E.M. Silinsky
2016 REVIEW WORKBOOK/STUDY GUIDE
FOR THE PERIPHERALNEUROPHARMACOLOGY (PNP) MINI-MODULE
These questions have been written in rough order of the lectures so you can try them as the lectures proceed (or wait until they are over). At the end of the lecture series, please solve the puzzle on page 21 in the Learning Guide for the “Adrenergics” Lecture. Feel free to look at the lecture material if you forget the characteristics of any of the drugs.
We will begin the Review Session with a formal solution to this puzzle. (This puzzle represents a very complex version of the type of USMLE Step 1 question termed an “experimental vignette” by the National Board of Medical Examiners). The review session will then proceed with formal answers to the workbook questions, incorporating additional review material addressing questions that arose during the course of this mini-module.
Answers to the multiple choice questions have been posted.
I. SKELETAL NEUROMUSCULAR JUNCTION
A. THE USE OF ELECTROPHYSIOLOGICAL DEFLECTIONS TO DETERMINE THE LOCUS OR LOCI OF ACTION OF A PHARMACOLOGICAL AGENT OR THE SITE OF A DEFICIT IN A DISEASE STATE.
The following few questions relate to your understanding of these electrical 'blips'. For the sample multiple choice questions in this STUDY GUIDE, select the best single option.
1) The following represents the electrophysiological data made on an intercostal muscle biopsied from a normal patient and from a patient with an unknown treatment or disorder. Which one of the following is likely to produce the abnormal condition? [Some details: epp=end-plate potential, mepp= miniature epp, 1 micromolar ACh was applied to the muscle surface by iontophoresis, Ca2+ concentration reduced to prevent epps from being suprathreshold for muscle action potentials]
epp amplitude mepp amplitude response to ACh
Normal muscle 6 mv 1 mv 6 mv
Abnormal muscle 3 mv 0.5 mv 3 mv
A) Magnesium
B) Botulism
C) Myasthenia gravis
D) Hemicholinium-3
E) Myasthenic (Lambert-Eaton) Syndrome
ANSWER______
1a) Name a drug or a drug category that produces similar effects______
2) The following represents the electrophysiological data made on an intercostal muscle biopsied from a normal patient and from a patient with an unknown treatment or disorder. Which one of the following is likely to produce the abnormal condition? [Some details: epp=end-plate potential, mepp= miniature epp, 1 micromolar ACh was applied to the muscle surface by iontophoresis, Ca2+ concentration reduced to prevent epps from being suprathreshold for muscle action potentials]
epp amplitude mepp amplitude response to ACh
Normal muscle 6 mv 1 mv 6 mv
Abnormal muscle 3 mv 1 mv 6 mv
A) Succinylcholine
B) Cisatracurium
C) Myasthenia gravis
D) Hemicholinium-3
E) Botulism
ANSWER______
2a) Name an autoimmune disease that would produce similar effects______
TRICKY QUESTION:
3) A 29-year old pregnant woman who has myasthenia gravis is suffering from pre-eclampsia. She is treated with magnesium salts, which relieve some of the symptoms of pre-elampsia but she now complains of excessive fatigue. Which one of the following is the most likely electrophysiological correlate of transmission at the neuromuscular junctions of this patient?
epp amplitude mepp amplitude response to ACh
Normal muscle as before= 6 mv 1 mv 6 mv
epp amplitude mepp amplitude response to ACh
A) 6 mv 1 mv 3 mv
B) 3 mv 0.5 mv 6 mv
C) 3 mv 1 mv 6 mv
D) 3 mv 0.5 mv 3 mv
E) 1.5mv 0.5 mv 3 mv
ANSWER______
B. SPECIFIC NEUROMUSCULAR BLOCKING AGENTS
Please review the two phases of block by depolarizing agents, then answer the following question.
4) A 21-year-old man was treated with succinylcholine as a muscle relaxant prior to surgery to repair a torn rotator cuff. Intubation was performed during phase I block by succinylcholine. Phase I block (also termed block by depolarization) is associated with which one of the following?
A) normal excitability of the muscle at the end-plate region in response to direct muscle stimulation
B) a zone of inactivated, tetrodotoxin (TTX) sensitive sodium channels both at the end-plate
region and at non-end-plate regions
C) a zone of inactivated, tetrodotoxin (TTX) sensitive sodium channels at the end-plate region region only.
D) the blocked ACh receptor can be activated by exogenous ACh
E) Inhibition of calcium channels in the nerve endings
ANSWER______
5) A 75-year-old woman is undergoing a 2-hour gastrointestinal procedure. Relevant laboratory findings are as follows:
Aspartate aminotransferase (AST 272 U/L) normal 5-45
Alanine aminotransferase (ALT 150/U/L) normal 5-37
BUN 40 mg/dl (normal 8-21)
Serum creatinine 1.8mg/dl (normal 0.5-1.1)
Albumen (2.6g/dL) (normal 3.5-5)
Bilirubin (0.7mg/dl) (normal 2-18)
Which neuromuscular blocking agent is recommended for this patient?
A) Succinlycholine
B) Atracurium
C) Pancuronium
D) Cisatracurium
ANSWER______
6) A 40-year-old woman is suffering from severe idiopathic writer’s cramp.. To treat this dystonia, her physician prescribes a local injection of an agent that cleaves the protein SNAP-25 (synaptosomal associated protein of 25 KD) into the patient’s flexor pollicis longus muscle. Which one of the following agents was prescribed?
A) Bacolfen (a GABAB receptor agonist)
B) Botulinum toxin
C) Diazepam
D) Levodopa
E) Vecuronium
ANSWER______
Additional details on the diagnosis of botulism will be presented in the review session. The patient (picture to be shown during the review session) reported to his neurologist with descending skeletal muscle weakness. At rest he exhibited bilateral mild ptosis, dilated pupils, disconjugate gaze and symmetrical facial muscles. When asked to perform his maximum smile, there are no periorbital smile creases and minimal asymmetry. We will also discuss a quick way to distinguish botulism form LEMS and MG using an observation related to the autonomic nervous system.
With regards to the specific agents, peruse the drug list and try to recall the salient properties of the important drugs.
C.SYNERGISM
7) An experimental study was made on the interactions of pairs of drugs at the skeletal neuromuscular junction to determine whether the drugs acted synergistically or non-synergistically. Which one of the following pairs of agents act non-synergistically at the neuromuscular junction?
A) Pyridostigmine and calcium gluconate
B) Botulinum toxin and TTX
C) Atracurium and mivacurium
D) Neomycin and tubocurarine
E) Magnesium salts and pancuronium
ANSWER ______
II. THE DIVISIONS OF THE ANS
8) An experimental study was made on the pharmacological control of neuro-effector junctions in the sympathetic nervous system. Which one of the following direct effects of sympathetic nerve stimulation would be blocked by atropine at the end organ?
A) decrease in heart rate
B) decrease in airway resistance
C) prostate gland contraction
D) eccrine sweat gland secretion
E) dilation of the pupil
ANSWER______
9) A series of experiments were made to determine the effects of stimulation of autonomic nerves on the behavior of various tissues. Which one of the following effects is mediated by stimulation of the parasympathetic division of the autonomic nervous system?
A) pupillary miosis
B) sweating from the eccrine (temperature-regulating) sweat glands
C) contraction of the vas deferens
D) relaxation of bronchiolar smooth muscle
E) glycogenolysis
ANSWER______
10) What are the effects of intense sympathetic stimulation on urinary bladder function or colonic motility and why? (Discussion during the review session)
III. PARASYMPATHOMIMETICS
Please review the properties of the important agents, using the drug list as a guide, then answer the following question: Which effects of ACh mimic the effects of parasympathetic nerve stimulation and which do not?
11) A 69-year-old man with severe benign prostatic hypertrophy underwent surgery for a malignant melanoma. One day after surgery he reports to the ED because of severe postoperative urinary retention. After catheterization, a drug is prescribed that increases phosphoinositide turnover in smooth muscle cells of the bladder fundus with no effect on nicotinic synapses. Which drug was the most likely to be prescribed?
A) Bethanechol
B) Neostigmine
C) Carbamylcholine
D) Succinylcholine
ANSWER______
12) In August 2013, 23 children in India were poisoned by and agricultural insecticide monocrotophos which was present in the lunch containers associated with a government-sponsored free lunch program. The effects of this pesticide are similar to sarin. Which one of the following is the most likely to describe the symptoms observed by these children?
A).cycloplegia, bronchodilation, constipation, excessive urination,
B) defecation, micturition, excessive watering of the eyes, salivation
C) cyclospasm, pupillary dilation, tachycardia, increased force of voluntary muscle contractions.
D) decreased sweating, urinary retention, bradycardia, abdominal cramps
E) urinary retention, increased salivary secretion, mydriatic pupils
ANSWER______
IV. PARASYMPATHETIC ANTAGONISTS
Review the drug list for muscarinic antagonists, then answer the following:
13) A 55-year old man who has smoked most of his adult life is diagnosed with chronic obstructive pulmonary disease. A drug is prescribed that can be used once daily and is the most effective agent in its category as it does not block presynaptic autoinhibitory receptors. Which one of the following drugs was employed?
A) Atropine
B) Ipratropium
C) Scopolamine
D) Tolterodine
E) Tiotropium
ANSWER______
14) A 69-year-old woman is about to undergo a retinal examination. The attending physician on your ophthalmology clerkship asks you to choose an agent that produces mydriasis without cycloplegia for this examination. Which one of the following agents would you choose?
A) Pilocarpine
B) Neostigmine
C) Atropine
D) Phenylephrine
E) Tropicamide
ANSWER______
We will review atropine toxicity during the review session. In the meantime, please think about what the similarities and differences might be between atropine toxicity and ephedrine toxicity.
V. ADRENERGIC TRANSMISSION AND ADRENERGIC AGENTS
15) Epinephrine is injected into an experimental animal to determine the types of catecholamine receptors responsible for its actions. Which one of the following effects of epinephrine is mediated by an action on beta-2 receptors?
A) decrease in cardiac conduction velocity
B) inhibition of insulin release
C) contraction of gastrointestinal sphincters
D) increase in cardiac sinus rate
E) relaxation of vascular smooth muscle
ANSWER______
16) An 80-year-old man undergoes a colostomy. On postoperative day 3 he is suffering from septic shock. Antibiotic therapy is initiated in conjunction with volume expanders and dopamine but the patient continues to be hypotensive. A drug with the catecholamine structure that has selective actions on alpha-1 but minimal action on beta-2 adrenoreceptors is infused. Which one of the following drugs was the most likely to be employed?
A) Norepinephrine
B) Isoproterenol
C) Phenylephrine
D) Ephedrine
E) Epinephine
ANSWER______
With respect to the diagram on the effects of NE, EPI and ISO in man in the Adrenergics lecture:
17) Which of the three prototypes (EPI, NE, ISO) increase: a) the force of cardiac contraction,
b) the rate of cardiac contraction and c) cardiac output when administered in man in moderate doses?
WE WILL GO OVER THE CHART AGAIN IN CLASS.
Please REVIEW responses mediated by ALPHA 2 receptors (both cardiac and non-cardiac), then answer the following question. During the review session, a review of the primary, secondary and tertiary sites of alpha-2 agonist action will be provided.
18) A series of experiments were performed on the effects of non-selective alpha receptor blockers on a variety of biological effects. Which one of the following is a predicted effect of phenoxybenzamine on alpha 2 receptors?
A) inhibition of mydriasis
B) inhibition of emission
C) alleviating symptoms of benign prostatic hypertrophy
D) nasal congestion
E) increase in the release of the parasympathetic 'erectile' transmitter
ANSWER______
19) Name two drugs that are used synergistically in the Emergency Department to treat a severe asthmatic attack
ANSWER ______and ______
20) A 60-year-old man presents with a supine blood pressure of 160/100 mm Hg but also suffers from severe orthostatic hypotension, The attending physician on your Medicine clerkship asks you to chose an antihypertensive agent that would be the least likely to exacerbate the orthostatic hypotension. Which one of the following agents would you choose?
A) Phentolamine
B) Prazosin
C) Phenoxybenzamine
D) Propranolol
ANSWER______
21) A 72-year-old man is being treated with terazosin for benign prostatic hypertrophy (BPH). His symptoms are relieved by this agent but he complains to his physician that he gets very dizzy upon standing up. Which one of the following agents would be the most appropriate drug to substitute for terazosin to continue the symptomatic relief from his BPH without producing orthostatic hypotension?
A) Propranolol
B) Tamsulosin
C) Doxazosin
D) Prazosin
E) Dopamine
ANSWER______
22) A 50-year-old woman is brought to the ED after fainting at home. She had complained of fatigue, dizziness and labored breathing earlier in the day. Her blood pressure was 87/59 mm Hg, her heart rate=50. Her ECG reveals a normal QRS complex but the P->R interval is increased. Lung fields reveal the clinical signs of bronchospasm. She mentions she is being treated with a drug to reduce some of the ‘toxic’ effects of her thyroid disease. Based upon these complaints, which one of the following is the most likely agent responsible for her symptoms?
A) Clonidine
B) Propranolol
C) Prazosin
D) Phenylephrine
ANSWER______
VI. REVIEW OF OCULAR PHARMACOLOGY:
23) A 20-year-old woman suffered a unilateral cervical trauma after falling from her horse. Her left eye was sore and the eyelid drooped. After exercise, she did not sweat on the left side of her forehead. Physical exam reveals the left pupil is 2mm and did not dilate when placed in a dark room. The right pupil is 3mm and dilated in a dark room. The right pupil dilated normally in response to the topical ocular administration of either phenylephrine or hydroxyamphetamine. The left pupil did not respond to hydroxyamphetamine but dilated maximally to a low dose of phenylephrine. (This disorder is known as Horner’s syndrome). What is the locus of the problem?
A) sympathetic preganglionic
B) sympathetic postganglionic
C) parasympathetic preganglionic
D) parasympathetic postganglionic
ANSWER______
23a) What drug could have been substituted for hydroxyamphetamine in question 23?______
24) A 50-year old woman undergoes a retinal examination. She has been suffering from asthma for the past 30 years. The intraocular pressure is 24 mm Hg in each eye. The ophthalmologist prescribes a drug that inhibits the synthesis of aqueous humor by a process mediated via cell surface membrane receptors. Which drug was prescribed?