Autonomics question bank

D. Pralidoxime — Organophosphates phosphorylate acetylcholinesterase, flooding muscarinic and nicotinic synapses. Atropine competes only at muscarinic receptors and does not mitigate nicotinic effects, so neuromuscular weakness persists. Pralidoxime reactivates the phosphorylated enzyme — its most critical effect is relieving respiratory-muscle paralysis — but only before the enzyme ages. Glycopyrrolate is another antimuscarinic, and physostigmine and neostigmine are cholinesterase inhibitors that would add to the excess.

A. Withdraw the cholinesterase inhibitor and give atropine, with breathing support as needed — Muscarinic signs and fasciculations with rising weakness after dose escalation point to a cholinergic crisis: excess acetylcholine at the end plate blocks transmission. Myasthenic crisis is treated with more anticholinesterase, but cholinergic crisis calls for prompt withdrawal of these drugs and atropine; supportive care such as mechanical ventilation may be needed. Adding neostigmine or physostigmine would deepen the crisis, and bethanechol acts selectively at muscarinic receptors and does not ordinarily stimulate voluntary muscle.

E. Stimulating Gq-coupled muscarinic receptors on airway smooth muscle, raising intracellular calcium — This is a methacholine challenge: a fall in FEV1 of 20% or more is a positive test, and hyperreactive airways constrict at lower doses. Methacholine, a choline ester, agonizes airway muscarinic receptors; M3 receptors couple to Gq, phospholipase C and IP3, and the calcium rise contracts smooth muscle. It does not block β2 receptors or inhibit cholinesterase, and M2/Gi receptors lower — not raise — cAMP.

B. Systemic cholinesterase inhibition from the drops prolonged the action of succinylcholine — Echothiophate is a long-acting organophosphate cholinesterase inhibitor, and the drops depress both plasma and red-cell cholinesterase in most patients after a few weeks. Prolonged paralysis has been reported when succinylcholine is given with drugs that have anticholinesterase activity, so in these patients it is given only with great caution, if at all, because of possible respiratory or cardiovascular collapse. Echothiophate inhibits the enzyme rather than blocking receptors, skeletal muscle signals through nicotinic (not muscarinic) receptors at the neuromuscular junction, and reactivation is pralidoxime’s action.

C. It is not destroyed by cholinesterase and acts selectively at muscarinic receptors — Acetylcholine is rapidly hydrolyzed by cholinesterase, so its effects are transient. Bethanechol is not destroyed by the enzyme, its action is selective for muscarinic receptors (nicotinic effects are usually absent or minimal at therapeutic doses), and its charged quaternary amine keeps it out of the brain. It contracts the detrusor and is indicated only for nonobstructive retention — mechanical obstruction is a contraindication.

D. Pressing over the nasolacrimal (lacrimal) sac for 2–3 minutes after each drop — Drops that drain through the nasolacrimal system are absorbed systemically, and infants and young children are especially prone to cyclopentolate’s CNS effects (ataxia, restlessness, hallucinations). The label calls for pressure over the nasolacrimal sac for two to three minutes after instillation to minimize absorption, and for observing infants closely for at least 30 minutes. Pilocarpine, given afterward, gives conflicting and sometimes only partial reversal of the dilation. CNS disturbances are more likely with the stronger solutions, and to minimize absorption the label uses a single drop of the weakest solution per eye before the sac pressure; cyclopentolate also acts for a shorter time than atropine, not a longer one.

E. Inhibits acetylcholinesterase in the brain, raising acetylcholine enough to overcome a competitive block — This is the antimuscarinic toxidrome; the absence of sweating separates it from sympathomimetic toxicity. Antimuscarinic block is competitive and surmountable — overcome by raising acetylcholine with an anticholinesterase. Physostigmine is an acetylcholinesterase inhibitor active in both the central and peripheral nervous systems; it is used in severe cases with central and peripheral signs that are refractory to benzodiazepines. A quaternary anticholinesterase such as neostigmine does not cross the blood–brain barrier and treats only peripheral effects.

A. Its quaternary ammonium group limits passage across the blood–brain barrier, so CNS effects are fewer — Glycopyrrolate blunts neostigmine’s muscarinic effects (bradycardia, secretions, bronchoconstriction) while neostigmine restores neuromuscular transmission; the two are given together because their onsets are similar. Its highly polar quaternary group limits passage across the blood–brain barrier, so CNS side effects are lower than with tertiary atropine. Antimuscarinics cause minimal nicotinic blockade, and glycopyrrolate is mostly eliminated unchanged by the kidney.

B. The ciliary muscle — Blocking the ciliary muscle paralyzes accommodation (cycloplegia), which reduces near vision — the effect a refraction needs. Blocking the iris sphincter instead dilates the pupil (mydriasis), leaving the sympathetically driven dilator unopposed; that explains the wide pupils and light sensitivity, not the loss of near focus. Accommodation usually recovers within 6 to 24 hours after cyclopentolate.

C. Transdermal delivery bypasses first-pass CYP3A4 metabolism in the gut wall and liver — Oxybutynin is metabolized mainly by CYP3A4 in the liver and gut wall. After an oral dose, first-pass metabolism leaves about 6% bioavailability and a metabolite-to-parent (N-desethyloxybutynin) AUC ratio of 11.9:1. Transdermal administration bypasses first-pass gastrointestinal and hepatic metabolism — skin has little CYP3A4 — and the ratio falls to 1.3:1. Less than 0.1% of a dose is excreted unchanged.

C. Activation of Gs-coupled β3 receptors, raising cAMP — A β3 agonist (mirabegron or vibegron) relaxes the detrusor during filling through Gs-coupled β3 receptors and cAMP, opposing the M3 signal without antimuscarinic action; mirabegron showed no cognitive deterioration in patients 65 and older. M3 blockade is the antimuscarinic route she should avoid, and α1 blockade relaxes the bladder neck in outlet obstruction.

E. Inhibition of CYP2D6, raising metoprolol levels — Mirabegron is a moderate, time-dependent CYP2D6 inhibitor and raised metoprolol AUC by 229%, so metoprolol’s effect is amplified; it can also raise blood pressure. Antimuscarinics such as fesoterodine raise heart rate slightly rather than lowering it, and competition for tubular secretion is trospium’s interaction mechanism. Vibegron does not inhibit CYP2D6.

B. It is a charged, hydrophilic quaternary ammonium compound cleared largely by active tubular secretion — Trospium is a hydrophilic quaternary amine with limited ability to cross the blood–brain barrier. CYP does not contribute significantly to its elimination; its renal clearance is about 4-fold the GFR, reflecting active tubular secretion, and severe renal impairment raised its AUC 4.2-fold. Less than 10% is absorbed, and a high-fat meal lowers that by 70–80%.

A. Nonspecific esterases, not CYP2D6, convert fesoterodine to 5-HMT — Fesoterodine is rapidly hydrolyzed by nonspecific esterases to 5-hydroxymethyl tolterodine, the same active metabolite that tolterodine forms through CYP2D6; fesoterodine cannot be detected in plasma. Poor metabolizers clear 5-HMT more slowly (about 2-fold higher AUC). Tolterodine in poor metabolizers is dealkylated by CYP3A4 and forms negligible 5-HMT.

D. Muscarinic blockade weakening detrusor contraction against an obstructed outlet — Blocking detrusor M3 receptors can worsen emptying; with clinically significant bladder outlet obstruction an antimuscarinic may cause further retention and kidney injury, so it is not recommended there and is contraindicated in retention. Post-void residual is monitored in men with BPH. α1 stimulation tightens the bladder neck but is not an action of solifenacin.

E. Potassium efflux through upregulated nicotinic receptors after the burn — Succinylcholine depolarizes the end plate and lets potassium out of muscle, normally raising serum potassium by up to about 0.5 mEq/L. After the acute phase of a major burn, receptors — including immature ones that are sensitive to succinylcholine — upregulate, the risk peaking at about 7–10 days, so far more potassium is released and fatal arrhythmias can follow; succinylcholine is contraindicated in this setting. Succinylcholine has no direct effect on the myocardium, histamine release is uncommon with normal use, and reduced plasma cholinesterase prolongs paralysis rather than causing hyperkalemia. Malignant hyperthermia is a pharmacogenetic reaction triggered by succinylcholine with volatile anesthetics, not by the burn, and it builds as a hypermetabolic state with hypercarbia, rigidity and fever, whereas this arrest came seconds after the dose with peaked T waves.

C. Homozygous atypical plasma cholinesterase — Succinylcholine is ended by plasma cholinesterase, which normally clears a single dose within minutes. About 1 in 2,500 patients is homozygous for the atypical plasma cholinesterase gene and is extremely sensitive, with apnea or prolonged paralysis that is managed with controlled respiration; the dibucaine number helps confirm it. Phase II block follows prolonged exposure rather than one dose, malignant hyperthermia brings hypercarbia, rigidity and fever, and succinylcholine is not cleared by the liver. In a healthy patient the potassium rise (up to about 0.5 mEq/L) is clinically insignificant.

B. Phase II block, with desensitized receptors — With prolonged exposure the depolarizing (phase I) block changes to a phase II block that superficially resembles a nondepolarizing block: the response fades with successive stimuli, tachyphylaxis appears, and paralysis may be prolonged. Phase II is confirmed with a nerve stimulator before any anticholinesterase is considered, and an anticholinergic is given with it to prevent cardiac rhythm disturbances. Malignant hyperthermia would bring hypercarbia, rigidity and fever; sugammadex encapsulates only rocuronium and vecuronium and does not bind succinylcholine; and histamine-mediated flushing and hypotension are uncommon with normal clinical use.

D. Neostigmine together with glycopyrrolate — Cisatracurium is a benzylisoquinolinium, which sugammadex does not reverse — sugammadex encapsulates only rocuronium and vecuronium. Neostigmine inhibits acetylcholinesterase so acetylcholine outcompetes the blocker; because the extra acetylcholine also stimulates muscarinic receptors and neostigmine has direct cholinomimetic effects, atropine or glycopyrrolate is given before or with it. Cisatracurium was a sound choice here: Hofmann elimination does not depend on the kidney.

A. Interfering with calcium release from the sarcoplasmic reticulum of skeletal muscle — This is malignant hyperthermia: in susceptible muscle (RYR1 or CACNA1S variants, often familial) volatile anesthetics and succinylcholine raise myoplasmic calcium and drive hypermetabolism. Triggers are stopped and IV dantrolene is given; it acts beyond the neuromuscular junction, probably by interfering with calcium release from the sarcoplasmic reticulum, restoring myoplasmic calcium. A neuromuscular blocker, neostigmine, sugammadex or atropine does not touch the underlying calcium problem.

D. Covalent, irreversible binding to α1 and α2 receptors — Phenoxybenzamine is a nonselective, irreversible α-blocker that bonds covalently to the receptor, most likely at a cysteine residue. Its effects persist for 3 to 4 days after an IV dose and build up over about a week. Tyrosine hydroxylase inhibition is metyrosine; reversible blockade is phentolamine; β-blockade would be dangerous before α-blockade.

A. Unopposed catecholamine stimulation of α receptors after β blockade — A β-blocker should never be started before α-blockade: with β receptors blocked, circulating catecholamines act unopposed on α receptors and can precipitate a hypertensive crisis, raising afterload and myocardial oxygen demand. Once α-blockade is established, a β-blocker such as esmolol or metoprolol may be titrated for heart rate. Propranolol itself is a nonselective β-blocker with no other autonomic nervous system activity: it does not stimulate or block α receptors, or alter catecholamine reuptake or release — the catecholamines come from the tumor.

B. α1 blockade affecting the iris dilator muscle — The radial iris dilator is activated by α1 receptors; long-term α1 blockade may cause dysfunction or atrophy of that muscle, so the pupil cannot dilate adequately and the iris billows and prolapses — intraoperative floppy iris syndrome. It is most commonly associated with tamsulosin and can occur even after the drug has been stopped. Tamsulosin is an α1-adrenoceptor blocker selective for prostatic α1 receptors, so the complication comes from α1 blockade of the dilator, not from muscarinic, nicotinic, α2 or β2 effects.

C. Pressure falls further because its β effects are unopposed and the net effect is vasodilation — Epinephrine stimulates both α and β receptors. With α receptors blocked by phenoxybenzamine, the net effect is vasodilation and a further drop in blood pressure — epinephrine reversal — so epinephrine is contraindicated. Levarterenol, which stimulates mainly α receptors, can overcome the block in sufficient dose.

E. With CYP2D6 already deficient, inhibiting CYP3A4 removes the other main route and tamsulosin exposure can rise substantially — Tamsulosin is extensively metabolized, mainly by CYP3A4 and CYP2D6. Ketoconazole raised tamsulosin AUC 2.8-fold, and CYP2D6 poor metabolizers already have higher exposure; because poor metabolizers cannot be readily identified and the combination could raise exposure substantially, tamsulosin is not used with strong CYP3A4 inhibitors.

A. M3 — Gq, with IP3 and DAG raising intracellular Ca²⁺ — Pilocarpine is a direct muscarinic agonist. M3 receptors couple to Gq: phospholipase C forms IP3 and DAG, intracellular calcium rises, smooth muscle contracts — the iris sphincter (miosis) and bronchi — and exocrine glands secrete. β2 stimulation relaxes bronchial smooth muscle, and α1 stimulation causes mydriasis, not miosis. M2 receptors are in the SA and AV nodes, where they slow the heart, and Nm receptors are at the skeletal muscle endplate.

D. M2 receptors in the SA and AV nodes — M2 receptors are found predominantly in the SA and AV nodal cells; through Gi they open potassium channels and slow the heart, so a muscarinic antagonist binding M2 increases the heart rate. Blocking β1 would slow the heart, since β1 stimulation raises the rate. Antimuscarinics cause minimal blockade at nicotinic sites, M3 receptors mediate smooth-muscle and gland effects rather than heart rate, and α1 receptors mediate vasoconstriction.

B. β2 — Isoproterenol is a nonselective β1 and β2 agonist with very low affinity for α receptors. Tremor, along with tachycardia, palpitations and anxiety, is a β2 effect; β1 stimulation causes tachycardia, palpitations and tachyarrhythmias. α1 stimulation constricts vessels, M2 stimulation slows the heart, and D1 stimulation dilates renal, mesenteric and coronary vessels.

E. A rise in cAMP through Gs and adenylyl cyclase — Mirabegron is a β3 agonist: β3 stimulation activates adenylyl cyclase, cAMP rises, and the detrusor relaxes during filling, increasing bladder capacity. IP3, DAG and calcium are the Gq pathway of M3 and α1 receptors, which contracts smooth muscle; acetylcholine contracts the detrusor mainly through M3. Ligand-gated Na⁺ channels are nicotinic receptors, Gi-driven K⁺ efflux is how M2 slows the heart, and releasing norepinephrine is an indirect action, as with ephedrine, rather than mirabegron’s direct receptor agonism.

D. IV sodium bicarbonate — Tricyclic antidepressants such as amitriptyline have anticholinergic properties and can produce the anticholinergic toxidrome. If wide-complex dysrhythmias develop, IV sodium bicarbonate should be given; IV benzodiazepines are the first-line therapy for agitation, not for the rhythm. In general, physostigmine is recommended only for pure anticholinergic poisoning, and with tricyclic antidepressants acute cardiac arrest may be possible, so it is considered only under continuous ECG monitoring. Atropine is itself a muscarinic antagonist, and pralidoxime reactivates cholinesterase inhibited by organophosphates.

E. Atropine — Jimson weed contains the muscarinic antagonists atropine and scopolamine, and physostigmine, a cholinesterase inhibitor active in the central and peripheral nervous systems, is its antidote. Physostigmine overdose can cause bradycardia, hypersalivation and vomiting, and IV atropine is given until the symptoms normalize — which is why atropine should be ready before physostigmine is used. Neostigmine is another cholinesterase inhibitor and would add to the excess. Pralidoxime reactivates cholinesterase phosphorylated by organophosphates; its most critical effect is relieving paralysis of the respiratory muscles, and atropine is always required alongside it to block the accumulated acetylcholine. Sodium bicarbonate is for wide-complex dysrhythmias, and sugammadex binds only rocuronium and vecuronium.

C. Sugammadex — Sugammadex is a modified gamma cyclodextrin that encapsulates rocuronium or vecuronium, leaving less blocker available at nicotinic receptors, and it can quickly reverse both moderate and deep blockade. Neostigmine works by letting acetylcholine compete with the blocker and must be given after a relative degree of spontaneous recovery. Atropine blocks muscarinic receptors, which are not found at the neuromuscular junction. Dantrolene acts beyond the myoneural junction, on excitation–contraction coupling, and pralidoxime reactivates organophosphate-inhibited cholinesterase.

A. The phosphorylated enzyme has aged into a form that can no longer be reactivated — The organophosphate–enzyme bond can undergo aging, after which acetylcholinesterase can no longer be regenerated and de novo synthesis is needed; pralidoxime must be given before aging, a time frame specific to each compound. Pralidoxime reactivates cholinesterase mainly outside the central nervous system; it is atropine that competes with acetylcholine at muscarinic receptors, and atropine must be given before pralidoxime. Red blood cell acetylcholinesterase activity correlates more strongly with organophosphate toxicity than plasma butyrylcholinesterase.

D. α1 receptors on vascular smooth muscle — Dopamine’s receptor effects depend on its dose: at low rates it activates D1 and D2 receptors in the renal, mesenteric and coronary vessels, causing vasodilation; at intermediate rates β1 receptors raise heart rate and contractility; at high rates α1 receptors cause vasoconstriction and a rise in blood pressure. Excess dopamine can cause peripheral vasoconstriction severe enough to produce gangrenous extremities. Dilating vessels is what β2 receptors do, and V1 receptors are vasopressin’s, not dopamine’s.

B. Dobutamine — Norepinephrine is commonly used to reach the arterial-pressure goal in shock; if tissue and organ perfusion stays low, dobutamine can be added to increase cardiac output, raising contractility with minimal effect on blood pressure. More norepinephrine adds pressure rather than output, since its effect on cardiac output is generally neutral and can be a fall, and phenylephrine raises afterload more than preload and can reduce output. Vasopressin, added when hypotension is refractory, tends to decrease heart rate and cardiac output, and midodrine is an oral drug for symptomatic orthostatic hypotension.

E. Switch to a direct-acting α1 agonist such as phenylephrine — Repeated ephedrine doses can cause tachyphylaxis, and its label advises having an alternative pressor ready. Phenylephrine, a pure α1 agonist, is labelled for clinically important hypotension resulting from vasodilation in the setting of anesthesia. Adrenergic antagonists work against ephedrine: β-blockers and α-blockers such as phentolamine antagonize its pressor effect. Isoproterenol typically lowers mean arterial pressure, and midodrine is an oral drug for symptomatic orthostatic hypotension.

A. Peripheral α2 stimulation causing vasoconstriction — In clonidine overdose, cardiovascular effects often begin with early hypertension, likely due to initial peripheral α2 stimulation causing vasoconstriction, and progress to hypotension and bradycardia, with drowsiness, miosis and respiratory depression. Central α2 agonism in the brain stem is what reduces sympathetic outflow, heart rate and blood pressure — the later phase. Releasing norepinephrine from sympathetic nerves is ephedrine’s indirect action, clonidine slows the heart rather than stimulating it, and V1 receptors are vasopressin’s.

C. An excessive postural fall in blood pressure from α1 blockade, greatest with the first doses — Syncope after the first dose of an α1-blocker is believed to be due to an excessive postural hypotensive effect: the risk is greatest in the first 7 days of treatment, and it recurs when therapy is interrupted and restarted or the dose is increased. Terazosin is a selective α1 antagonist, not a β1-blocker, and it leaves the α2 brake on norepinephrine release intact, so norepinephrine spillover onto β receptors is less than with nonselective α-blockers. Central α2 agonism is clonidine’s action, and covalent blockade that builds up over about a week belongs to phenoxybenzamine.

E. Phentolamine blocks presynaptic α2 receptors, so more norepinephrine reaches β receptors — Phentolamine is a nonselective α-blocker: blocking the α2 brake on nerve endings increases norepinephrine release, and the spillover stimulates β receptors, causing tachycardia and tremulousness; it also has direct, less marked positive chronotropic effects. Prazosin is α1-selective and leaves α2 intact, so reflex tachycardia is smaller. Phentolamine binds reversibly (phenoxybenzamine is the irreversible one), prostatic α1A selectivity belongs to uroselective agents such as tamsulosin and silodosin, and tyrosine hydroxylase is inhibited by metyrosine.

B. Given IV it blocks β receptors far more than α receptors, leaving tumor catecholamines acting on α — Intravenous labetalol has an α:β ratio of about 1:7, so β blockade dominates; with β receptors blocked before adequate α-blockade, circulating catecholamines act unopposed at α receptors, and paradoxical hypertensive responses have been reported in a few patients with this tumor. Its α1 blockade is selective and competitive, not irreversible and not α2, and its β1 intrinsic sympathomimetic activity is minimal.

D. Higher levels of R(+) carvedilol, which blocks α1 receptors and dilates vessels — CYP2D6 poor metabolizers have 2–3-fold higher R(+) carvedilol but only about 20–25% more S(−) carvedilol, and they have more dizziness during up-titration, presumably from the vasodilating effect of the α-blocking R(+) enantiomer. Carvedilol’s α blockade is at α1, it has no intrinsic sympathomimetic activity, and its α1 blockade lowers blood pressure more standing than supine.

E. Organophosphates also inhibit plasma cholinesterase, so succinylcholine is not broken down and paralysis is prolonged — Plasma cholinesterase activity is diminished by irreversible inhibitors of plasma cholinesterase such as organophosphates, and in organophosphate poisoning succinylcholine should be avoided during intubation because it cannot be metabolized and leads to prolonged paralysis. Organophosphates raise acetylcholine at nicotinic as well as muscarinic synapses rather than blocking them. Malignant hyperthermia is pharmacogenetic, linked to RYR1 and CACNA1S variants; the dangerous hyperkalemia of succinylcholine occurs when postjunctional receptors are upregulated, as after major burns or denervation; and neuromuscular blockers have no effect on consciousness.

B. Pralidoxime — Pralidoxime is not indicated as an antidote for pesticides of the carbamate class, because it may increase the toxicity of carbaryl; it is used to reactivate cholinesterase inhibited by organophosphates. Atropine blocks muscarinic receptors and abolishes the bradycardia produced by anticholinesterase agents. Sodium bicarbonate is given for wide-complex dysrhythmias in anticholinergic toxicity, sugammadex binds only rocuronium and vecuronium, and dantrolene acts beyond the myoneural junction, on excitation–contraction coupling.

C. Atropine — Succinylcholine stimulates autonomic ganglia and muscarinic receptors, and bradycardia — which may progress to asystole — is more frequent after a second dose and more severe in children; atropine or glycopyrrolate reduces it. Neostigmine itself causes bradycardia, and esmolol is a β1-selective blocker, while β1 stimulation is what raises the heart rate. Sugammadex does not bind succinylcholine, and dantrolene is the treatment for malignant hyperthermia.

A. Neostigmine — Glycopyrrolate is a quaternary ammonium compound with limited passage across the blood–brain barrier. Its label advises a quaternary anticholinesterase such as neostigmine, which does not cross the blood–brain barrier, for peripheral anticholinergic effects, and physostigmine, which does cross it, if CNS symptoms occur — he has none. Pralidoxime reactivates cholinesterase inhibited by organophosphates, sodium bicarbonate is for wide-complex dysrhythmias, and atropine is itself an antimuscarinic.

D. Possible cardiac conduction disturbances — Oral pilocarpine is used with caution with β-blockers because of the possibility of conduction disturbances. The label’s other interaction cautions concern other drug classes: additive effects with other parasympathomimetics, and possible antagonism of anticholinergic co-medications such as atropine or inhaled ipratropium. Pilocarpine’s effects are not confined to the salivary glands — sweating, nausea, urinary urgency and blurred vision are among its common adverse effects.

C. Tropicamide may interfere with pilocarpine’s pressure-lowering action — Tropicamide may interfere with the antihypertensive action of carbachol, pilocarpine or ophthalmic cholinesterase inhibitors. Tropicamide is an antimuscarinic that blocks the iris sphincter and ciliary muscle, causing mydriasis and cycloplegia — it does not constrict the pupil or inhibit cholinesterase — whereas pilocarpine contracts the iris sphincter and causes miosis.

E. An α1-blocker such as tamsulosin — relaxing prostate and bladder-neck smooth muscle will ease the obstruction — Bethanechol is for nonobstructive retention and is contraindicated in mechanical obstruction, as are neostigmine and pyridostigmine. In BPH, smooth-muscle tone in the prostate and bladder neck constricts the outlet, and α1 blockade relaxes it, improving urine flow. Oxybutynin and other antimuscarinics are contraindicated in urinary retention, and α1 stimulation contracts the bladder neck — sympathetic stimulation prevents micturition.

D. Atropine has masked the muscarinic warning signs while excess pyridostigmine causes cholinergic crisis weakness — Atropine used to reduce pyridostigmine’s gastrointestinal side effects can mask the signs of overdosage and allow a cholinergic crisis to develop. Cholinergic crisis causes increasing muscle weakness that can involve the respiratory muscles, and it calls for withdrawing the drug, not giving more. Muscarinic receptors are not found at the neuromuscular junction, so atropine does not block it, and pyridostigmine is a quaternary amine that does not cross the blood–brain barrier.

B. Gentamicin impairs neuromuscular transmission — Infection and drugs that impair neuromuscular transmission, including antibiotics such as gentamicin, can precipitate myasthenic worsening; aminoglycosides have their own nondepolarizing blocking action and potentiate neuromuscular blockade. A cholinergic crisis follows overdose of a cholinesterase inhibitor — her dose has not changed and she has no muscarinic signs — and muscarinic receptors are not found at the neuromuscular junction.

A. Nebivolol — Nebivolol is a cardioselective, third-generation β-blocker whose β3 agonism activates endothelial nitric oxide synthase, producing NO-mediated vasodilation; it has no α1 blockade at clinical doses. Mirabegron and vibegron are β3 agonists that relax the detrusor. Carvedilol vasodilates through α1 blockade, esmolol is a very short-acting β1-selective blocker given only intravenously and without α-adrenergic blockade, and pindolol is a nonselective blocker with intrinsic sympathomimetic activity.

B. Vibegron — Vibegron is indicated for overactive bladder with urge urinary incontinence, urgency and frequency in adult men on pharmacological therapy for BPH. Solifenacin is labelled for adults with overactive bladder in general and is not recommended in clinically significant bladder outlet obstruction, bethanechol is contraindicated in mechanical obstruction, and silodosin is another α-blocker, which should not be combined with other α-blockers. Glycopyrrolate by mouth is contraindicated in obstructive uropathy, including prostatic hypertrophy.

A. Phentolamine — Phentolamine is indicated for the prevention or treatment of dermal necrosis and sloughing after intravenous administration or extravasation of norepinephrine. Extravasated pressor causes intense local α1-mediated vasoconstriction, ischemia and possible necrosis, and phentolamine, a nonselective α-adrenergic antagonist, reverses the vasoconstriction and restores perfusion. Phenylephrine is an α1 agonist, atropine blocks muscarinic receptors, and propranolol has no α-blocking activity.