical data to this effect is available.³ The section 5.1 sentence is stated more confidently than the section 5.2 sentence supports. This page quotes both and badges the mechanistic step inferred. An auditor should check that no argument elsewhere on the page silently promotes it.
The Burns study is retrospective, single-centre, and describes patients referred to a toxicology consultation service — a selected population, not consecutive emergency attendances. Its authors state that a prospective controlled study is necessary.⁴ The 96% / 87% figures are the numbers on this page most likely to be quoted out of context, including by this page, and they are printed with the design attached for that reason.
The ToxIC analysis is a registry of patients seen by medical toxicologists, which is not the population most anticholinergic delirium presents to. The intubation comparison — 1.9% versus 8.4%, OR 0.21 (0.05–0.87) — is unadjusted for severity in what is cited here, and confounding by indication runs in both directions: physostigmine was preferentially given for agents with primarily anticholinergic effects (26.6% versus 15.1%, P < 0.001), which are plausibly the less complicated poisonings.⁵ The wide confidence interval is consistent with a small effect.
The physostigmine badge is a treatment-safety downgrade and is scoped deliberately. It applies to the general teaching that physostigmine is too dangerous to use in anticholinergic delirium, and its citation for the doubt is the measured complication rate of 7% versus 46% in the comparison group.⁴ It does not apply to the tricyclic patient, to the wide QRS, or to any conduction abnormality, where the prohibition is not contested by anything cited here and where quetiapine's label independently contraindicates the drug. This exemption is stated on the page rather than left implicit, and a reviewer who judges the badge too broad would be making a fair argument.
The Pentel and Peterson report is two patients, in 1980, given physostigmine for seizures in tricyclic overdose.⁶ It is cited as the origin of a prohibition and as a genuine warning about a subgroup. It is not evidence about physostigmine in anticholinergic delirium, and the page says so — but two case reports of asystole are not nothing, and nothing here argues they should be dismissed.
The procyclidine label's dismissal of cholinergic agents is quoted in full and is not explained away. It is a current UK regulatory document and it contradicts the comparative data. This page records the conflict as a conflict. An auditor should resist the temptation to resolve it in either direction on the material cited here.
The 1-to-4-day delirium is a label observation from recorded cases with no denominator¹, and the three explanations offered for it are explicitly not endorsed. No mechanism for the mismatch between a 12-hour half-life and a four-day syndrome is asserted.
The sweat-gland argument — sympathetic innervation, cholinergic transmission — is standard physiology and is cited to no primary source here. It is the single most-used bedside discriminator in this syndrome and it is badged established on textbook grounds, which carries the same risk as the thion-to-oxon badge on the organophosphates page. If it cannot be sourced, the page's most practical recommendation is affected rather than a sentence.
No dose of physostigmine appears anywhere on this page, and no lethal or toxic dose of any antimuscarinic appears either. The one dose figure that exists in a source used here — the physostigmine dose on quetiapine's label — is deliberately not reproduced.
Three of the four labels cited on this page are for drugs that are not the common causes of this toxidrome in UK practice. The common causes are antihistamines, tricyclics and antipsychotics, each of which has its own page here. Procyclidine, hyoscine hydrobromide and hyoscine butylbromide were chosen because they isolate the pure syndrome and the charge experiment — the page trades representativeness for mechanistic clarity, and an auditor should decide whether that trade is declared clearly enough.

How this page connects to the rest of the library

It completes two sets. It is the third class-defined entry, alongside sodium-channel blockade (a channel) and methaemoglobin inducers (an oxidation state); the methaemoglobin page already names sodium-channel blockade as the library's other class-defined entry. And it is the blocked-receptor counterpart to organophosphates and carbamates, where the same transmitter accumulates instead — with physostigmine, a carbamate, as the antidote here and atropine, an antimuscarinic, as the antidote there. Each poisoning's antidote is the other poisoning's mechanism. Its causative agents are covered on antihistamines, tricyclics and antipsychotics; abd.resusdoc.uk lists anticholinergic delirium among its six toxidromes as a bedside differentiator and cross-links here rather than explaining the mechanism.

References

1
Kemadrin Tablets 5 mg (procyclidine hydrochloride) — Summary of Product Characteristics. electronic medicines compendium, product 5460. Sections 4.9 (Overdose) and 5.2 (Pharmacokinetic properties). medicines.org.uk/emc/product/5460
2
Kwells 300 microgram tablets (hyoscine hydrobromide) — Summary of Product Characteristics. electronic medicines compendium, product 11746. Section 4.9 (Overdose). medicines.org.uk/emc/product/11746
3
Buscopan 10 mg Tablets (hyoscine butylbromide) — Summary of Product Characteristics. electronic medicines compendium, product 1775. Sections 5.1 (Pharmacodynamic properties) and 5.2 (Pharmacokinetic properties). Cited for both the central-exclusion claim and the label's own disclosure that the supporting studies are animal. medicines.org.uk/emc/product/1775
4
Burns MJ, Linden CH, Graudins A, et al. A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning. Annals of Emergency Medicine 2000 Apr;35(4):374–81. PMID 10736125. Retrospective, 52 consecutive patients referred to a university hospital toxicology consultation service. The citation for the doubt behind this page's evidence-tier downgrade.
5
Watkins JW, Schwarz ES, Arroyo-Plasencia AM, et al. The Use of Physostigmine by Toxicologists in Anticholinergic Toxicity. Journal of Medical Toxicology 2015 Jun;11(2):179–84. PMID 25510306. Retrospective analysis of 815 consecutive anticholinergic toxidromes in the ToxIC registry.
6
Pentel P, Peterson CD. Asystole complicating physostigmine treatment of tricyclic antidepressant overdose. Annals of Emergency Medicine 1980 Nov;9(11):588–90. PMID 7001962. Two patients, given physostigmine to treat seizures in tricyclic toxicity.
7
EXTRIP Workgroup — published recommendations index. Extracorporeal Treatments in Poisoning Workgroup. Cited for the absence of any recommendation covering any antimuscarinic agent. extrip-workgroup.org/recommendations

The anticholinergic toxidrome

At a glance