The autonomic neuroeffector–junction effects of acetylcholine and similar drugs are best termed:
A. Sympatholytic effects
B. Nicotinomimetic effects
C. Adrenergic effects
D. Parasympathomimetic effects

D. Parasympathomimetic effects

A researcher classifies cholinoceptors by transmembrane signaling mechanism. Which pairing is correct?
A. Muscarinic—G protein; Nicotinic—ion channel
B. Muscarinic—ion channel; Nicotinic—G protein
C. Both are ligand-gated channels
D. Both are G protein–linked

A. Muscarinic—G protein; Nicotinic—ion channel

Which site is most consistent with muscarinic receptor localization described in autonomic pharmacology?
A. Synaptic vesicle membrane
B. Mitochondrial inner membrane
C. Effector-cell plasma membrane
D. Nuclear envelope membrane

C. Effector-cell plasma membrane

What agents bind to and activate muscarinic or nicotinic receptors?

Direct-acting

Which produce their primary effects by inhibiting acetylcholinesterase?

Indirect-acting

Acetylcholinesterase breaks Ach into?
A. Acetate and ethanol
B. Choline and acetic acid
C. Choline and propionic acid
D. Acetyl-CoA and choline

B. Choline and acetic acid

A quaternary choline ester shows minimal CNS effects even at high doses. The most direct physicochemical explanation is that it is relatively:
A. Nonpolar in plasma
B. Highly protein-bound
C. Rapidly metabolized hepatically
D. Insoluble in lipids

D. Insoluble in lipids

Two enantiomers of bethanechol are compared in vitro. One is ~1000× more potent at muscarinic receptors. Which configuration is more potent?
A. cis-bethanechol
B. trans-bethanechol
C. (S)-bethanechol
D. (R)-bethanechol

C. (S)-bethanechol

A toxicology consult notes that certain natural cholinomimetic alkaloids are well absorbed from most sites because they are tertiary amines. List them:
A. pilocarpine, nicotine, lobeline
B. pilocarpine, nicotine, muscarine
C. pilocarpine, nicotine, bethanechol
D. pilocarpine, methacholine, lobeline

A. pilocarpine, nicotine, lobeline

Several people develop cholinergic toxicity after eating wild mushrooms. Which agent is specifically noted as a quaternary amine that can still enter the brain and be toxic when ingested?
A. Carbachol
B. Methacholine
C. Muscarine
D. Bethanechol

C. Muscarine

A patient ingests a tertiary-amine cholinomimetic. Which intervention would accelerate clearance based on urinary handling?
A. Urine alkalinization
B. Forced diuresis only
C. Activated charcoal only
D. Urine acidification

D. Urine acidification

In a salivary gland acinar cell, a muscarinic agonist produces increased secretion via a classic second-messenger cascade. Which pathway is most consistent with M1/M3/M5 activation?
A. cAMP/PKA rise
B. cGMP/PKG rise
C. IP3/DAG signaling
D. JAK/STAT signaling

C. IP3/DAG signaling

In classic studies of nicotinic receptors, which tool most directly enabled receptor labeling and isolation because it binds very tightly?
A. α-bungarotoxin
B. Atropine
C. Hexamethonium
D. Physostigmine

A. α-bungarotoxin

Why were electric organs especially useful for detailed nicotinic receptor studies?
A. Minimal receptor density
B. Exclusive M3 expression
C. No ionic currents present
D. Extremely high receptor density

D. Extremely high receptor density

A patch-clamp experiment activates neuronal nicotinic receptors. Which immediate measurable change best supports successful activation as described?
A. Nuclear transcription rise
B. Ionic conductance change
C. DNA methylation shift
D. Lysosomal pH change

B. Ionic conductance change

A pharmacologist focuses on neuronal nicotinic receptors. Their subunit composition is best described as containing:
A. Only δ and ε subunits
B. α with γ only
C. α and β only
D. α with δ only

C. α and β only

A drug is desired to produce muscarinic effects with a higher likelihood of systemic absorption from multiple administration sites compared with quaternary choline esters. Which agent best fits that property?
A. Carbachol
B. Bethanechol
C. Methacholine
D. Nicotine

D. Nicotine

A resident wants a cholinomimetic with poor CNS penetration due to hydrophilicity and limited distribution. Which choice best matches?
A. Lobeline
B. Bethanechol
C. Pilocarpine
D. Nicotine

B. Bethanechol

A patient receives a cholinesterase inhibitor and develops marked muscarinic effects. The drug class responsible for the primary pharmacologic effect is best characterized as inhibiting:
A. Acetylcholinesterase
B. Choline acetyltransferase
C. Vesicular ACh transporter
D. Nicotinic receptor opening

A. Acetylcholinesterase

A patient with open-angle glaucoma receives a muscarinic agonist drop. Which ocular action most directly produces the key pupillary change?
A. Iris radial contraction
B. Ciliary muscle relaxation
C. Lens flattening
D. Iris sphincter contraction

D. Iris sphincter contraction

After the same drop, the patient can read fine print better. Which mechanism explains this near-vision effect?
A. Ciliary muscle contraction
B. Zonal fiber tightening
C. Lens flattening
D. Pupillary dilation

A. Ciliary muscle contraction

A healthy volunteer receives a minimally effective IV acetylcholine infusion (20–50 mcg/min). What pattern is most expected?
A. Hypertension with bradycardia
B. Hypertension with tachycardia
C. Hypotension with tachycardia
D. Hypotension with bradycardia

C. Hypotension with tachycardia

With larger IV acetylcholine doses, which heart-rate response becomes prominent from direct cardiac effects?
A. Bradycardia
B. Sinus tachycardia
C. Ventricular tachycardia
D. No rate change

A. Bradycardia

In isolated atrial tissue, a muscarinic agonist directly reduces the slow inward calcium current. Which current is decreased?
A. INa
B. ICa
C. IK1
D. Ito

B. ICa

A pacemaker-cell study shows slower phase 4 depolarization after a muscarinic agonist. Which current is reduced?
A. IKs
B. IKr
C. If
D. ICa

C. If

A patient has only mild net bradycardia after a muscarinic agonist despite strong direct SA slowing. Best explanation?
A. Reflex sympathetic discharge
B. SA receptor downregulation
C. Increased vagal tone
D. Direct β1 stimulation

A. Reflex sympathetic discharge

In an artery-ring lab, endothelium is mechanically removed. Which acetylcholine vascular response is most affected?
A. Increased venous tone
B. Increased arterial stiffness
C. Enhanced smooth muscle growth
D. Endothelium-dependent vasodilation

D. Endothelium-dependent vasodilation

The receptor subtype responsible for acetylcholine-induced vasodilation on intact endothelium is:
A. M1
B. M3
C. M2
D. M5

B. M3

A vasodilatory response to muscarinic stimulation depends on release of endothelium-derived relaxing factor. The mediator is:
A. Endothelin-1
B. Thromboxane A2
C. Nitric oxide
D. Histamine

C. Nitric oxide

A patient with asthma receives a systemic muscarinic agonist. Which airway effect is most likely?
A. Bronchial smooth muscle contraction
B. Bronchial smooth muscle relaxation
C. Reduced mucus secretion
D. Increased ciliary beat frequency

A. Bronchial smooth muscle contraction

After cholinomimetic exposure, a patient develops cramping and diarrhea. Which GI change best explains this?
A. Decreased motility and secretion
B. Decreased motility only
C. Increased secretion only
D. Increased motility and secretion

D. Increased motility and secretion

A muscarinic agonist is given for urinary retention. Which coordinated bladder effect promotes voiding?
A. Detrusor relaxes; sphincter contracts
B. Detrusor contracts; sphincter relaxes
C. Trigone contracts; detrusor relaxes
D. Sphincter contracts; trigone contracts

B. Detrusor contracts; sphincter relaxes

A patient on a muscarinic agonist reports watery eyes, runny nose, and heavy sweating. Which glands are directly stimulated?
A. Sebaceous glands, lacrimal, nasal
B. Apocrine sweat glands, lacrimal, nasal
C. Thermoregulatory sweat, lacrimal, nasal
D. Thyroid and parotid glands, lacrimal, nasal

C. Thermoregulatory sweat, lacrimal, nasal

A cognition study targets the muscarinic subtype richly expressed in brain regions involved in cognition. Which subtype is it?
A. M2
B. M3
C. M4
D. M1

D. M1

Despite fewer nicotinic than muscarinic receptors, nicotine and lobeline strongly affect which CNS regions?
A. Brain stem and cortex
B. Cerebellum and thalamus
C. Basal ganglia and pons
D. Spinal cord and midbrain

A. Brain stem and cortex

In hippocampal circuits, acetylcholine regulates norepinephrine release via which nicotinic receptor subtype?
A. α4β2
B. α7
C. α3β4
D. α1β1γδ

C. α3β4

A presynaptic mechanism in hippocampus and cortex limits further cholinergic signaling. What effect is described?
A. Increased acetylcholine release
B. Inhibited acetylcholine release
C. Increased norepinephrine reuptake
D. Decreased dopamine synthesis

B. Inhibited acetylcholine release

The most abundant nicotinic receptor oligomer in the brain is:
A. α3β4
B. α3
C. α7
D. α4β2

D. α4β2

Chronic nicotine exposure produces which sequence at nicotinic receptors?
A. Depolarization then desensitization
B. Desensitization then depolarization
C. Blockade then sensitization
D. Internalization then activation

A. Depolarization then desensitization

A patient ingests high-concentration nicotine and develops tremor and emesis. What additional central effect best fits?
A. Respiratory center suppression
B. Phrenic nerve blockade
C. Respiratory center stimulation
D. Central chemoreceptor inhibition

C. Respiratory center stimulation

A drug-development team targets a nicotinic subtype linked to cognition and pain perception. Which subtype matches?
A. α3
B. α7
C. α4β2
D. α3β4

B. α7

Proposed anti-inflammatory actions of α7 nicotinic receptors are based on their presence on:
A. Hepatocytes
B. Skeletal myocytes
C. Erythrocytes
D. Immune nonneuronal cells

D. Immune nonneuronal cells

Fast excitatory transmission in autonomic ganglia is primarily mediated by which nicotinic subtype?
A. α3
B. α4β2
C. α7
D. α3β4

A. α3

In autonomic ganglia and adrenal medulla, heteromeric neuronal nAChRs commonly include α3 plus:
A. β1 and β3 subunits
B. β2 only
C. β2 and β4 subunits
D. δ and ε subunits

C. β2 and β4 subunits

Compared with skeletal muscle nAChRs, nicotine has somewhat greater affinity for:
A. Neuronal nicotinic receptors
B. Muscarinic M3 receptors
C. Skeletal nicotinic receptors
D. GABA-A receptors

A. Neuronal nicotinic receptors

Which best fits deficiency? Microcystis, microcolon, and intestinal hypoperistalsis syndrome, urinary incontinence, urinary bladder distention, and mydriasis.
A. a3
B. b2
C. b4
D. m3

D. m3

A depolarizing nicotinic agonist that is not rapidly hydrolyzed causes weakness after initial activation. The transmission block most directly reflects:
A. Depolarization blockade
B. Competitive antagonism
C. Vesicular ACh depletion
D. Presynaptic Ca2+ blockade

A. Depolarization blockade

Nicotinic agonist applied to an end plate by iontophoresis causes immediate depolarization. The primary ionic basis is increased permeability to:
A. Ca2+ and Cl−
B. Na+ and K+
C. K+ and Cl−
D. Na+ and Ca2+

B. Na+ and K+

A very brief-acting cholinesterase inhibitor is used diagnostically because it is a simple alcohol with a quaternary ammonium. Which drug fits?
A. Neostigmine
B. Physostigmine
C. Echothiophate
D. Edrophonium

D. Edrophonium

Which agent is a carbamic acid ester cholinesterase inhibitor (carbamate) used clinically?
A. Neostigmine
B. Echothiophate
C. Edrophonium
D. Sarin

A. Neostigmine

Which drug is an organophosphate cholinesterase inhibitor used clinically?
A. Physostigmine
B. Neostigmine
C. Echothiophate
D. Edrophonium

C. Echothiophate

An insecticide is engineered for very high lipid solubility to speed absorption into insects and rapid CNS distribution. Which is typical?
A. Echothiophate
B. Carbaryl
C. Edrophonium
D. Physostigmine

B. Carbaryl

A clinician prefers an organophosphate with very long duration but improved stability in aqueous solution. Which agent best matches?
A. Sarin
B. Echothiophate
C. Carbaryl
D. Neostigmine

B. Echothiophate

A military exposure causes profound cholinergic crisis; the agent is an extremely potent “nerve gas.” Which is most consistent?
A. Sarin
B. Edrophonium
C. Physostigmine
D. Neostigmine

A. Sarin

A quaternary ammonium carbamate (such as Neostigmine) requires an oral dose that is significantly higher than its parenteral dose to achieve the same therapeutic effect. What is the primary pharmacokinetic reason for this difference?

A. High rates of first-pass metabolism in the liver.

B. Extensive binding to plasma albumin, reducing free drug levels

C. A permanent positive charge that limits lipid membrane permeability.

D. Rapid active secretion by the renal proximal tubules.

C. A permanent positive charge that limits lipid membrane permeability.

An AChE inhibitor is well absorbed from all sites and can be used topically in the eye. Which drug fits?
A. Neostigmine
B. Edrophonium
C. Echothiophate
D. Physostigmine

D. Physostigmine

Most organophosphate cholinesterase inhibitors are dangerous to humans because they are:
A. Poorly absorbed from skin
B. Well absorbed from mucosa
C. Selective for plasma enzymes
D. Rapidly hydrolyzed in blood

B. Well absorbed from mucosa

Which organophosphate is noted as highly polar and more stable than most others?
A. Echothiophate
B. Sarin
C. Malathion
D. Carbaryl

A. Echothiophate

You want an AChE inhibitor lasting about 5–15 minutes. Which duration matches best?
A. Physostigmine
B. Pyridostigmine
C. Edrophonium
D. Echothiophate

C. Edrophonium

A postoperative patient needs an AChE inhibitor with 0.5–4 hour action. Which agent best matches?
A. Pyridostigmine
B. Neostigmine
C. Echothiophate
D. Edrophonium

B. Neostigmine

A patient needs sustained symptomatic coverage with an AChE inhibitor lasting 4–6 hours. Which duration fits?
A. Neostigmine
B. Physostigmine
C. Echothiophate
D. Pyridostigmine

D. Pyridostigmine

A clinician selects an AChE inhibitor with 0.5–2 hour duration and good absorption from all sites. Which best fits?
A. Physostigmine
B. Edrophonium
C. Neostigmine
D. Pyridostigmine

A. Physostigmine

A glaucoma regimen uses an AChE inhibitor with ~100-hour duration. Which drug matches?
A. Neostigmine
B. Echothiophate
C. Physostigmine
D. Edrophonium

B. Echothiophate

Beyond acetylcholinesterase, these inhibitors also inhibit which enzyme?
A. Monoamine oxidase
B. Butyrylcholinesterase
C. Dopamine β-hydroxylase
D. Catechol-O-methyltransferase

B. Butyrylcholinesterase

A child with α3-subunit deficiency is evaluated. Which combination best matches the syndrome?
A. Microcolon and hyperperistalsis
B. Microcystis and microcolon
C. Megacystis and megacolon
D. Microcystis and tachycardia

B. Microcystis and microcolon

A pathologist samples adrenal medulla ganglion-like tissue. Which nAChR subunit pattern is most expected there?
A. α1β1γδ only
B. α7 only
C. α3 with β2/β4
D. α4β2 only

C. α3 with β2/β4

A new AChE inhibitor forms a covalent carbamoylated enzyme that is slowly hydrolyzed, prolonging recovery for 30 minutes to 6 hours. This mechanism best fits:
A. Quaternary alcohol inhibitors
B. Direct muscarinic agonists
C. Organophosphate nerve agents
D. Carbamate ester inhibitors

D. Carbamate ester inhibitors

Which pair are classic examples of carbamate ester AChE inhibitors?
A. Edrophonium and atropine
B. Neostigmine and physostigmine
C. Echothiophate and sarin
D. Pilocarpine and cevimeline

B. Neostigmine and physostigmine

The most prominent pharmacologic effects of cholinesterase inhibitors are most evident in:
A. CV, GI, eye, NMJ
B. Liver, kidney, spleen, bone
C. Thyroid, pancreas, testes, skin
D. Lung, pleura, marrow, lymph

A. CV, GI, eye, NMJ

A lipid-soluble AChE inhibitor at low concentration produces diffuse EEG activation and subjective alertness. This effect most directly reflects:
A. Neuromuscular transmission failure
B. Primary vascular smooth muscle action
C. Peripheral muscarinic blockade
D. Central cholinergic stimulation

D. Central cholinergic stimulation

At high concentrations, lipid-soluble AChE inhibitors can cause generalized convulsions followed by coma and:
A. Severe hyperthermia
B. Respiratory arrest
C. Acute hepatic necrosis
D. Ventricular fibrillation

B. Respiratory arrest

A patient exposed to an AChE inhibitor shows increased autonomic outflow. These drugs can increase activity in:
A. Only parasympathetic ganglia
B. Only sympathetic ganglia
C. Both sympathetic and parasympathetic
D. Only postganglionic terminals

C. Both sympathetic and parasympathetic

Edrophonium, neostigmine, and physostigmine most closely mimic which physiologic input on the heart?
A. Renin-angiotensin activation
B. Carotid body stimulation
C. Cardiac β1 stimulation
D. Vagal nerve activation

D. Vagal nerve activation

Cholinesterase inhibitors have minimal effects by direct action on vascular smooth muscle because:
A. Most beds lack cholinergic innervation
B. Vascular AChE is absent
C. Vascular muscle lacks muscarinic receptors
D. Blood vessels lack smooth muscle

A. Most beds lack cholinergic innervation

Moderate doses of AChE inhibitors can raise blood pressure primarily by increasing systemic:
A. Venous capacitance
B. Stroke volume
C. Vascular resistance
D. Plasma volume

C. Vascular resistance

In quaternary nitrogen AChE inhibitors, the pressor response is initiated mainly at:
A. Carotid baroreceptors
B. Sympathetic ganglia
C. Ventricular myocardium
D. Renal juxtaglomerular cells

B. Sympathetic ganglia

In lipid-soluble AChE inhibitors, the pressor response can also be initiated at:
A. Central sympathetic centers
B. Ventral horn motor neurons
C. Endothelial M3 receptors
D. AV nodal pacemakers

A. Central sympathetic centers

A patient given an AChE inhibitor develops increased BP and plasma norepinephrine; atropine prevents both. This best implies atropine acts:
A. At NMJ
B. At endothelium
C. At parasympathetic ganglia
D. In central and peripheral sites

D. In central and peripheral sites

A patient has weakness after a curare-like blocker. An AChE inhibitor improves strength mainly by increasing:
A. Contraction strength at NMJ
B. Myosin ATPase activity
C. Calcium release from SR
D. Sodium channel inactivation

A. Contraction strength at NMJ

A key clinical use category of cholinomimetics is treatment of:
A. Essential hypertension
B. Hyperthyroidism
C. Bacterial meningitis
D. Alzheimer’s disease

D. Alzheimer’s disease

Muscarinic stimulants and AChE inhibitors reduce intraocular pressure chiefly by:
A. Iris radial contraction
B. Decreased episcleral venous pressure
C. Ciliary body contraction
D. Increased aqueous production

C. Ciliary body contraction

In depressed smooth muscle activity without obstruction, cholinomimetics may be helpful. Before use, the clinician must exclude:
A. Hypovolemia
B. Mechanical obstruction
C. Fever
D. Hypercalcemia

B. Mechanical obstruction

Among choline ester cholinomimetics, the most widely used for GI/GU disorders is:
A. Acetylcholine
B. Bethanechol
C. Carbachol
D. Methacholine

B. Bethanechol

A patient with chronic xerostomia is treated with a long-used agent to increase salivary secretion. Which fits?
A. Pilocarpine
B. Echothiophate
C. Pyridostigmine
D. Atropine

A. Pilocarpine

A patient with Sjögren syndrome and dry mouth is started on a newer direct-acting muscarinic agonist. Which drug is intended?
A. Physostigmine
B. Cevimeline
C. Neostigmine
D. Edrophonium

B. Cevimeline

In myasthenia gravis, antibodies target the main immunogenic region on which nicotinic receptor subunit?

α1

One MG mechanism reduces receptor number, accelerating internalization and degradation. This is best described as:
A. Complement inhibition
B. Presynaptic blockade
C. Receptor cross-linking
D. Vesicular depletion

C. Receptor cross-linking

Another MG mechanism reduces transmission when antibodies bind the receptor and:
A. Inhibit receptor function
B. Increase ACh release
C. Enhance channel opening
D. Activate G proteins

A. Inhibit receptor function

A patient with generalized MG remains weak despite optimized pyridostigmine. Which adjunct is most appropriate for more widespread weakness?
A. Immunosuppressant therapy
B. Chronic β-agonist therapy
C. High-dose atropine daily
D. Long-term organophosphate

A. Immunosuppressant therapy

Following edrophonium in true MG, improvement in strength typically lasts about:
A. 30 seconds
B. 30 minutes
C. 2 hours
D. 5 minutes

D. 5 minutes

Long-term symptomatic therapy for MG is most commonly maintained with:
A. Tacrine
B. Donepezil
C. Pyridostigmine
D. Echothiophate

C. Pyridostigmine

If pyridostigmine cannot be used for MG maintenance, the classic alternative is:
A. Neostigmine
B. Physostigmine
C. Edrophonium
D. Galantamine

A. Neostigmine

Because AChE inhibitors are short-acting, pyridostigmine often requires dosing about every:
A. 2 hours
B. 4 hours
C. 6 hours
D. 12 hours

C. 6 hours

Neostigmine often requires dosing about every:
A. 4 hours
B. 6 hours
C. 8 hours
D. 24 hours

A. 4 hours

After surgery, rapid reversal of nondepolarizing neuromuscular blockade is commonly accomplished with:
A. Neostigmine or edrophonium
B. Tacrine or donepezil
C. Pilocarpine or cevimeline
D. Atropine or scopolamine

A. Neostigmine or edrophonium

Which toxidrome is potentially lethal in children and can cause prolonged behavioral disturbance and arrhythmias in adults?
A. Nicotine intoxication
B. Atropine intoxication
C. Cholinergic crisis
D. Opioid intoxication

B. Atropine intoxication

A suicidal ingestion causes severe muscarinic blockade and QRS widening risk. Which drug class is classically implicated?
A. SSRIs
B. Tricyclic antidepressants
C. MAO inhibitors
D. Antipsychotics

B. Tricyclic antidepressants

The first drug used for mild-to-moderate Alzheimer’s disease with anticholinesterase and other cholinomimetic actions was:
A. Tacrine
B. Rivastigmine
C. Galantamine
D. Donepezil

A. Tacrine

Which set are newer, more selective AChE inhibitors with similar marginal benefit but less toxicity than tacrine?
A. Donepezil, galantamine, rivastigmine
B. Neostigmine, edrophonium, physostigmine
C. Pilocarpine, cevimeline, bethanechol
D. Atropine, scopolamine, ipratropium

A. Donepezil, galantamine, rivastigmine

Overdose of pilocarpine or choline esters most predictably causes:
A. Muscarinic excess signs
B. Pure nicotinic blockade
C. Isolated CNS depression
D. α-adrenergic activation

A. Muscarinic excess signs

Which symptom set best matches muscarinic excess from cholinomimetic overdose?
A. Urinary urgency and sweating
B. Mydriasis and dry skin
C. Constipation and tachycardia
D. Hyperthermia and delirium

A. Urinary urgency and sweating

The most dangerous toxic effect of large nicotine doses includes central stimulation causing:
A. Hyporeflexia
B. Convulsions
C. Catatonia
D. Miosis

B. Convulsions

Another dangerous nicotine toxicity mechanism is end-plate:
A. Hyperpolarization
B. Depolarization
C. Demyelination
D. Calcium depletion

B. Depolarization

Severe nicotine toxicity can also produce hypertension with cardiac:
A. Asystole only
B. Arrhythmias
C. Tamponade
D. Pericarditis

B. Arrhythmias

The primary neurotransmitter of the parasympathetic nervous system is:
A. Dopamine
B. Norepinephrine
C. Acetylcholine
D. Serotonin

C. Acetylcholine

Muscarinic receptors are GPCRs with how many transmembrane domains?

7

The muscarinic receptor domain classically coupled to G proteins is the:
A. 1st extracellular loop
B. 2nd extracellular loop
C. 2nd cytoplasmic loop
D. 3rd cytoplasmic loop

D. 3rd cytoplasmic loop

Nicotinic receptors are primarily found in which set of locations?
A. Autonomic ganglia, skeletal NMJ, adrenal
B. Thyroid, liver, kidney
C. Retina, cochlea, lens
D. Spleen, pancreas, marrow

A. Autonomic ganglia, skeletal NMJ, adrenal

M1 receptor—best matching location, G protein, and pathway:
A. Heart; Gi; ↓cAMP
B. CNS/nerves; Gq; IP3/DAG
C. Smooth muscle; Gi; ↓cAMP
D. Glands; Gs; ↑cAMP

B. CNS/nerves; Gq; IP3/DAG

M2 receptor—best matching location, G protein, and pathway:
A. Heart nodes; Gi; ↓cAMP
B. CNS; Gq; IP3/DAG
C. Smooth muscle; Gq; IP3/DAG
D. Glands; Gi; ↓cAMP

A. Heart nodes; Gi; ↓cAMP

M3 receptor—best matching location, G protein, and pathway:
A. Heart; Gi; ↓cAMP
B. CNS; Gi; ↓cAMP
C. Smooth muscle/glands; Gq; IP3/DAG
D. Skeletal NMJ; ion channel

C. Smooth muscle/glands; Gq; IP3/DAG

M4 and M5 are CNS receptors. Which pairing is correct?
A. M4: Gq/IP3; M5: Gi/↓cAMP
B. M4: Gi/↓cAMP; M5: Gq/IP3
C. M4: Gs/↑cAMP; M5: Gi/↓cAMP
D. M4: ion channel; M5: Gq/IP3

B. M4: Gi/↓cAMP; M5: Gq/IP3

In a healthy artery with intact endothelium, acetylcholine activates M3 receptors. Net vascular effect is:
A. Vasoconstriction via Ca2+ influx
B. No change in vascular tone
C. Vasodilation via NO release
D. Vasoconstriction via endothelin

C. Vasodilation via NO release

The key smooth-muscle second messenger that mediates NO-driven relaxation is:
A. cGMP
B. IP3
C. cAMP
D. DAG

A. cGMP

In an endothelium-denuded vessel ring, acetylcholine most likely causes:
A. Vasodilation via prostacyclin
B. Vasodilation via NO
C. No response without endothelium
D. Vasoconstriction via IP3-Ca2+

D. Vasoconstriction via IP3-Ca2+

A direct-acting cholinomimetic produces effects primarily by:
A. Blocking vesicular ACh uptake
B. Activating M or N receptors
C. Inhibiting COMT
D. Stimulating NE release

B. Activating M or N receptors

Butyrylcholinesterase inhibition matters clinically because it can act as a:
A. Cardiac pacemaker stabilizer
B. Muscarinic receptor chaperone
C. Nicotinic channel pore blocker
D. Biological scavenger enzyme

D. Biological scavenger enzyme

Which list contains only choline ester direct agonists?
A. Nicotine, muscarine, lobeline, pilocarpine
B. ACh, methacholine, carbachol, bethanechol
C. Neostigmine, pyridostigmine, edrophonium, physostigmine
D. Atropine, scopolamine, ipratropium, tiotropium

B. ACh, methacholine, carbachol, bethanechol

Choline ester lipid insolubility is mainly due to:
A. Multiple aromatic rings
B. High molecular weight
C. Sulfhydryl side chains
D. Quaternary ammonium charge

D. Quaternary ammonium charge

Which list contains only alkaloid direct agonists?
A. ACh, methacholine, carbachol, bethanechol
B. Neostigmine, physostigmine, echothiophate, edrophonium
C. Muscarine, pilocarpine, nicotine, lobeline
D. Atropine, scopolamine, tiotropium, ipratropium

C. Muscarine, pilocarpine, nicotine, lobeline

Which agent reliably activates both muscarinic and nicotinic receptors?
A. Carbachol
B. Bethanechol
C. Pilocarpine
D. Muscarine

A. Carbachol

Neonicotinoid insecticides act primarily at:
A. Muscarinic receptors
B. GABA-A receptors
C. Nicotinic receptors
D. Dopamine receptors

C. Nicotinic receptors

In the PLC pathway, DAG primarily:
A. Releases Ca2+ from SR
B. Inhibits adenylate cyclase
C. Activates guanylyl cyclase
D. Activates protein kinase C

D. Activates protein kinase C

In the PLC pathway, IP3 primarily:
A. Opens Na+ channels
B. Releases Ca2+ from stores
C. Inhibits phosphodiesterase
D. Activates PKC directly

B. Releases Ca2+ from stores

M2 and M4 receptor signaling most directly:
A. Activates PLC
B. Activates tyrosine kinase
C. Inhibits adenylate cyclase
D. Opens NMJ Na+ channels

C. Inhibits adenylate cyclase

In cardiac tissue, muscarinic stimulation most characteristically:
A. Increases K+ flux
B. Decreases K+ flux
C. Increases Na+ flux
D. Decreases Cl− flux

A. Increases K+ flux

In autonomic ganglia and many smooth muscles, muscarinic stimulation tends to:
A. Increase K+ efflux
B. Increase K+ influx
C. Increase Ca2+ influx
D. Decrease K+ flux

D. Decrease K+ flux

With nicotinic receptors, binding both agonist sites:
A. Closes the channel rapidly
B. Prevents ion selectivity
C. Lowers opening probability
D. Greatly increases opening probability

D. Greatly increases opening probability

Binding only one nicotinic site typically:
A. Abolishes channel opening
B. Forces full channel opening
C. Increases opening probability
D. Converts receptor to GPCR

C. Increases opening probability

A glaucoma drop causes miosis and accommodation. These changes:
A. Reduce Schlemm canal flow
B. Increase aqueous outflow
C. Increase aqueous production
D. Block trabecular drainage

B. Increase aqueous outflow

The aqueous humor drainage structure most directly facilitated is the:
A. Canal of Schlemm
B. Ciliary processes
C. Vitreous chamber
D. Choroid plexus

A. Canal of Schlemm

A muscarinic agonist slows the SA node primarily by:
A. Increasing conduction velocity
B. Decreasing firing rate
C. Increasing contractile force
D. Shortening refractoriness

B. Decreasing firing rate

At the AV node, muscarinic activation most characteristically:
A. Increases conduction velocity
B. Shortens refractory period
C. Slows conduction; ↑ refractory
D. Triggers ventricular ectopy

C. Slows conduction; ↑ refractory

In the atria, muscarinic stimulation most characteristically:
A. Decreases strength; ↓ refractory
B. Increases force; ↓ refractory
C. Decreases force; ↑ refractory
D. Increases force; ↑ refractory

A. Decreases strength; ↓ refractory

In the ventricles, muscarinic stimulation produces a:
A. Large force increase
B. Small strength decrease
C. Large force decrease
D. No change in force

B. Small strength decrease

Muscarinic slowing of diastolic depolarization includes reducing:
A. Hyperpolarization-activated current
B. Rapid Na current
C. Transient outward K current
D. L-type Ca current

A. Hyperpolarization-activated current

Without intact endothelium, ACh can constrict vessels because M3 on VSM triggers:
A. cGMP fall with relaxation
B. IP3-mediated Ca2+ rise
C. cAMP rise with relaxation
D. β2-mediated hyperpolarization

B. IP3-mediated Ca2+ rise

A systemic muscarinic agonist most predictably causes:
A. Bronchoconstriction
B. Bronchodilation
C. Reduced airway mucus
D. Increased dead-space ventilation

A. Bronchoconstriction

Typical GI effects of muscarinic stimulation include:
A. ↓ peristalsis; ↑ sphincters
B. ↑ peristalsis; ↑ sphincters
C. ↑ peristalsis; ↓ sphincters
D. ↓ secretion; ↑ sphincters

C. ↑ peristalsis; ↓ sphincters

Choline esters are well/poorly absorbed and distributed in the CNS

poorly

Relative abundance is best summarized as:
A. Brain muscarinic; spinal nicotinic
B. Brain nicotinic; spinal muscarinic
C. Brain muscarinic; spinal muscarinic
D. Brain nicotinic; spinal nicotinic

A. Brain muscarinic; spinal nicotinic

M1 knockout is associated with:
A. Increased appetite and obesity
B. Severe neuromuscular paralysis
C. Impaired forebrain plasticity
D. Loss of spinal pain reflexes

C. Impaired forebrain plasticity

M2 knockout is associated with:

A. Increased appetite and obesity
B. Severe neuromuscular paralysis
C. Impaired forebrain plasticity
D. Tremor and lack of pain

D. Tremor and lack of pain

Hypothalamic M3 receptor knockout is associated with:
A. Increased body fat mass
B. Increased appetite signals
C. Hyperphagia with obesity
D. Reduced appetite and fat

D. Reduced appetite and fat

Regarding autonomic ganglia, nicotine’s action on sympathetic vs parasympathetic is:
A. Same direction in both
B. Opposite direction in both
C. Only parasympathetic affected
D. Only sympathetic affected

A. Same direction in both

Nicotine’s cardiovascular effects are best described as:
A. Parasympathomimetic
B. Sympathomimetic
C. Purely muscarinic
D. Purely ganglionic block

B. Sympathomimetic

Nicotine’s GI and urinary effects are best described as:
A. Sympathomimetic
B. Antimuscarinic
C. Parasympathomimetic
D. Purely nicotinic blockade

C. Parasympathomimetic

Which agent is muscarinic-selective and a choline ester?
A. Carbachol
B. Nicotine
C. Lobeline
D. Bethanechol

D. Bethanechol

A pharmacology exam asks for two carbamate indirect-acting cholinomimetics. Which pair is correct?
A. Edrophonium, pyridostigmine
B. Neostigmine, physostigmine
C. Echothiophate, sarin
D. Pilocarpine, bethanechol

B. Neostigmine, physostigmine

A farmer presents after insecticide exposure; you suspect an organophosphate. Which set contains only organophosphate examples from your notes?
A. Echothiophate, sarin, malathion
B. Neostigmine, sarin, bethanechol
C. Edrophonium, physostigmine, sarin
D. Pilocarpine, parathion, neostigmine

A. Echothiophate, sarin, malathion

Parathion and malathion are best characterized as:
A. Active phosphates in humans
B. Quaternary carbamate salts
C. Thiophosphate prodrugs
D. Direct muscarinic agonists

C. Thiophosphate prodrugs

You need a very short-acting alcohol AChE inhibitor for bedside testing. Best choice?
A. Edrophonium
B. Neostigmine
C. Physostigmine
D. Echothiophate

A. Edrophonium

Which class is generally better absorbed and therefore more dangerous to humans (and effective insecticides)?
A. Quaternary alcohols
B. Carbamates
C. Choline esters
D. Organophosphates

D. Organophosphates

Which group typically has poor absorption because of permanent charge, requiring larger oral doses?
A. Lipid-soluble organophosphates
B. Quaternary carbamates
C. Thiophosphate nerve gases
D. Tertiary AChE inhibitors

B. Quaternary carbamates

The functional result of carbamate/organophosphate AChE inhibition is best summarized as:
A. Increased choline uptake
B. Increased ACh synthesis
C. Direct receptor antagonism
D. Blocked ACh hydrolysis

D. Blocked ACh hydrolysis

Rank duration (longest → shortest): edrophonium, carbamates, organophosphates.
A. Carbamates > edrophonium > organophosphates
B. Organophosphates > carbamates > edrophonium
C. Edrophonium > organophosphates > carbamates
D. Organophosphates > edrophonium > carbamates

B. Organophosphates > carbamates > edrophonium

A student asks what is most prescribed now for chronic glaucoma (instead of cholinomimetics). Best answer?
A. Pilocarpine plus neostigmine
B. Atropine plus timolol
C. PG analogs and topical β-blockers
D. Methacholine and acetazolamide

C. PG analogs and topical β-blockers

Acute angle-closure glaucoma is a medical emergency. Initial medical therapy commonly includes:
A. Pilocarpine
B. Donepezil
C. Atropine
D. Varenicline

A. Pilocarpine

A 5-year-old with hyperopia develops strabismus triggered by focusing effort. This fits:
A. Convergence spasm
B. Accommodative esotropia
C. CN VI palsy
D. Internuclear ophthalmoplegia

B. Accommodative esotropia

Bethanechol’s clinical profile is best described as:
A. Increases GI/GU motility, secretions
B. Selective nicotinic ganglionic blocker
C. CNS-only acetylcholinesterase inhibitor
D. Long-acting organophosphate insecticide

A. Increases GI/GU motility, secretions

Another MG mechanism reduces transmission via:
A. Terminal sprouting failure
B. Reduced ACh synthesis
C. Postsynaptic membrane lysis
D. Increased ACh breakdown

C. Postsynaptic membrane lysis

MG antibodies can also bind the receptor and:
A. Increase channel open time
B. Inhibit receptor function
C. Enhance ACh release
D. Activate G proteins

B. Inhibit receptor function

A patient has ptosis and fatigable proximal weakness. Which bedside diagnostic drug is used IV?
A. Pyridostigmine
B. Bethanechol
C. Donepezil
D. Edrophonium

D. Edrophonium

MG patients are notably sensitive to which agents during anesthesia?
A. Curariform blockers
B. β-agonists
C. Nitrates
D. Acetazolamide

A. Curariform blockers

A nondepolarizing neuromuscular relaxant listed as an anesthesia adjunct is:
A. Pancuronium
B. Succinylcholine
C. Lidocaine
D. Diazepam

A. Pancuronium

Immediate reversal of pharmacologic nondepolarizing paralysis post-op commonly uses:
A. Donepezil and rivastigmine
B. Pilocarpine and bethanechol
C. Neostigmine and edrophonium
D. Malathion and parathion

C. Neostigmine and edrophonium

Which finding is least consistent with classic AChE inhibitor toxicity (DUMBBELS)?
A. Bronchospasm
B. Lacrimation
C. Bradycardia
D. Mydriasis

D. Mydriasis

Flaccid paralysis in severe AChE inhibitor poisoning is most directly due to:
A. NMJ AChR overactivation
B. Direct myosin inhibition
C. Na+ channel blockade
D. NMJ receptor destruction

A. NMJ AChR overactivation

A patient eats Inocybe mushrooms and develops salivation, diarrhea, bronchospasm. Best antidote?
A. Pralidoxime
B. Physostigmine
C. Atropine
D. Neostigmine

C. Atropine

Nicotine replacement with varenicline works because it is a partial agonist at:
A. α7 nAChR
B. α4β2 nAChR
C. M2 receptor
D. GABA-A receptor

B. α4β2 nAChR

Varenicline reduces nicotine reinforcement mainly by reducing presynaptic:
A. GABA release
B. Serotonin release
C. NE reuptake
D. Dopamine release

D. Dopamine release

The major cause of acute cholinergic toxicity worldwide is exposure to:
A. Organophosphate insecticides
B. Tricyclic antidepressants
C. Belladonna alkaloids
D. Antihistamines

A. Organophosphate insecticides

If given quickly, nucleophiles like _______ can be used as cholinesterase regenerators for organophosphate poisoning?
A. Donepezil
B. Atropine
C. Pralidoxime
D. Pilocarpine

C. Pralidoxime

In organophosphate poisoning, which drug reverses central and peripheral muscarinic toxicity but not flaccid paralysis?
A. Pralidoxime
B. Atropine
C. Pyridostigmine
D. Rivastigmine

B. Atropine

Chronic cholinesterase inhibitor exposure can cause delayed neuropathy via NTE inhibition. Prototype agent?
A. Malathion
B. Echothiophate
C. Sarin
D. Triorthocresyl phosphate

D. Triorthocresyl phosphate

Which cholinomimetic is used for asthma challenge testing due to bronchoconstriction?
A. Bethanechol
B. Methacholine
C. Pilocarpine
D. Varenicline

B. Methacholine

Varenicline use may be limited by which adverse-effect cluster?
A. Nephrolithiasis, rash, anemia
B. Hypotension, bradycardia, syncope
C. Hepatitis, pancreatitis, arrhythmia
D. Nausea, insomnia, psychiatric worsening

D. Nausea, insomnia, psychiatric worsening

Typical severe organophosphate poisoning progression is best described as:
A. Nicotinic → CNS → muscarinic
B. Muscarinic → CNS → nicotinic
C. CNS → muscarinic → nicotinic
D. CNS → nicotinic → muscarinic

B. Muscarinic → CNS → nicotinic

Pralidoxime’s limitation in organophosphate poisoning is that it:
A. Cannot enter CNS
B. Worsens bronchospasm
C. Blocks nicotinic receptors
D. Causes irreversible AChE inhibition

A. Cannot enter CNS

Parathion and malathion insecticides are “inactive” because they require conversion to:
A. Carbamate derivatives
B. Quaternary alcohols
C. Phosphate derivatives
D. Muscarinic antagonists

C. Phosphate derivatives

Muscarinic agonists for use in the eye must be tailored to which muscarinic receptor?

M3

No improvement in a patient's condition after administration of edrophonium is indicative that the patient is undergoing (myasthenic/cholinergic) crisis

cholinergic

A marked improvement in one's condition after the administration of edrophonium is indicative of the patient undergoing (myasthenic/cholinergic) crisis

myasthenic

True or False: Amifampridine is indicated for MG?

False. Lambert-Eaton myasthenic syndrome