A 35-year-old farmer was brought to the emergency room complaining of severe
abdominal cramps, vomiting and excess salivation. His skin was flushed, warm, and moist
to the touch. He stated that he was working in his field with an organophosphate pesticide.
Which of the following mechanisms best explains the cause of the flushed skin in this
E. NO-induced increase in cGMP
The signs and symptoms of the patients are consistent with the diagnosis of organophosphate
poisoning and are all due to an excessive amount of acetylcholine at the synaptic cleft of
cholinergic terminals. The arteriolar vasodilation that causes the flushed skin is mainly due to the
acetylcholine induced activation of non innervated M3 receptors which in turn trigger the release of
NO. NO acts by increasing the synthesis of cGMP which is a powerful smooth muscle relaxant.
A) By activating Nn receptors on autonomic ganglia acetylcholine can increase the firing of
efferent vagal fibers, but this cannot explain the flushed skin (in fact this activation increases the
firing of sympathetic fibers too).
B) (see explanation above)
C) Activation of presynaptic M2 receptors actually causes a decrease of acetylcholine release from
D) Acetylcholine can inhibit the release of norepinephrine from adrenergic terminals (by activating
M2 receptors) but this is not the main action that causes the flushed skin.
A 58-year-old man resident in a nursing facility was recently diagnosed with urinary
incontinence and a treatment with bethanechol was prescribed. Which of the following
actions most likely mediated the therapeutic effectiveness of the drug in this patient?
C. Decreased compliance of the bladder
Bethanechol is a cholinergic agonist which activates mainly M3 receptors. This activation causes a
contraction of the detrusor muscle of the bladder and therefore the amount of bladder space that
can be filled (i.e. the distensibility of the bladder, that is its compliance) is decreased
A, B, F) Actually activation of M3 receptors causes effects opposite to those described
D) Diuresis refers to the production of urine by the kidney. Bethanechol does not affect diuresis.
E) The prostate capsule has mainly alpha-1 receptors. Anyhow an increased tone of prostate
capsule would hinder the voiding of the bladder.
A 52-year-old farmer, brought unconscious to the emergency department, was salivating
profusely and was incontinent with regard to both urine and feces. His skin was warm and
moist, pupils were pinpoint in size, respiration was shallow and the extremities showed
subcutaneous muscle fasciculations. Blood pressure was 110/65 mm Hg, pulse 56 bpm. The
patient died shortly after admission. Which of the following disorders most likely caused
the death of this patient?
D. Respiratory failure
The signs of the patient suggest that he was poisoned by an anticholinesterase drug, likely an
organophosphate insecticide. Death from organophosphate poisoning is most frequently the
consequence of respiratory failure, often accompanied by a secondary cardiovascular component.
The respiratory failure is mainly due to the following actions:
a) Bronchoconstriction, laryngospasm, increased bronchial secretions
b) Paralysis of respiratory center.
c) Central respiratory paralysis
A, B) The death from these disorders usually occurs after a long history of disease.
C, E) Actually anticholinesterase poisoning causes .hypotension and fecal incontinence so
hypertensive crisis and adynamic ileus are quite unlikely.
A 42-year-old man was brought to the emergency department because of severe
vomiting and diarrhea which initiated about one hour after meal. The patient showed
profuse salivation, lacrimation and wheezing. His skin was warm and moist, and pupils were
miotic. Skeletal muscle movements were normal. Blood pressure was 80/50 mm Hg, pulse
46/min. Poisoning of this patient was most likely due to which of the following agents?
A. Muscarine-containing mushrooms
The signs and symptoms of the patients are consistent with the diagnosis of muscarine poisoning.
High concentrations of muscarine are present in various species of Inocybe and Clitocybe
mushrooms and poisoning is not exceptional because of the habit to consume wild mushrooms.
The symptoms of muscarine intoxication start within one hour after the ingestion and are all
attributable to activation of muscarinic receptors.
B) Nicotine poisoning results from the activation, and later the blockade, of Nn and Nm receptors.
Activation of Nn receptors in ganglia and adrenal medulla causes increase in sympathetic firing
and increased release of norepinephrine. Early signs include cold sweat, rapid and irregular pulse
and hypertension, followed by hypotension and collapse. Moreover the activation of Nm receptors
at the motor end plate would cause muscle paralysis due to depolarization blockade.
C) Poisoning by organophosphates causes all symptoms due to activation of muscarinic receptors,
but in addition there are also symptoms due to activation of nicotinic receptors (ie. skeletal muscle
paralysis due to depolarization blockade).
D) Some mushroom species contain atropine. The symptoms of atropine poisoning are due to
blockade of muscarinic receptors, so are the opposite of those exhibited by the patient.
E) Carbamate insecticides are reversible cholinesterase inhibitors. Symptoms of poisoning by
these agents are the same as the symptoms of poisoning by organophosphates.
A 62-year-old man suffering from open-angle glaucoma has been receiving an
ophthalmic medication (one drop four times a day) for one month. The disease is well
controlled but now the man complains of brow ache and difficulty in far vision and in poor
light. Which of the following drugs was most likely administered?
Pilocarpine is a cholinergic agonist that activates only M1, M2 and M3 receptors (activation of
nicotinic receptors is negligible). Activation of M3 receptors in the ciliary muscle causes
cyclospasm which in turn increases the lens curvature. The eye is accommodated for near vision
and far vision becomes difficult. Activation of M3 receptors in the sphincter muscle of iris causes
miosis which impairs the vision in poor light.
B, C) These drugs decrease the production of aqueous humor but have negligible effect on
D, E) These drugs activate alpha-1 receptors in the radial muscle of iris. This would cause
mydriasis which would favor, not impair, the vision in poor light.
F) Neostigmine is a cholinesterase inhibitor that could have caused effect similar to those of
pilocarpine. However it has been approved only for the treatment of myasthenia gravis and of
some gastrointestinal and urological problems. It is not used to treat glaucoma.
A 63-year-old woman underwent total abdominal hysterectomy to remove an
endometrial carcinoma. General anesthesia was induced with thiopental sodium,
maintained with halothane and nitrous oxide, and supplemented with tubocurarine. Which
of the following drugs did the patient most likely receive after the operation, in order to
reverse the skeletal muscle paralysis?
Reversible cholinesterase inhibitors are currently used to reverse the paralysis induced by
nondepolarizing neuromuscular blocking drugs, like tubocurarine. This drug blocks Nm receptors
at the motor end plate while acetylcholine activates these receptors. The two drugs competitively
antagonize each other and an increase availability of acetylcholine at the motor end plate can
therefore reverse the muscle paralysis induced by tubocurarine. Neostigmine is the preferred drug
since it does not enter the brain and it is therefore free of central adverse effects.
A) Physostigmine is not indicated since it can cross the blood brain barrier.
B) Edrophonium is not indicated since it has a very short duration of action (its half-life is 1-10 min)
C, E) These drugs do not act at Nm receptors.
A 55-year-old man, recently diagnosed with myasthenia gravis, was treated with a
cholinesterase inhibitor and with a second drug which should antagonize some of the
adverse effects of the first one. Which of the following pairs of drugs were most likely
B. Neostigmine and atropine
Neostigmine is a drug of choice for myasthenia gravis. The drug increases the availability of
acetylcholine at the motor end plate and it can also activate directly Nm receptors. Both actions
contributes to the therapeutic effect of improvement of skeletal muscle strength. Neostigmine
increases the availability of acetylcholine at all cholinergic synapses and can therefore elicits
muscarinic effects, mainly in the gastrointestinal tract. In order to block these unwanted effects
atropine is often given concurrently.
A, D) These cholinesterase inhibitors are not used in myasthenic patients since they enter the
brain and can cause central adverse effects.
C, E) Pralidoxime is a cholinesterase regenerator used only in case of poisoning by
A 45-year-old man was admitted to the emergency room because of extreme muscle
weakness, ptosis, diplopia, difficulty in swallowing, speaking and breathing. The man,
recently diagnosed with severe myasthenia gravis has been receiving neostigmine for the
past three months. Which of the following responses to 2 mg edrophonium IV would
indicate a cholinergic crisis?
B. Fasciculations, decreased muscle strength
Myasthenic patients under treatment with cholinesterase inhibitors may exhibit decrease muscle
strength, because of an excessive concentration of acetylcholine that causes depolarization
blockade of the motor end plate. This is called cholinergic crisis. On the other hand, these patients
may also exhibit decrease muscle strength because of a sudden exacerbation of the disease. This
is called myasthenic crisis. Edrophonium can be used to distinguish between the two syndromes.
In fact ,in case of cholinergic crisis edrophonium administration will produce no relief or worsen the
syndrome. (a decrease in muscle strength) whereas in case of myasthenic crisis the drug will
improve the syndrome (an increase in muscle strength).
Moreover an edrophonium-induced decrease of muscle strength is accompanied by fasciculations
(brief muscle contractions before the paralysis) since acetylcholine activates nicotinic receptors,
whereas an increase in muscle strength is not accompanied by fasciculations.
A, C, D , E) (see explanation above)
A 23-year-old man told his physician that he had frequent and painful bowel movements.
The man, recently diagnosed with myasthenia gravis, started a treatment with neostigmine
few days previously. Which of the following complains could also be expected by the
All cholinesterase inhibitors (neostigmine, physostigmine, organophosphates ,etc.) increase the
amount of acetylcholine available at cholinergic synapses, so causing both muscarinic and
nicotinic effects. Sweat glands are sympathetically innervated but the neurotransmitter is
acetylcholine. Therefore sweating can be an adverse effect of neostigmine administration..
A) Acetylcholine causes miosis, so photophobia is unlikely.
B) Overflow incontinence is due to relaxation of the detrusor muscle. Acetylcholine contract the
detrusor muscle, which in turn can cause urge, not overflow, incontinence.
C) Acetylcholine tends to cause bradycardia, so palpitations are unlikely.
E) An increase availability of acetylcholine in the brain causes mainly excitatory effects (unless
huge concentrations are present) so drowsiness is unlikely.
A 52-year-old diabetic woman presented to the emergency room with severe ocular pain
and redness, decreased vision, colored halos, and nausea and vomiting. Ophthalmoscopy
revealed anterior chamber inflammation and tonometry measured an intraocular pressure of
48 mm Hg in the right eye (normal 10-20). A diagnosis of acute glaucoma attack was made
and two drugs were instilled into the conjunctival sac. Another drug was given by the same
route 15 minutes later. Which of the following three drugs were most likely administered?
A. Timolol, apraclonidine and pilocarpine
Answer : A
An acute glaucoma attack is usually the first symptom of an acute angle-closure glaucoma, a
disease associated with a closed anterior chambre angle. When this occurs intraocular pressure
raises because the normal drainage of aqueous humor from the eye is prevented by the
obstruction of peripheral iris. An acute glaucoma attack is a medical emergency, because vision
can be lost quickly. The production of the aqueous humor must be decreased and therefore a
topical beta-blocker and an alpha-2 agonist are immediately administered. Then pilocarpine is
given to increase aqueous humor outflow ( cholinergic drugs alone are generally ineffective when
the intraocular pressure is > 40 mm Hg).
B, C, D) Scopolamine and homatropine are contraindicated in angle-closure glaucoma since they
induce mydriasis which increase the risk of closing the anterior chamber.
E) Prazosin is ineffective in glaucoma. Mannitol is not given topically, but IV, and is used to lower
the intraocular pressure only if the response to the first treatment is inadequate.
A 81-year-old woman underwent ocular surgery for cataract extraction. Upon completion
of the surgery she received a drug that is able to lower the intraocular pressure by
activating both Nn and M3 receptors. Which of the following drugs was most likely
Carbachol is currently used to lower intraocular pressure after cataract extraction. This is
accomplished by contracting the ciliary muscle, which in turn opens the pores of the trabecular
meshwork, so facilitating the outflow of the aqueous humor into the Schlemm’s canal. Ciliary
muscle receives mainly a parasympathetic innervation and the receptors on the muscle membrane
are M3. By activating those receptors as well as the Nn receptors on parasympathetic ganglia
carbachol can enhance significantly the parasympathetic activity.
A) C) Pilocarpine an bethanechol can lower intraocular pressure by activating M3 receptors but
are devoid of significant activity on Nn receptors.
B, E) Timolol and apraclonidine can reduce aqueous humor production but have negligible effect
on aqueous humor outflow.
A 54-year-old woman presented to the hospital because of a gradual onset of a scratchy
sensation on both eyes and an extreme dryness of the mouth and lips. Lab exams showed
elevated levels of antibodies against gamma-globulin. A diagnosis of Sjögren’s syndrome
was made and a drug was prescribed to relieve patient’s xerostomia. Which of the following
drugs was most likely administered?
Sjögren’s syndrome is a diffuse connective tissue disease in which lymphocytes infiltrate mucosal
and other tissues. Lymphocytic infiltration in salivary glands causes gland atrophy. Saliva
diminishes, resulting in extreme dryness of the mouth and lips. If glands are not severely
atrophied, pilocarpine can be used to stimulate salivary production.
A) Acetylcholine is not used for systemic therapy, because of its very short duration of action.
B, C, D) These drugs have little effects on salivary production.
A 63-year-old man underwent a surgical operation to remove a colonic carcinoma. Tree
days after surgery he developed fever (103° F), abdominal distension and vomiting.
Palpation showed tenderness over the entire abdomen, and auscultation revealed no bowel
sound. Which of the following therapeutic measures is absolutely contraindicated in this
D. SC administration of neostigmine
The signs and symptoms of the patient strongly suggest the diagnosis of adynamic ileus, due to
intraperitoneal infection (see the high grade fever). Ileus means paralysis of the gut. When this
paralysis is due only to a lack of autonomic neurotransmission (as in most cases of postoperative
ileus), a drug that increases the levels of acetylcholine can help to restore the motor activity of the
gut. On the other hand, when the paralysis is due to obstruction or inflammation of the gut,
cholinergic drugs are absolutely contraindicated since to increase the gut motility in these
conditions can exacerbate the inflammation and lead to the perforation of the intestine.
A, B, C, E) All these therapeutic measures are indicated in case of ileus due to intraperitoneal
A 74-year-old man complained to his physician of an increasing memory impairment
over the past 2 months. He also referred that he had increasing difficulty in recognizing
familiar objects and in planning everyday activities like shopping. Physical examination
revealed no neurological deficits, but the man performed very poorly in the Folstein Mini-
Mental Status Exam. The physician prescribed a drug which might help to slow the
progression of the patient’s symptoms. Which of the following statements best explains the
central mechanism of action of that drug?
D. Inhibition of cholinesterase
The symptoms of the patient and the results of the Mini-Mental Status Exam indicate that he is
most likely in the early stages of Alzheimer’s disease (AD). To date no drugs are available that can
alt or reverse the progression of the disease, but drug are approved for the treatment of memory
deficit associated with the AD. Acetylcholine is significantly reduced in AD and drugs that can
increase its levels in the brain have shown moderate success in slowing down the progression of
Donepezil selectively inhibits cholinesterase in the CNS with less effect on cholinesterase in
peripheral tissues and was most likely the drug prescribed by the physician.
A, B, C, E, F) (see explanation above)
A 63-year-old man recently diagnosed with open angle glaucoma started a treatment
which included pilocarpine eye drops. Which of the following is most likely the main site of
the therapeutic action of this drug?
C. Ciliary muscle
By activating M3 receptors in the eye pilocarpine constricts the ciliary muscle. which in turn opens
the pores of the trabecular meshwork, so facilitating the outflow of the aqueous humor into the
Schlemm’s canal. In this way intraocular pressure is decreased.
F) Pilocarpine constricts the sphincter muscle of iris so causing miosis, but miosis is not related to
the decrease in intraocular pressure.
A, B, D , E, G) Pilocarpine action on these structures is negligible.