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Phar 752
Exam #l , 14 October 2004
Page 1
Name (La! S tue
This test consists of 43 questions worth a total of 100 points (Questions #I-34 are 2 pts
each; #35-43 are variable). There are a total of 13 pages. Check that your test is complete- Record your answers for questiops #l-34 on a scantmn sheet and turn in BOTH the (^). (^4) Ppjj printed exam and the scantron sheet. (^) -CB '
For questions 1-6 below choose from the following:
A: ' Gas B. Gai (3. Goq D. Gpy
E. None of the above
1. Which G protein subtype mediates increased GI tract longitudinal motility? t i 4 i I H i - + $ r M, = o ~ g 2. Which G protein subtype directly activates potassium channels? 3. & Which G protein subtype directly mediates skeletal muscle c o n t r a ~ t i o n? ~ -- flM A E
w
- & Which G protein subtype mediates PKA activation in smooth muscle?
- -^ C. Which^ G pulrponary mucus secretions?^9 *?.,
d%
- @ Which G k o k i n subtype mediates the cardiac response of the buoRfler to decreased blood pressure?^ -^ % - = = - + =? 2. 1 gk = 3 @ d ~ , h f ~ , 1
7. The parasympathetic and sympathetic nervous systems function in a cooperative
(non-oppositional) manner to affect (2 pts)
A. heart rate B. bronchi01 smooth muscle tone
C. vascular smooth muscle tone
liver glycogenolysis sexual response
Phar 752.
Exam #1,14 October 2004
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Name (Last, First) Student ID #
C 8. -& Which of the following pairs of compounds would be considered physiological
muscarine and physostigmine -kW i t h b 1 4 b
9. One problematic side effect of oxybutinin can be (2 pts)
k,dizziness and motion sickness^4. s a & ' d d : ~ 1
hallucinations w-- \ a^ postural hypotension^ ~ w C & \ L ; C^ +t44^ - & incontinence dry mouth Pd-iB
10. Phase I is different from phase II blockade because (2 pts)
k the agonist is removed during phase II blockade
. (^) only muscular, not neuron4 nicotinic receptors experience phase I1 blockade > muscarinic receptors only experience phase I blockade D. the polarization state of the neuron differs during different phases of blockade h phase I evokes an EPSP and phase II evokes an IPSP
' ' The primary benefit of the use of ipratropium compared to other drugs in its class is related to its (2 pts)
h. duration of action X. absorption hom GI
4b
"2,
T'q decreased nicotinic effects decreased effect on secretions efficacy to induce mydriasis
Phar 752
Exam #I, 14 October 2004
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Name (Last, First) Student ID #
17. -^ C M2 selective agonists would most likely cause which of the following effects? (2 pts)
A. inhibition of vomiting (to treat motion sickness) relaxation of iris sphincter C inhibition of norepinephrine release Q inhibition of peptic acid secretion inhibiion of nitric oxide release
18. A wornan is treated with bethanechol after surgery. Which of the following
additional conditions would be of most concern in this case? (2 pts) (^) %A
a history of glaucoma Mwc.alr ;?v4 ~ Q D$ P '% ~ B a history of peptic ulcer disease 6 a history of atrial tachycardia (^) &\J*$c. 0 = ~ 0 7 5 ~ D. a history of depression % a history of Sjijgren's syndrome
- Sotulin toxin is used to !everse the facial appearance of aging by (2 pts)
A. i ~ ~ ~secretions ~ i n for moister, younger-lookingg skin
B. tightening^ the^ underlying muscles of^ the^ mouth^ and^ amund^ the^ eyes, mimicking
a facelift @ relaxing the muscle around the eyes and in the forehead to smooth the skin D. (^) reducing worry and anxiety through CNS effects
E. blurring the vision of the user until wrinkles disappear in the mirror
c 20. =fthc-synptom distingnbbes cchoWopbie poi~oningbimtoju'e mushroom (muscarine) poisoning? (2 pts)
?- X, constricted air passages resulting in wheezing A a eyes and mouth covered in tears and saliva skeletal muscle rigidity \9 pippoint pupils
Rag h i 0 %v U S P ~ A *p E. slow pulse vx
k24j
b u p - i :,,@ .)\ pj[, t2;:-k I i b + ~ ~ ~ - L k ; - j r-,
Yhar 752 Exam #1,14 October 2004
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Name (Last, First) Student ID #
21. Carbachol^ used^ to^ treat^ chronic open angle^ g l a u m^ will^ (2^ pts)
reduce aqueous humor production constrict the iris radial muscles to improve aqueous humor flow = & /di constrict the ciliary muscle to improve aqueous humor flow increase passage of aqueous humor into general circulation through the Canal of Schemm
E. allof the above
- 4 Which of the following pieces of information could most likely change the decision to use succinylcholine during an intubation procedure? (2 pts)
Q the patient has liver disease
93. the patient is on.dialysisfor a renal disease k, the patient is taking antibiitics 'a the patient has a history of allergic asthma )""""
E. the patient experienced significant blood loss
23. - ( 2 ,Mecamylamine analogues may be logically explored as therapeutics for all of the
following indications EXCEPT (2 pts)
'. ~ Z A. . -^3 ><&~LJ,C^ '^ JJiytLCV- -:
LJ^ A.^ hypertension
wA drdyfiQ,u$\ik
..B: nausea and vomiting a ptemature labor '8, memDry loss YL analgesia 4 b q i diCU- LI:~-.+~.,.? $;ln, db 4+JUWJ p&w -$Q
24. If you wen an evil sorcerer controlling the population of a small island through
and knowledge of pharmacology, you might expect that of^ the^ zombies^ you crea.ted through would also suffer fiom (2 pts)
4. delirium and CNS confusion
B itchy hives^ fiom^ excess histamine release
9 hyperthennia D. excess salivation
E. liver disease
rnar /sz ~ a m e(~ast,fiirst)
Exam #l,14 October 2004 Student ID
Page 7
f
- & Which of the following statements regarding pilocarpine is true? (2 pts)
Epimerization of pilocarpine does not affect its ability to act as an agonist.
6 B.^ Hydrolysipinactive.^ of^ pilowpine^ produces^ pilocarpic^ acid, which^ is^ completely
kPilocarpine is a compound that follows classical muscarinic agonist SAR. hB, Pilocarpine is a quaternary ammonium compound that can have good systemic distribution. \E, Pilocarpine^ is^ a prototype plant^ natural^ product^ similar^ in^ structureto^ atropine.
- a Which of tbe following is not included in the SAR for muscarinic antagonists?
(2 pts)
X. The X substitueht in the most potent anticholinergics is an ester.
b, The N p u p is a tertiary axnine or quaternary ammonium salt, with the akyl substituents usually methyl, ethyl, or isopropyl. \ 'IIEdistance between the X p u p and the amine nitrogen can vary from 2 to 4
carbons; the most potent agents have two methylene units in the chain.
@ The R3 substituent should be a primary amino, a hydroxyl, or a hydroxylamine
group, capable of participating in hydrogen-bonds.
. The size of the Rl and R2 groups should be no larger than a phenyl group. 7
- & Tomatoes and potatoes produce compounds called solaoaceous glyco*ids (SGAs) that are inhibitors of (^) lcholinesterase (pseudocholinesterase). It has
been proposed that the levels-of SGAs m body may affect the metabolism of
certain drugs. If you were to ingest these foods prior to surgexy, which neuromuscular blocking went might be affected in its duration of action in the Fresence of the SGAs (or in other words, a prolonged newmuscular block would be seen)? (2 pts) 4
A. Tubocurarine ' B. Rocuronium C. Atracurium Pipecuronium
E Succinylcholine
6
Phar 752
- (^) Exam #l , 14 October 2004 Page 8
Name (Last, First) Student ID #
- -^8 Which of the following statements about modifications to the acetylcholine structure ( is false? (2 pts) - 6
\ Changing the acetyl group to a carbamate group increases the resistance to hydrolysis, leading to a longer duration of action. W e r methyl or ethyl groups can be added to the ethylene bridge or the
quaternary nitrogen and still retain good agonist activity.
h, Behnechol combines a methyl group on the ethylene bridge along with a
.L
carbamate group to provide a muscarinic selective agent which can be used orally. ear;J ads\ - !D The^ S-enantiomer^ of^ B-methylcholine^ is^ more potent as an^ agonist^ than^ the^ R- enantiorner. - _5 ,a_* '
Addition of a $-methyl group provides for mscarinic receptor selectivity, while bia YdF (^) addition of an a-&thyl group leads to nicotinic receptor selectivity.
- & Which of the following statements regarding an acetylcholinesterasereactivator is inaccurate? (2 pts) L19r-
\ A reactivator should have an aromatic ring and a nitrogen that can carry a positive charge to provide &ty and selectivity for the AChE enzyme. \ The readvator shoukl carry a hydroxylamine--like nucleophile into close proximity with the phosphorylated enzyme intermediate. ' \6j .A Mcfivator should be administered as soon a f k exposure to the Ache
iqhibitor as possible; administration later than 24 h after exposure will likely
have little effect.
Aged enzyme will not be reactivated to any significant extent by a retivator.
E (^) Reactivators are effective for reversing AChE inhibition by covalent reversible 6 inhibitors, wn-cova~entreversible inhibitors, and irreversible inhibitors.
9 33.^3 - Even though both malathion and sarin are considered irreversible inhibitors of X h E , malathion is a much safer compound. Which of the statements below
regarding these compounds is true? (2 pts)
\ The oxidative activation of malathion is slow in humans, which reduces toxicity
of an acute exposure.
B (^) M@athion is a modified dimethyl organophosphate which which would lead to faster regeneration of any o f f e phosphorylated AClE relative to the phosphorylated AChE derived fiom the isopropyl organophosphateof sarin. \6, Iqactivation by ester hydrolysis of malathion in humans occurs faster than oxidation to the active AChE inhibitor. \ Malathion is n quaternary ammonium compound which reduces absorption
relathe 'to sarin, which is highly lipopwc
\ A reactivator could be an effective treatment for the excess exposure to either of these agents.
Phar 752
Exam #1,14 October 2004
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Name (Last, Fmt) Student ID #
- (6 pts) Tubocurarine and succinylcholinecan both be toxic in combination with specific other drugs. Both of these toxicities are related to effects on calcium.- -are these dangerous combinations and how is calcium involved in each case?
%,: :<
- (2 pts) Draw the structure of the fungal natural product that selectively activates fiuscariuic receptors (correct stereochemistry, if present, is required).
Phar 752
Exam #I, 14 October 2004
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Name (Last, First) Student ID #
38. (4 pts) Phenserine is an acetylcholinesterase inhibitor that is currently in Phase IlI trials.
(A) Draw the structure of the modified-me
intermediate that vou would expect to be formed ~ A C ~ E - ~ e r - O Hcan be used as shorthand for the enzyme structure). L w^4 .. G w - s w -0 0- sw, 9*
(B) A portion of the phenserine molecule is released h m the enzyme after modification of
the active site serine. Draw the structure for this expected by-product.
39. (3 pts) Which is the preferred- conformation of:e - a
Synclinal (Gauche)
Antiplanar
a) In solution?
b) As a m u ~ agonist?c
c) As a nicotinic agonist?
Phar 752
Exam #1,14 October 2004 Page 13
Name (Last, First) Student ID #
42. (3 pts) What are the two enzymes involved in tolterodine metabolism (place enzyme name
in the appropriate box)? Indicate if either of these metabolites is active,
Tolterodine Detroldi)
N - ~ p > / r r. U & &
- P^ = C^ 3 :: r h .ld+>,~..^ C .,-.. *,.d o.j..D.;:i..l:l:i;k, Q
43. (3 pts) The structures of two acetylcholinesterase inhibitors are shown below. Circle the
one that you would expect to have the longest duration of action. Explain your
u a-
H3-7-c H
cH 3 -^ I
Oregon State University Test Scoring (A)
' 2 )NSE CORRECT ( *)=QUESTION IGNORED A-E=CORRECT RESPONSE B .=CORRECT ANSWER -=NOT ANSWERED =MULTIPLE ANSWER
PAGE 30 14 -0CT-04 16 : 53
SECTION: ALL FORM: ALL
000000015 FORM: 1 SECTION: 000
. 56.0 OUT OF 68.0 ( 82.3%) AVERAGE: 53.9 MEDIAN: 56.
Question 0 1 1 2 2 3 3 4 4 5 5 6 6 7 Number 1---5----0----5----0----5----0----5----0----5----0----5----0----5---- 0 KEY CDEACBECEDDACEAACBCCCACBDDDBDEBEDD ANSWER ..... A.A.. ..... C. .. E.. .... E.....B. POINTS 22222 2 2222222 222 222222 22222 2
