Pharm Autonomics W Exp Part 2

Answer: C
The hydroxylation of tyrosine to DOPA is the rate limiting step in norepinephrine biosynthesis
and is catalyzed by the enzyme tyrosine hydroxylase. The inhibition of this enzyme can
therefore cause a big reduction of the biosynthesis of the final product.
A) This enzyme transforms DOPA into dopamine.
B) This enzyme transforms dopamine into norepinephrine.
D) This enzyme transforms norepinephrine into epinephrine.
E) This enzyme transforms norepinephrine and epinephrine into dihydroxymandelic acid and
dopamine into dihydroxyphenylacetic acid.

Answer: D
Symptoms like xerostomia, anhydrosis and vaginal dryness indicate an impairment of
secretions from exocrine glands. Symptoms like abdominal distension, constipation and urinary
retention indicate an impairment of contraction of nonvascular smooth muscles. Exocrine gland
secretion and nonvascular smooth muscle contraction are elicited by the activation of M3
receptors.
A) Blockade of alpha-1 receptors would cause mainly vasodilation which in turn would
decrease the blood pressure.
B) Alpha-2 receptors are mainly presynaptic receptors. A blockade of these receptors would
cause mainly an increase of norepinephrine release from adrenergic terminals.
C) Blockade of M2 receptors would decrease the parasympathetic control of heart activity so
leading to an increase in heart rate and contractility.
E) Blockade of Nm receptors would cause a paralysis of skeletal muscles.

Answer: D
Activation of M3 receptors located on the sphincter of iris causes contraction of the muscle so
causing miosis. On the contrary blockade of these receptors causes mydriasis and impairment
of the pupillary constriction in bright light (the light pupillary reflex) so leading to photophobia.
Activation of M3 receptors located on the ciliary muscle causes contraction of the muscle,
which in turn increases lens curvature. The process, called accommodation, allows the eye to
focus on near objects. On the contrary blockade of these receptors relaxes the ciliary muscle
(cycloplegia) and impairs the accommodation process.
A, B, C, E) (see explanation above)

Answer: E
The activation of all beta receptors increases the synthesis of cAMP by activating adenylyl
cyclase.
A, B, C, D) (see explanation above)

Answer: C
The woman was most likely taking amitriptyline, an antidepressant medication with pronounced
antimuscarinic effects. Palpitations is due to blockade of M2 receptors whereas dry mouth,
blurred vision and constipation are due to blockade of M3 receptors.
A, B, D, E) blockade These pairs of receptors do caused the symptoms reported by the patient.

Answer: A
Activation of alpha-1 receptors constrict the vessels so counteracting the postural hypotension
of the patient. The postreceptor mechanism which mediates the effect must be one that
increases intracellular calcium, since calcium is needed for contraction. Alpha-1 receptor
activation increases the This is achieved by activating phospholipase C which in turn in
creased the synthesis of IP3 and DAG.
B, C, D, E) (see explanation above)

Answer: B
Activation of beta-2 receptors increases liver gluconeogenesis, inhibits degranulation of mast
cells and decrease plasma K (because of increased K uptake by skeletal muscle). Activation of
beta-3 receptors in fat cells increases lipolysis with enhanced release of free fatty acid into the
blood.
C) Beta-1 receptor activation is not involved since the secretion of renin is unaffected.
A, D, E, F) These pairs of receptors can mediate some, but not all the effects listed.

Answer: E
During the ejaculation the contraction of vas deferens and prostate capsule put the semen into
the urethra. This contraction is mediated by an increased sympathetic firing which causes the
activation of alpha-1 receptors located on the smooth muscle of those organs.
A, B, C, D) These receptors are not involved in the ejaculation process.

Answer: A
Pupillary diameter can be increased either by the activation of alpha-1 receptors (which
contracts the radial muscle of iris) or by the blockade of M3 receptors (which relaxes the
sphincter muscle of iris). The question asks for an activation of a receptor and therefore the
alpha-1 receptor must be involved. Intraocular pressure can be decreased by a decreased
production or by an increased outflow of the aqueous humor. A decreased production can
follow either the activation of alpha-2 receptor or the blockade of beta-2 receptors. The question
asks for an activation of a receptor and therefore the alpha-2 receptor must be involved.
B) Beta-2 receptor activation would cause an increased production of aqueous humor and
therefore would increase, not decrease, the intraocular pressure.
C) Activation of Nn receptors would cause an increase in sympathetic as well as
parasympathetic firing. Since in the eye the parasympathetic system is predominant this would
lead to an activation of M3 receptors in the ciliary muscle which would increase the lens
curvature and an activation of sphincter muscle of iris which would decrease, not increase, the
pupillary diameter. Activation of Nm receptors causes the contraction of skeletal muscles only
and therefore can affect the extrinsic, not the intrinsic eye muscles.
D) (see answer to item C)
E) (see answer to item B)

Answer: C
Drugs that inhibit cholinesterase are able to increase the amount of acetylcholine released by
all cholinergic terminals, that is preganglionic terminals, postganglionic parasympathetic
terminals and neuromuscular junction. In the parasympathetic ganglia located in the bladder
acetylcholine activates Nn receptors so increasing postganglionic firing. Acetylcholine also
activates M3 receptors located on the detrusor muscle. Both action contribute to the
contraction of the detrusor muscle and therefore voiding was improved.
A, B, D, E) The activation of these receptors does not elicit the contraction of the detrusor
muscle of the bladder.

Answer: A
Dopamine beta-hydroxylase is the enzyme that catalyzes the conversion of dopamine into
norepinephrine. Since the enzyme is lacking plasma levels of norepinephrine will be very low.
B) Plasma levels of dopamine would be high, not low.
C) Epinephrine is synthesized from norepinephrine. Since plasma levels of norepinephrine are
low, also plasma levels of epinephrine must be low, not high.
D) Normetanephrine is a urinary metabolite of norepinephrine. Since plasma levels of
norepinephrine are low, also normetanephrine must be low, not high.
E) Homovanillic acid is the main urinary metabolite of dopamine. Since plasma levels of
dopamine are high, also homovanillic acid must be high, not low.

Answer: D
M2 receptors are mainly located on the heart and their activation decreases the heart rate and,
to a lesser extent, heart contractility. Systolic blood pressure, which is also dependent on heart
contractility, will be decreased slightly. Diastolic blood pressure depends on total peripheral
resistance and therefore is not affected by the activation of M2 receptors that has nothing to do
with the contractility of vascular smooth muscle.
A) Activation of alpha-1 receptors would cause vasoconstriction and therefore an increase of
systolic as well as diastolic blood pressure.
B) Activation of beta-1 receptors would increase cardiac contractility and rate.
C) Activation of D-1 receptors would cause dilation of mesenteric and renal vessels, so
decreasing the diastolic blood pressure.
E) Activation of M3 receptors would cause a release of nitric oxide from the vascular
endothelium, so decreasing the diastolic blood pressure.

Answer: A
Activation of beta-2 uterine receptors can relax both non pregnant and pregnant uterus and
beta-2 agonists are sometimes used to prevent premature labor.
B, C, D, E, F) These receptors either are not involved in or actually increase uterine
contractions.

Answer: B
Activation of alpha-2 receptors located on pancreatic beta cells inhibits insulin secretion. This is
one of the actions that contribute to the final hyperglycemic effect of epinephrine.
A, D) These effects are due to activation of alpha-1, not alpha-2, receptors.
C, E) These effects is due to activation of beta-1 receptors
F) This effect is due to activation of beta-2 receptors

Answer: A
A decrease in pupillary diameter (miosis) is due to the contraction of the sphincter muscle of
iris, which is elicited by the activation of M3 receptors. An increase in lens curvature is due to
the contraction of the ciliary muscle which is also elicited by the activation of M3 receptors. The
main postreceptor mechanism of M3 receptors is the increased synthesis of IP3 and DAG
which in turn increases intracellular CA++. Calcium is needed for several parasympathetic
actions including smooth muscle contraction and exocrine gland secretion.
B) This postreceptor mechanism is triggered by the activation of alpha-1 receptors.
C) This postreceptor mechanism is triggered by the activation of M2 receptors.
D) This postreceptor mechanism is triggered by the activation of Nm receptors.
E) This postreceptor mechanism is triggered by the activation of beta receptors.

Answer: E
Activation of beta-1 and beta-2 receptors increases cardiac contractility and rate. Activation of
beta-2 receptors causes vasodilation which in turn causes reflex tachycardia. So the heart rate
is increased because of both direct and reflex effects. The increase in heart rate and
contractility in turn lead to an increase in cardiac output.
A, B, C, D, F) Activation of these receptors does not cause all the effects listed in the table.

Answer: D
Activation of beta-2 receptors often causes palpitations that most likely occur for the following
reasons.
1) The activation causes dilation of the skeletal muscle vessels which in turn may cause reflex
tachycardia.
2) The activation of beta-2 receptors in the heart may contribute to the increase in heart rate
[direct cardiac effects are determined largely (60-80%) by activation of beta-1 receptors, but
activation of beta-2 receptors is also involved (20-40%)]
A, B) These adverse effects are mainly due to parasympathetic activation.
C) A skin rash is due to an allergic reaction in most cases.
E) Beta-2 receptor activation relaxes the ciliary muscle and therefore the far vision should be
improved, not impaired. The effect however is weak and accommodation is not disturbed.

Answer: B
Activation of nicotinic receptors in sympathetic ganglia cause an increased sympathetic firing
which in turn releases norepinephrine from adrenergic terminals. This activates alpha-1
receptors so causing skin vasoconstriction. Therefore the skin becomes pale and cold. The
increased sympathetic firing also release acetylcholine from terminal innervating sweat glands.
Sweating is increased and the skin becomes wet.
A, C, D, E) All these symptoms are due to activation of nicotinic receptors in parasympathetic
ganglia

Answer: C
The increased firing of the vagus nerve caused an increased release of acetylcholine in the
heart. The neurotransmitter activated M2 receptors which in turn open ligand gate K+ channels.
This slows SA node depolarization so decreasing the heart rate.
A, B, D, E) (see explanation above)

Answer: E
Nm receptors are found only in the motor endplate and therefore the symptoms must refer to
skeletal muscles. When Nm receptor are activated by acetylcholine the ion channel opens so
allowing Na+ to enter the cell. The endplate membrane become depolarized and this
depolarization is called endplate potential. If its amplitude reaches the threshold for excitation
voltage-gated Na+ channels open, so generating an action potential that propagates the
depolarization and causes the contraction of the skeletal muscle. The endplate depolarization
is short-lasting, since acetylcholine is rapidly metabolized. However when an excessive amount
of acetylcholine causes a persistent activation of Nm receptors, a loss of electrical excitability
of the muscle cell occurs. The main reason for this loss is that, even if the membrane is still
depolarized because of the activation of Nm receptors, voltage-sensitive sodium channels
become inactivated and therefore not able to open in response to a brief depolarizing stimulus.
This loss of electrical excitability in the presence of a depolarized membrane is called
“Depolarization blockade”. The main consequence of this block in skeletal muscle cells is the
paralysis of the muscle. It should be noted that this paralysis is not due to the blockade of Nm
receptors but to the persistent activation of those receptors. When the paralysis involves the
extrinsic muscles of the eye, diplopia results. The paralysis of the striated muscles of the
pharynx causes difficulty in swallowing.
A, B, C, D) All these effects are due to the activation of muscarinic receptors.