Pharm Anti Cholinergic W Exp Part 2

Explanation
Answer: C
Atrial fibrillation results from cardiac impulses that go mad within the atrial muscle mass,
stimulating first one portion of the atrial muscle, then another portion, then another and
eventually feeding back onto itself to re-excite the same atrial muscle over and over. When this
occurs many small portions of the atrial muscle will be contracting at the same time while other
portions will be relaxing. Except for the connection through the AV bundle, the atrial muscle
mass is separated from the ventricular muscle mass by fibrous tissue. Therefore impulses from
the atria can get into the ventricles only through the AV bundle.
When the atria are fibrillating, impulses arrive from the atrial muscle to the AV node rapidly but
also irregularly. Because the AV node will not pass a second impulse for about 0.35 seconds
after a previous one, at least 0.35 seconds must elapse between one ventricular contraction to
the next. An additional but variable interval of 0 to 0.6 seconds occurs before one of the
fibrillatory impulses can get into the AV node. Thus the interval between successive ventricular
contraction varies from a minimum of about 0.35 seconds to a maximum of about 0.95 seconds,
causing an irregular heartbeat between 65 to 170 bpm.
Atrial fibrillation tends to occur paroxysmally before becoming constant. Palpitations, pallor,
weakness and nausea usually occur during the attack . Sometimes there is also a need to
urinate, which is the consequence of an increased urine formation by the kidney, due to the
secretion of the atrial natriuretic peptide.
Antimuscarinic drugs are present in many over-the-counter antidiarrheal preparations, sold in
several countries. These drugs increase the AV conduction so allowing more impulses to pass
into ventricles. Therefore they can trigger a paroxysmal attack, like in the present case.
A, B, D) These drugs can increase AV conduction but they are not used as antidiarrheal agents.
E) Beta blockers actually decrease AV conduction.

Explanation
Answer: E
Antimuscarinic drugs relax the detrusor muscle, so voiding of the bladder becomes more difficult.
This can be especially dangerous in patients with prostatic hyperplasia who have already
difficulty in micturition, due to prostate-induced narrowing of the urethra. In these patients
antimuscarinic drugs can precipitate an acute urinary retention.
A) Alpha-1 antagonists like prazosin are actually indicated in prostatic hyperplasia since they
relax the internal sphincter of the bladder.
B, C) Beta blockers tend to contract the smooth muscle since they block the beta-2 receptor
mediated relaxation. However these drugs have little influence on nonvascular smooth muscles
that are mainly under parasympathetic control.
D) Clonidine is an alpha-2 receptor agonist. Alpha-2 receptors are mainly presynaptic receptors,
which modulate the release of different neurotransmitters (mainly norepinephrine). This
modulation is usually too weak to affect significantly the contractility of nonvascular smooth
muscle.

Explanation
Answer: E
Atropine is always used to treat poisoning by a cholinesterase inhibitors, since it is able to
counteract both the central and peripheral symptoms of acetylcholine excess.
A) Pralidoxime rapidly regenerates the phosphorylated acetylcholinesterase and therefore is
useful for the treatment of poisoning due to organophosphates (irreversible cholinesterase
inhibitors). The drug instead is contraindicated when poisoning is due to reversible
cholinesterase inhibitors, like in the present case. In fact the drug is not able to regenerate the
acetylcholinesterase blocked by carbamates and has itself a weak anticholinesterase activity.
B, C) Sympathomimetic drug are useless in case of poisoning by cholinesterase inhibitors.
D) Glycopyrrolate is a quaternary ammonium antimuscarinic drug. Therefore it would not be able
to counteract the central effects of acetylcholine excess because it crosses poorly the blood
brain barrier.

Explanation
Answer: D
In the past, antimuscarinic drugs were used to treat bronchospastic disorder. However it has
been realized that most antimuscarinic drugs reduce the volume of bronchial secretion, which
becomes thick. This viscid material is difficult to remove from the respiratory tree and can
dangerously obstruct airflow. Moreover antimuscarinic drugs decrease mucociliary clearance, an
important function for the cleaning of the bronchial tree. Therefore today these drugs (except
Ipratropium) are actually contraindicated in respiratory disorder. Ipratropium has, for unknown
reasons, negligible effects on bronchial secretions and mucociliary clearance. Thus, its
anticholinergic properties can be safely exploited in the treatment of bronchospastic disease.
A) Potency (i.e. the inverse of the dose needed to get a predetermined effect) is almost never
the a reason for the choice of a specific drug.
B) ipratropium is given only by inhalatory route, so oral bioavailability is not an issue. Moreover
oral bioavailability is very low since the drug is a quaternary ammonium compound.
C) By definition, absorption refers to the passage of the drug into the general circulation. When
given by inhalatory route, absorption of ipratropium is negligible.
E) Central effects of ipratropium are negligible (the drug is poorly absorbed), but this is not the
reason why ipratropium is the preferred antimuscarinic drug to treat bronchospastic disorders.

Explanation
Answer: C
Gastroesophageal reflux disease is one of the most prevalent gastrointestinal disorders.
Population based studies show that it affects up to 15% of individuals. The disease is due to
incompetence of the lower esophageal sphincter. This sphincter receives mainly
parasympathetic innervation and remains tonically constricted. When this constriction is
insufficient the gastric content can go back into the esophagus. The esophageal mucosa is not
capable of resisting the digestive action of gastric secretion and erosion occurs. This explains
the heartburn, which is the most prominent symptom of the disease.
All drugs that relax smooth muscle are contraindicated in gastrointestinal reflux disease.
Antimuscarinic drugs can be especially dangerous, since the sphincter is rich of M3 cholinergic
receptors.
A, B) Contraction of the smooth muscle is not mediated by beta-1 receptors.
D) M3-agonist increase the contraction of lower esophageal sphincter. Therefore these drugs
would be indicated, not contraindicated, in gastroesophageal reflux disease.
E) Alpha-2 agonists have negligible effects on nonvascular smooth muscle

Explanation
Answer: D
Asystole is the complete ECG absence of electrical activity. Its development usually indicates a
prolonged cardiac arrest and carries a very grave prognosis.
In the treatment of asystole epinephrine is the initial agent of choice to hopefully generate a
rhythm. Since enhanced parasympathetic tone, possibly also due to chest compression, may
play a role in inhibiting supraventricular and ventricular pacemakers, anticholinergic drugs may
be beneficial, and atropine is usually tried when epinephrine fails.
A) Neostigmine increases cholinergic activity and is therefore absolutely contraindicated in this
setting.
B, C) When epinephrine does not work, the choice of other sympathomimetic drugs is
irrational.
E) Ipratropium is an anticholinergic agent but is only used by inhalatory route in bronchospastic
disorders.

Explanation
Answer: F
Ipratropium is an antimuscarinic drug that also has significant Nn receptor blocking activity.
Since the activation of Nn receptor in autonomic ganglia mediates the fast EPSP production,
blockade of these receptors can prevent the EPSP.
B) Neostigmine is a cholinesterase inhibitor and therefore it increases acetylcholine availability
at all cholinergic synapses. As a consequence the fast EPSP would be enhanced, not,
prevented.
A, C, D, E) These drugs have negligible blocking activity on Nn receptors and therefore have no
effect on fast EPSP.

Explanation
Answer: B
The excitation of respiration is a prominent action of nicotine. The drug stimulates the respiratory
center both directly, acting on the medulla, and reflexly by excitation of chemoreceptors of the
carotid and aortic bodies. With toxic doses the stimulation is followed by depression due to both
central paralysis and peripheral blockade of muscle of respiration.
A, C, D, E) Moderate doses of nicotine actually stimulates the reticular formation, the vomiting
center, the vasomotor centers, and the secretion of ADH from the post hypophysis.

Explanation
Answer: A
Prolonged activation of nicotinic receptors causes a persistent depolarization of postjunctional
cell membrane that prevent the return to the resting state . Since it is the change in the resting
potential that triggers the action potential, the depolarized membrane is resistant to further
depolarization and neuronal transmission is blocked (‘depolarization blockade’).
B, C) Blockade of ganglionic M2 and M1 receptors would prevent the production of IPSP and
early slow EPSP. These potentials are not involved in the production of the action potential .
D, E) Nicotine does not prevent acetylcholine release or catecholamine release

Explanation
Answer: C
Norepinephrine increases the mean blood pressure. This increase causes a stimulation of aortic
baroreceptors which activates the baroreceptor reflex. The increased vagal discharge
overcomes the direct effect of norepinephrine on the heart rate (an increase due to the activation
of beta-1 receptors), so the final effects is a decrease in heart rate. Ganglionic blockers impair
the baroreceptor reflex and therefore bradycardia is abolished.
A) Neostigmine is a cholinesterase inhibitor that increases the availability of acetylcholine at
every cholinergic synapse. Acetylcholine activates M3 receptors in the gut and Nn receptors in
the autonomic ganglia. Both actions contribute to the increase in intestinal peristalsis. A
ganglionic blocker can prevent the activation of Nn receptors but has no effect on the activation
of M3 receptors. Therefore peristalsis will be decreased, but not completely abolished.
B) Nicotine-induced contraction of skeletal muscle is due to activation of Nm receptors.
Ganglionic blocker have negligible activity on these receptors.
D) Epinephrine induced tachycardia is due to the activation of cardiac beta-1 and beta-2
receptors. A ganglionic blocker cannot block these receptors.
E). Ganglionic blockers actually cause hypotension by blocking the sympathetic discharge to the
vessels. Therefore the propranolol-induced hypotension is in fact enhanced, not prevented.

Explanation
Answer: C
The history of the patient together with his signs and symptoms are consistent with the diagnosis
of nicotine poisoning. Nicotine is sold in transdermal patches for use as an aid in the treatment
of nicotine withdrawal following cessation of smoking. The drug causes a rapid activation of both
the sympathetic and parasympathetic nervous system, as well as a stimulation of different areas
of the brain. Signs of this patient due to parasympathetic activation are vomiting, loss of urine
and feces, and profuse salivation. Sings of sympathetic activation are cold sweat (sweat glands
are stimulated and skin vessels are constricted), and rapid and irregular pulse (activation of Nn
receptors releases epinephrine from adrenal medulla). Central stimulation accounts for the
mental confusion and the to tonic clonic seizure.
A) Clonidine is sold in transdermal patches for the therapy of hypertension, but it does not cause
most of the symptoms exhibited by the patient.
B) Scopolamine is sold in transdermal patches for the prevention of motion sickness. The drug is
a muscarinic antagonist and therefore the symptoms of overdose would be the opposite of those
exhibited by the patient
C) Bethanechol is a muscarinic agonist. Symptoms of overdose would be limited to
parasympathetic activation.
E) Neostigmine is a. cholinesterase inhibitors. Many symptoms of poisoning by cholinesterase
inhibitors are similar to those of nicotine overdose (both drugs can activate, directly or indirectly,
nicotinic receptors). In cholinesterase inhibitor overdose however the cardiovascular effects are
usually bradycardia and vasodilation, due to the peripheral actions of accumulated
acetylcholine. Moreover, since the skin vessels are dilated, the sweat would not be “cold”. In
addition, in the case of neostigmine central effects would be negligible since the drug crosses
poorly the blood brain barrier

Explanation
Answer: B
Blood pressure (BP) is equal to cardiac output (CO) by total peripheral resistance (TPR).
Therefore, in order to decrease the mean BP a drug must decrease either CO or TPR or both.
Among the listed drugs, acetylcholine and propranolol ( mainly by decreasing CO) and histamine
( mainly by decreasing TPR) would cause a fall in mean blood pressure. The fall is not blocked
by a pretreatment with a ganglion blocker, suggesting that the depressor effect must be evoked
at a site distal to the ganglia. The fall is instead blocked by atropine and therefore a direct acting
muscarinic stimulant like acetylcholine must be the drug under study. The drop in BP is actually
greater in the present of ganglion blockade. Likely the acetylcholine-induced vasodilation has
elicited a reflex sympathetic discharge that has blunted the full depressor action of the drug in
the untreated animal.
A, D) Epinephrine and nicotine usually increase, not decrease, the mean blood pressure.
C) Propranolol-induced decrease of blood pressure would not be antagonized by atropine. In
fact, by blocking the parasympathetic action in the heart atropine can cause a sympatheticallymediated
increase in cardiac rate (and therefore in cardiac output) but this cannot occur when
the animal is treated with propranolol.
E) Histamine-induced decrease of blood pressure would not be antagonized by atropine. In fact
the decrease is due to peripheral vasodilation and atropine has very little effect on vessels.

Explanation
Answer: E
The drug causes an increase in heart rate that is not influenced by any of the blockers.
Therefore the drug must activate directly beta-1 receptors in the heart.
A, B) Drugs that activate indirectly (anticholinesterase drugs) or directly (M2 receptor agonists)
muscarinic receptors on the heart would tend to cause a decrease, not an increase, in heart rate.
C) A drug that activates alpha-1 receptors causes vasodilation and therefore a decrease in
blood pressure. This decrease in turn can cause reflex tachycardia. However this tachycardia
would have been prevented by a pretreatment with a ganglionic blocker, which blocks the
neuronal transmission in the efferent portion of the reflex arch.
D) A drug that activate alpha-2 receptors causes a decreased release of norepinephrine from
cardiac adrenergic terminals, therefore causing a decrease, not an increase, in heart rate.

Explanation
Answer: B
The drug causes an increase in mean blood pressure when given alone. This suggests that it
must be similar to nicotine, angiotensin II or epinephrine. The increase is blocked by a ganglion
blocker and is instead increased by atropine. This indicated that the increase is due to
ganglionic sympathetic stimulation which is more evident when the vagal activity to the heart is
blocked by atropine.
A, E) Acetylcholine and neostigmine usually cause a decrease of mean blood pressure.
C) Epinephrine-induced increase of mean blood pressure is due to beta-receptor activation on
the heart and alpha-receptor activation on he vessels. Therefore it would not be prevented by
ganglionic blockade.
D) Angiotensin II- induced increase of mean blood pressure is due to activation of angiotensin
receptors in the vessel. Therefore it would not be prevented by ganglionic blockade.

Explanation
Answer: D
The drug causes an increase in diastolic blood pressure and a decrease in heart rate. This
suggests that the increased blood pressure has caused a reflex bradycardia. Among the listed
drugs only norepinephrine and phenylephrine can cause these effects, due in both cases to
alpha-1 receptor activation. In fact both effects are prevented by a pretreatment with prazosin
and unaffected by pretreatment with propranolol or atropine.
A) Norepinephrine-induced decrease in heart rate is due to reflex bradycardia which overcomes
the direct tachycardic effect due to beta-receptor activation. A pretreatment with atropine would
antagonize the reflex bradycardia (which is vagal-mediated) so unmasking the direct tachycardic
effect. By the same token a pretreatment with propranolol would antagonize the direct
tachycardic, effect so enhancing the reflex bradycardia. This does not occur with phenylephrine
which is a pure alpha agonist with no direct effects on the heart.
B) Epinephrine usually does not cause an increase in diastolic blood pressure since the alpha-1
mediated vasoconstriction is counterbalanced by the beta-2 mediated vasodilation.
C, E) Isoproterenol and acetylcholine decrease, not increase, the diastolic blood pressure.