Pharmacologie testes

USMLE WORLD STEP 1

PHARMACOLOGY Question List

Pharmacology Q No:

1

Hepatobiliary system

Pharmacology Q No:

42

Cardiology

Pharmacology Q No:

2

Blood vessels

Pharmacology Q No:

43

Endocrinology

Pharmacology Q No:

3

Hematology

Pharmacology Q No:

44

Hematology

Pharmacology Q No:

4

Head and neck 

Pharmacology Q No:

45

Dermatology

Pharmacology Q No:

5

Gastrointestinal system

Pharmacology Q No:

46

Musculoskeletal

Pharmacology Q No:

6

 Neurology

Pharmacology Q No:

47

 Neurology

Pharmacology Q No:

7

Head and neck 

Pharmacology Q No:

48

Gastrointestinal system

Pharmacology Q No:

8

Musculoskeletal

Pharmacology Q No:

49

 Neurology

Pharmacology Q No:

9

 Neurology

Pharmacology Q No:

50

 Neurology

Pharmacology Q No:

10

 N euro logy

Pharmacology Q No:

51

Gastrointestinal system

Pharmacology Q No:

11

Blood vessels

Pharmacology Q No:

52

 Neurology

Pharmacology Q No:

12

Musculoskeletal

Pharmacology Q No:

53

Musculoskeletal

Pharmacology Q No:

13

Head and neck 

Pharmacology Q No:

54

Oncology

Pharmacology Q No:

14

 Neurology

Pharmacology Q No:

55

 Neurology

Pharmacology Q No:

15

Endocrinology

Pharmacology Q No:

56

Blood vessels

Pharmacology Q No:

16

 Neurology

Pharmacology Q No:

57

 Neurology

Pharmacology Q No:

17

 Neurology

Pharmacology Q No:

58

Hematology

Pharmacology Q No:

18

Blood vessels

Pharmacology Q No:

59

Cardiology

Pharmacology Q No:

19

Pulmonology

Pharmacology Q No:

60

Blood vessels

Pharmacology Q No:

20

Endocrinology

Pharmacology Q No:

61

 Neurology

Pharmacology Q No:

21

 Neurology

Pharmacology Q No:

62

Dermatology

Pharmacology Q No:

22

Genitourinary

Pharmacology Q No:

63

 Neurology

Pharmacology Q No:

23

Hematology

Pharmacology Q No:

64

Endocrinology

Pharmacology Q No:

24

 Neurology

Pharmacology Q No:

65

 Neurology

Pharmacology Q No:

25

 Neurology

Pharmacology Q No:

66

Cardiology

Pharmacology Q No:

26

Genitourinary

Pharmacology Q No:

67

Cardiology

Pharmacology Q No:

27

 Neurology

Pharmacology Q No:

68

 Neurology

Pharmacology Q No:

28

Cardiology

Pharmacology Q No:

69

Pulmonology

Pharmacology Q No:

29

 Neurology

Pharmacology Q No:

70

Hematology

Pharmacology Q No:

30

Cardiology

Pharmacology Q No:

71

Cardiology

Pharmacology Q No:

31

Cardiology

Pharmacology Q No:

72

Renal

Pharmacology Q No:

32

Genitourinary

Pharmacology Q No:

73

 Neurology

Pharmacology Q No:

33

 Neurology

Pharmacology Q No:

74

Blood vessels

Pharmacology Q No:

34

Renal

Pharmacology Q No:

75

Hematology

Pharmacology Q No:

35

Oncology

Pharmacology Q No:

76

Musculoskeletal

Pharmacology Q No:

36

Endocrinology

Pharmacology Q No:

77

 Neurology

Pharmacology Q No:

37

Hepatobiliary system

Pharmacology Q No:

78

 Neurology

Pharmacology Q No:

38

Renal

Pharmacology Q No:

79

Endocrinology

Pharmacology Q No:

39

Hepatobiliary system

Pharmacology Q No:

80

 Neurology

Pharmacology Q No:

40

Endocrinology

Pharmacology Q No:

81

Pulmonology

Pharmacology Q No:

41

Cardiology

Pharmacology Q No:

82

Head and neck 

1

USMLE WORLD STEP 1

PHARMACOLOGY

Parmacology ! No"

#$

Neurology

Parmacology ! No"

%&'

Pulmonology

Parmacology ! No"

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Hematology

Parmacology ! No"

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Blood vessels

Parmacology ! No"

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Pulmonology

Parmacology ! No"

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Cardiology

Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Par Parm maco acolog logy ! No" No"

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Neu Neurolo rolog gy

Parmacology ! No"

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Musculoskeletal

Parmacology ! No"

%$#

Head and neck  

Parmacology ! No"

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Blood vessels

Parmacology ! No"

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Neurology

Parmacology ! No"

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Neurology

Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Genito urinary

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Neurology

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Musc ul uloskeletal

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Hepatobiliary syste m

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Endocrinology

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Parmacology ! No"

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Pulmonology

Parmacology ! No"

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Pulmonology

Parmacology ! No"

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Neurology

Parmacology ! No"

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Blood vessels

P a ar ma macology ! No"

%,#

Musc ul uloskeletal

Par ma macology ! No"

%',

Endocr in inology

Parmacology ! No"

%,+

Blood vessels

Parmacology ! No"

%'%

Hematology

Parmacology ! No"

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Pulmonology

Parmacology ! No"

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Cardiology

Parmacology ! No"

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Neurology

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Neurology

Parmacology ! No"

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Parm Parmac acol olog ogy y ! No" No"

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Gast Gastro roin inte test stin inal al syst system em

Parm Parmac acol olog ogy y ! No" No"

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Endo Endocri crino nolo logy gy

Parmacology ! No"

%%'

Cardiology

Parmacology ! No"

%'*

Endocrinology

Parmacology ! No"

%%)

Blood vessels

Parmacology ! No"

%'#

Musculoskeletal

Parmacology ! No"

%%*

Pulmonology

Parmacology ! No"

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Parmacology ! No"

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Neurology

Parmacology ! No"

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Hematology

Parmacology ! No"

%%+

Pulmonology

Parmacology ! No"

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Head and neck  

P a ar ma macology ! No"

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Musc ul uloskeletal

Par ma macology ! No"

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Hepatobiliary syste m

Parm Parmac acol olog ogy y ! No" No"

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Parm Parmac acol olog ogy y ! No" No"

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Bloo Blood d vess vessel elss

Parmacology ! No"

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Cardiology

Parmacology ! No"

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Pulmonology

P a ar ma macology ! No"

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Musc ul uloskeletal

Par ma macology ! No"

%)'

Cardiology

Parmacology ! No"

%&(

Endocrinology

Parmacology ! No"

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Oncology

2

USMLE WORLD STEP 1

PHARMACOLOGY

Parmacology ! No"

#$

Neurology

Parmacology ! No"

%&'

Pulmonology

Parmacology ! No"

#(

Hematology

Parmacology ! No"

%&)

Blood vessels

Parmacology ! No"

#'

Pulmonology

Parmacology ! No"

%&*

Cardiology

Parmacology ! No"

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Oncology

Parmacology ! No"

%&#

Blood vessels

Parmacology ! No"

#*

Pulmonology

Parmacology ! No"

%&+

Renal

Parmacology ! No"

##

Blood vessels

Parmacology ! No"

%$,

Neurology

Parmacology ! No"

#+

Neurology

Parmacology ! No"

%

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Endocrinology

Parmacology ! No"

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Cardiology

Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Genitourinary

Parmacology ! No"

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Parmacology ! No"

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Oncology

Parmacology ! No"

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Cardiology

Par Parm maco acolog logy ! No" No"

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Hep Hepato atobilia iliary ry syst system em

Par Parm maco acology ogy ! No" No"

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Neu Neurolo rolog gy

Parmacology ! No"

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Musculoskeletal

Parmacology ! No"

%$#

Head and neck  

Parmacology ! No"

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Blood vessels

Parmacology ! No"

%$+

Neurology

Parmacology ! No"

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Neurology

Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Genito urinary

Parmacology ! No"

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Cardiology

Parmacology ! No"

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Parmacology ! No"

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Neurology

P a ar ma macology ! No"

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Musc ul uloskeletal

Par ma macology ! No"

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Hepatobiliary syste m

Parmacology ! No"

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Endocrinology

Parmacology ! No"

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Pulmonology

Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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P a ar ma macology ! No"

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Par ma macology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Parmacology ! No"

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Cardiology

Parmacology ! No"

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Endocrinology

Parmacology ! No"

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Oncology

2

USMLE WORLD STEP 1

PHARMACOLOGY

Parmacology ! No"

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Parmacology ! No"

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USMLE WORLD STEP 1

PHARMACOLOGY

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Parmacology ! No"

$%'

Blood vessels

Parmacology ! No"

&**

Blood vessels

Parmacology ! No"

$%)

Neurology

Parmacology ! No"

&*#

Neurology

Parmacology ! No"

$%*

Neurology

Parmacology ! No"

&*+

Endocrinology

Parmacology ! No"

$%#

Blood vessels

Parmacology ! No"

&#,

Musculoskeletal

Parmacology ! No"

$%+

Neurology

Parmacology ! No"

&#%

Hematology

Parmacology ! No"

$&,

Pulmonology

Parmacology ! No"

&#&

Musculoskeleta l

Parma cology ! No"

$&%

Head a nd neck  

Parmacology ! No"

&#$

Blood vessels

Parmacology ! No"

$&&

Blood vessels

Parmacology ! No"

&#(

Genitourinary

Parmacology ! No"

$&$

Genitourinary

Parmacology ! No"

&#'

Renal

Parmacology ! No"

$&(

Blood vessels

Parmacology ! No"

&#)

Endocrinology

Parmacology ! No"

$&'

Musculoskeletal

Parmacology ! No"

&#*

Neurology

Parmacology ! No"

$&)

Neurology

Parmacology ! No"

&##

Neurology

Parmacology ! No"

$&*

Gastrointestinal system

Parmacology ! No"

&#+

Endocrinology

Parmacology ! No"

$&#

Neurology

4

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 1: After a positive PPD test, a 64!earo"# $a"e %e&i's iso'ia(i# t)erap!* O'e $o't) "ater )e prese'ts +o$p"ai'i'& of fever, a'oreia a'# 'a-sea* W)at is t)e $ost "i.e"! +a-se of )is +-rre't s!$pto$s/

A. B. C. D. E.

Peripheral nerve damage Hepatocyte damage Gastric mucosal damage Serum sickness Factitious disorder

Explanation: sonia!id "#H$ is directly hepatoto%ic in &'()'* o+ patients causing acute mild hepatic dys+unction ,ith transient increases in serum AS"SGP-$ A- "SGP-$ and /iliru/in and symptoms like +ever0 anore%ia0 and nausea. -his adverse e++ect usually occurs during the +irst 1(2 months o+ treatment and in most cases liver +unction tests return to /aseline ,ith continued #H therapy. n rare instances ho,ever severe hepatitis and progressive liver dys+unction /iliru/inuria0 and 3aundice occur. "Choice A$ Peripheral neuropathy is also a potential side e++ect o+ #H therapy i+ simultaneous pyrido%ine is not administered. Ho,ever peripheral neuropathy ,ould not cause the a/ove symptoms. "Choice D$ Serum sickness drug hypersensitivity generally causes +ever urticaria0 arthralgias0 proteinuria and lymphadenopathy 4(&' days a+ter e%posure to the drug "antigen$. -his patient does not have arthralgias or skin +indings.

Educational 5/3ective6 sonia!id "#H$ can /e directly hepatoto%ic causing acute mild hepatic dys+unction in &'()'* o+ patients. n a smaller percentage o+ cases +rank hepatitis may develop causing +ever anore%ia and nausea.

5

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 2: A 40!earo"# Ca-+asia' fe$a"e as #ia&'ose# it) )!per"ipi#e$ia t)at respo'#e# poor"! to #ietar! +)a'&es* Her past $e#i+a" )istor! is si&'ifi+a't for a+-te +)o"e+!stitis t)at re2-ire# a five#a! )ospita"i(atio'* Her fat)er #ie# of a $!o+ar#ia" i'far+tio' at t)e a&e of 34 a'# )er $ot)er )a# #ia%etes $e""it-s* W)i+) of t)e fo""oi'& #r-& +o$%i'atio's is $ost "i.e"! to pre+ipitate &a""sto'e for$atio' i' t)is patie't/ A. B. C. D. E. F.

Atorvastatin and e!etimi/e Atorvastatin and cholestyramine Atorvastatin and gem+i/ro!il Gem+i/ro!il and cholestyramine #iacin and e!etimi/e #iacin and gem+i/ro!il

Explanation: Bile acid(/inding resins "cholestyramine0 colestipol0 colesevelam$ ,ork /y /inding to /ile acid in the gastrointestinal tract0 inter+ering ,ith its enterohepatic circulation. D is reduced as a conse7uence0 /ecause hepatic cholesterol is consumed in the re(synthesis o+ /ile acids0 ,hich in turn increases the uptake o+ D +rom the circulation. Bile acid production and secretion is increased &'(+old /ecause o+ the interruption in the enterohepatic circulation o+ /ile acids. Bile acid( /inding agents increase the cholesterol content o+ /ile0 increasing the risk o+ gallstone +ormation. Fi/rates also increase the cholesterol content o+ /ile0 and thus also increase the risk +or gallstones. Both +i/rates and /ile acid(/inding resins should /e used ,ith caution in patients ,ith pree%isting gall/ladder disease.

Educational 5/3ective6 Both gem+i/ro!il and cholestyramine increase cholesterol e%cretion /y the liver. Along ,ith the reduction in serum D there is an increased risk +or gallstone +ormation.

6

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 3: A 6!earo"# fe$a"e is %ro-&)t to t)e R it) fever, )ea#a+)e a'# +o'f-sio'* T)e fa$i"! 'otes t)at t)ree !ears a&o s)e s-ffere# a severe a""er&i+ rea+tio' to pe'i+i""i' t)at re2-ire# )ospita"i(atio'* S)e is a#$itte#, a'# o' #a!4 of )er )ospita"i(atio', )er C5C s)os Complete /lood count Hemoglo/in 8.' g9 Erythrocyte count ).) mln9mm: Platelets 8''''9mm: eukocyte count )4''9mm: -he patient most likely received treatment ,ith6 A. B. C. D. E.

Clindamycin Gentamycin Chloramphenicol ;etronida!ole
Explanation: -he patient=s CBC sho,s pancytopenia "decreased erythrocytes0 leukocytes0 and platelets$. -his condition is also called aplastic anemia. t occurs due to suppression o+ stem cell +unction in the /one marro,. Common causes o+ ac7uired pancytopenia include radiation e%posure0 environmental to%ins "e.g. /en!ene0 arsenicals$0 certain in+ections0 and drugs. Chloramphenicol can cause /oth dose(dependent and dose( independent aplastic anemia. Chloramphenicol elicits its anti/acterial e++ect /y /inding to the ri/osomal 4'S su/unit and inhi/iting the peptidyl trans+erase en!yme. -hus0 it suppresses /acterial protein synthesis. Dose(dependent aplastic anemia associated ,ith chloramphenicol is reversi/le a+ter the medication is ,ithdra,n. Dose( independent anemia is usually severe and may /e +atal. "Choice A$ Clindamycin is active against Bacteroides and Gram positive cocci. -he most signi+icant side e++ect o+ clindamycin is pseudomem/ranous colitis. "Choice B$ Side e++ects o+ gentamycin include vesti/ular and cochlear ototo%icity0 nephroto%icity and neuromuscular paralysis ",ith large dose or intrapleural administration$. "Choice D$ -he common side e++ects o+ metronida!ole are gastrointestinal "nausea0 vomiting0 crampy a/dominal pain$ and neurologic "paresthesias0 di!!iness$. >hen taken ,ith alcohol0 metronida!ole induces a disul+iram(like reaction. "Choice E$ ?apid administration o+ vancomycin can cause histamine release ,hich results in +lushing "@red man syndrome$. -his anti/iotic may also cause dose(related ototo%icity.

Educational 5/3ective6 Aplastic anemia "pancytopenia$ is caused /y many drugs and environmental to%ins. Chloramphenicol can lead to /oth dose(dependent "reversi/le$ and dose(independent "o+ten irreversi/le$ pancytopenia.

7

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 4: A +)e$ot)erape-ti+ a&e't is s)o' to %i'# i' vitro it) vira" e'+o#e# e'(!$es s-+) as D7A po"!$erase, R7A po"!$erase, a'# reverse tra's+riptase* T)e a&e't #oes 'ot re2-ire i'tra+e""-"ar a+tivatio' to #e$o'strate its a'tivira" effe+t* W)i+) of t)e fo""oi'& a&e'ts is st-#ie# i' t)e eperi$e't/ A. B. C. D. E. F. G.

Acyclovir Foscarnet amivudine Sa7uinavir Ganciclovir Amantadine 5seltamivir

Explanation: Foscarnet is a pyrophosphate analog that does not re7uire intracellular activation. t directly inhi/its /oth D#A polymerase in herpesvirus and reverse transcriptase in human immunode+iciency virus "H<$. Foscarnet must /e administered intravenously and is most commonly used in treating advanced ADS patients ,ho have acyclovir(resistant herpesvirus in+ections or ganciclovir(resistant cytomegalovirus in+ections. "Choice A$ Acyclovir is a nucleoside analog that must /e intracellularly converted to its monophosphate +orm /y a virally encoded thymidine kinase. Cellular kinases convert the monophosphate +orm into a triphosphate +orm0 ,hich inhi/its herpesviral D#A polymerase(mediated replication. "Choice C$ amivudine is a cytosine analog classi+ied as a nucleoside reverse transcriptase inhi/itor "#?-$. t must /e phosphorylated to its active +orm0 lamivudine triphosphate0 /y intracellular kinases. amivudine inhi/its H< reverse transcription through viral D#A chain termination. "Choice D$ Sa7uinavir does not re7uire intracellular activation. t is a protease inhi/itor that /inds to the catalytic site o+ an H< aspartic protease0 preventing the cleavage o+ polyprotein precursors necessary +or the generation o+ +unctional viral proteins. "Choice E$ Ganciclovir is a guanine nucleoside analogue that is structurally similar to acyclovir. t re7uires intracellular conversion to its monophosphate +orm /y a virally encoded kinase0 and has greater activity than acyclovir against cytomegalovirus D#A polymerase. "Choice F$ Amantadine is an antiviral agent that does not re7uire intracellular activation. t /inds to and inhi/its the ;) ion channel protein o+ in+luen!a A viruses0 /locking viral un coating a+ter host cell endocytosis. "Choice G$ 5seltamivir is an antiviral agent that does not re7uire intracellular activation. t is a sialic acid analogue inhi/itor o+ in+luen!a A and B virus neuraminidase.

Educational 5/3ective6 5+ all the antiviral agents that /ind and inhi/it D#A polymerase in herpesvirus and reverse transcriptase in H< the pyrophosphate analog +oscarnet is one o+ +e, that do not re7uire intracellular activation /y viral or cellular kinases.

8

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 5: E'tero+o++i strai's iso"ate# fro$ a patie't it) %a+tere$ia are .'o' to s-%stit-te Da"a'i'e for D"a+tate i' t)e s!'t)esis of pe'tapepti#e proteo&"!+a' pre+-rsors* T)is s-%stit-tio' #e+reases pe'tapepti#e %i'#i'& for )i+) of t)e fo""oi'& a'ti%ioti+s/

A. B. C. D. E. F.


Explanation:
Educational 5/3ective6 -he mechanism o+ vancomycin resistance in organisms such as
USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 6: A 81!earo"# Ca-+asia' $a"e is %ro-&)t to t)e ER it) pro"o'&e# to'i+ +"o'i+ sei(-res* His ife sa!s t)at )e )a# a si$i"ar episo#e t)ree $o't)s a&o for )i+) )e as pres+ri%e# so$e $e#i+atio's t)at )e 'ever too.* 9: "ora(epa$ is a#$i'istere# i' t)e ER, a'# t)e sei(-res stop* A' i'trave'o-s i'f-sio' of a'ot)er #r-& is si$-"ta'eo-s"! i'stit-te# to preve't sei(-re re+-rre'+e* W)i+) of t)e fo""oi'& is t)e $ost "i.e"! $e+)a'is$ of a+tio' of t)e se+o'# #r-& i'f-se# i' t)is patie't/ A. B. C. D. E.

Decreases calcium current in thalamic neurons Decreases sodium current in cortical neurons ncreases chloride current on multiple levels Blocks #;DA receptors in hippocampal neurons Blocks outgoing potassium current on multiple levels

Explanation: ?ecurrent or continuous generali!ed tonic(clonic sei!ures that last +or more than :' minutes ,ithout a return to consciousness are called status epilepticus. t is a li+e(threatening condition that has a num/er o+ systemic e++ects0 including hypertension tachycardia0 cardiac arrhythmias0 and lactic acidosis. -reatment o+ status epilepticus should /e started immediately. t consists o+ the +ollo,ing6 &. Ben!odia!epines are the +irst(line drugs +or management o+ status epilepticus. ora!epam is the drug o+ choice. ). Phenytoin "or +osphenytoin$ is administered simultaneously to prevent the recurrence o+ sei!ures. Ben!odia!epines are pre+erred to phenytoin +or initial sei!ure management /ecause /en!odia!epines have a more rapid onset o+ action. -he onset o+ action o+ phenytoin is a/out &4 minutes a+ter < in+usion/en!odia!epines /egin ,orking ,ithin a +e, minutes. + sei!ure does not stop a+ter /en!odia!epines and phenytoin is administered pheno/ar/ital is indicated. Alternatively mida!olam0 propo+ol0 or inhaled anesthetics may /e used to induce a state o+ general anesthesia. 10

USMLE WORLD STEP 1

PHARMACOLOGY

Phenytoin inhi/its neuronal high(+re7uency +iring /y reducing the a/ility o+ sodium channels to recover +rom inactivation. -hus at high( +re7uency +iring rates the neuron /ecomes re+ractory to reactivation and reduces sei!ure activity. "Choice A$ Ethosu%imide acts /y /locking -(type calcium channels in the thalamic neurons. t is +irst(line treatment +or a/sence sei!ures. Ethosu%imide is not e++ective in status epilepticus. "Choice C$ Ben!odia!epines0 /ar/iturates and alcohol /ind to the component o+ GABAA receptor that is a ligand gated chloride channel. -hese su/stances enhance the inhi/itory action o+ GABA on the receptor and increase chloride current. "Choices D and E$
11

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 7: A 46!earo"# '-rse is %ro-&)t to t)e e$er&e'+! roo$ it) +o'f-sio' a'# fever* O' p)!si+a" ea$, )er s.i' is f"-s)e#* Her ora" $-+osa is #r!, a'# )er p-pi"s are #i"ate# a'# poor"! respo'sive to "i&)t* A %ott"e of atropi'e is fo-'# i' )er po+.et* W)i+) of t)e fo""oi'& #r-&s +a' +a-se a si$i"ar +"i'i+a" prese'tatio'/

A. B. C. D. E.

Dia!epam Amitriptyline Propranolol Car/ama!epine Pra!osin

Explanation: Classic signs and symptoms o+ anticholinergic to%icity include +ever0 mucosal and a%illary di!!iness0 cutaneous +lushing0 mydriasis0 cycloplegia0 and delirium "use the mnemonic @hot as a hare dry as a /one0 red as a /eet0 /lind as a /at0 and mad as a hatter$. 5+ the drugs listed0 amitriptyline has the most potent anticholinergic side e++ects. Amitriptyline and the other tricyclic antidepressants have these e++ects /ecause they /lock muscarinic receptors. 5verdose can cause anticholinergic symptoms mimicking atropine to%icity. "Choice A$ -ypical symptoms o+ /en!odia!epine overdose include sedation anterograde amnesia and respiratory depression. Ben!odia!epines are rarely +atal in overdose. "Choice C$ Adverse e++ects associated ,ith nonselective :(adrenergic /lockers include /ronchial constriction0 masked symptoms o+ hypoglycemia in dia/etics0 /radyarrhythmias0 ,orsening o+ ?aynaud phenomenon0 and C#S depression. "Choice D$ Car/ama!epine is an anticonvulsant used in sei!ure disorders trigeminal neuralgia and /ipolar disorder. n overdose0 its to%ic e++ects include stupor0 coma and increased sei!ure risk. "Choice E$ Pra!osin is an al(adrenergic /locker used to treat hypertension and urinary retention due to /enign prostatic hypertrophy. ts ma3or adverse e++ect is hypotension "especially postural hypotension$.

Educational 5/3ective6 Fever0 cutaneous +lushing0 dry oral mucosa0 dilated poorly reactive pupils and con+usion are all signs o+ anticholinergic to%icity. -ricyclic antidepressants0 particularly amitriptyline0 have antimuscarinic side e++ects that may mimic atropine to%i city.

12

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 8: A 63!earo"# fe$a"e is )ospita"i(e# it) a )ip fra+t-re* Her %o'e #e'sit!, $eas-re# %! 2-a'titative ;ra! #e'sito$etr!, +orrespo'#s to t)e "oest 1<=* Her +o$or%i#ities i'+"-#e )!perte'sio'> #ia%etes $e""it-s, t!pe 8> a'# +o'&estive )eart fai"-re ?CHE@* T)e atte'#i'& p)!si+ia' s-&&ests t)at if t)is patie't )a# re+eive# "o'&ter$ treat$e't it) a #r-& affe+ti'& +a"+i-$ $eta%o"is$ )er fra+t-re +o-"# )ave %ee' avoi#e#* W)i+) #r-& is $ost "i.e"! $e'tio'e# %! t)e p)!si+ia'/

A. B. C. D. E. F. G.

Furosemide Hydrochlorothia!ide Spironolactone Digo%in Enalapril Gly/uride Acar/ose

Explanation: -his patient has osteoporosis0 ,hich is re+lected /y her very lo, /one density and her +ractured hip. Hydrochlorothia!ide is a diuretic agent used to treat hypertension and to treat congestive heart disease. An opportune side e++ect o+ hydrochlorothia!ide is that it increases the a/sorption o+ calcium +rom the distal convoluted tu/ules0 making it an ideal agent +or treating hypertension9CHE in a ,oman ,ho is also at risk +or osteoporosis. Studies have sho,n that patients ,ho are on thia!ide diuretics have relatively higher /one mineral densities. Hydrochlorothia!ide has another +ortuitous side e++ectthe increased renal calcium a/sorption causes hypocalciuria0 ,hich helps prevent pain+ul renal stones in some patients. "Choice A$ Furosemide is a loop diuretic used to treat hypertension and CHF. t causes an increase in urinary calcium loss that could only ,orsen osteoporosis in this ,oman. "Choice C$ Spironolactone inhi/its action o+ other steroid hormones0 such as testosterone. -he antiandrogenic action o+ spironolactone is utili!ed +or the treatment o+ hirsutism and androgen(dependent malignancies. t does not have an a++ect on calcium homeostasis. "Choice D$ -herapeutic digo%in levels do not lead to a signi+icant alteration in calcium levels. Ho,ever0 digitalis to%icity is associated ,ith hypercalcemia. -his is not the correct ans,er /ecause the risk o+ digitalis to%icity +ar out,eighs any possi/le /ene+it o+ an increased calcium level. "Choice E$ Enalapril has not /een associated ,ith signi+icant change in /one mineral density. "Choice F and G$ Gly/uride and acar/ose are oral hypoglycemic agents used to treat type ) dia/etes mellitus. Both o+ these medications have an insigni+icant e++ect on /one mineral density.

Educational 5/3ective6 -hia!ide diuretics decrease urinary calcium e%cretion and may improve /one density. Furosemide ,ill increase urinary calcium loss0 making it a possi/le treatment +or hypercalcemia0 /ut not +or ,omen ,ith porus /ones. E%tremely important concept

13

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 9: A 8!earo"# fe$a"e prese'ts to t)e ER it) +)est pai' #!sp'ea, pa"pitatio's periora" '-$%'ess a'# seati'&* Soo' after treat$e't it) "ora(epa$ t)e patie't fee"s %etter a'# a'ts to &o )o$e* Car#ia+ e'(!$es are 'or$a" a'# a' ECG s)os 'or$a" si'-s r)!t)$ it) 'o ST se&$e't or Tave a%'or$a"ities* W)i+) of t)e fo""oi'& i'#i+ates t)e site of a+tio' of t)e #r-& o' t)e #ia&ra$ %e"o/

A. B. C. D. E. F.

A B C D E F

Explanation: GABA "y(amino/utyric acid$ is the main inhi/itory neurotransmitter in the C#S. ts synthesis +rom glutamate is mediated /y glutamate decar/o%ylase "GAD$ ,ithin neurons. ;eta/olism o+ GABA occurs /y means o+ transamination per+ormed /y en!yme GABA transaminase "GABA(-$. Both GAD and GABA(- use
-his case scenario descri/es use o+ the /en!odia!epine lora!epam +or treatment o+ a panic attack. Ben!odia!epines act /y /inding to the GABAA receptor and stimulating the in+lu% o+ chloride ions into the neurons. Binding to the ?eceptor +acilitates the inhi/itory action o+ GABA in the C#S. Bar/iturates0 alcohol and !olpidem display a similar mechanism o+ action. -hese su/stances0 ho,ever0 /ind to a di++erent component o+ the GABAA receptor than do /en!odia!epines. 14

USMLE WORLD STEP 1

PHARMACOLOGY

"Choice A$ Ben!odia!epines0 /ar/iturates0 !olpidem and alcohol are all GABA(agonists. -hey act /y /inding to GABAA receptor0 not to GABA itsel+. "Choice C$ Stimulation o+ the GABAA receptor leads to activation o+ ion channels and increased chloride in+lu% into the cell. GABA agonists do not /ind to the ion channels directly they /ind to the receptor /inding sites. "Choices D0 E and F$ Stimulation o+ the GABA2 receptor leads to activation o+ an inhi/itory G(protein ,ith a su/se7uent change in activity o+ an ion channel. t results in inhi/ition o+ adenylyl cyclase0 a decrease in calcium in+lu% and an increase in potassium e++lu%. Educational 5/3ective6 -he GABAA and GABAC receptors are ion channels0 ,hile the GABAB receptor is linked to a G( protein. Ben!odia!epines0 !olpidem0 /ar/iturates and alcohol /ind to a component o+ GABAA receptors and +acilitate the inhi/itory action o+ GABA in the C#S.

15

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 10: A 6<!earo"#fe$a"e prese'ts to !o-r offi+e +o$p"ai'i'& of i'vo"-'tar! fa+e a'# to'&-e $ove$e'ts* Yo- 'ote t)at a"t)o-&) a#e2-ate"! respo'#i'& to !o-r 2-estio's, t)e patie't appears to &ri$a+e a'# rit)e* S)e sa!s t)at t)e s!$pto$s &et orse after e$otio'a" stress a'# fati&-e* Her past $e#i+a" )istor! is si&'ifi+a't for "o'&sta'#i'& s+)i(op)re'ia effe+tive"! +o'tro""e# it) $e#i+atio's* W)i+) of t)e fo""oi'& is t)e $ost "i.e"! #ia&'osis i' t)is patie't/ A. B. C. D. E. F. G.

Acute dystonia #euroleptic(induced Parkinsonism Akathisia -ardive dyskinesia ;anic episode #euroleptic malignant syndrome Drug(induced delirium

Explanation: E%trapyramidal symptoms "EPS$ occur +re7uently as side e++ects o+ typical antipsychotics /ut may also occasionally occur ,ith the use o+ atypical antipsychotics. -his patient has developed tardive dyskinesia as a side e++ect o+ antipsychotic usage. -ardive dyskinesia is characteri!ed /y involuntary pen oral movements such as /iting0 che,ing0 grimacing0 and tongue protrusions. nvoluntary choreoathetoid movements o+ the head0 lim/s0 and trunk may also /e o/served. -he condition usually arises /et,een +our months and +our years o+ treatment and may /e irreversi/le. ?isperidone is the atypical antipsychotic most likely to cause EPS ,hile clo!apine is the atypical antipsychotic least likely to cause EPS. -here+ore tardive dyskinesia is /est managed /y decreasing the dose or discontinuing the o++ending antipsychotic and replacing it ,ith clo!apine. Because clo!apine is associated ,ith agranulocytosis0 it is typically considered to /e a medication o+ last resort. "Choice A$ Acute dystonia can develop a/ruptly at any point /et,een +our hours and +our days a+ter receiving an antipsychotic medication. -he condition is characteri!ed /y muscle spasms or sti++ness0 tongue protrusions or t,isting opisthotonus0 and oculogyric crisis "a +orced sustained elevation o+ the eyes in an up,ard position$. -reatment o+ acute dystonia is ,ith antihistamines "eg0 diphenhydramine$ or anticholinergics "eg0 /en!tropine or trihe%yphenidyl$. "Choice B$ Parkinsonism can also occur0 developing /et,een +our days and +our months a+ter receiving an antipsychotic medication. t presents ,ith cog,heel rigidity0 masked +acies0 /radykinesis0 pill( rolling +inger tremors and shu++ling gait. -reatment is ,ith anticholinergics such as /en!tropine. "Choice C$ Akathisia is a su/3ective +eeling o+ restlessness that compels patients to constantly move around. t can occur at anytime during treatment ,ith antipsychotics. "Choice E$ Acute mania is marked /y grandiose delusions "millions o+ dollars are held in trust +or them the President calls them they are chosen /y God +or a magni+icent purpose etc.$. Flight o+ ideas and pressured speech /ecome very intense and hyperactivity and impulsivity /ecomes more pronounced. "Choice F$ #euroleptic malignant syndrome is a rare and potentially +atal syndrome characteri!ed primarily /y delirium +ever muscle rigidity0 and autonomic insta/ility.

16

USMLE WORLD STEP 1

PHARMACOLOGY

"Choice G$-he hallmark o+ delirium is con+usion ora clouding o+ the sensorium. Patients may appear some,hat da!ed and unclear a/out their surroundings. Disorientation to time and place are common accompanying +eatures. Educational 5/3ective6 -ardive dyskinesia is characteri!ed /y involuntary perioral movements such as /iting0 che,ing0 grimacing0 and tongue protrusions. nvoluntary choreoathetoid movements o+ the head0 lim/s0 and trunk may also /e o/served. -he condition usually arises /et,een +our months and +our years o+ treatment and may/e irreversi/le.

17

USMLE WORLD STEP 1

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Q NO 11: A $e#i+a" st-#e't is +o'#-+ti'& a p)ar$a+o"o&! eperi$e't* He i'f-ses Dr-& ; i'trave'o-s"! over #iffere't #ose ra'&es a'# $eas-res severa" i$porta't )e$o#!'a$i+ para$eters* Grap)s p"otti'& t)e re+or#e# $eas-re$e'ts of re'a" %"oo# f"o a'# +ar#ia+ o-tp-t +)a'&e it) i'+reasi'& #oses of Dr-& ; are s)o' %e"o* W)i+) of t)e fo""oi'& is $ost "i.e"! to %e t)e #r-& -se# i' t)e eperi$e't/

A. B. C. D. E.

Epinephrine Phenylephrine Dopamine Edrophonium Esmolol

Explanation: Dopamine is uni7ue among adrenergic stimulators due to its a/ility to simultaneously increase /oth myocardial contractility and renal /lood +lo,. Because o+ this uni7ue e++ect dopamine is used to increase renal per+usion in lo,( output cardiac states0 such as hypovolemic and cardiogenic shock. Dopamine e%ecutes its renal e++ects via stimulation o+ D& adrenergic receptors in the ,alls o+ renal /lood vessels. -hese D& adrenergic receptors are also located in the splanchnic and mesenteric arteries0 ,hich are also dilated /y dopamine=s e++ects. Dopaminergic increases in renal /lood +lo, results in increased glomerular +iltration0 increased urinary output0 and increased sodium e%cretion. -he dose o+ dopamine that a++ects Dl receptors o+ renal arteries also acts as an agonist on & receptors o+ myocardium0 increasing /oth heart rate and myocardial contractility0 leading to overall increases in cardiac output. Systolic /lood pressure su/se7uently increases due to the rise in cardiac output. Higher doses o+ dopamine stimulate al( adrenoreceptors in the arteries o+ skin and viscera "including kidneys$0 resulting in vasoconstriction. See the ta/le /elo, +or comparison o+ the e++ects o+ dopamine ,ith epinephrine "a and agonist$ and phenylephrine "a agonist$.

"Choice A$ Epinephrine stimulates /oth I and  adrenoreceptors and increases myocardial contractility and cardiac output " stimulation$0 ,hile decreasing renal /lood +lo, "al stimulation$.

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"Choice B$ Phenylephrine is a selective agonist o+ a(adrenoreceptors that does not a++ect :& receptors o+ myocardium. Stimulation o+ al receptors causes renal splanchnic and mesenteric vasoconstriction. "Choice D$ Edrophonium is a short(acting cholinesterase inhi/itor used in the diagnosis o+ myasthenia gravis. -hrough its cholinergic e++ects edrophonium reduces heart rate0 cardiac conduction0 and cardiac contractility. "Choice E$ Esmolol is a cardioselective  /locker ,ith a short duration o+ action. Esmolol decreases heart rate0 myocardial contractility0 and cardiac conduction ,ithout a++ecting renal /lood +lo,. Educational 5/3ective6 o, doses o+ dopamine stimulate /oth Dl receptors in renal and splanchnic /lood as ,ell as & receptors o+ the myocardium0 leading to increases in /oth renal /lood +lo, and myocardial contractility. 5n the other hand0 high doses o+ dopamine stimulate I& receptors0 resulting in peripheral vasoconstriction.

19

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 12: A 3B!earo"# fe$a"e it) a "o'& )istor! of r)e-$atoi# art)ritis a'# pepti+ -"+er #isease prese'ts to t)e e$er&e'+! roo$ it) a+-te "o %a+. pai' after too 2-i+."! sitti'& #o' o'to a )ar#oo# +)air* S)e reports t)at s)e ta.es $a'! $e#i+atio's, a'# )as %ee' for severa" !ears* ;ra! s)os a fra+t-re of t)e fo-rt) "-$%ar verte%ra* W)i+) of t)e fo""oi'& $a! )ave +o'tri%-te# to t)is i'-r!/ A. B. C. D. E.

?heumatoid arthritis progression ;ethotre%ate side e++ect Prednisone side e++ect ndomethacin side e++ect 5mepra!ole side e++ect

Explanation: -his patient presents ,ith a pathologic +racture o+ a lum/ar verte/ra. A pathologic +racture is one that results +rom a +orce signi+icantly less than that re7uired to +racture a normal /one. nderlying /one pathology is generally present. Patients taking as little as J.4mg o+ daily prednisone +or longer than si% months can develop osteoporotic /one changes0 and :'(4'* o+ patients on prolonged systemic glucocorticoids may develop pathologic verte/ral /ody +ractures. ong term use o+ systemic steroids is thought to promote osteoporosis /y causing decreased synthesis o+ /one matri%0 inhi/iting the intestinal action o+ vitamin D to promote calcium a/sorption0 and causing increased parathyroid hormone levels. "Choice A$ ?heumatoid arthritis "?A$ is an autoimmune in+lammatory disorder that predominantly a++ects synovial 3oints in the hands and +eet0 /ut also a++ects larger 3oints like the ,rists and shoulders. nterverte/ral /ody 3oints lack a synovial space. ?A ,ould /e unlikely to directly cause a pathologic thoracolum/ar verte/ral +racture. "Choices B0 D and E$ ;ethotre%ate0 #SADs and proton pump inhi/itors are not kno,n to cause osteoporosis.

Educational 5/3ective6 5steoporosis is a common cause o+ pathological verte/ral +ractures. Chronic systemic use o+ corticosteroids like prednisone promotes osteoporosis and there+ore may cause such +ractures.

20

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PHARMACOLOGY

Q NO 13: A +)e$ot)erape-ti+ a&e't +"assifie# as a &-a'osi'e #erivative #e$o'strates si&'ifi+a't a'tivira" a+tivit! a&ai'st )erpes si$p"evir-s t!pe 1 )erpes si$p"evir-s t!pe 8, a'# vari+e""a (oster vir-s* T)e sa$e a&e't #e$o'strates ea. a'tivira" a+tivit! a&ai'st Epstei'5arr vir-s a'# +!to$e&a"! vir-s* W)i+) of t)e fo""oi'& %est ep"ai's t)is #iffere'+e i' vira" s-s+epti%i"it! to t)e #r-&/

A.
protease activity B. D#A polymerase structure C. Structural protein composition D. Drug phosphorylation rate E. Drug degradation rate

Explanation: -he chemotherapeutic agent descri/ed here is most likely acyclovir0 a guanosine analog. 5nce acyclovir enters the herpesvirus(in+ected host cell0 it is converted to acyclovir monophosphate principally via a virally(encoded thymidine kinase "-K$. -his is the rate(limiting step in the activation o+ acyclovir. -he acyclovir monophosphate is then phosphorated /y cellular en!ymes into the active triphosphate +orm0 ,hich impairs viral D#A polymerase(mediated replication o+ the virus. Epstein(Barr virus "EB<$ and cytomegalovirus "C;<$ do not produce the same thymidine kinase that herpes simple% viruses "HS<$ and varicella !oster virus "
USMLE WORLD STEP 1

PHARMACOLOGY

+our drugs listed re7uire mono phosphorylation /y a virally(encoded kinase. Because these drugs are activated en!ymatically0 the structural protein composition o+ the virus does not a++ect drug sensitivity. "Choice E$-he drug degradation rate is not responsi/le +or di++erences in viral suscepti/ility to acyclovir. Educational 5/3ective6 ;ono phosphorylation o+ acyclovir /y a viral thymidine kinase is the +irst "and rate(limiting$ step in the conversion o+ acyclovir to its active triphosphate +orm. Acyclovir and related drugs "eg0 +amciclovir0 valaciclovir$ are more e++ective against herpes simple% virus and varicella !oster virus than cytomegalovirus and Epstein(Barr virus.

22

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Q NO 14: A B!earo"# trave"er prese'ts to !o-r offi+e for a ro-ti'e +)e+.-p* He i"" %e "eavi'& for a +r-ise 'et ee., a'# as.s for a #r-& t)at o-"# preve't t)e severe 'a-sea a'# vo$iti'& )e eperie'+es o' s)ips* After re+o$$e'#i'& t)e appropriate #r-&, !o- ar' a%o-t )i+) of t)e fo""oi'& si#e effe+ts/ A. B. C. D. E.

Diarrhea #asal congestion Cough Dry mouth Fre7uent urination

Explanation: Antihistaminics0 or Hi histamine receptor /lockers0 are very use+ul drugs in the treatment o+ allergy. Hi receptor /lockers decrease the activity o+ this receptor /y increasing the proportion o+ inactive Hi receptors0 via a process kno,n as reverse /lockade. n addition to /locking Hi receptors0 +irst(generation antihistaminics have antimuscarinic0 antiadrenergic and anti serotonergic properties. n motion sickness0 the muscarinic ;i and histaminic Hi path,ays are stimulated0 resulting in the nausea and vomiting o+ motion sickness. Because o+ their anti muscarinic and antihistaminic properties0 +irst( generation antihistaminic drugs like mecli!ine and dimenhydrinate are e++ective at preventing these symptoms. 5ther +irst generation drugs are also e++ective0 /ut are generally avoided /ecause o+ their sedating properties. Scopolamine has only antimuscarinic e++ects and is also e++ective at preventing the symptoms o+ motion sickness. Side e++ects o+ antimuscarinics include /lurry vision0 dry mouth0 palpitations0 urinary retention and constipation. -he options in choices A0 B0 C and E occur ,ith stimulation rather than /lockade o+ the muscarinic path,ay.

Educational 5/3ective6 Antimuscarinic agents and antihistamines ,ith antimuscarinic action are most e++ective +or motion sickness prevention.

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Q NO 15: A 'e #r-& is %ei'& #eve"ope# for t)e treat$e't of #ia%etes* T)is #r-& a+tivates t)e peroiso$e pro"iferatora+tivate# re+eptor &a$$a ?PPAR&a$$a@, a '-+"ear re+eptor a'# tra's+riptio' fa+tor* A+tivatio' of t)is re+eptor o-"# $ost "i.e"! res-"t i' )i+) of t)e fo""oi'&/ A. B. C. D. E.

Do,n regulation o+ leptin activity ncreased insulin release Decreased insulin resistance ncreased +ree +atty acid levels Do,nregulation o+ adiponectin

Explanation: -hia!olidinediones "-LD4$ e%ert their glucose(lo,ering e++ect /y decreasing insulin resistance. -LDs /ind to pero%isome proli+erator activated receptor gamma "PPA?(gamma$0 ,hich is a transcriptional regulator o+ the genes involved in glucose and lipid meta/olism. 5ne o+ the most crucial genes regulated /y PPA?(gamma is adiponectin0 ,hich is a cytokine secreted /y +at tissue "adipocytokine$. Adiponectin levels are lo, in type ) dia/etes ,hich -LDs alter. As the glucose lo,ering e++ect o+ -LDs re7uires alteration in gene transcription and protein synthesis0 it takes days to ,eeks a+ter initiation o+ therapy to o/serve a signi+icant reduction in glucose levels. -LDs do not cause hypoglycemia. -he main side e++ects o+ -LDs are +luid retention0 ,eight gain0 and the precipitation o+ congestive heart +ailure +rom +luid retention. "Choice A$ eptin is the hormone secreted /y +at cells. t is responsi/le +or appetite suppression and decreased insulin resistance0 ,hich is mediated via the central nervous system. Although PPA?(gamma activation increases +at cell mass0 circulating leptin levels are essentially unchanged. Some studies have sho,n that PPA?(gamma activation leads to suppression o+ the transcription o+ the leptin 24

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gene. -he activity o+ leptin is not signi+icantly altered ,ith PPA? gamma activation0 ho,ever. "Choice B$ PPA?(gamma is present in small amounts in pancreatic /eta cells. -LDs do not directly alter insulin secretion6 ho,ever0 as insulin resistance diminishes0 circulating levels o+ insulin tend to decrease overtime. "Choice D$ PPA?(gamma activation leads to an increase in +at mass secondary to the increased di++erentiation o+ preadipocytes into mature adipocytes. -he movement o+ +ree +atty acids into +at cells is increased0 and circulating +ree +atty acids levels decrease. "Choice E$ Adiponectin is a ne,ly(discovered cytokine secreted /y +at cells. Adiponectin levels are decreased in patients ,ith type ) dia/etes mellitus. 5ne o+ the mechanisms /y ,hich PPA?(gamma activation decreases insulin resistance is /y increased e%pression o+ the adiponectin gene. Educational 5/3ective6 -LDs activate PPA?(gamma0 ,hich is the nuclear receptor that alters the transcription o+ genes responsi/le +or +at and lipid meta/olism. -hia!olidinediones "-LD4$ e%ert their glucose(lo,ering e++ect /y decreasing insulin resistance.

25

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 16: A 18!earo"# $a"e is )ospita"i(e# it) )ea#a+)e, 'a-sea a'# fever* A p)!si+a" ea$i'atio' ea$i'atio' is si&'ifi+a't for 'e+. stiff'ess* Gra$'e&ative +o++i i' pairs are revea"e# #-ri'& CS $i+ros+op!* W)i+) of t)e fo""oi'& is t)e %est a! to preve't i'fe+tio' i' )is +"ose +o'ta+ts/ A. B. C. D. E. F.

Capsular polysaccharide vaccine Pilus protein vaccine ipopolysaccharide vaccine Penicillin Sul+ametho%a!ole ?i+ampin

Explanation: -he gram stain description o+ gram(negative cocci in pairs makes the etiologic agent o+ this in+ection most likely #eisseria meningitidis. Because the agent is transmitted /y direct contact ,ith contaminated respiratory secretions or air/orne droplets0 +amily mem/ers and other close contacts o+ persons ,ith meningococcal disease are at high risk o+ ac7uiring the disease or /ecoming carriers and must receive immediate prophyla%is. ?i+ampin has /een used success+ully since the &82'=s +or chemoprophyla%is +or house hold mem/ers and close contacts o+ patients ,ith invasive meningococcal disease and is the most likely chemo prophylactic agent to /e administered in this su/3ect. ?i+ampin is used +or chemoprophyla%is /ecause it penetrates ,ell into the respiratory tract and ,ill eliminate nasopharyngeal coloni!ation. ?i+ampin=s most nota/le side e++ect is an orange discoloration o+ secretions "urine0 /reast milk and tears$0 and patients should /e alerted to the +act that contact lenses ,ill /e permanently stained orange. Also0 remem/er that ri+ A;P in @A;Pli+ies CMP145 and ,ill increase the meta/olism o+ drugs such as ,ar+arin that are processed /y this system. "Choice A$ hile penicillin is the pre+erred agent +or treatment o+ #. meningitidis in+ections0 it is not use+ul +or prophyla%is ,here ri+ampin0 +ollo,ed /y ce+tria%one0 is the drug o+ choice. -he reason +or this is that only ri+ampin and the third generation cephalosporins have /een sho,n to eliminate nasal carriage. "Choice E$ Sul+ametho%a!ole ,as historically used as chemoprophyla%is +or contacts o+ an inde% case o+ meningococcal disease0 /ut presently this ,ould not /e a correct choice due to the +act that #. meningitidis

26

USMLE WORLD STEP 1

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has developed ,idespread resistance to sul+onamides0 so these drugs are no longer used. Educational 5/3ective6 ?i+ampin is most typically used as chemoprophyla%is o+ meningococcal meningitis. t must /e prescri/ed to all close contacts o+ any patient ,ho has active disease ,ithin ) ,eeks o+ diagnosis in order to /e e++ective.
27

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 17:  A 3<!earo"# 3<!earo"# $a' is %ro-&)t to e$er&e'+! roo$ after #eve"opi'& %"-rre# visio' )i"e +-tti'& severa" trees i' )is &ar#e'* His past $e#i+a" )istor! is i'si&'ifi+a't i'si&'ifi+a't a'# )e is 'ot ta.i'& a'! $e#i+atio's* He )as 'o )istor! of i""i+it #r-& -se* His te$perat-re is B*C ?1<8@, %"oo# press-re is 1<
Dia!epam Haloperidol Ben!tropine Physostigmine ;etoprolol Atropine -hiamine ;orphine #alo%one

Explanation: -his patient most likely has Nimson >eed "Datura stramonium$ poisoning. -his condition is also called as @Gardener=s mydriasis. Nimson >eed produces to%ins "/elladonna alkaloids$ that possess strong anticholinergic properties. Nimson ,eed and atropine poisoning are strikingly similar. Blockade o+ visceral muscarinic receptors produces the +ollo,ing e++ects6 &. Heart6 diminished vagal tone at the SA node causes relative tachycardia. ). Blood vessels6 vasoconstriction via muscarinic receptor /lockade in endothelial cells results in decreased nitric o%ide synthesis. n spite o+ this e++ect atropine poisoning is associated ,ith cutaneous +lushing the pathogenesis o+ this e++ect is unkno,n. :. G6 delayed gastric emptying0 decreased intestinal motility0 and secretion. 1. ?espirators=6 /ronchodilatation. 4. G6 urinary retention via detrusor rela%ation and contraction o+ the e%ternal urethral sphincter. 2. Secretions6 decreased lacrimation "dry eyes$0 salivation "dry mouth$ and s,eating "dry and hot skin$. Atropine decreases one=s a/ility to s,eat0 contri/uting to hyperthermia. J. Eye6 mydriasis "dilated pupils$ and cycloplegia "ina/ility to +ocus on the near o/3ects /lurry vision$. O. C#S6 hallucinations0 agitation and delirium. Atropine=s antimuscarinic e++ects can /e counteracted /y increasing the concentration o+ acetylcholine in the synaptic cle+t. ncreased acetylcholine concentrations are produced /y cholinesterase inhi/itors that suppress acetylcholine degradation. Physostigmine0 a cholinesterase inhi/itor can /e used +or treatment o+ atropine overdose. "Choice A$ Dia!epam is a long(acting /en!odia!epine that +acilitates GABA action /y increasing the +re7uency o+ chloride channel opening. Dia!epam is used to treat sei!ures associated ,ith atropine poisoning /ut does not a++ect muscarinic cholinergic receptors. "Choice B$ Haloperidol is a neuroleptic drug that /locks dopamine receptors in the C#S. t also has anticholinergic and antihistamine properties. 28

USMLE WORLD STEP 1

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"Choice C$ Ben!tropine is a centrally acting anti(cholinergic medication used +or treatment o+ idiopathic and drug induced Parkinson=s disease. ts administration ,ould increase the patient=s symptoms. "Choice E$ ;etoprolol is a selective (adrenergic receptor antagonist. t is used to treat angina acute coronary syndromes heart +ailure0 hypertension and arrhythmias. ;etoprolol does not have any e++ect on muscarinic cholinergic receptors. Educational 5/3ective6 -he mnemonic +or the clinical mani+estations o+ atropine poisoning is6 @/lind as a /at0 mad as a hatter0 red as a /eet. Hot as a hare0 dry as a /one0 the /o,el and /ladder lose their tone0 and the heart runs alone. Atropine is a reversi/le cholinergic antagonist that acts selectively on muscarinic receptors. ts e++ects can /e reversed /y cholinesterase inhi/itors "physostigmine$.

29

USMLE WORLD STEP 1

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Q NO 18: A 'e #r-& t)at is -se# to treat )!perte'sive e$er&e'+ies +a-ses arterio"ar #i"atio'* 9t a"so i'+reases re'a" perf-sio' a'# pro$otes 'atri-resis* T)e #r-& #es+ri%e# a%ove is $ost si$i"ar  it) )i+) of t)e fo""oi'& a&e'ts/ A. B. C. D. E. F.

Dia!o%ide #itroprusside Hydrala!ine Esmolol #icardipine Fenoldopam

Explanation: -he management o+ hypertensive emergency re7uires immediate /ut gradual /lood pressure reduction over minutes to hours to minimi!e target organ damage. ntravenous therapy is necessary to allo, immediate e++ects and the pre+erred and optimal parenteral agent ,ill vary according to the patient=s clinical situation and presence o+ coe%isting conditions and disease states. Fenoldopam is a ne,er0 novel intravenous agent that is a /en!a!epines derivative o+ dopamine. n contrast to dopamine0 itis a selective dopamine(i receptor agonist ,ith no e++ect on alpha or /eta receptors. Dopamine(i receptor stimulation activates adenylyl cyclase and raises intracellular cyclic A;P0 resulting in vasodilation o+ most arterial /eds0 especially renal0 mesenteric0 and coronary /eds. -he main e++ect is a signi+icant reduction in systemic vascular resistance. Stimulation o+ dopamine(receptors in the kidneys not only improves renal /lood +lo,0 /ut also leads to increased sodium and ,ater e%cretion. -hus +enoldopam is the only availa/le intravenous agent that improves renal per+usion ,hile it lo,ers /lood pressure. Fenoldopam is indicated +or short term management o+ severe hypertension and can /e sa+ely used in all hypertensive emergencies. t may /e e%ceptionally /ene+icial in patients ,ith concomitant renal insu++iciency. "Choices A and C$ Although dia!o%ide and hydrala!ine are /oth arterial vasodilators0 neither agent therapeutically improves renal per+usion. Both agents cause signi+icant re+le% sympathetic activation0 resulting in increased heart rate and contractility and e%tensive sodium and +luid retention. -hey are usually considered third line agents and are not recommended in hypertensive emergencies ,ith aortic dissection. Hydrala!ine is considered sa+e and use+ul in pregnancy related hypertensive emergency. "Choice B$ #itroprusside is a very potent direct acting arterial and venous vasodilator. Due to its +avora/le pharmacokinetics pro+ile "7uick onset and short duration o+ action$0 it is considered the most e++ective agent +or most cases o+ hypertensive emergency. #itroprusside causes slight re+le% sympathetic activation0 and thus can cause modest tachycardia and sodium and +luid retention. Since nitroprusside is meta/oli!ed to cyanide and thiocyanate0 the primary limiting +actor to its use is the risk +or cyanide to%icity ,ith prolonged use0 high doses0 and renal insu++iciency. "Choice D$ Esmolol is a short acting selective /eta(i receptor antagonist that decreases heart rate contractility0 and cardiac output. t has an immediate onset o+ action and upon discontinuation o+ esmolol the e++ects are reversed ,ithin )' minutes. Esmolol can cause /radycardia0 le+t ventricular dys+unction0 and /ronchospasm. t is mainly used in the setting o+ postoperative hypertension and may /e 30

USMLE WORLD STEP 1

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pre+erred in critical patients ,here rapid ,ithdra,al o+ drug e++ects is needed. "Choice E$ #icardipine is a dihydropyridine calcium channel /locker that ,orks /y /locking calcium channels in the vascular smooth muscle and the myocardium0 resulting in rela%ation o+ smooth muscles and coronary arteries. Because nicardipine causes signi+icant arterial vasodilation0 it can cause mild to moderate tachycardia. 5ther side e++ects include +lushing0 headache0 and venous irritation. Since nicardipine has a longer hal+ li+e compared to other agents0 the hypotensive e++ect may /e prolonged and rapid titration o+ the agent is di++icult. Educational 5/3ective6 Fenoldopam is a ne,er parenteral agent that is classi+ied as a selective dopamine(& receptor agonist. t causes arteriolar dilation and natriuresis leading to decreased systemic vascular resistance and /lood pressure reduction. Since +enoldopam is the only intravenous agent that improves renal per+usion0 it may /e e%ceptionally /ene+icial in hypertensive patients ,ith concomitant renal insu++iciency.

31

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Q NO 19: 9so"ates of M* t-%er+-"osis o%tai'e# fro$ a 4!earo"# H9 :positive $a"e #e$o'strate resista'+e to a '-$%er of a'ti%ioti+s* W)i+) of t)e fo""oi'& %est ep"ai's resista'+e to strepto$!+i' i' t)ese %a+teria/ A. Decreased activity o+ /acterial catalase(pero%idase B. ncreased activity o+ en!ymes involved in cell ,all polysaccharide synthesis C. Altered structure o+ /acterial ri/osomal proteins D. Altered structure o+ en!ymes involved in D#A ,inding(un,inding E. Altered structure o+ en!ymes involved in ?#A synthesis Explanation: -he treatment o+ active ;yco/acterium tu/erculosis in+ection is /est accomplished through the use o+ isonia!id and ri+ampin in addition to any com/ination o+ streptomycin0 pyra!inamide0 etham/utol or +luoro7uinolone. Because streptomycin is one o+ the older drugs in the aminoglycoside +amily0 /acterial resistance to this anti/iotic is ,idespread. As a result streptomycin usage is currently limited to the treatment o+ tu/erculosis plague0 and tularemia. ike all other aminoglycosides0 streptomycin can only /e administered parenterally0 and it ,orks /y inhi/iting the /acterial :'S ri/osomal su/unit "ultimately preventing /acterial protein synthesis$. ;utations o+ the genes that encode ri/osomal proteins are responsi/le +or aminoglycoside resistance /ecause they modi+y the ri/osomal /inding sites +or these drugs. "Choice A$ Decreased activity o+ /acterial catalase(pero%idase is one mechanism o+ myco/acterial resistance to isonia!id. ;yco/acterial catalase(pero%idase is re7uired +or the initial en!ymatic conversion o+ isonia!id to its active meta/olite ,ithin the myco/acterial cells ,ithout this en!yme isonia!id is una/le to inhi/it myco/acterial mycolic acid synthesis. "Choice B$ ncreased activity o+ en!ymes involved in cell ,all polysaccharide synthesis is the means /y ,hich myco/acteria develop resistance to etham/utol. Etham/utol inter+eres speci+ically ,ith myco/acterial peptidoglycan cell ,all synthesis through an unclear mechanism that appears to di++er +rom that o+ isonia!id. -his drug is ine++ective against organisms other than myco/acteria. "Choice D$ Structural alteration o+ en!ymes involved in D#A ,inding( un,inding is the means /y ,hich many microorganisms /ecome resistant to +luoro7uinolone anti/iotics. Fluoro7uinolones inhi/it the /acterial en!yme D#A gyrase "topoisomerase $. "Choice E$ Structural alteration o+ en!ymes involved in ?#A synthesis is the mechanism through ,hich organisms /ecome resistant to ri+ampin. ?i+ampin inhi/its the /acterial D#A(dependent ?#A polymerase0 there/y preventing the transcription o+ D#A into m?#A.

Educational 5/3ective6  -he aminoglycoside streptomycin inhi/its protein synthesis /y inactivating the :'S "small$ ri/osomal su/unit. Q Decreased activity o+ /acterial catalase(pero%idase is one mechanism o+ myco/acterial resistance to isonia!id.  Structural alteration o+ en!ymes involved in ?#A synthesis "D#A( dependent ?#A polymerase$ is the mechanism through ,hich organisms /ecome resistant to ri+ampin.

32

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 20: A 6<!earo"# Ca-+asia' $a"e +o$es to !o-r offi+e it) a 8$o't) )istor! of %a+. pai' t)at is 'ot respo'sive to overt)e+o-'ter pai' re"ievers* T)e pai' is orse at 'i&)t a'# i'terferes it) )is s"eep* L-$%ar verte%rae are te'#er to per+-ssio', a'# t)e prostate is e'"ar&e# a'# fir$* After a t)oro-&) eva"-atio', !o#e+i#e to pro+ee# it) "e-pro"i#e t)erap!* W)i+) of t)e fo""oi'& +)a'&es i' testostero'e ?T@ a'# #i)!#rotestostero'e ?DHT@ "eve"s are $ost "i.e"! i' t)is patie't after i'itiatio' of t)e t)erap!/ A. Steady decrease in /oth - and DH- levels B. First concordant increase0 then concordant decrease in - and DHlevels C. Discordant decrease in DH- level D. First discordant increase0 then discordant decrease in DH- level E. #o change in - and DH- levels Explanation: Pulsatile release o+ gonadotropin(releasing hormone "Gn?H$ +rom the hypothalamus is the natural state o+ human +unctioning causing release o+ gonadotrophins +rom the pituitary that in turn stimulates release o+ testosterone in a man. -estosterone is converted to DH- in target tissues /y the en!yme 4(alpha reductase. Alternatively i+ Gn?H levels are constantly elevated. ?ather than pulsed the secretion o+ luteini!ing hormone "H$ and +ollicle(stimulating hormone "FSH$ +rom the pituitary ,ill /e suppressed. A num/er o+ Gn?H analogs such as leuprolide0 have /een generated /y amino acid su/stitutionsalterations that allo, longer hal+ lives and increased activity. euprolide is a long(acting Gn?H analog that causes continuous Gn?H activity. -he result is ultimately a suppression o+ the pituitagonadal a%is +or the duration o+ treatment although there is a /rie+ period o+ initial stimulation sometimes called a @start up +lare. An increase in gonadotrophin levels during the initial +lare(up period causes an increase in /oth testosterone and DH- levels "a concordant increase$. Soon the start up +lare /urns out and /oth testosterone and DH- are typically suppressed to castrate levels. -hese ye, lo, levels o+ androgens are use+ul +or the treatment o+ androgen( dependent cancers such as prostate cancer. "Choice A$ >ith the use o+ a Gn?H analog androgen levels are suppressed a+ter a transient increase so the @decrease only option here cannot /e correct. Suppression o+ testosterone and DH- ,ithout an initial +lare is seen ,ith the use o+ Gn?H antagonists. "Choices C and D$ euprolide has no e++ect on 4(alpha reductase activity. -here+ore the changes in testosterone and DH- levels are al,ays concordant +ollo,ing leuprolide administration. Finasteride is a 4(alpha(reductase inhi/itor used +or the treatment o+ /enign prostatic hypertrophy. t prevents the conversion o+ testosterone to DH-0 causing a discordant decrease in DH- levels. "Choice E$ -he purpose o+ administering a Gn?H is to change androgen levels "testosterone and DH- levels$ so @no change cannot possi/ly /e correct.

Educational 5/3ective6 euprolide is a Gn?H agonist that causes +irst a transient increase0 then a decrease in /oth testosterone and DH- levels. Finasteride causes a discordant decrease in DH- level.

33

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 21: A 1!earo"# Ca-+asia' fe$a"e is %ro-&)t to t)e ER after a to'i++"o'i+ sei(-re* S)e as #ia&'ose# it) epi"eps! severa" !ears a&o a'# )as %ee' s-++essf-""! treate# it) p)e'!toi'* 5"oo# tests revea" )er p"as$a p)e'!toi' "eve" to %e "o* S)e states t)at s)e )as %ee' +o$p"ia't it) )er $e#i+atio'* W)i+) of t)e fo""oi'& #r-&s $a! %e respo'si%"e for t)is patie'ts +o'#itio' if +o a#$i'istere# it) p)e'!toi'/ A. B. C. D. E. F. G.

Amo%icillin ?i+ampin ;etronida!ole Flucona!ole Cimetidine 5mepra!ole 5ral contraceptives

Explanation: As ,ith many other medications phenytoin is meta/oli!ed /y hepatic P14' o%idase. Plasma drug level0 e++icacy0 and the severity o+ side e++ects are directly in+luenced /y the rate o+ meta/olism o+ phenytoin. -he +ollo,ing +eatures o+ phenytoin meta/olism are important6 &. Hepatic hydro%ylation o+ phenytoin is dose(dependent. >hen lo, doses o+ phenytoin are administered0 a su++icient num/er o+ en!yme molecules are availa/le0 and the drug is eliminated rapidly. Higher doses o+ phenytoin may +ully saturate the en!yme hence0 increasing the dose a/ove the saturation limit causes an ina/ility to meta/oli!e the drug and a rapid rise in plasma levels. Even a small increase in phenytoin intake a/ove the prescri/ed dose may lead to severe to%icity. ). Phenytoin is an inducer o+ P14' o%idase. nduction o+ this en!yme increases the consumption o+ many medications that are meta/oli!ed /y the liver0 such as oral contraceptives. >hen the P14' o%idase system is induced0 the serum concentration o+ such medications ,ill decrease0 there/y reducing e++icacy. :. Because phenytoin is meta/oli!ed /y P14' en!ymes its level i+ a++ected ,hen it is co(administered ,ith other medications that induce or inhi/it the P14' system. -he co(administration o+ phenytoin ,ith P14' inducers decreases concentration o+ phenytoin in plasma and diminishes its e++ectiveness. Some P14' inducers are /ar/iturates ri+ampin0 car/ama!epine0 griseo+ulvin0 and chronic alcohol consumption. P14' inhi/itors slo, hepatic meta/olism0 ,hich increases the to%icity o+ phenytoin. Some o+ P14' inhi/itors are isonia!id0 cimetidine0 macrolides0 a!ole anti+ungals0 and grape 3uice. "Choices A and F$ Amo%icillin and omepra!ole do not a++ect the hepatic meta/olism o+ phenytoin. "Choices C and G$ Both metronida!ole and oral contraceptives are meta/oli!ed /y hepatic P14' o%idase0 /ut these t,o drugs neither induce nor inhi/it the activity o+ P14' o%idase. "Choices D and E$ Flucona!ole and cimetidine inhi/it P14' en!ymes and increase the concentration o+ phenytoin in the serum. Educational 5/3ective6 Phenytoin meta/olism depends on the +unction o+ hepatic P14' o%idases and is dose(dependent. Drugs that induce hepatic microsomal en!ymes "pheno/ar/ital0 car/ama!epine0 and ri+ampin$ enhance phenytoin meta/olism and decrease its serum concentration. Mou should kno, all o+ the commonly(prescri/ed medications that are meta/oli!ed /y the P14' system and you should kno, ,hich drugs induce or inhi/it the +unction o+ these en!ymes. 34

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 22: A 63!earo"# $a"e treate# it) si"#e'afi" eperie'+es si&'ifi+a't i$prove$e't i' )is se-a" perfor$a'+e* T)e 'et i'tra+e""-"ar effe+t of t)is #r-& is $ost si$i"ar to t)at of )i+) of t)e fo""oi'& s-%sta'+es/

A.

nsulin B. Platelet(derived gro,th +actor "PDGE$ C. lnterleukin() "()$ D. Atrial natriuretic peptide E. &0 )4(dihydro%3cholecalci+erol F. Gamma(amino/utyric acid "GABA$ Explanation: Atrial natriuretic peptide "A#P$ and nitric o%ide "#50 endothelium derived rela%ing +actor$ are hormones that e%ert their intracellular e++ects /y /inding a receptor protein that also has a guanylate cyclase en!ymatic a/ility. -his is kno,n as the cG;P second messenger system. -he cG;P second messenger system is similar to the cA;P second messenger system in that hormone /inding causes +ormation o+ a cyclic nucleotide monophosphate +rom a nucleotide triphosphate. -hese systems are also similar in that the cyclic nucleotide monophosphate is a/le to activate a protein kinase to carry out the intracellular e++ects o+ the hormone and also in that the e++ect o+ the hormone is terminated /y degradation o+ the cyclic nucleotide monophosphate /y phosphodiesterase. -he cG;P system is di++erent /ecause the receptor and guanylate cyclase are part o+ the same protein "as opposed to the cA;P system0 ,hich consists o+ +our distinct proteins$. -his receptor guanylate cyclase protein e%ists in /oth transmem/rane +orm "+or A#P$ and in a +ree cytosolic +orm "+or #5 ,hich can +reely di++use through cell mem/ranes. Sildena+il causes a net increase in the intracellular cG;P concentration /y inhi/iting cG;P phosphodiesterase in target cells. -his e++ect is similar to that o+ nitric o%ide "#5$ and atrial natriuretic peptide "A#P$ in that these hormones activate a cG;P second messenger system upon /inding to their speci+ic receptors0 and activation o+ the cG;P second messenger system ,ill also lead to increased intracellular cG;P. t is important to note though that #5 and A#P increase intracellular cG;P /y a di++erent mechanism than that o+ the drug sildena+il ,hich inhi/its /reakdo,n o+ cG;P /y inhi/iting phosphodiesterase. -hese hormones increase production o+ cG;P they do not decrease degradation o+ cG;P as sildena+il does. "Choice A$ nsulin acts /y the tyrosine kinase second messenger system. "Choice B$ Platelet(derived gro,th +actor "PDGF$ is a +actor that stimulates cell gro,th and division including angiogenesis. t also acts via a tyrosine kinase receptor. "Choice C$ lnterleukin() "()$ is a cytokine that primarily +unctions in an autocrine manner ,here/y activated - lymphocytes provide costimulus to themselves /y secreting () and producing () receptors. "Choice E$ &0 )4(dihydro%==cholecalci+erol is the active +orm o+
35

USMLE WORLD STEP 1

PHARMACOLOGY

Educational 5/3ective6 Sildena+il is a selective inhi/itor o+ the cG;P phosphodiesterase0 and use o+ this drug ,ill prevent degradation o+ cG;P leading to higher intracellular levels. #itric o%ide and atrial natriuretic peptide act via a cG;P second messenger system "#5 /eing primarily responsi/le +or causing erection$0 and /inding o+ these hormones to their receptors ,ill also increase intracellular cG;P concentrations.

36

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 23: A 60!earo"# $a"e +o$es to t)e p)!si+ia's offi+e +o$p"ai'i'& of $o-t) -"+ers a'# fever* His past $e#i+a" )istor! is si&'ifi+a't for "o'&ter$ )!perte'sio' a'# a' episo#e of tra'sie't is+)e$i+ atta+. )i+) o++-rre# o'e $o't) a&o a'# "aste# 8< $i'-tes* His +o$p"ete %"oo# +o-'t s)os H/ &:.) g9d >BC &&''9mm: Platelet &O''''9mm: >hich o+ the +ollo,ing drugs is most likely to /e associated ,ith this patient=s conditionR A. B. C. D. E. F. G. H.

Heparin Argatro/an >ar+arin tPA Aspirin -iclopidine A/ci%ima/ Cilosta!ol

37

USMLE WORLD STEP 1

PHARMACOLOGY

Explanation: Antiplatelet drugs ,ork /y one o+ three /asic mechanisms6 &$ +ormation o+ ligands "aspirin decreases throm/o%ane A) +ormation$0 )$ /locking interaction o+ ligands ,ith receptors on platelets "clopidogrel and ticlopidine ,ork as ADP antagonists$0 or :$ inter+ering ,ith intracellular signaling "cilosta!ol and dipyridamole increase cA;P /y decreasing phosphodiesterase activity$. -iclopidine and clopidogrel are use+ul in the treatment and prevention o+ ischemic strokes0 acute coronary syndrome and peripheral vascular disease. -hese agents can /e com/ined ,ith aspirin to get an additive antiplatelet e++ect0 as the mechanism o+ action o+ ticlopidine and clopidogrel is di++erent +rom aspirin. Sometimes patients are allergic to or cannot tolerate aspirin or clopidogrel "the t,o +irst line drugs$ and in those patients ticlopidine is the other option. 5ther,ise ticlopidine is rarely used due to the occurrence o+ serious side e++ects. #eutropenia is seen in a/out percent o+ patients on ticlopidine and typically presents ,ith +ever and mouth ulcers. -hough this is rare0 it is a serious complication and complete /lood count should /e monitored /i,eekly +or the +irst three months. "Choice A$ Heparin usually causes throm/ocytopenia /ut not neutropenia. "Choice G$ A/ci%ima/ and other /9a inhi/itors are also associated ,ith signi+icant throm/ocytopenia typically ,ithin )1 hours. -hey are typically used in acute coronary syndrome and a+ter stent placement. "Choices B0 C0 D0 E and H$ -hese drugs do not cause neutropenia.

Educational 5/3ective6 #eutropenia is seen in a/out percent o+ patients on ticlopidine and typically presents ,ith +ever and mouth ulcers. -hough this is rare0 itis a serious complication and complete /lood count should /e monitored /i,eekly +or the +irst three months.

38

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 24: A 0B!earo"# $a"e i'patie't a%o-t to -'#er&o %ro'+)os+op! is pre$e#i+ate# it) i'tra$-s+-"ar atropi'e a'# %e+o$es a+-te"! rest"ess, #isorie'te#, a'# +o$%ative* O' p)!si+a" ea$i'atio', )is p-pi"s are i#e"! #i"ate# a'# 'o'rea+tive to "i&)t* A' EO $o'itor s)os si'-s ta+)!+ar#ia* W)i+) of t)e fo""oi'& a&e'ts i"" reverse aFi of t)is patie'ts

A.

Haloperidol B. Physostigmine C. Dia!epam D. #eostigmine E. Edrophonium Explanation: Atropine can /e administered prior to /ronchoscopy to decrease respiratory mucous secretions and promote /ronchodilation. Ho,ever0 this patient is no, mani+esting symptoms o+ 5#S and peripheral anti( muscarinic to%icity. n the elderly "patients J' years o+ age$ atropine=s hal+(li+e may /e prolonged +rom its usual : hours to up to &'(:' hours due to reduced clearance0 causing an increased suscepti/ility to to%icity. An organic delirium or psychosis can result +rom /lockade o+ muscarinic receptors in the C#S. n severe atropine overdose0 C#S e++ects may progress to coma and respiratory +ailure. Peripherally0 atropine can cause6 dry and +lushed skin0 hyperthermia "atropine +ever$0 mydriasis and cycloplegia0 /ronchodilation0 tachycardia constipation and urinary retention. Physostigmine inhi/its acetylcholinesterase /oth peripherally and centrally "a tertiary amine0 physostigmine is capa/le o+ crossing the /lood(/rain /arrier$. -he increased acetylcholine availa/ility counteracts atropine=s /lockade o+ muscarinic cholinergic receptors. "Choice A$ -he antipsychotic haloperidol may sedate this patient and suppress his C#S symptoms0 /ut it ,ould not reverse the other anticholinergic mani+estations "e.g. mydriasis0 tachycardia$ o+ his atropine to%icity. "Choice C$ Dia!epam is sedating and is sometimes used to treat atropine(induced agitation. Ho,ever0 it ,ould not reverse the peripheral antimuscarinic e++ects. "Choices D and E$ -hese are anticholinesterase drugs ,ith actions similar to physostigmine. Ho,ever0 they /oth have a 7uaternary ammonium structure that prevents penetration o+ the /lood(/rain /arrier at moderate doses. -hese drugs ,ould thus +ail to alleviate the patient=s 5#S symptoms.

Educational 5/3ective6 -he tertiary amine physostigmine can reverse /oth the C#S and peripheral symptoms o+ severe atropine to%icity. -he anticholinesterase agents neostigmine and edrophonium have a 7uaternary ammonium structure that limits C#S penetration.

39

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 25: A 6!earo"# $a"e is -'#er&oi'& a $aor s-r&i+a" pro+e#-re -'#er &e'era" a'est)esia* A f"-ori'ate# i')a"e# a'est)eti+ ?isof"-ra'e@ is -se# to a+)ieve t)e #esira%"e #ept) of +e'tra" 'ervo-s s!ste$ #epressio'* A' i'+rease i' )i+) of t)e fo""oi'& para$eters is $ost "i.e"! to )appe' #-ri'& t)e a'est)esia i' t)is patie't/ A. B. C. D. E.

Glomerular +iltration rate "GF?$ E++ective renal plasma +lo, e+t ventricular e3ection +raction "EP$ Hepatic /lood +lo, Cere/ral /lood +lo,

Explanation: General anesthesia encompasses loss o+ consciousness0 analgesia0 amnesia0 skeletal muscle rela%ation and inhi/ition o+ re+le%es. -his comple% o+ symptoms occurs due to the inhi/ition o+ electrical activity o+ neurons. ;ost o+ inhalation anesthetics0 /ar/iturates0 and /en!odia!epines achieve C#S depression /y in+luencing GABA receptors and increasing the inhi/itory action o+ GABA. nhaled anesthetics have also /een sho,n to a++ect potassium channels in the neuronal mem/ranes and lock them in the state o+ hyperpolari!ation. -hey may also a++ect nicotinic and glycine receptors. Apart +rom their desira/le action on C#S inhalation anesthetics a++ect almost all organ systems o+ the /ody. &. Cardiovascular e++ects include myocardial depression that leads to a decrease in cardiac output and an increase in atrial and ventricular pressures. Hypotension associated ,ith +luorinated anesthetics is a result o+ decrease in cardiac output. ). ?espiratory6 all inhalation anesthetics0 e%cept nitrous o%ide0 are respiratory depressants. -hey decrease tidal volume and minute ventilation and cause hypercapnia. Another undesira/le e++ect is the suppression o+ mucociliary clearance0 ,hich may predispose to postoperative atelectasis. Halothane and sevo+lurane have /ronchodilation properties and are pre+erred in patients ,ith asthma. :. n the /rain0 +luorinated anesthetics decrease vascular resistance and lead to an increase in cere/ral /lood +lo,. t is an undesira/le e++ect as it results in increased intracranial pressure. 1. n kidneys0 inhaled anesthetics decrease glomerular +iltration rate0 increase renal vascular resistance and decrease renal plasma +lo,. 4. Fluorinated anesthetics decrease hepatic /lood +lo,. "Choices A and B$ ?enal +unction in general anesthesia is characteri!ed /y decrease in glomerular +iltration rate and decrease in renal plasma +lo,. "Choice C$ Fluorinated anesthetics are myocardial depressants. -hey decrease cardiac output ,hich leads to hypotension. "Choice D$ Fluorinated anesthetics decrease hepatic /lood +lo,.

Educational 5/3ective6 Almost all volatile anesthetics increase cere/ral /lood +lo,. t is an undesira/le e++ect as it results in increased CP. 5ther important e++ects o+ inhalation anesthetics are myocardial depression0 hypotension0 respiratory0 depression and decreased renal +unction.

40

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 26: A !earo"# Ca-+asia' fe$a"e %e&i's treat$e't it) t)e a%ortifa+ie't $ifepristo'e si ee.s after )er "ast $e'str-a" perio#* S)e eperie'+es a%#o$i'a" +ra$ps, 'a-sea a'# va&i'a" %"ee#i'& soo' after i'itiati'& t)erap!* W)i+) of t)e fo""oi'& effe+ts is $ost "i.e"! respo'si%"e for t)is patie'ts s!$pto$s/ A. B. C. D. E. F.

Anti(progestin nhi/ition o+ progesterone synthesis Prostaglandin agonist nhi/ition o+ cell division Anti(glucocorticoid Anti(mineralocorticoid

Explanation: ;i+epristone "previously called ?(1O2$ is an a/orti+acient approved /y the EDA +or clinical use. t can /e used +or therapeutic a/ortions up to 18 days a+ter conception. ;i+epristone is a progesterone antagonist ,ith an a++inity +or the progesterone receptor +ive times that o+ natural progesterone. Progesterone is necessary +or implantation and maintenance o+ pregnancy. >hen its e++ects are antagoni!ed /y mi+epristone0 there is decidual necrosis and e%pulsion o+ the products o+ conception. -he success rate o+ mi+epristone at inducing medical termination o+ pregnancy is a/out O'*6 ho,ever0 the success rate is higher ,hen mi+epristone is com/ined ,ith the prostaglandin analog misoprostol. "Choice B$ Epostane and trilostane inhi/it the +ormation o+ progesterone +rom pregnenolone /y inhi/iting the en!yme :(( hydro%ysteroid dehydrogenase. -hese agents have /een studied +or use in the medical termination o+ pregnancy0 /ut their success rates have /een 7uite limited. "Choice C$ Endogenous prostaglandin causes uterine contraction and cervical dilatation0 important steps in the process o+ la/or. Prostaglandin analogues have /een used +or years in the medical termination o+ pregnancy. -he prostaglandin(E& analogue0 misoprostol0 is availa/le +or clinical use in com/ination ,ith the a/orti+acient0 mi+epristone. ";isoprostol has limited success in pregnancy termination ,hen used alone0 /ut enhances the e++icacy o+ mi+epristone.$ Additionally0 misoprostol is sometimes used +or the prevention o+ #SAD(induced gastrointestinal ulceration. "Choice D$ Folic acid antagonists like methotre%ate inhi/it tropho/last division thus decreasing tropho/last survival0 hindering implantation and encouraging e%pulsion. n studies methotre%ate has a higher success rate ,hen com/ined ,ith vaginal misoprostol. ;ethotre%ate is also used +or the treatment o+ ectopic pregnancy. "Choices E and F$ ;i+epristone has mild anti(glucocorticoid and anti( mineralocorticoid e++ects. Ho,ever0 these e++ects do not contri/ute to its utility as an agent +or the medical termination o+ pregnancy.

Educational 5/3ective6 ;i+epristone is an anti(progestin agent that can /e used to terminate early pregnancy. -he prostaglandin(E& analogue0 misoprostol0 is availa/le +or clinical use in com/ination ,ith the a/orti+acient0 mi+epristone.

41

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 27: A 63!earo"# Ca-+asia' $a"e is -'#er&oi'& re)a%i"itatio' after a stro.e* Yo- pres+ri%e #ia(epa$ to t)is patie't i' or#er to #e+rease $-s+"e spasti+it! of i'vo"ve# etre$ities* T)e patie't s)o-"# %e +a-tio'e# to avoi# )i+) of t)e fo""oi'& #r-&s/ A. B. C. D. E. F.

Chlorpheniramine oratadine Acetaminophen ?anitidine 5mepra!ole Folic acid

Explanation: Dia!epam is a long(acting /en!odia!epine indicated as +ollo,s6 &. As an an%iolytic0 it is e++ective +or the management o+ generali!ed an%iety disorder and panic attacks. ). -he sedative(hypnotic e++ect o+ dia!epam is use+ul +or the short( term treatment o+ insomnia. :. As an anticonvulsant0 dia!epam is indicated +or tonic(clonic sei!ures. tis a +irst(line agent "along ,ith chlordia!epo%ide$ +or the treatment o+ sei!ures associated ,ith alcohol ,ithdra,al. 1. As a muscle rela%ant0 dia!epam can stop the spasticity caused /y upper motor neuron disorders "multiple sclerosis0 strokes0 and spinal cord trauma$ and tetanus. 4. Due to its sedative and amnestic properties0 dia!epam is used as an ad3unct to anesthesia. -he most common side e++ect o+ dia!epam is sedation. Dia!epam may also impair coordination and /alance "sometimes avoided in the elderly +or +ear o+ +alls$ decrease memory and concentration0 and produce con+usion. -hese e++ects are ampli+ied /y the co(administration o+ other C#S(depressants. As a class0 all /en!odia!epines should /e e%cluded +rom use in con3unction ,ith alcohol0 /ar/iturates0 neuroleptics0 or &st generation antihistamines. Among drugs listed in the ans,er choices0 only chlorpheniramine causes sedation and should not /e used ,ith dia!epam. Chlorpheniramine is a &4t generation antihistamine that acts /y /locking /oth central and peripheral Hi receptors. Chlorpheniramine and other &4t generation antihistamines can /e very sedating /ecause they easily penetrate the /lood(/rain /arrier and accumulate in the C#S. -he most sedating o+ this generation o+ antihistamines are diphenhydramine "Benadryl$0 prometha!ine0 and hydro%y!ine. Despite the associated sedation these antihistamines are o+ten still used to prevent9treat allergic reactions and motion sickness and as antiemetics. "Choice B$ oratadine is a second(generation antihistamine that /locks peripheral H& histamine receptors. t does not enter the C#S and does not cause dro,siness.

Educational 5/3ective6 First generation H&(histamine receptor antagonists including diphenhydramine and chlorpheniramine can cause signi+icant sedation especially ,hen used ,ith other medications that cause C#S depression "such as /en!odia!epines$.

42

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 28: 9' a patie't it) severe"! i$paire# "eft ve'tri+-"ar f-'+tio', 9: #i&oi' a#$i'istratio' i'+reases +ar#ia+ o-tp-t a'# #e+reases ri&)t atria" press-re a'# p-"$o'ar! +api""ar! e#&e press-re* W)i+) of t)e fo""oi'& is t)e i'itia" +e""-"ar eve't tri&&eri'& t)is respo'se to #i&oi'/ A. B. C. D. E.

Decreased sodium e++lu% ncreased calcium in+lu% ncreased potassium in+lu% ncreased cA;P concentration -roponin sensiti!ation to calcium

Explanation: Digo%in inhi/its #a(K(A-Pase0 causing an increase in intracellular sodium0 ,hich in turn decreases the transmem/rane sodium gradient that acts as the driving +orce o+ the #a(Ca transporter. -his leads to calcium accumulation in the cell. n e%citation(contraction coupling0 ,hen a cardiac myocyte is depolari!ed sodium and calcium enter the cell and potassium e%its. -his depolari!ation causes the release o+ a large amount o+ calcium +rom the sarcoplasmic reticulum ,ithin the cell0 and this high calcium concentration allo,s the /inding o+ calcium to troponin C and su/se7uent actin(myosin cross /ridge +ormation and muscle contraction. -he greater the intracellular calcium concentration0 the greater the contraction ,ill /e. Cardiac rela%ation then occurs via se7uestration o+ calcium /ack into the sarcoplasmic reticulum.

43

USMLE WORLD STEP 1

PHARMACOLOGY

-hus calcium gluconate should not /e given to patients +or hyperkalemia in the setting o+ digo%in to%icity. Digo%in and potassium compete ,ith each other +or #a(K( A-Pase thus digo%in to%icity results in hyperkalemia. Hypokalemia ,orsens digo%in to%icity. "Choice A$ Digo%in e%erts its e++ect on the #a(K(A-Pase thus causing decreased sodium e++lu% +rom the cardiac myocyte. "Choice B$ Digo%in causes decreased calcium e++lu%0 not increased calcium in+lu%. High levels o+ intracellular calcium are necessary +or e%citation(contraction coupling leading to contraction o+ the myocyte. "Choice C$ -he #a(K(A-Pase causes K in+lu% and #a e++lu%. Digo%in acts to inhi/it the #a(K(A-Pase. "Choice D$ Cyclic A;P "cA;P$ is an important second messenger in e%citation(contraction coupling though digo%in has no e++ect on the production o+ cA;P. cA;P is +ormed +rom AlP /y adenylyl cyclase0 the activity o+ ,hich is stimulated /y /eta agonists. cA;P increases the conductance o+ the calcium channels in the sarcoplasmic reticulum. As a result0 more calcium can enter the cell and strengthen the +orce o+ contraction. "Choice E$ Digo%in does not cause increased troponin sensitivity to calcium. #e, drugs are /eing developed to increase the sensitivity o+ calcium. Educational 5/3ective6 -he mechanism o+ action o+ digitalis is the inhi/ition o+ the #a(K( A-Pase in cardiac pacemaker cells leading to A< nodal /lockade "increased diastolic +illing time +or greater contraction /y the Frank( Starling mechanism$ and increased contractility +rom increased intracellular calcium.

44

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 29: A 63!earo"# $a"e prese'ts to !o-r offi+e it) i$paire# visio'* He sa!s t)at t)e pro%"e$s it) )is visio' starte# a "o'& ti$e a&o a'# &ra#-a""! pro&resse# overti$e* His past $e#i+a" )istor! is si&'ifi+a't for "o'&sta'#i'& s+)i(op)re'ia effe+tive"! +o'tro""e# %! $e#i+atio's* Op)t)a"$os+op! s-&&ests t)e #ia&'osis of reti'itis pi&$e'tosa i' t)is patie't* W)i+) of t)e fo""oi'& a'tips!+)oti+ a&e'ts )as $ost "i.e"! %ee' -se# i' t)is patie't/ A. B. C. D. E. F.

Chlorproma!ine Haloperidol Liprasidone -hiorida!ine 5lan!apine Clo!apine

Explanation: -hiorida!ine is an anti(psychotic medication that may cause retinal deposits that resem/le retinitis pigmentosa. "Choice A$ Chlorproma!ine is associated ,ith corneal deposits. "Choice B$ Haloperidol is associated ,ith e%trapyramidal symptoms. "Choice C$ Liprasidone is associated ,ith prolonged -. "Choice E$ 5lan!apine is associated ,ith ,eight gain. "Choice F$ Clo!apine is associated ,ith agranulocytosis and sei!ures.

Educational 5/3ective6 -hiorida!ine causes retinal deposits that resem/le retinitis pigmentosa. Chlorproma!ine is associated ,ith corneal deposits.

45

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 30: A 'e a'tiarr)!t)$i+ #r-& ?Dr-& A@ is teste# i' a series of eperi$e'ts* T)ese eperi$e'ts $eas-re io' f"o +)a'&es i' +ar#ia+ $-s+"e +e""s as t)e res-"t of t)e a+tio' of t)e #r-& it) i'ar# io' f"o represe'te# as a positive va"-e a'# o-tar# io' f"o represe'te# as a 'e&ative va"-e* T)e fo""oi'& +)art )as %ee' o%tai'e#* Dr-& A )as a' a'tiarr)!t)$i+ effe+t $ost si$i"ar to )i+) of t)e fo""oi'& #r-&s/

A. B. C. D. E. F. G. H.

46

uinidine idocaine Flecainide Do+etilide
USMLE WORLD STEP 1

PHARMACOLOGY

Explanation: An e++ect typical o+ the class ll antiarrhythmic agents is demonstrated on this graph ,here potassium e++lu% +rom the cell "negative /lack line$ as ,ell as the length o+ the action potential is prolonged ,hile the movement o+ sodium "positive /lue line$ and calcium "positive /lack line$ are relatively una++ected. Do+etilide "Choice D$0 i/utilide0 amiodarone and sotalol are representative o+ class  agents. "Choice A$ uinidine is a class A antiarrhythmic agent. t /locks sodium channels and has the e++ect on phase ' depolari!ation and phase : repolari!ation. "Choice B$ idocaine is a class B antiarrhythmic agent and acts /y /locking sodium channels only in veri rapidly depolari!ing cells. t does not have much e++ect on potassium e++lu%. "Choice C$ Flecainide is a class C antiarrhythmic agent. t /locks sodium channels and primarily acts /y slo,ing phase ' depolari!ation. "Choice E$
Educational 5/3ective6 Class ll antiarrhythmics such as amiodarone0 sotalol0 i/utilide and do+etilide ,ill slo, potassium e++lu% +rom the ventricular myocyte0 prolong repolari!ation and prolong the re+ractory period.

47

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 31: A 6<!earo"# $a"e prese'ts it) orse'i'& fati&-e a'# #!sp'ea o' eertio' t)at )ave re+e't"! "i$ite# )is #ai"! a+tivities* He a"so 'otes t)at re+e't"! )e )as re2-ire# fo-r pi""os to s"eep at 'i&)t* His past $e#i+a" )istor! is si&'ifi+a't for a $!o+ar#ia" i'far+tio' 8 !ears a&o* P)!si+a" ea$i'atio' revea"s %i"atera" "-'& +ra+."es a'# "oer etre$it! e#e$a* C)est ra! s)os +ar#io$e&a"!* He is a#$itte# to t)e )ospita", )ere )is %"oo# press-re is sta%"e at 13<16
Hydrochlorothia!ide -era!osin isinopril Amlodipine ;ino%idil ;ethyldopa

Explanation: -his patient is persistently hypertensive in the setting o+ a previous myocardial in+raction and current congestive heart +ailure. 5+ the antihypertensives listed0 only ACE inhi/itors "lisinopril$ have /een sho,n to inhi/it the chronic angiotensin l(mediated le+t ventricular hypertrophy and remodeling that occurs in association ,ith myocardial +ailure. 5vertime0 such remodeling diminishes contractile +unction. A /eta /locker ,ould also /e /ene+icial +or this patient. "Choice A$ A thia!ide diuretic is the /est initial treatment +or essential hypertension in a patient ,ithout congestive heart +ailure or dia/etes. n patients ,ith CH or dia/etes. ACE inhi/itors should /e used instead. "Choice B$ -era!osin is sometimes chosen +or patients ,ith /oth hypertension and /enign prostatic hypertrophy. "Choices D  F$ -hese agents are considered second( or third(line +or the treatment o+ hypertension.

Educational 5/3ective6 n patients ,ith hypertension and chronic ischemic myocardial +ailure0 ACE inhi/itors are considered +irst(line treatment0 as they inhi/it myocardial remodeling and the associated deterioration o+ ventricular contractile +unction in addition to reducing /lood pressure. A /eta /locker ,ould also /e /ene+icial +or these patients.

48

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 32: A 8!earo"# $i"#"! o%ese o$a' is treate# for i'ferti"it!* Her $e'str-a" +!+"es are irre&-"ar o++-rri'& o'+e ever! to to t)ree $o't)s* Ea$i'atio' s)os )irs-tis$* O'+e treat$e't is starte#, )er ser-$ pro&estero'e "eve" i'+reases s)arp"! a'# se+retor! +)a'&es are 'ote# o' e'#o$etria" sa$p"i'&* W)i+) of t)e fo""oi'& a&e'ts )as %ee' $ost "i.e"! -se# i' t)is patie't/ A. B. C. D. E.

Progesterone antagonist Estrogen antagonist Androgen antagonist Aromatase inhi/itor Gn?H antagonist

Explanation: 5/esity0 oligomenorrhea0 hyperandrogenism "hirsutism0 acne$ and in+ertility in a young ,oman are suggestive o+ polycystic ovarian syndrome "PC5S0 Stein(eventhal syndrome$. -his disease is characteri!ed /y increased circulating androgens and H0 and a high H9FSH ratio. Hypersecretion o+ H /y the anterior pituitary is considered a primary a/normality in PC5S. ncreased H stimulates secretion o+ androgens /y ovarian theca cells. Elevated H and androgen levels coupled ,ith decreased ESH levels lead to dysregulation o+ the menstrual cycle and anovulation due to +ailure o+ +ollicular maturation. Decreased +re7uency o+ ovulation in PC5S causes menstrual irregularities "oligomenorrhea$ and in+ertility. nopposed estrogen in+luence on the endometrium leads to endometrial proli+eration and an increased risk o+ endometrial carcinoma. 5ther complications o+ PC5S include dia/etes mellitus due to peripheral insulin resistance and an increased risk o+ cardiovascular disease due to elevated triglycerides and cholesterol. n+ertility in P5DS is treated ,ith clomiphene and ,eight loss. Clomiphene structurally resem/les estrogen and reacts ,ith estrogen receptors in the 5#S "Choice B$. >hen estrogens are secreted in su++icient 7uantities0 they elicit negative +eed/ack on the hypothalamus and inhi/it production o+ gonadotropin(releasing hormone "Gn?H$. Clomiphene /locks these receptor sites there/y suppressing negative +eed/ack on the hypothalamohypophysial a%is /y estrogen. -he result o+ clomiphene therapy is continued secretion o+ gonadotropins despite normal or elevated estrogen levels. ncreased amounts o+ ESH and H ultimately stimulate ovulation. "Choice A$ ;i+epristone "?1O2$ is a progesterone antagonist. + administered to pregnant ,omen0 this drug inter+eres ,ith the action o+ progesterone causing +ailure o+ maintenance o+ the endometrium and sensiti!ation o+ the uterus to procontractile hormones such as PGE() there/y inducing a/ortion. "Choice C$-he androgen antagonists cyproterone and +lutamide competitively inhi/it the action o+ androgens /y interacting ,ith receptors on the target cells. Flutamide is used occasionally +or the treatment o+ prostate cancer though Gn?H agonists are pre+erred0 ,hile cyproterone is indicated to treat hirsute +emales. "Choice D$ Aromatase inhi/itors include anastro!ole and letro!ole. -hey inhi/it peripheral conversion o+ androgens into estrogens and are used in ,omen ,ith estrogen(receptor(positive /reast cancer. "Choice E$ Gn?H agonists include leuprolide and goserelin. Continuous administration o+ these drugs inhi/its production o+ gonadotropin( releasing hormone /y the hypothalamus /y causing do,nregulation o+ the 49

USMLE WORLD STEP 1

PHARMACOLOGY

Gn?H receptor. -hey are indicated in prostate cancer0 precocious pu/erty and endometriosis. Educational 5/3ective6 5/esity0 oligomenorrhea and in+ertility are seen in patients ,ith polycystic ovarian syndrome "P5DS$. n+ertility in P5DS occurs due to anovulation resulting +rom a/normal FSH and H levels. Clomiphene is an estrogen antagonist that increases secretion o+ gonadotropins and stimulates ovulation.

50

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 33: A 66!earo"# Ca-+asia' $a"e as re+e't"! #ia&'ose# it) Par.i'so' #isease* His +-rre't $e#i+atio' is "evo#opaF+ar%i#opa* He prese'ts to !o-r offi+e +o$p"ai'i'& of i'+rease# $otio' restri+tio' a"t)o-&) )e reports t)at )e is )i&)"! +o$p"ia't it) )is $e#i+atio's* His ot)er $e#i+a" pro%"e$s i'+"-#e pepti+ -"+er #isease )!perte'sio', a'# osteoart)ritis of )is ri&)t .'ee* W)i+) of t)e fo""oi'& $e#i+atio's $a! %e respo'si%"e for t)is patie'ts restri+tio' of $otio'/ A. B. C. D. E.

Beta(/lockers +or hypertension Cimetidine +or peptic ulcer disease /upro+en +or osteoarthritis A @/a/y aspirin +or stroke prevention An over(the(counter multivitamin

Explanation: ;ost over(the(counter vitamins contain B2.
Educational 5/3ective6
51

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 34: A 40!earo"# Ca-+asia' $a"e -'#er&oi'& treat$e't it) a$p)oteri+i' 5 for #isse$i'ate# )istop"as$osis +o$p"ai's of ea.'ess a'# pa"pitatio's* A' ECG revea"s fre2-e't pre$at-re ve'tri+-"ar %eats* 9f +a-se# %! #r-& toi+it!, t)ese 'e si&'s a'# s!$pto$s are $ost "i.e"! re"ate# to A. B. C. D. E.

Cardiac muscle cell damage Bone marro, suppression ?enal tu/ular dys+unction Hepatocyte necrosis Pulmonary hypertension

Amphotericin B is the drug o+ choice +or many systemic mycoses. t is also the most to%ic anti+ungal medication. -he most dangerous adverse e++ect o+ amphotericin B is its nephroto%icity. Amphotericin B causes /oth a decrease in the glomerular +iltration rate and direct to%ic e++ects on the tu/ular epithelium. Anemia and electrolyte a/normalities may stem +rom amphotericin B(associated nephroto%icity. Hypokalemia and hypomagnesemia are common0 due to an increase in the mem/rane permea/ility o+ the distal tu/ule. Hypokalemia can cause ,eakness and arrhythmias. ECG +indings in hypokalemia include -(,ave +lattening0 S-( segment depression0 prominent  ,aves0 and premature atrial and ventricular contractions. Pro+ound hypokalemia can cause ventricular tachycardia or +i/rillation. "Choice A$ Do%oru/icin and daunoru/icin are associated ,ith irreversi/le dose(dependent cardioto%icity. -his is not a side e++ect o+ amphotericin B. "Choice B$ Bone marro, suppression is associated ,ith chloramphenicol0 !idovudine0 phenyl/uta!one0 and gold( containing medications. Bone marro, suppression ,ould not cause ECG changes. "Choice D$ Acetaminophen and halothane are e%amples o+ medications that can cause liver necrosis. Amphotericin B is not hepatoto%ic. "Choice E$ Busul+an and /leomycin are e%amples o+ the drugs that cause pulmonary +i/rosis and can lead to pulmonary hypertension. Educational 5/3ective6 Hypokalemia and hypomagnesemia are common electrolyte distur/ances in patients undergoing treatment ,ith amphotericin B. Hypokalemia and hypomagnesemia re+lect an increase in distal tu/ular mem/rane permea/ility.

52

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 35: A 63!earo"# fe$a"e it) ovaria' +a'+er is %ei'& treate# it) +isp"ati' %ase# +)e$ot)erap!* W)i+) of t)e fo""oi'& prop)!"a+ti+ $eas-res o-"# $ost "i.e"! "i$it t)e toi+it! asso+iate# it) t)is +)e$ot)erap! re&i$e'/ A. B. C. D. E. F.

#(acetylcysteine Folinic acid Filgrastim Fomepi!ole De%ra!o%ane Ami+ostine

Explanation: Cisplatin is a platinum(containing compound that e%erts its chemotherapeutic e++ect /y +orming a reactive o%ygen species that can +orm D#A cross links. -he most prominent adverse e++ect associated ,ith use o+ cisplatin is nephroto%icity. -his drug causes acute tu/ular in3ury0 and a signi+icant percentage o+ patients ,ill develop mild renal insu++iciency a+ter the +irst course o+ therapy i+ preventative measures are not taken. Ami+ostine is a thiol(/ased cytoprotective +ree(radical scavenging agent used to decrease the cumulative nephroto%icity associated ,ith platinum(containing agents0 there/y disallo,ing reaction ,ith the renal tu/ules. Another preventative measure is esta/lishing a chloride diuresis "via intravenous normal saline$ /ecause cisplatin stays in a nonreactive state ,hen in a higher chloride concentration. "Choice A$ #(acetylcysteine "#AC$ ,orks in acetaminophen overdose /y enhancing glutathione production and con3ugation o+ the to%ic #AP meta/olite. #AC is also used as a mucolytic agent in patients ,ith in+luen!a0 /ronchitis0 and cystic +i/rosis. Additionally0 in patients ,ith renal insu++iciency ,ho re7uire an <(contrast C- scan. #AG prevents radiocontrast(induced nephropathy. "Choice B$ eucovorin0 or +olinic acid0 is a drug used in the treatment o+ methotre%ate overdose. "Choice C$ Filgrastim is granulocyte colony(stimulating +actor "G(CSF$ analog0 produced /y recom/inant D#A technology0 used to stimulate the proli+eration and di++erentiation o+ granulocytes. "Choice D$ Fomepi!ole is used as an antidote in suspected methanol "ru//ing alcohol$ or ethylene glycol "anti+ree!e$ poisoning. t is a competitive antagonist o+ alcohol dehydrogenase0 and there/y prevents the conversion o+ methanol and ethylene glycol into their to%ic meta/olites. "Choice E$ De%ra!o%ane is an iron(chelating agent that can help prevent anthracycline(induced "i.e. do%oru/icin$ cardioto%icity "CHF$.

Educational 5/3ective6 Aggressive hydration and ami+ostine should /e utili!ed to prevent nephroto%icity in patients receiving a platinum( /ased chemotherapeutic regimen.

53

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 36: A 4B!earo"# $a"e is #ia&'ose# it) #ia%etes $e""it-s* After eva"-ati'& vario-s treat$e't $o#a"ities, !o- re+o$$e'# $o'ot)erap! it) pio&"ita(o'e* W)i+) of t)e fo""oi'& s)o-"# %e +)e+.e# perio#i+a""! if t)e patie't a&rees to pro+ee# it) pio&"ita(o'e t)erap!/ A. B. C. D. E.

-hyroid +unction tests B# and creatinine iver +unction tests CBC ,ith di++erential E3ection +raction

Explanation: -hia!olidinediones "-LD4$ are a ne, group o+ antidia/etic medication that reduces insulin resistance. -roglita!one ,as the +irst -LD released +or clinical use ho,ever it ,as ,ithdra,n a+ter t,o years /ecause o+ a high incidence in severe hepatoto%icity. -he ne,er -LDs0 pioglita!one and rosiglita!one0 have a lo,er incidence o+ hepatoto%icity. Ho,ever0 liver +unction tests should /e monitored in all patients started on -LDs. iver +unction tests chie+ly alanine aminotrans+erase "A-$are measured at /aseline0 &) ,eeks a+ter starting treatment0 and periodically therea+ter. n addition to treating type ) dia/etes -LDs are also very use+ul medications in the treatment o+ meta/olic syndrome0 nonalcoholic +atly liver disease "also called @#ASH$0 and polycystic ovarian disease. nsulin resistance is crucial in the development o+ these disorders. "Choice A$ -hyroid +unction tests are not re7uired +or any antidia/etic medication. -hyroid +unction tests are routinely per+ormed on patients taking lithium and amiodarone. "Choice B$ ?enal +ailure is an a/solute contraindication +or met+ormin use. Creatinine is typically monitored on a yearly /asis in patients on met+ormin therapy /ecause its use in the +ace o+ renal +ailure increases the risk o+ lactic acidosis. A creatinine o+ &.4 mg9d in males and &.1 mg9d in +emales is contraindication +or the use o+ met+ormin. "Choice D$ Hematological side e++ects are very rarely seen ,ith treatment ,ith oral antidia/etic medications0 and a CBC is not routinely re7uired. "Choice E$-he side e++ects o+ -LDs include +luid retention and the aggravation o+ congestive heart +ailure. Patients on concurrent insulin and -LD therapy have the highest risk +or congestive heart +ailure. #MHA class ll and class < heart +ailure is an a/solute contraindication +or -LD use. For class land  heart +ailure0 the decision ,hether to start -LD is /ased on clinical evaluation. Determining e3ection +raction is not mandatory /e+ore or during treatment ,ith -LDs.

Educational 5/3ective6 &. Because troglita!one ,as ,ith dra,n +rom the market due to hepatoto%icity0 periodic liver +unction tests are no, recommended in all patients treated ,ith thia!olidinediones. ). -he other important side e++ect o+ -LDs includes +luid retention ,hich can e%acer/ate congestive heart +ailure in patients ,ith underlying cardiac dys+unction.

54

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 37: A &ro-p of i'vesti&ators is perfor$i'& a' eperi$e't #esi&'e# to assess &e'eti+ varia%i"it! i' #r-& %iotra'sfor$atio'* A fie# #ose of iso'ia(i# is &ive' to a &ro-p of vo"-'teers a'# t)e p"as$a #r-& +o'+e'tratio' is $eas-re# fo-r )o-rs fo""oi'& a#$i'istratio' of t)e #r-&* T)e fo""oi'& #istri%-tio' of p"as$a #r-& +o'+e'tratio' i' t)ese s-%e+ts is o%tai'e#* :ariatio' of )i+) of t)e fo""oi'& pro+esses provi#es t)e %est ep"a'atio' for t)e s)a#e# area of t)e +-rve/

A. B. C. D. E.

;ethylation Glucuronidation Hydrolysis Acetylation Amine o%idation

Explanation: -he rate and e%tent o+ drug meta/olism normally varies +rom person to person. -hese slight interpersonal variations in the a/ility to meta/oli!e drugs are typically re+lected graphically /y a unimodal distri/ution0 usually in the shape o+ a /ell curve0 ,hen plasma levels o+ drug are measured at a +i%ed time +ollo,ing a +i%ed dose o+ drug. -his is the method that ,as used to generate the graph given in the 7uestion stem. >ith most drugs0 the ma3ority o+ people +all ,ithin one standard deviation and 84* o+ people +all ,ithin t,o standard deviations o+ the population mean o+ plasma concentration. A single peak in this type o+ graph indicates that the population /eing tested possesses a similar genetic drug meta/oli!ing capacity. A /imodal "discontinuous polymorphic$ curve0 as sho,n in the 7uestion stem0 results +rom the presence o+ t,o apparently distinct groups ,ithin the study population and suggests a pharmacogenetics polymorphism in drug meta/oli!ing capacity. n other ,ords0 the t,o peaks indicate t,o sets o+ responders to the drug ,ithin the population6 one that rapidly converts the drug into its meta/olite "considered normal$ and another that converts the drug slo,ly0 leading to accumulation o+ the original drug in the plasma. sonia!id is meta/oli!ed /y acetylation to #(acetyl(isonia!id in the hepatic microsomal system /y the en!yme #(acetyl trans+erase and is su/se7uently e%creted in the urine. -he +irst and second peaks in the a/ove graph represent +ast and slo, acetylators0 respectively. Slo, acetylators o+ isonia!id also meta/oli!e "acetylate$ dapsone0 hydrala!ine0 and procainamide slo,ly0 causing accumulation o+ these drugs as ,ell. Slo, acetylators o+ these drugs are at increased risk o+ to%ic e++ects0 ,hile +ast acetylators may re7uire much higher therapeutic doses to achieve a therapeutic e++ect. "Choice A$ ;ethylation is an important drug /iotrans+ormation method to consider ,hen prescri/ing drugs such as a!athioprine and 2( mercaptopurine0 drugs used in the treatment o+ some in+lammatory disorders o+ the /o,el and skin. "Choice B$ Glucuronidation is a /iotrans+ormation path,ay utili!ed +or the meta/olism o+ numerous drugs as ,ell as endogenous su/stances such 55

USMLE WORLD STEP 1

PHARMACOLOGY

as /iliru/in. #o /imodality has /een descri/ed ,ith this path,ay0 /ut conditions such as Gil/ert syndrome involve dys+unction o+ the glucuronyl trans+erase system that can lead to to%ic accumulation o+ some drugs. "Choice C$ Hydrolysis occurs ,ith en!ymes such as esterases and amidases. sonia!id is not meta/oli!ed /y this path,ay0 and hydrolysis does not e%hi/it polymorphic meta/olism. "Choice E$ Amine o%idation is usually undertaken /y monoamine o%idases or /y cytochrome o%idative deamination. #either process meta/oli!es isonia!id nor e%hi/its /imodality. Educational 5/3ective6 sonia!id is meta/oli!ed /y acetylation. -he speed ,ith ,hich a patient is a/le to acetylate drugs depends on ,hether they are genetically @+ast or @slo, acetylators. -he presence o+ +ast and slo, acetylators ,ithin the same population results in a /imodal distri/ution o+ the speed o+ isonia!id meta/olism. Slo, acetylators are at increased risk o+ adverse side e++ects.

56

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 38: A 4!earo"# $a"e it) a#va'+e# H9: i'fe+tio' is a#$itte# for i$paire# visio'* O' t)e t)ir# #a! of )ospita"i(atio', )e #eve"ops &e'era"i(e# sei(-res a'# is fo-'# to %e )!po+a"+e$i+ a'# )!po$a&'ese$i+* W)i+) of t)e fo""oi'& #r-&s is $ost "i.e"! respo'si%"e for t)e o%serve# effe+ts/ A. B. C. D. E.

Acyclovir Ganciclovir Foscarnet ndinavir amivudine

Explanation:
Educational 5/3ective6 Foscarnet is an analog o+ pyrophosphate that can chelate calcium and promote nephroto%ic renal magnesium ,asting. -hese to%icities can result in symptomatic hypocalcemia and hypomagnesemia.

57

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 39: After a series of p)ar$a+o.i'eti+ st-#ies, it is #eter$i'e# t)at a 'e"! #eve"ope# 'o'opioi# +o-&) s-ppressa't )as a vo"-$e of #istri%-tio' of 1< L a'# +"eara'+e of 0 LF) for a )ea"t)! 0<.& $a'* Ho "o'& o-"# it ta.e for 03= of t)is #r-& to %e e+rete# after a si'&"e #ose/ A. B. C. D. E.

& hour &.4 hours ) hours ).4 hours : hours

Explanation: -he hal+(li+e "t&9)$ o+ a drug is the time period re7uired +or the plasma concentration o+ a drug to decrease /y 4'*. -his de+inition assumes a one(compartment model ,ith linear pharmacokinetics "as opposed to multi(compartment models0 ,hich undergo separate distri/ution and elimination phases$. -he hal+(li+e o+ a drug depends on its physicochemical properties such as lipid solu/ility0 protein /inding0 volume o+ distri/ution0 and meta/olic conversion or elimination path,ays. -he hal+(li+e o+ a drug a+ter administration o+ a single dose can /e calculated +rom the volume o+ distri/ution and the clearance rate as +ollo,s6 t&9)T"here ith the passage o+ each su/se7uent hal+(li+e hal+ o+ the remaining drug is eliminated. For e%ample at time !ero &''* o+ the drug is present +ollo,ing intravenous dosing. A+ter hal+(li+e 4'* is eliminated and 4'* remains. A+ter ) hal+(li+e intervals0 hal+ o+ the remaining 4'* "4'*  "hal+ o+ 4'*$$ or J4* o+ the original total dose is eliminated. A+ter : hal+(li+e intervals0 J4*  "hal+ o+ )4*$ OJ.4* is eliminated. A+ter1 hal+(li+e intervals0 OJ.4*  "hal+ o+ &).4*$ T 8:.J4* is eliminated. A+ter 4 hal+(li+e intervals0 8:.J4*  "hal+ o+ 2.)4*$ T 82.OJ4* is eliminated. Conse7uently0 a drug is virtually totally eliminated a+ter +ive hal+(li+e intervals. >ith respect to the 7uestion0 the e7uation a/ove can /e used ,ith the values provided in the 7uestion stem to calculate the hal+(li+e as +ollo,s6 t&9)T"&' % '.J$ 9 J9hr T & hour t takes t,o hal+(li+e intervals to eliminate J4* o+ the drug6 there+ore. t ,ill take ) hours to e%crete J4* o+ a drug ,ith a t&9) o+ & hour.

Educational 5/3ective6 -he hal+(li+e o+ a drug "t&9)$ is a measure o+ ho, 7uickly a drug is eliminated +rom the /ody and ho, soon steady(state concentrations are achieved a+ter repeated dosing. Generally the hal+(li+e o+ a drug in plasma is a determinant o+ the duration o+ its pharmacologic e++ects in the /ody. A drug is virtually totally eliminated a+ter 4 hal+(li+e intervals. -o calculate hal+(li+e0 use the +ormula6 t&9) "
USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 40: A 88!earo"# fe$a"e is #ia&'ose# it) )!pert)!roi#is$ after prese'ti'& it) pa"pitatio's, ei&)t "oss, a'# i'so$'ia* Met)i$a(o"e $o'ot)erapies i'itiate#> to $o't)s "ater, )er +o'#itio' i$proves si&'ifi+a't"!* 9')i%itio' of )i+) of t)e fo""oi'& pro+esses is $ost "i.e"! respo'si%"e for i$prove$e't i' t)is patie't/ A. B. C. D. E.

odine uptake /y the thyroid odine organi+ication and coupling o+ iodotyrosine Colloid deposition Peripheral -1 to -: conversion -:9-1 e++ect on target tissues

Explanation: -he normal thyroid takes up iodine "iodine trapping$ against a concentration gradient /y an energy(dependent process0 using a sodium iodine symporter. A+ter dietary0 inorganic iodine enters the thyroid +ollicular cells0 it is o%idi!ed to organic iodide /y the en!yme thyroid pero%idase0 in a process kno,n as @organi+ication. -he iodine then /inds to tyrosine residues in the thyroglo/ulin to +orm monoiodotyrosine. Several com/inations are then possi/le. -,o monoiodotyrosine can com/ine to +orm diiodotyrosine0 ,hich can then unite ,ith another diiodotyrosine to +orm thyro%ine "-1$. Alternatively0 a monoiodotyrosine can link ,ith a diiodotyrosine to make triiodothyronine "-:$. -he thyroid +ollicular cells then engul+ thyroglo/ulin0 ,hich contains any and all o+ the iodinated tyrosine compounds "mono( and diiodotyrosine0 -:0 and -1$ /y pinocytosis. n the thyroid cytoplasm0 the iodinated tyrosine residues is removed +rom the rest o+ the thyroglo/ulin and secreted +rom the /asolateral /order. -he non+unctional mono( and diiodotyrosine are de(iodinated so that iodine in the thyroglo/ulin mi% can /e reused "deiodination and iodine recycling$. -hyroid pero%idase is responsi/le +or o%idation o+ inorganic iodine0 +ormation o+ mono and diiodotyrosine0 and coupling ,hich +orms -: and -1. ;ethima!ole acts as an anti(thyroid drug /y inhi/iting thyroid pero%idase0 there/y treating hyperthyroidism. "Choice A$ -he thyroid gland uptakes iodine against the concentration gradient using a sodium iodine symporter. -he activity o+ this pump is energy dependent. -here are other +actors that determine the degree o+ iodine uptake. For instance0 several other ions like perchlorate and thiocyanate can compete against the iodine +or entry into the thyroid gland0 hence+orth reducing iodine uptake /y the thyroid +ollicular cells. Alternatively0 iodine uptake is positively up(regulated /y -SH. "Choice C$ Colloid is the gelatinous product o+ the thyroid gland0 consisting mainly o+ thyroglo/ulin0 a high(molecular( ,eight glycosylated protein. -SH secreted +rom the pituitary increases the synthesis o+ thyroglo/ulin /y increasing its gene transcription. -hyroglo/ulin synthesis is not increased /y thyroid pero%idase en!yme and is not a++ected /y methima!ole. "Choice D$ ;ethima!ole does not inhi/it the peripheral conversion o+ the inactive -1 to the active-:. -his might /e a tempting choice0 ho,ever0 /ecause another antithyroid medication0 propylthiouracil "P-$ /oth inhi/its thyroid pero%idase and decreases conversion o+ -1 to -:. "Choice E$-he e++ect o+ thyroid hormones on the peripheral tissues is accomplished /y interaction o+ -: ,ith an intracellular thyroid hormone receptor. -here are no antithyroid drugs that e++ect thyroid hormone receptor interaction. 59

USMLE WORLD STEP 1

PHARMACOLOGY

Educational 5/3ective6 -hionamide "methima!ole and propylthiouracil$ act as antithyroid medications0 /y decreasing the +ormation o+ thyroid hormones via inhi/ition o+ the en!yme thyroid pero%idase. Propylthiouracil also decreases the peripheral conversion o+ -1 to &:

60

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 41: A 'e a'tiarr)!t)$i+ #r-& is fo-'# to %e effe+tive a&ai'st %ot) atria" a'# ve'tri+-"ar arr)!t)$ias* O' EG it +a-ses ORS pro"o'&atio' %-t )as "itt"e effe+t o' t)e IT i'terva" #-ratio'* W)i+) of t)e fo""oi'& parts of t)e a+tio' pote'tia" +-rve pi+t-re# %e"o is $ost affe+te# %! t)is #r-&/

A. B. C. D. E.

A B C D E

Explanation: -he 5?S comple% corresponds to ventricular depolari!ation. ,hich occurs during phase ' o+ the ventricular myocyte action potential and is represented a/ove /y Choice B. Depolari!ation occurs ,hen there is rapid sodium movement into the cardiac myocyte0 thus this ne, medication most likely /locks sodium in+lu% "phase '$0 as do class  antiarrhythmics. Additionally0 /ecause this drug does not prolong the - interval itis most similar to the class C agents "e.g. propa+enone$. "Choice A$ -his is phase 1 o+ the myocyte action potential0 the resting portion o+ the curve ,here ingoing and outgoing currents are /alanced. Antiarrhythmic drugs do not a++ect phase 1 o+ the myocyte action potential0 /ut they can a++ect phase 1 o+ the pacemaker cell action potential ,hich slo,ly depolari!es and is mediated /y sodium in+lu%. "Choice C$ -his is phase o+ the action potential0 a /rie+ period o+ repolari!ation corresponding to a sharp decrease in sodium conductance and an increase in potassium permea/ility. t is not modulated to an apprecia/le e%tent /y anti arrhythmic medications. "Choice D$ -his is phase ) o+ the cardiac myocyte action potential the @plateau o+ the action potential ,here movement o+ calcium ions into the cell and potassium ions out o+ the cell is relatively e7ual. "Choice E$ Phase : o+ the action potential is the main repolari!ation phase o+ the ventricular myocyte. ?epolari!ation is mediated /y an out,ard movement o+ potassium ions and can /e modulated /y class : antiarrhythmic agents. -hese medications prolong phase : repolari!ation and the 5- interval on EKG.

Educational 5/3ective6 -he 5?S comple% corresponds to ventricular depolari!ation and phase ' on the action potential graph.
61

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 42: A 63!earo"# Ca-+asia' $a"e prese'ts to !o-r offi+e af ter a "o'& perio# it)o-t $e#i+a" fo""o-p +o$p"ai'i'& of #ist-r%e# +o"or per+eptio' a'oreia, 'a-sea vo$iti'& a'# #iarr)ea* His past $e#i+a" )istor! is si&'ifi+a't for +o'&estive )eart fai"-re t)at is effe+tive"! +o'tro""e# it) $-"tip"e $e#i+atio's* W)i+) of t)e fo""oi'& is t)e $ost "i.e"! +o$p"i+atio' of t)is patie'ts +-rre't +o'#itio'/ A. B. C. D. E. F.

Arrythmia Angioedema Bronchoconstriction Pulmonary edema ?enal +ailure Hypotension

Explanation: -he key to getting this 7uestion correct is the kno,ledge that digo%in to%icity can lead to changes in color vision as a characteristic side e++ect and nausea and decreased appetite as common side e++ects. 5nce you have determined that digo%in is responsi/le +or this patient=s constellation o+ symptoms0 you need to recall that ventricular tachyarrhythmias "Choice A$ are the most serious and potentially +atal e++ects o+ digo%in to%icity and need to /e treated ,ith management o+ hyperkalemia and possi/ly ,ith anti(digo%in anti/ody +ragments. "Choice B$ Angioedema is a severe side e++ect clinically mani+est as edema o+ the lips and laryn%. 5+ the drugs used to treat heart +ailure0 it is most commonly associated ,ith the angiotensin converting en!yme inhi/itors "ACE($. ACE( s do not cause the side e++ects mentioned0 and angioedema is not a kno,n side e++ect o+ digo%in. "Choice C$ Bronchoconstriction is a +eared side e++ect o+ nonspeci+ic /eta(adrenergic /lockers in patients ,ith chronic o/structive pulmonary disease and asthma. Beta(/lockers such as metoprolol have /een sho,n to /e use+ul in patients a+ter myocardial in+arction and in treating patients ,ith heart +ailure. Bronchoconstriction is not a kno,n side e++ect o+ digo%in. "Choice D$ Pulmonary edema may occur ,ith uncontrolled heart +ailure. n systolic dys+unction0 the e3ection +raction is lo, and there is poor +or,ard +lo, causing /lood to pool in the lungs and pulmonary edema results. n diastolic dys+unction0 the e3ection +raction can /e normal or even high0 /ut high heart rate or poor ventricular compliance causes insu++icient diastolic +illing time. -his result in an inade7uate volume o+ /lood /eing pumped +or,ard leading to accumulation in the lungs and pulmonary edema. "Choice E$ ?enal +ailure can /e precipitated /y a variety o+ drugs +rom antimicro/ials such as amphotericin B and aminoglycosides to drugs used commonly +or heart +ailure such as +urosemide. 5ver diuresis ,ith the loop diuretic +urosemide can cause a decrease in intravascular volume leading to prerenal acute renal insu++iciency +rom poor renal /lood +lo,. "Choice F$ Digo%in is an inotropic agent and causes increased cardiac output. t ,ould lead to hypotension only i+ ventricular +i/rillation set in +rom digo%in to%icity leading to poor +or,ard +lo,. Educational 5/3ective6 n this case0 digo%in to%icity mani+ested as changes in color vision and anore%ia. Digo%in to%icity can also cause ventricular dysrhythmias0 headache0 +atigue and con+usion.

62

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 43: A 83!earo"# Ca-+asia' fe$a"e prese'ts to !o-r offi+e +o$p"ai'i'& of e+essive )air &rot) o' )er fa+e* S)e is ver! +o'+er'e# %e+a-se s)e t)i'.s t)at it $a.es )er "oo. J-&"!* Her past $e#i+a" )istor! is i'si&'ifi+a't* Her $e'str-a" perio#s are re&-"ar, o++-rri'& ever! 84 #a!s* S)e is 'ot se-a""! a+tive a'# )er "ast $e'str-a" perio# as 8 ee.s a&o* W)i+) of t)e fo""oi'& is t)e %est treat$e't optio' for t)is patie't/ A. B. C. D. E. F.

Clomiphene ;itotane ;edro%yprogesterone ;i+epristone Dana!ol Spironolactone

Explanation: -erminal hair gro,th in a male(like pattern in +emale is called hirsutism. t should /e distinguished +rom virili!ation that consists o+ hirsutism in association ,ith clitoromegaly0 increased muscle mass0 acne0 increased li/ido and voice deepening. -he gro,th o+ terminal hair "coarse0 curly and pigmented$ is dependent on the action o+ a testosterone meta/olite dihydrotestosterone "DH-$ that is synthesi!ed /y 4(a(reductase. Hirsutism may occur due to increased testosterone production "such as in polycystic ovary syndrome0 Cushing syndrome0 ovarian and adrenal tumors$. diopathic hirsutism develops due to increased conversion o+ testosterone into DH/y 4(a(reductase or due to higher sensitivity o+ hair +ollicles to DH-. n ,omen ,ith regular menstrual cycles and no symptoms o+ virili!ation0 increased hair gro,th is likely to /e caused /y idiopathic hirsutism. t is treated /y inhi/ition o+ testosterone synthesis or its e++ect on skin. Among the drugs listed in the ans,er choices0 only spironolactone has anti(androgenic properties. t /locks androgen receptors at the hair +ollicles0 and decreases testosterone production. Apart +rom its anti( androgenic properties0 spironolactone is ,idely used as a potassium( sparing diuretic. Spironolactone causes gynecomastia and testicular atrophy in men. -he other drugs that can /e used +or hirsutism include antiandrogens +lutamide "testosterone receptor antagonist$ and +inasteride "4(alpha( reductase inhi/itor$. "Choice A$ Clomiphene is an antiestrogen. t inter+eres ,ith the negative +eed/ack o+ estrogens on hypothalamus and pituitary. t increases the synthesis o+ Gn(?H and0 conse7uently gonadotropins. t is used +or treating in+ertility especially ,hen associated ,ith anovulation. "Choice B$ ;itotane is an adrenocorticolytic drug used primarily +or the treatment o+ adrenocortical carcinoma. "Choice C$ ;edro%yprogesterone "Depo Provera$ is a progesterone(only contraceptive administered as an intramuscular in3ection once every &) ,eeks. "Choice D$ ;i+epristone "?(1O2$ is a synthetic steroid ,ith anti( progestin and anti(glucocorticoid e++ects. t is used primarily as an a/orti+acient. "Choice E$ Dana!ol is a synthetic androgen used +or the treatment o+ endometriosis and hereditary angioedema. ts side e++ects include hirsutism0 masculini!ation0 +luid retention and ,eight gain. 63

USMLE WORLD STEP 1

PHARMACOLOGY

Educational 5/3ective6 Hirsutism is an e%cessive gro,th o+ terminal hair in a male(like pattern. t occurs due to increased testosterone secretion or increased conversion o+ testosterone to DH-. Spironolactone has anti(androgenic properties and is used +or treatment o+ hirsutism. -he other drugs that can /e used +or hirsutism include antiandrogens +lutamide "inhi/its /inding to testosterone receptors$ and +inasteride "4(alpha(reductase inhi/itor$.

64

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 44: A 84!earo"# pre&'a't fe$a"e +o$es to t)e p)!si+ia's offi+e %e+a-se of ri&)t "e& se""i'& a'# pai'* S)e is B ee.s pre&'a't* Dopp"er ea$i'atio' of t)e "e& s)os #eep ve'o-s t)ro$%osis* W)i+) of t)e fo""oi'& is t)e $ost effe+tive a'ti+oa&-"atio' for t)is patie't #-ri'& )er pre&'a'+!/ A. B. C. D. E.

Aspirin >ar+arin Heparin Clopidogrel t(PA

Explanation: Pregnancy itsel+ is an independent risk +actor +or deep venous throm/osis "D<-$ due to several reasons. During pregnancy0 there are increased levels o+ clotting +actors0 decreased +i/rinolysis0 and reduced levels o+ the natural anticoagulant protein S. Additionally0 decreased venous tone and the pressure o+ the gravid uterus on the in+erior vena cava predispose pregnant ,omen to venous stasis. DH$ has more activity against +actor Ua than un+ractionated heparin. "Choice A$ Aspirin inhi/its platelet aggregation /y suppressing the synthesis o+ throm/o%ane A) in platelets. Aspirin alone is not an e++ective anticoagulant +or deep venous throm/osis. Aspirin is ade7uate +or the treatment and prevention o+ myocardial in+arction and ischemic strokes0 ho,ever. "Choice B$ >ar+arin is the /est long(term anticoagulant used +or the treatment o+ D<-. Ho,ever0 ,ar+arin is contraindicated in pregnancy /ecause it is teratogenic0 capa/le o+ causing a constellation o+ em/ryopathy termed @+etal ,ar+arin syndrome. "Choice D$ Clopidogrel inhi/its ADP mediated platelet aggregation. t is used in the treatment o+ coronary artery disease0 peripheral vascular disease0 and cere/rovascular disease0 /ut not +or D<-. "Choice E$ t(PA "tissue plasminogen activator$ is a throm/olytic drug that converts plasminogen to plasmin and +acilitates the dissolution o+ throm/i. -his and other throm/olytics are used in the management o+ Selevation acute myocardial in+arction and ischemic stroke.

Educational 5/3ective6 n pregnant ,omen heparin is used to treat DM-. Heparin increases antithrom/in  activity. Although ,ar+arin is normally the drug o+ choice +or D<- it is contraindicated in pregnancy /ecause it is teratogenic. #either aspirin nor clopidogrel are independently su++icient to treat D<-.

65

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 45: A 86!earo"# $a"e prese'ts to !o-r offi+e +o$p"ai'i'& of )air "oss* He sa!s )e fears &oi'& %a"# "i.e )is fat)er* P)!si+a" ea$i'atio' revea"s $o#erate )air "oss fro$ t)e a'terior s+a"p a'# verte* W)i+) of t)e fo""oi'& #r-&s +a' %e -se# to treat t)is patie'ts +o'#itio'/ A. B. C. D. E.

ocal glucocorticoids sotretinoin Progesterone Finasteride -er/ina+ine

Explanation: n adults age &O(14& the three most common causes o+ hair loss0 in order o+ +re7uency0 are6 male pattern /aldness "androgenetic alopecia$0 tinea capitis "ring,orm$0 and telogen e++luvium. 5+ these only androgenetic alopecia is inherited "polygenic or autosomal dominant inheritance$. -he pattern o+ hair loss descri/ed a/ove is classic +or androgenetic alopecia. -his type o+ hair loss generally +ollo,s the progression pictured /elo,.

-he pathogenesis o+ male pattern /aldness is thought to involve scalp 4(a(reductase activity and the androgenic e++ects o+ the dihydrotestosterone produced. -hus0 this condition may /e treated /y androgen antagonists0 in particular 4(a(reductase inhi/itors like +inasteride. n contrast tinea capitis causes isolated pruritic lesions on the scalp. -he lesions typically have a central clearing producing a ring( like con+iguration "hence0 @ring,orm$. -er/ina+ine "Choice E$ is an oral anti(+ungal agent "s7ualene epo%ides inhi/itor$. Systemic medications are used to treat tinea capitis /ecause topical agents do not ade7uately penetrate the hair +ollicle. 66

USMLE WORLD STEP 1

PHARMACOLOGY

"Choice A$ -opical corticosteroids are used to treat alopecia areata0 an autoimmune disorder that causes patchy or di++use hair loss. "Choice B$ 5ral isotretinoin is used to treat severe acne. ike other retinoids0 it inhi/its +ollicular epidermal keratini!ation. Educational 5/3ective6 ;ale pattern /aldness is an inherited trait that produces a distinctive pattern o+ progressive hair loss. -he anterior "+rontal$ scalp is a++ected +irst0 then the verte%. Pathogenesis involves scalp 4(a( reductase activity and the androgenic e++ects o+ the resulting dihydrotestosterone. 4(a(reductase inhi/itors like +inasteride can /e used to treat this condition.

67

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 46: A 43!earo"# Ca-+asia' fe$a"e is %ei'& treate# for severe oi't pai' a'# se""i'&* Soo' after %e&i''i'& treat$e't s)e prese'ts it) pai'f-" $o-t) -"+ers a'# 'a-sea* Liver f-'+tio' tests revea" AST a'# ALT e"evatio's* W)i+) of t)e fo""oi'& $e#i+atio's is $ost "i.e"! respo'si%"e/ A. B. C. D. E.

#apro%en ;ethotre%ate Hydro%ychloro7uine Prednisone ;inocycline

Explanation: ;ethotre%ate is the pre+erred +irst(line disease(modi+ying treatment +or most patients ,ith moderate to severe rheumatoid arthritis. t produces su/stantial improvements in disease activity in 2'(J'* o+ patients. e+lunomide and -#F(a inhi/itors are other disease(modi+ying agents that may /e used in com/ination ,ith methotre%ate i+ the patient does not respond to methotre%ate alone. ;ethotre%ate ,orks /y inhi/iting the en!yme dihydro+olate reductase to /lock +olinic acid synthesis. Although it is generally ,ell tolerated0 serious adverse e++ects can occur0 including stomatitis "pain+ul mouth ulcers$ and hepatoto%icity "hepatitis0 +i/rosis0 and cirrhosis$. 5ther potential adverse e++ects include myelosuppression0 increased risk +or opportunistic in+ections0 B(cell lymphomas0 and pulmonary +i/rosis. ;ethotre%ate is contraindicated during pregnancy. Supplementation o+ +olic acid reduces the occurrence o+ stomatitis. "Choice A$ #apro%en is a nonsteroidal anti(in+lammatory drug "#SAD$ that ,orks /y /locking prostaglandin synthesis. Gastrointestinal /leeding0 +luid retention0 and ,orsening o+ hypertension are important potential side e++ects o+ #SAD therapy. -here may /e mild elevations o+ liver +unction en!ymes in a small percentage o+ patients. iver changes are generally asymptomatic and nonprogressive. ;outh ulcerations do not typically occur ,ith #SAD therapy. "Choice C$ Hydro%ychloro7uine can /e used to treat early mild seronegative rheumatoid arthritis0 though it is more commonly used in the treatment o+ systemic lupus erythematosus. A serious potential adverse e++ect o+ hydro%ychloro7uine is permanent retinal damage. Baseline and +ollo,(up retinal e%aminations are necessary +or all patients using this medication. "Choice D$ Corticosteroids are typically used +or a short period o+ time in patients ,ho have acute 3oint pain and s,elling0 as a /ridge to relie+ +rom other therapies. Side e++ects o+ prolonged corticosteroid use include ,eight gain "especially centrally$0 hyperglycemia0 decreased /one density0 skin striae0 and pro%imal muscle ,eakness. >hen used ,ith #SADs0 corticosteroids potentiate the risk +or gastrointestinal /leeding. "Choice E$ ike sul+asala!ine and hydro%ychloro7uine0 minocycline can /e used in some patients ,ith early mild rheumatoid arthritis. Side e++ects are minimal0 and include photosensitivity.

Educational 5/3ective6 ;ethotre%ate is the pre+erred disease(modi+ying treatment +or patients ,ith moderate to severe rheumatoid arthritis. ;ethotre%ate treatment may cause stomatitis and liver +unction a/normalities.

68

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 47: A 44!earo"# Ca-+asia' $a"e )o is )ospita"i(e# for ope' +)o"e+!ste+to$! %e+o$es severe"! a&itate# a'# tre$-"o-s to #a!s after a#$issio'* He #e'ies a'! i""i+it #r-& -se, %-t a#$its to 4 %eers ever! #a! for t)e "ast severa" !ears* He )as 'o .'o' #r-& a""er&ies, a'# )is fa$i"! )istor! is i'si&'ifi+a't* His 5P is 13
A. Baclo+en B.

Haloperidol C. Dia!epam D. Car/ama!epine E. Propranolol F. Pheno/ar/ital G. Phenytoin Explanation: Alcohol is a C#S depressant that a++ects GABAA receptors and enhances the inhi/itory e++ect o+ GABA in the /rain. ong(term alcohol consumption leads to do,n(regulation o+ GABA receptors there+ore0 discontinuation o+ alcohol can cause C#S e%citation ",ithdra,al$. Alcohol(,ithdra,al symptoms typically start ,ithin O(&) hours a+ter the last drink and include insomnia0 tremulousness0 mild an%iety0 headache0 and autonomic hyperactivity "varia/le BP0 diaphoresis0 and tachycardia$. + untreated0 delirium tremens "generali!ed tonic(clonic sei!ures and hallucinosis$ may develop0 usually on the third day ,ithout alcohol. Alcohol0 /ar/iturates0 and /en!odia!epines have similar e++ects on GABA receptors and act /y enhancing GABA action. Ben!odia!epines have a /etter sa+ety pro+ile than /ar/iturates0 and are the drugs o+ choice in the treatment o+ alcohol ,ithdra,al. ong(acting /en!odia!epines0 such as dia!epam or chlordia!epo%ide0 are pre+erred in the ma3ority o+ patients. -hey have a prolonged hal+(li+e "up to a +e, days$ and are meta/oli!ed /y the liver into active meta/olites. Short(acting /en!odia!epines0 such as lora!epam0 are indicated +or patients ,ith advanced liver disease. "Choice A$ Baclo+en is an agonist o+ GABA2 receptors and is used to treat spastic conditions. t is not the drug o+ +irst choice +or alcohol ,ithdra,al. "Choice B$ Phenothia!ines and /utyrophenones "including haloperidol$ lo,er the sei!ure threshold. -hey should not /e used in patients su++ering +rom alcohol ,ithdra,al /ecause these patients are already at signi+icant risk +or sei!ure. "Choices D and G$ -he role o+ anticonvulsants such as phenytoin in alcohol(,ithdra,al associated sei!ures is controversial. Ho,ever0 car/ama!epine should never /e used to treat alcohol ,ithdra,al. "Choice E$ Propranolol can treat /oth tremor and hypertension. Ho,ever0 administering /en!odia!epines is the most crucial step in the management o+ these patients. + a patient is still symptomatic a+ter /en!odia!epine administration0 propranolol can /e tried. "Choice F$ Pheno/ar/ital is a /ar/iturate anticonvulsant that enhances GABA activity. t is not +irst(line treatment +or alcohol ,ithdra,al as it has a ,orse sa+ety pro+ile than /en!odia!epines.

69

USMLE WORLD STEP 1

PHARMACOLOGY

Educational 5/3ective6 Ben!odia!epines su/stitute +or the action o+ alcohol on GABA receptors and are indicated +or the treatment o+ alcohol ,ithdra,al. ong(acting /en!odia!epines "chlordia!epo%ide0 dia!epam$ are +irst(line medications. Short(acting /en!odia!epines "lora!epam0 o%a!epam$ are pre+erred in patients ,ith advanced liver dys+unction.

70

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 48: A 0B!earo"# '-rsi'& )o$e resi#e't )as 'ot )a# a %oe" $ove$e't for t)e "ast five #a!s* He )as s-ffere# fro$ +o'stipatio' for $a'! !ears> )e is #e$e'te# a'# spe'#s $ost of )is ti$e i' %e#* Ma&'esi-$ )!#roi#e as a#$i'istere# a'# pro#-+e# a %oe" $ove$e't i' a fe )o-rs* T)e $e+)a'is$ of t)e +"i'i+a" effe+t o%serve# i' t)is patie't $i$i+s t)e pat)op)!sio"o&! of )i+) of t)e fo""oi'& #isor#ers/ A. B. C. D. E.

rrita/le /o,el syndrome Crohn=s disease actase de+iciency Carcinoid syndrome ?ectal prolapse

Explanation: Constipation is common in elderly0 de/ilitated patients as ,ell as those on chronic opiate therapy. Factors that contri/ute to development o+ constipation are inactivity0 lo,(Fi/er diet0 medications "such as opioids or -CAs$ and hypercalcemia. As li+estyle changes are not an option in patients such as the one mentioned in the 7uestion stem0 constipation in this population is commonly treated ,ith osmotic la%atives such as magnesium hydro%ide0 stool so+teners and enemas. ;agnesium(containing oral drugs such as magnesium hydro%ide and magnesium citrate0 as ,ell as preparations such as lactulose and GoM-EM "polyethylene glycol$ are osmotic la%atives. -hey are non( a/sor/a/le or poorly a/sor/a/le su/stances that attract ,ater into the intestinal lumen0 thus distending the intestinal ,all and increasing peristalsis. -he la%ative e++ect is usually rapid. actase de+iciency is a disease state characteri!ed /y osmotic diarrhea "Choice C$. nherited or ac7uired de+iciency o+ the intestinal /rush /order en!yme lactase "disaccharidase$ causes ina/ility to /reak do,n lactose into glucose and +ructose. ndigested lactose is a non( a/sor/a/le osmotic su/stance0 and its accumulation in the small intestine leads to increase in secretion o+ ,ater and electrolytes into the intestinal lumen. actase de+iciency "lactose intolerance$ presents ,ith a/dominal pain0 distension and ,atery diarrhea. A/dominal pain and distention result +rom meta/olism o+ lactose /y normal gut +lora /y +ermentation causing production o+ gas. -he symptoms resolve ,hen milk( containing products are eliminated +rom the diet. "Choice A$ rrita/le /o,el syndrome is a +unctional intestinal disorder that presents ,ith diarrhea alternating ,ith constipation0 a/dominal pain and distention ,ithout organic cause. Fecal ,ater and electrolyte content in BS is normal. "Choice B$ Diarrhea in Crohn=s disease is o+ the secretory type ,hich is characteri!ed /y high electrolyte content due to poor a/sorption and increased losses +rom the in+lamed intestinal mucosa. "Choice D$ Diarrhea in carcinoid syndrome is secretory and high in electrolytes. "Choice E$ ?ectal prolapse is a protrusion o+ rectal mucosa through the anus associated ,ith pregnancy and constipation it is not associated ,ith diarrhea. Educational 5/3ective6 ;agnesium hydro%ide causes osmotic diarrhea /ecause magnesium ions are poorly a/sor/ed in the gut. Diarrhea associated ,ith lactase de+iciency is also osmotic and occurs due to accumulation o+ non(a/sor/a/le lactose in the intestinal lumen. 71

USMLE WORLD STEP 1

PHARMACOLOGY

Q NO 49: A 4!earo"# $a"e %e&i's treat$e't for #epressio'* Severa" ee.s after starti'& t)e $e#i+atio', )e 'otes t)at )is #epressive s!$pto$s )ave i$prove# $ar.e#"!, %-t t)at )e is 'o eperie'+i'& i$paire# se-a" perfor$a'+e* He re2-ests a' a"ter'ative treat$e't, it)o-t se-a" si#e effe+ts* W)i+) of t)e fo""oi'& #r-&s is $ost appropriate for t)is patie't/

A. B. C. D. E.

Fluo%etine Phenel!ine Bupropion mipramine -ra!odone

Explanation: Bupropion is an antidepressant medication that does not cause se%ual dys+unction. Side e++ects o+ /upropion can include agitation0 insomnia0 and sei!ures. t is thought that /upropion e%erts its e++ects /y acting on norepinephrine transmission0 ,ithout signi+icantly in+luencing serotonin0 acetylcholine0 or histamine meta/olism. Bupropion is use+ul +or the treatment o+ depression ,ith associated psychomotor retardation or hypersomnia0 /ecause it has stimulatory e++ects. Bupropion is also e++ective in the treatment o+ nicotine dependence. "Choice A$ Fluo%etine is a selective serotonin reuptake inhi/itor "SS?$. Se%ual dys+unction is a relatively common side e++ect o+ the SS?s and limits their use +or many patients. "Choice B$ ;onoamine o%idase inhi/itors ";A54$0 such as phenel!ine and tranylcypromine0 are not considered +irst( line antidepressant medications /ecause o+ necessary dietary restrictions "cheese0 ,ine$0 potential drug(drug interactions "-5A4$0 and numerous other side e++ects. "Choice D$ mipramine is a tricyclic anti(depressant ,ith numerous side e++ects. t is not a +irst(line treatment +or depression. "Choice E$ -ra!odone is a highly sedating anti(depressant that can /e help+ul +or patients ,ith insomnia. -ra!odone can cause priapism and other se%ual side e++ects.

Educational 5/3ective6 Se%ual dys+unction is seen in up to 4'* o+ patients treated ,ith SS?s. Symptoms include decreased li/ido0 anorgasmia0 and increased latency to e3aculation. Bupropion is an e%cellent alternative.

72