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4TH
GaIT C.
ProfesSor
Department
.md
COLOGY
1'11.0.
Integra tin> Biology nd Pharmacology
Graduate s .• : h+o. of Biomedical Scie,c{'s
i\ssl stanl for Education Programs
Medical School at Houston
Dm'i d Loose, 1'11.0.
Associate ""'1"'"'
Department . Integrated [l iology and Pharmacology
ilnd
Graduat(' Seh,,101 of Biomedical SciellCl's
of Medical School . .It Iioustoll
I
With sp,celat contributions by
Medilla IIshell, ,\I.D.
Will iam  
Royal Oak,
Todd \.
William  
Royal Oak,
.\J.D., 1'11.1).


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Third Edition,
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Rosenfeld, Ga ry C.
Pharmacology /
Kushell, Todd A.
p. ;
Includes index.
ISfiN-13:
Loose, David .
C. Rosenfeld, Dav d S. Loose; with special contributions by Medina
I. ted.
(alk. paper) I. Pharmacology-Examinations, questions, etc. l.
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This conci se
and others
for !
tiuns of
the mual
lati on of
e to the Fourth Edition
of medical pharmacology is designed for medi cal students, dental students.
health care professions. It is intended primarily to help students prepare
such as the Un ited States Medical Licensing Examination Step 1
examinations. This book presents condensed and succinct descrip-
and current Boord·dJi ven i nformation pertaining to pharmacology without
-j details. 11 is not rneant to be a for the comprehensive presen·
and difficult (oncepts found in standard pharmacology l{?xtS.
The fourth - ion begins with a chap: er devoted to the general principles of action, fol-
lowed   concerned with dLlgs acting on the maj or body systems. Other chapters
discuss a " ergots, antiinflamnatory and Immunosuppressive agents, drugs used to
treat anemias disorders of hemos asis, infeCl ious diseases, ca nccr. and tOXicology.
Each indudes a presentali)n of specific drugs with a discussion of their general
propert ies, n ism of action, pharmacologic effects, thcrapeutic uses, and ad,'crsc effects.
A drug li sl, and figures surnmaTizc essential drug information included in all chapters,
Clinical ly USMLE·style rfview questions and answers with cxplanations follow
each chapter help st udents assess their understa nding of the information, Similarl y, a com·
prehen:.i,"e comisting of USMLE-stylc questi ons is included at the end of the
book. serve. as a self-a.\scssment tool to help determine their fund
of knowledge diagnose any weakr esses in pharmacology.
• current drug infurmat ic'il
• review tests feat ure updatr.-d questions
• 2·colo! ""'"" summarize (sscntial lnformation for qukk recall

Drug !iSH

Addiltonal comprehellSi\-e examination questions and explanatIons
Gary C. Rosl'lI{,eld, PII.o.
Dm'ill S. i (K)\C, Pl!.lJ.
v
Acknowledgments
The aullmrs a ' knowledge and thank our   for their .'IUppor! allll contributions to
thi s boo!.. and our medical students fo)r being OUf hars hest
vii
Contents
Preface v
Acknowledgn cnts vii
1 Gener I Principles of [)rug Action ......... . . .. . .. . . . . .. 1
I. D( se-Response Relation ;hips 1
II . 0 g Absorption 6
III . Dr g Dist ribution 9
IV. Dr g Elimi nation and Tt' rmi nat ion of Action 10
V. Bl )tramformal ion (Met,bolism) of Drugs 11
VI. E --ret lon of Drug.. \.;
VII . P rmacokinct in. 16
Re , ·iew cs t 19
2 Drugs cting on the Autonomic Nervous System .... 25
I. TI Peripheral Efferent Nervous System 2S
II . Pa asympat homimetit: Crug.. 10
III . :V1 scari ni c· Receptor Antagonists .15
IV. G< nglionic-Blocking On. gs 3 7
V. Sk 'leta! Muscle Relaxanl'i 37
VI . Sy npathomimetic 42
VII . A energic Ikceptor Antlgonhls 47
Review r e:<ol 53
3 Drugs cling on the System ................ . . ... 60
I. Oi retics 60
II . N ndiuretic Inhi bi tors o · Tubular Transpurt 66
Review cst 69
Drugs cting on the Cardiovascular System · . . . . . .. . ... 73
I. ' nh Used to Treat Congestive Ileart J:ailure (CHF) 73
II . AI   Dmgs 79
III. A ia ngi nal Agenh 81
IV. A ihypertcnsin' 86
v. Dr Igs that Lower Plasma Li pids 92
Review est 96
ix
X
5 Drugs
on the Central Nervous System · .......... 101
I.
.. Drugs 101
II. .. (Neuroleptic) Drugs 106
III. Drugs ItO
IV. I1 S
V. Analgesics dnd Ant,lgonists L 16
VI . Drugs and Drugs Used to Treat Alzhdnll' r's Dise<lSl' 123
VII . 12.
VIII . 1JO
IX. ns
X. 117
Review 148
6 Ergots, Antiinflammatory Agents,
and Apnts ········ ········ IS3
I. and Anti histamines 153
II. and Seroto nin A ltagonists 157
Ill. 1 S9
IV.
V.
VI.
VII .

 
161
Antiinflammatory Drugs (:-.JSAIDs) 164
Used for Gout 171
VIII .
Imnilm''''' PI'''''''''' Agent -, 172
177
7 u,eo in Anemia and Disorders of Hemostasis .... 180
Used in the Treat me It of ISO
Act ing o n \-fyelo id (ells 184
III. USN in Hemostat ic )iso rders 184
Review 192
8 Drugs
on the Gast rointestinaJ Tract · ........... 197
I. and Ant iemet ics 197
II . and Appet it" En hancers 199
III. f or Upper Gas :rointestinai !"ract 200
IV. Agents 205
V. Used to Disso lve Gallstones 20:5
VI.
VII .
Enzyme Hepl acements 20:5
A that Act on the LmH'r Gast rointestinal Tract 206
Review 210
9 Drugs
on the Pulmonary System ............... 214
I. 10 to Pulmonary l)isorders 2 14
II. Used to Treat Asthma and Other Bronchial I)isorders 21 S
III. Used to Treat Rhi nit S and Cough 220
Re view 223
10 Drugs
on the Endoc;rine System ................ 225
I. Recepto<s 22:
II. The 225
Ill. The.
IV. Th('
  229
, Pituitary :!31
c ot\, F. :,

TS xi
V.
!rugs Acting on the G'Jnadai and Reproductive Sys tem 232
VI . h e Adrenal Cortex 2-11
VII. he Thyroid 245
VIII. - he Pancreas and GlueJsc 2-1 7
IX. he Calcium Ho meost.lt ic System 252
x. I eti noie Aci d and Deri ' ati ves 256
Revie Test 260
11 Dru Used in Treatm.ent of Infectious Diseases ... . .... 262
I. l l fcc tioLLS Di sease Tht' lapy 262
II. ntibacterials 263
III . . ntimycobacterial Age1b 276
IV. f nti fungal Agent s  
v. ntiparasit ic Drugs 282
VI. I nti viral Drugs 2R6
Rcvie Test 293
12 Cane r Chemotherapy ........................... . .... 298
I. r rinciples of Cancer Chemotherapy 29S
II . lkylat ing Agents 299
III . t nt imetabolites 30:;
IV. atural l'rodm1s 1[6
V. I iscellaneous Agents 308
VI . . ewid Hormones and 4..ntagonists and Rel at ed Drugs 3 t 1
VIT. d junct Agents 313
Revie ' Test 315
13 'foxi logy . . . . ................... . ..... . . . . . . .. ..... 320
I. I inci ples ami Tl'rminology 320
II , ir Pollutanb 322
III . S )Ivents 324
IV. J lsec ticides and lIerbi Cldes 324
V. F Jlll igants and Rodenticides .326
VI . r avy Metal POisoning and Ma nagrml' nt
VII. l rug Poison ing 330
Revic Test 333
Com rehensive Exami nation ............... , .. . . . .. . . 335
lode .. ... .... ..... · ·.·.· . ··.···· .. · . ··.· ·. ····.·· · · 353
I
)
I
General Principles
of Drug Action
Relati onships
.\ (' fh 1\ are producl'd by alteJing t he normal funclions of and in t he body
via orl

Related Interests

of fou general mechanisms:
I. /1111'1 <14 i OIl IIi'" rn, p/on, n,lturally occurring target th,lt mediate th£'
cffe('l s )f endogenous physiolo!,iC suu)tanoc's such as neurotrallSmitters and  
a. figu e 1-1 illustrat t:'s the four majm ela s)e) of drug-receptor intl' TKtions. using specific
cxar lples of endogenous li gands.
(1) .iga nd-acti

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atcd ion dlannels. Figure J-IA illustrat es aC{,I)' lcholi ne interacting
ilh a n icotinic receptor ttlat b a nonspecific Na' (K' tr<lmmembranc ion channt'!.
teract ion of a moltlllie :If acetylcholine wit h each subunit of Ihe channel produces
conformational change that permits the passage of Na' and K'. Ot her ch,mnels that
re targets for include SpKifK Cab and K chan neb.
(2) ;-pro l cin--<oupled rcctplOrs (Fig. l -I B- lJ). G-protcitl-(: oll pled reu!ptors com·
ose the largest of receptors. The receptors al l have 7 tra nsmembrane scg-
lents, 3 intracellular 10Jps, and an intracellul,H t·arboxy-terminal tail. The bio-
glc activit} of the r{'('ertors is rnaliated via interaction with a number o f G (GTP
I inding)-proteins .
·1) Ga,-coupled receptors. Figure I-IB il lustrat es a B-adn.': IH.Kef)Wr, which when
<Ktivated h} ligand linding (e,g., epi nephrine) eXChanges GDP for GTI'. Thi s
the migrat on of Get., (Gu,"m"l"'o,,) and its int eraction with adenylyl
t·}"dase rAC). Cru.,-bound AC the pnxh,il"lion of cAMl' from ATP; cAMP
activates protein kin;.se 1\ , whirh acts to phosphorylate and acti-
vate a number of effe ctor proteins. The [iy dimer may also :Ktivate some efte<:-
Hydrolysis of GTP bound to the Go. to GOP terminates the signal.
) GOI
I
(G1nhobowr,)-i.:ouplet.l rt'Ccptors (Fig. I- IC). Ligand binding (e.g., somat ostatin),
to Gu; (Ga,nIub,,,,,, )<Ol pl ed ft'(·eptors, simi larly €.\(hangt'!> G'I I' for li DI', but Go,
adenylyl ere asc, leading to reduced cAMl' prOOuftion.
{-l (and GIl)-coupletl ft'ceptors (Fig. 1-1.D). (and G,,) int eract with ligand
(e .g., serotonin )-,Kti " ated recept ors and increa se the 3cth ity of phospholi -
pa'ie C (PLC). PLe: cI 'aves the membrane phosphOlipid phosphatidylinmitol
(Pil l) to diacylglycerol (DAG) and inositoll,4,S-triphosphate
(II'; ). lJAG protein kinase C. which can subsequently phosphoryl ate
and acti\aie a n umb. 'f of cellula r prot eins; II'. cau'ies the release of Ca
2
• from
the endoplasmic ret iculum int o the cyt oplasm, where it can activat e many
cellular processes.
B
o
c
Figure 1-1 Four m,liar
A. Acetylcholine i
[l'Captors. B. Epinephrine
(G",h,b<,C<"·J-<..'oupil'd
ATP cAMP
ACh nicotinic receptor
-Ion channel
Na+ Acetylcholine
Epi lephrine
l5-adrenoreceptor coupled to Gas
Somatostatin
ATP
cAMP _ PKA
/\
Multiple cellular
effects
Somatostatin receptor
coupled to Gaj
Serotonin receptor
coupled to G
q
P1P2f'\
IP, +DAG
/ \
Ca
2
+ Activates
PKe
of drug-I('n:'ptor inter.Ktiam, with specific examples of l'mlog<.'num ligillids.
with a nilOtinic [('(cpIO! , I ligand-activated ion channel. IJ-O. (j·protdn ...... uupll'd
i Witll a GCI.,-coupled p-<1drenoceptur. C.   jTlIl'[J(liOrl with J G()'
Serotonin interaction wLh a G" (and Gil l-coupled receptor. (Colltinucd)
\
,liuta.
,
""
""
G
\
:tlVates
PKe
E
I utin receptor
00
y y
F
HSP90 !
o A
  I'RI",C!l' L1'5 OF DRU( , Acno:'\ 3
Ins Jlin receptor-activated tyrOSlr'le
kinase activity
Insulin
C>
po,
00 po,
y y
IRS f\
IRS - P0
4
\
PI3· K
\
AKT
I \
:Orlisol actIVatIOn of
9 ucocor1lcold receptor
0
Cortisol
:
\
"{
\
e
HSP90
Pol II
:

CoA
NA NA
Transcription
figure 1· 1 t(, "imlt'n) E. In\ulin inlf'ral"ti. )11 with a trn»iUl' l in,IS('. F. COIIJ'101 interact ion
"ith an In\ .3r.'1 lar nudear R'O"pLor_
(3) ccptor-acthated t yrm inc l;:inaSel> (Fig. I- I E). Many growth-rt'l ated si gnal s
.g .. are mediated via m<;, mbr;mi..' rCCCplor\ that int ri nsi c tyrosine
nasI" acthLty iIIusl ral('d f{) r the ren·ptor. Liga nd hi nding CillN'S confor-
t al ional changes in the n ccpt or; '>OfHe fl-'('eptor tyrosi m,' l,:inascs arc rnOllOmE'r:'> that
mcrilt> upon ligand hilK ing. The liga ndl-d recepto rs then aut ophosphorylatt> tyro-
4 URS
(4)
sine which recruits cytoplasmiC proteim to the plasma membrane where
aho tyrosine phosphor.dated and aClh'aled.
'n''''''t'",,, nudear receptor.; (Fig. l - lF). (e.g .. corliwl) for nuclear recep-
lipophilic and can diffuse rapidly IhrouRh the plasma membrane. In Ihe
of ligand. nuclear receptors are inaClh'e bccau\(' o f t heir inl eranion ,,-Uh
proteins such as heal -shock pro tei ns like IISP-90. Binding of ligand pro-
changes in the receptor t hai facili late of chaperones.
receptors in lo the nuclt-us, hetcfo- or homodilllt'li l Jtion of receptor" .• md

interaction with tl e lJ:'\IA of tarRet genes. I>NA-bound nuclear rt"(:ep-
la rs to recruit a d iverse numix' r of prOteins called coacti

Related Interests

alors. which suh-
act to increa'>C t ramcripUon of the target gene.
2. \lft'1<I1 i"" III <It I il'i/I "/ ! 1//1/1/," t y activation or inhibition of 111(' ell l-rllle's catalytic
activit y
3. III/illll'/.,/mii ! in which the dnlg. acting a nonfunctiona l analo),:ue of a naturally
interferes with m 'rmal metabolism
4. ###BOT_TEXT###quot;II'lh', iii" 'I
I or pIli ,;uil ;111,'. ,I< ti u/ /\ such those caused by antacids. osmotic
agents. and
II. II\(' ,l( r.Hkd rt"I)(1!l\e ,1111 " e,'press,·s al1 individual ' s response to increasing doses of a
given dHl,g, a pharmacologic response is proportlon"l to the number of lereptors
"'Ith which a d I interacts (Fig. 1. The graded curve Includes the fol-
lowing
1.   is graded; that is, it willl the dose lip to the
maximal of the system. ami it is often lIt'pirtt'd a func-l ion of Ihe logMithrn of
the dose (t o see the relat O \ ' {'T a " 'ide range of doses ).
2. II) is the that produces the half-lla.\;. imal response; the thrt'Shold doS<' is that which
:1.
noticeable effect .
I lltrill,i, ' /1 is t he ability of a drug to elici t a response.
a .
b,
Agonists
(I) Full
(2)
drugs
cap.lble o f bindi 19 to, and activating, a receptor.
OCCUP}' receptoT<; ,md have an activit y of I .
can ou;upy rl'lt'ptors but (annot el idt a ma.\ima l Such
I an intrinsic activitY ::l f less than 1 (Fig. l -.{; drug C).
",",g' <ni ' i' bind to the receptor Ul t do not initiat e a response; Ih.lt is. they block the
agonist or endogenous substance that works through the recepl or.
e"m,,,,tiliY' antagonists comb ne " 'ith the same site on the t('<eptor as the a),:onist
little or 110 efficacy and an intrinsit' activity of O. COrllpcliti\(' antagonists
>n"vb, iccYC"iblcor irreversible. Reversible, or equilibrium. competitive antagonists
"'" no' f·"y"''''''y "OIm".,hift the dose- respome cucve for the agonist to the cight.
Intrinsic ac,;vt'y

log (drug dose)
rigun:' 1-2 GrJ,kd
flUV(-" .
Flgun." ) ·1 Grad d do:;e.-r{"!;pome
for two ago! (A and Bl and
a <l 1/;()nist ( I.
GF-NEIl\!: ('IUNCH'LES Of DRUG ACTIO); 5
Drug A Drug B
DrogC
ED50 (A) EDso (B) = EDso (C)
log (drug dose)
a intTease tht ED'i<'; tha is, more agoni st is required to dicit a r('<;pollSe in the
pr ',ence of the antagonist (I'ig. 1-4). Hccaust hightr of agonist ,all overcome
til ! inhibition, the maxim,!! response can obtai nl'd.
(2) N ncompetitive antagonists bind to the rccl'ptor a t a si te o ther than the agonist -
bi ding site (Fig. 1-5) and Pi t her preven t the from binding correctly or pre-
\ 1t it from activati ng the '('(ept or. Con<.<'quent ly, the effcct i

Related Interests

(' amount of receptor
is educed. Recept ors unocl upied hy retain the same affmity for agonist ,
a t he ED,',(J is unchanged
4. ",,/, /III I" .11'11,\ reflect s t he relati ve amount of drug nceded 10 produce a gil'en response.
The pol cy of a d rug is determ ned by the affinity of a drug for its recept o r and t he
amount .f admi nistered drug thaI the r('Ceptar si te. The relat h'e potenry of a drug
can be d monstrated by comparir g the f.D'io) values of two fuJI agonbt); l he dnl g \ ith t he
lower E is mo re potent. (for exampl(', in Fig. 1-3. drug A is more potellllhall drug H. )
S. , I" 1'f/1. ,., <If ,/ ,/111.,: is the maXIma l d ru)! eff('cI t hat can be achl('

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N.1 in a p.llit'nt under
a given s t of conditions. I:.fti.cacy may be .lffec\('(\ by stlt"h fanor) tilE' number of d rug-
f('Ceptor omplexes formed, the at ility of the drug 10 11\ "fe the receptor OIlC(' \t is hound.
and t he . atus of the target organ or reil.
6. \ '''I't' is t easured at the mid portion of the dose- rtspumt' run·t. TIll' varifs for differ-
ent drug. and different responses. Steep   inliil',!\(' that a change
in dose p oduces a large change ir
7. I ,,,ia/li/', refled.s the differenre , bttwetn illdividual s in r('spOrlSC to a given drug.
R. III( '''1.'' Ih illdt·\ (1/) relates the desired thtrapt uti c tfftrt \(J toxicity; it is
dctl'rmin 'd using data provided b" the quantal cur

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. The therapeutic index
1 (gurl' 1_4 GrJ{ ed do\e- respoo\e
('UI'

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es iII ustrltlng he of COlll-
[It'tl l l

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p aIllJ$oni\
Drug X alone Drug X plus antagonist
MaJ;;mum response
unchanged
ED50 - Rtghl
Drug X dose (log scale)
6 BRS 1'11"","0"'1'''
Is dcflllcd a,
)X!pullltion 10

respome '
Dr J9 X alone
MaximuM response
DOJ9 X plus
al tagonlst
ED5Q unchanged
X dose (log scale)
FigUT{· 1-5
curyt's 111,' "ff, .. __ I,,,f "0"-
lOl11].X'ti ti n' antag:oni,I,.
the ratio o[ th"   that pmduce, ,\ tU'I;ir l'ffl'ct in h,llf uf tile
Ill al the desi red effect in hall of I he populati on). Nu\(' that
i index should be ' vith caution In wilen tile qH,mtd l du'>t'-
tor the desirt'd and tox ( effects arc not )laralll'l.
I h< qU,IILI,LI [ rl'\jloLL\(' < Ul\ e (Fi gs. I 6'\ and J-6BJ rda les Ihe dosage of J drug to the fre-
quency with   response will 'Jl"(ur within" population. r he may he an
(e.g. , t' tht'f do Of do not fall askep after h'1,:ei

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