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7/25/2019 Doc Sayon Cl Word

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PHARMACOKINETICS IN THE MEDICALLY ILL

Pharmacokinetics describes the absortion! distrib"tion! metabo#ism! and

e$cretion o% dr"&s!

harmacod'namics re%ers to the e%%ects o% dr"&s! rimari#' in the brain(

)( Absortion

Ora##' administered dr"&s absorbed thro"&h the &astrointestina# tract ma' be

e$tensi*e#' a#tered b' +%irst,ass- heatic metabo#ism be%ore enterin& the

s'stemic circ"#ation( S"b#in&"a# and toica# administration o% dr"&s minimi.es this

%irst,ass e%%ect! and recta# administration ma' red"ce the %irst,ass e%%ect b'

/01(

Dr"& %orm"#ation! dr"& interactions! &as, tric moti#it'! and the characteristics o%

the absorti*e s"r, %ace a## in%#"ence the rate o% absortion! a ke' %actor 2hen

raid onset is desired( The e$tent o% dr"& absortion! ho2e*er! is more imortant

2ith chronic administration( The bioa*ai#abi#it' o% a dr"& describes the rate ande$tent to 2hich the dr"& in&redient is absorbed %rom the dr"& rod"ct and

a*ai#ab#e %or dr"& action( Intra*eno"s dr"& de#i*er' has )001 bioa*ai#abi#it'(

3( Distrib"tion

S'stemic dr"& distrib"tion is in%#"enced b' ser"m H! b#ood %#o2! rotein bindin&!

#iid so#"bi#it'! and the de, &ree o% ioni.ation(

In &enera#! acidic dr"&s 4e(&(! *a#roic acid! barbit", rates5 bind most#' to

a#b"min! and more basic dr"&s 4e(&(! henothia.ines! tric'c#ic antideressants

6TCAs7! am, hetamines! most ben.odia.eines5 bind to ob"#ins( In &enera#!

on#' %ree 4"nbo"nd to #asma roteins5 dr"& is harmaco#o&ica##' acti*e(

Decreases in rotein bindin& increase a*ai#abi#it' o% the +%ree- dr"& to

harmaco#o&ica# action! metabo#ism! and e$cretion(

8o#"me o% distrib"tion is a %"nction o% a dr"&9s #iid so#, "bi#it' and #asma, and

tiss"e,bindin& roerties( Most s'chotroic dr"&s are #iohi#ic b"t are a#so

e$tensi*e#' bo"nd to #asma roteins(

:(Metabo#ism 4or ;iotrans%ormation5 and E#imination o% Dr"&s

;iotrans%ormation occ"rs thro"&ho"t the bod'! 2ith the &reatest acti*it' in the#i*er and &"t 2a##( Most s'chotro, ic dr"&s are e#iminated b' heatic

metabo#ism and rena# e$cretion(

The heatic c#earance o% dr"&s ma' be #imited b' either the rate o% de#i*er' 4i(e(!

heatic b#ood %#o25 o% the dr"& to the heatic metabo#i.in& en.'mes or the

intrinsic caacit' o% the en.'mes to metabo#i.e the s"bstrate( C#inica##' si&ni%,

icant decreases in heatic b#ood %#o2 occ"r on#' in se*ere cirrhosis! and 2hen


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ossib#e! arentera# administration o% dr"&s is re%erred(

The kidne'9s rimar' harmacokinetic ro#e is dr"& e#imination( Ho2e*er! rena#

disease ma' a%%ect absor, tion! distrib"tion! and metabo#ism o% dr"&s( Creatinine

c#earance is a more "se%"# indicator o% rena# %"nction than ser"m creatinine(

DRdr"& interactions(

Co..a et a#( 4300:5 ad*ised that h'sicians rescribin& in a o#'harmac'

en*ironment sho"#d! 2hene*er ossib#e! a*oid medications that si&ni%icant#'

inhibit or ind"ce c'tochrome P@/0 en.'mes and re%er those that are e#iminated

b' m"#ti#e ath2a's and ha*e a 2ide sa%et' mar&in(

Identi%ication o% Potentia# Pharmacokinetic Interactions

Most harmacokinetic dr"&>dr"& interactions in*o#*e the e%%ects o% an interactin&

dr"& on the c'tochrome P@/0> mediated metabo#ism o% a s"bstrate dr"&( The


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interactin& dr"& ma' be either an inhibitor or an ind"cer o% the crit, ica# P@/0

iso.'mes in*o#*ed in the s"bstrate dr"&9s metab, o#ism(

Metabo#ic dr"& interactions are most #ike#' to occ"r in three sit"ations addition o%

an interactin& dr"& 4inhibitor or ind"cer5 to an e$istin& critica# s"bstrate dr"&B

2ith, dra2a# o% an interactin& dr"& %rom a dosin& re&imen con, tainin& a s"bstrate

dr"&B or addition o% a s"bstrate dr"& to an e$istin& re&imen containin& an

interactin& dr"&(

The addition o% an interactin& dr"& to a medication re&imen containin& a

s"bstrate dr"& at stead',state #e*e#s 2i## dramatica##' a#ter the concentration o%

the s"bstrate dr"&( I% the interactin& dr"& is an inhibitor! s"bstrate dr"&

concentrations 2i## rise as its e#imination is red"ced( This rise in s"bstrate #e*e#s

ma' res"#t in to$icit' beca"se o% the dr"&9s narro2 therae"tic inde$( Con*erse#'!

addition o% an en.'me ind"cer 2i## increase e#imination o% the s"b, strate! thereb'#o2erin& its concentration and therae"tic e%%ect(

ithdra2a# o% an interactin& dr"& %rom a dr"& re&i, men containin& a critica#

s"bstrate dr"& can a#so res"#t in a dr"& interaction( The dosa&e o% s"bstrate dr"&

2i## ha*e been titrated! in the resence o% the interactin& dr"&! to otimi.e

therae"tic e%%ect and minimi.e ad*erse e%%ects( ithdra2a# o% an en.'me

inhibitor 2i## a##o2 metabo#ism to ret"rn 4increase5 to norma# #e*e#s( This

increased me, tabo#ism o% the s"bstrate dr"& 2i## #o2er its #e*e#s and de, crease

therae"tic e%%ect( In contrast! remo*a# o% an en, .'me ind"cer 2i## res"#t in an

increase in s"bstrate dr"& #e*e#s and dr"& to$icit' as metabo#ism o% the s"bstrate

de, creases to a norma# rate(

The addition o% a critica# s"bstrate dr"& to a dr"& re&, imen containin& an

interactin& dr"& can res"#t in a c#ini, ca##' si&ni%icant interaction i% the s"bstrate is

dosed ac, cordin& to estab#ished &"ide#ines( Dosin& &"ide#ines do not acco"nt %or

the resence o% a metabo#ic inhibitor or ind"cer and th"s ma' #ead to s"bstrate

concentrations that are! resecti*e#'! to$ic or s"btherae"tic(

Dr"& interactions that a%%ect rena# dr"& e#imination are c#inica##' si&ni%icant on#' i%

the arent dr"& or its ac, ti*e metabo#ite "nder&oes areciab#e rena# e#imination(

A( Side E%%ects and To$icit'


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)( Se#ecti*e Serotonin Re"take Inhibitors and No*e#Mi$ed,Action A&ents

Ad*erse e%%ects o% se#ecti*e serotonin re"take inhibitors 4SSRIs5 and

no*e#mi$ed,action a&ents are common! b"t the' are "s"a##' mi#d! dose re#ated!

and abate o*er time( Ho2e*er! serotoner&ic a&ents! esecia##' 2hen "sed in

combination! can ind"ce the otentia##' %ata# serotonin s'ndrome

Common short,term side e%%ects 2ith SSRIs and *en#a%a$ine inc#"de na"sea!

*omitin&! an$iet'! headache! se, dation! tremors! and anore$ia( Common #on&,

term side e%%ects inc#"de se$"a# d's%"nction! dr' mo"th! s2eatin&! imaired

s#ee! and otentia# 2ei&ht &ain(

Mirta.aine is associated 2ith a hi&h incidence o% sedation! increased aetite!

and 2ei&ht &ain 4Ne#son )F5( Common ad, *erse e%%ects o% b"roion inc#"de

a&itation! insomnia! an$iet'! dr' mo"th! constiation! ost"ra# h'otension!

tach'cardia! and cardiac arrh'thmias( Na"sea and *omitin& are m"ch #esscommon 2ith b"roion than 2ith SSRIs

Centra# ner*o"s s'stem( An association bet2een SSRI "se and increased

s"icida# ideation 2as roosed b' Teicher in )0 on the basis o% case reorts

4Teicher et a#( )05(


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The incidence o% the s'ndrome is "nkno2n! art#' d"e to the #ack o% "ni%orm

dia&nostic criteria( 8irt"a##' a## medica, tions that otentiate serotoner&ic

ne"rotransmission in the CNS ha*e been reorted in association 2ith serotonin

s'ndrome( The antideressant combinations most com, mon#' im#icated ha*e

been monoamine o$idase inhibitors 4MAOIsB re*ersib#e and irre*ersib#e5 and

TCAs! MAOIs and SSRIs! and MAOIs and *en#a%a$ine(

Th"s! the di%%erentia# dia&nosis %or serotonin s'ndrome is simi#ar to that %or

ne"ro#etic ma#i&nant s'n, drome 4NMS5 4see +Ne"ro#etic Ma#i&nant S'ndrome-

s"bsection #ater in the chater5( Di%%erentiatin& serotonin s'ndrome %rom NMS

can be *er' di%%ic"#t in atients recei*in& both serotoner&ic and antis'chotic

medications(

Serotonin s'ndrome is o%ten se#%,#imited and "s"a##' reso#*es ?"ick#' a%terdiscontin"ation o% serotoner&ic a&ents( Mana&ement inc#"des the %o##o2in& basic

rinci, #es )5 ro*ide necessar' s"orti*e care! 35 discontin"e a## serotoner&ic

a&ents! :5 anticiate otentia# com#ica, tions! @5 consider administerin&

antiserotoner&ic a&ents! and /5 reassess the need %or s'choharmaco#o&ica#

ther,

a' be%ore reinstit"tin& dr"& thera' 4Keck and Arno#d 30005( Some atients 2i##

re?"ire admission to an inten, si*e care "nit! b"t most 2i## sho2 some

imro*ement 2ithin 3@ ho"rs 2ith s"orti*e care a#one( There are no seci%ic

antidotes a*ai#ab#e %or the treatment o% serotonin s'ndrome( The antihistamine

c'rohetadine is the most consistent#' e%%ecti*e serotonin anta&onist reorted(

The recommended ad"#t dose is @> m& and ma' be reeated e*er' )>@ ho"rs

" to a ma$im"m dai#' dose o% :3 m&(

A"tonomic and cardio*asc"#ar( The SSRIs and the no*e# mi$ed,action

antideressants ha*e a m"ch sa%er cardio, *asc"#ar ro%i#e than the TCAs and

MAOIs( In &enera#!

;"roion is reorted to ca"se h', ertension 2itho"t a%%ectin& heart rate in

some atients( In atients "sin& transderma# nicotine! b"roion is asso, ciated2ith a ()1 incidence o% h'ertension 4Kha2aa and einstein 300:5( Rebo$etine

has a#so been associated 2ith an increase in heart rate o% >)) beatsmin"te

4#ei, shaker et a#( 300)5! b"t 2itho"t an' si&ni%icant e%%ect on

e#ectrocardio&rah' 4Andreo#i et a#( 30035(

=astrointestina#( Na"sea is the most common ad*erse e%%ect associated 2ith the


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serotoner&ic antideressants(

ei&ht &ain#oss( ei&ht &ain is a re#ati*e#' common rob#em d"rin& both ac"te

and #on&,term treatment 2ith antideressants( TCAs and MAOIs are more #ike#'

to ca"se 2ei&ht &ain than other antideressants! 2ith the e$cetion o%

mirta.aine( Paro$etine ma' be more #ike#' than other SSRIs to ca"se 2ei&ht

&ain d"rin& #on&,term treatment( ;"roion rare#' ca"ses 2ei&ht &ain 4a*a

30005(

Abr"t discontin"ation o% SSRIs! esecia##' those 2ith short ha#%,#i*es! ma' &i*e

rise to a discontin"ation s'ndrome characteri.ed b' a 2ide *ariet' o% s'mtoms!

inc#"din& &astrointestina#! s'chiatric! ne"ro#o&ica#! and %#"#ike s'mtomsB s#ee

dist"rbancesB and headache 4Had, dad )5! "s"a##' reso#*in& 2ithin : 2eeks(

Antideres, sants! #ike a## s'choacti*e medications! sho"#d be &rad, "a##'

2ithdra2n( Discontin"ation s'mtoms can ca"se misdia&nosis and inaroriate

treatment! artic"#ar#' in a atient 2ith an acti*e medica# i##ness! as 2e## as erode%", t"re com#iance(

TCAs are no2 *ie2ed as second,#ine treatments %or deression beca"se their

ad*erse e%%ect ro%i#e is #ess beni&n than that o% SSRIs(

TCAs are anta&onists at histamine H)! adrener&ic a#ha)! and m"scarinic

recetors and ha*e t'e,)A antiarrh'thmic 4?"inidine,#ike5 e%%ects as a res"#t o%

their b#ockade o% *o#ta&e,deendent Na,channe#s(

Ad*erse e%%ects o% the TCAs inc#"de sedation! anticho#iner&ic e%%ects 4dr' mo"th!

dr' e'es! constiation! "rinar' retention! decreased s2eatin&! con%"sion! memor'

imairment! tach'cardia! b#"rred *ision5! and ost"ra# h'otension( To#erance to

these e%%ects "s"a##' de*e#os o*er time(

TCAs can ca"se heart b#ock! arrh'thmias! a#itations! tach'cardia! s'ncoe!

and heart %ai#"re and sho"#d be "sed 2ith ca"tion in a, tients 2ith ree$istin&

cardio*asc"#ar disease or at risk o% s"icide(

Dr"& interactions( The combination o% TCAs and other dr"&s 2ith sedatin&!

h'otensi*e! antiarrh'thmic! or sei, ."re thresho#d>#o2erin& roerties ma' #eadto additi*e to$icit'(

To$icit'o*erdose( TCA o*erdose carries a risk o% death %rom cardiac cond"ction

abnorma#ities that res"#t in ma,

#i&nant *entric"#ar arrh'thmias( Initia# s'mtoms o% o*erdose in*o#*e CNS


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stim"#ation! in art d"e to anti, cho#iner&ic e%%ects! and inc#"de h'er're$ia!

de#iri"m! h'ertension! ha##"cinations! sei."re! a&itation! h'erre, %#e$ia! and

arkinsonian s'mtoms(

Treatment %or o*erdose inc#"des remo*a# o% an' "nab, sorbed medication %rom

the stomach 4&astric #a*a&e or emesis 2ith asiration reca"tions and then

acti*ated charcoa# to red"ce absortion5! %o##o2ed b' s"orti*e thera' and

c#ose monitorin&( Cardiac cond"ction abnor, ma#ities! arrh'thmias! and

h'otension ma' be treated 2ith administration o% intra*eno"s sodi"m

bicarbonate to rod"ce a ser"m H o% F(@>F(/(

Abr"t discontin"ation o% TCAs ma' &i*e rise to a discontin"ation s'ndrome

characteri.ed b' di..iness! #ethar&'! headache! ni&htmares! and s'mtoms o%

anti, cho#iner&ic rebo"nd! inc#"din& &astrointestina# "set! na"sea! *omitin&!

diarrhea! e$cessi*e sa#i*ation! s2eatin&! an$iet'! rest#essness! i#oerection! and

de#iri"m

:( Monoamine O$idase Inhibitors

Monoamine o$idase inhibitors 4MAOIs5! 2ith the ossib#e e$cetion o%

moc#obemide 4not a*ai#ab#e in the


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anticon*"#sant mood stabi#i.ers(

A( Side E%%ects and To$icit'

)( Lithi"m

Most atients "sin& #ithi"m e$erience some side e%%ects! both ac"te

4&astrointestina# distress and tremor5 and #on&, term 4o#'"ria and o#'disia!

h'oth'roidism! 2ei&ht &ain! imaired co&nition! sedation! imaired coordination!

edema! acne! and hair #oss5! most o% 2hich are mi#d and dose re#ated 4Peet and

Pratt ):5( Ad*erse e%%ects o% #ith, i"m can be minimi.ed b' red"cin& the dose

or decreasin& the rate o% absortion %rom the &"t b' administerin& the dr"& either

in di*ided doses 2ith mea#s or in a s#o2,re#ease %orm(

Centra# ner*o"s s'stem( Headache! %ati&"e! hand tremor! and mi#d co&niti*e

imairment are reorted b' " to /01 o% atients be&innin& #ithi"m treatment(Hand tremor is "s"a##' a beni&n! %ine! raid intention tremor that reso#*es o*er

time or can be mana&ed b' dose red"ction or #o2, dose beta,b#ockers( Mi#d

co&niti*e imairment ma' be e$erienced d"rin& the %irst > months o%

treatmentB a#tho"&h rare#' ro&ressi*e! this imairment is the most common

reason %or noncom#iance

A"tonomic and cardio*asc"#ar( Lithi"m ca"ses beni&n re*ersib#e reo#ari.ation

e#ectrocardio&rahic chan&es in 301>:01 o% atients 4Mitche## and Macken.ie

)35! in, c#"din& T,2a*e deression and in*ersion( Other cardio, *asc"#ar

e%%ects o% #ithi"m inc#"de decreased heart rate and! rare#'! cardiac cond"ction

abnorma#ities and arrh'th, mias 4;"r&&ra% )F5(

Rena#( Lithi"m red"ces rena# resonse to antidi"retic hormone! res"#tin& in

o#'"ria andor o#'disia initia##' in :01>/01 o% atients and ersistin& in )01>

3/1( Stoin& #ithi"m "s"a##' re*erses this nehro&enic diabetes insiid"s

4McE*o' 300:5( Aart %rom dr' mo"th! atients do not &enera##' e$hibit si&ns o%

deh'dration( Mana&ement o% o#'"ria ma' inc#"de chan&in& to a sine dai#'

bedtime dose o% #ithi"m! decreasin& dosa&e! andor administerin& thia.ide

di"retics or ami#oride( I% thia.ide di"retics are added! #ithi"m dosa&e t'ica##' 2i##

ha*e to be red"ced b' /01 to comensate %or thia.ide,ind"ced red"ction o%#ithi"m e$cretion 4Ge%%erson et a#( )F5(

Most in*esti&ators contin"e to a&ree that the risk o% rena# d's%"nction d"rin&

chronic "se is %ar #ess than the risk o% s'chiatric morbidit' 4Perr' )5(

Endocrine and metabo#ic( The re*a#ence o% o*ert h'o, th'roidism has been


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reorted to be as hi&h as 1>)1 %or

atients takin& #ithi"m! comared 2ith a re*a#ence o% 0(/1>)(1 in the &enera#

o"#ation(

E#e*ated th'roid,stim"#atin& hormone is resent in aro$imate#' :01 o% atients

tak, in& #ithi"m %or months or more! and ro&ression to o*ert h'oth'roidism

4e#e*ated th'roid,stim"#atin& hormone and #o2 %ree T@5 ma' occ"r in as man' as

/1>)01 o% a, tients er 'ear 4K#einer et a#( )5( Th'roid %"nction sho"#d be

assessed be%ore #ithi"m is started and eriodi, ca##' d"rin& thera'(

H'oth'roidism can be treated 2ith L,th'ro$ine and is not a contraindication to

contin"in& #ithi"m

ei&ht &ain is the second most common reason cited b' atients %or #ithi"m

noncom#iance 4=it#in et a#( )5( ei&ht &ain is a conse?"ence o% increased

ca#oric intake in art d"e to cons"mtion o% hi&h,ca#orie %#"ids in re, sonse to

increased thirst

Dermato#o&ica#( Dermato#o&ica# ad*erse e%%ects inc#"de dr' skin and acne(

Occ"rrin& in abo"t )1 o% atients tak, in& #ithi"m 4Ge%%erson et a#( )F5! these

e%%ects "s"a##' re, sond to standard treatment and rare#' re?"ire #ithi"m

discontin"ation( A#oecia and e$acerbation o% soriasis occ"r #ess %re?"ent#'

Dr"& interactions( Lithi"m is a#most entire#' rena##' e$, creted! and most #ithi"m

%i#tered b' the omer"#i is reab, sorbed 2ith sodi"m in the ro$ima# t"b"#e(

Ser"m #ith, i"m #e*e#s are increased b' thia.ide di"retics! NSAIDs! an&iotensin,

con*ertin& en.'me inhibitors! sodi"m de#e, tion! and deh'dration

To$icit'o*erdose( To$icit' increases marked#' as ser"m #ithi"m #e*e#s e$ceed )(/

mE?L! and ser"m #e*e#s &reater than 3(0 mE?L are dan&ero"s( Ho2e*er! some

atients e$erience to$icit' at +therae"tic- #e*e#s( Initia# s'm, toms o% to$icit'

inc#"de marked tremor! na"sea! diarrhea! b#"rred *ision! *erti&o! con%"sion! and

increased dee tendon re%#e$es! ro&ressin& to sei."res! coma! cardiac ar,

rh'thmia! and ossib#' ermanent ne"ro#o&ica# imair, ment as #ithi"m #e*e#s

increase(

Treatment %or #ithi"m to$icit' inc#"des &astric #a*a&e or emesis %o##o2ed b'

s"orti*e meas"res( These mea, s"res inc#"de *o#"me res"scitation 2ith

isotonic or one, ha#% isotonic sodi"m ch#oride so#"tion to enhance rena#e#imination o% #ithi"m in indi*id"a#s 2ith mi#d,to,moderate to$icit'! or hemodia#'sis

%or atients 2ith se*ere to$icit' andor #ithi"m #e*e#s o% :(/ mE?L or hi&her

3( Anticon*"#sants

The anticon*"#sants *a#roate! carbama.eine! &abaentin! #amotri&ine!

o$carba.eine! toiramate! tia&abine! .onisamide! and #e*etiracetam share a


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simi#ar ro%i#e o% CNS ad*erse e%%ects( Sedation! ata$ia! di..iness! m"sc#e

2eakness! %ati&"e! and *ision dis, t"rbances s"ch as n'sta&m"s and di#oia are

common and o%ten reso#*e 2ith time! dosa&e red"ction! or discon, tin"ation(

Co&niti*e imairment is a com, mon com#ication o% anticon*"#sant "se( Amon&

anti, con*"#sants "sed in s'chiatr'! the rankin& o% co&niti*e ro%i#e is 4best to

2orst5 &abaentin! #amotri&ine! *a#, roate and carbama.eine! and toiramate

=astrointestina#( S'mtoms o% &astrointestina# distress! inc#"din& na"sea!

*omitin&! d'sesia! diarrhea! and an, ore$ia! are the most %re?"ent ad*erse

e%%ects e$erienced 2ith most anticon*"#sants( These e%%ects are o%ten dose

re#ated and transient! and can be minimi.ed b' &i*in& the dr"& in di*ided doses!

2ith mea#s! or 2ith s#o2 titration( =astrointestina# e%%ects aear #ess o%ten 2ith

di*a#, roe$ sodi"m than 2ith *a#roic acid or sodi"m *a#, roate(

Hemato#o&ica#( Carbama.eine is %re?"ent#' associated 2ith transient #e"koenia

and rare#' ma' ca"se a#astic anemia( Carbama.eine sho"#d be discontin"ed in

a, tients 2ith 2hite b#ood ce## co"nts #ess than :(0 )0L or ne"trohi# co"nts

#ess than )(0 )0L! and atients m"st be ed"cated to reort ear#' si&ns o%

anemia! in%ec, tion! or b#eedin& 4Sobotka et a#( )05(

Mi#d! as'mtomatic #e"koenia and thromboc'toe, nia ha*e been obser*ed 2ith

*a#roate and are &enera##' re*ersib#e 2ith dosa&e red"ction or discontin"ation(

More se*ere cases o% thromboc'toenia and a&ran"#oc'tosis ha*e a#so been

reorted 4insterer et a#( 300)5

(

Rena#( Carbama.eine and o$carba.eine %re?"ent#' ca"se the s'ndrome o%

inaroriate antidi"retic hor, mone secretion 4SIADH5! #eadin& to h'onatremia

and 2ater into$ication(

Endocrine and metabo#ic( Transient e#e*ations in #i*er en.'mes occ"r common#'

2ith anticon*"#sants( Si&ni%i, cant chan&es in heatic %"nction are "s"a##'

re*ersib#e 2ith dosa&e red"ction or discontin"ation(

ei&ht &ain is a common %actor in noncom#iance 4Mend#e2ic. et a#( )5(

ei&ht &ain is esecia##' a rob, #em 2ith *a#roate! 2ith 3/1 o% atients &ainin&

" to 30 k& 4Pi# and Meinders )5( =abaentin is reorted to res"#t in abo"t)01 &ain o% bod' 2ei&ht in 3/1 o% a, tients 4DeTo#edo et a#( )F5( A#tho"&h

carbama.eine is a#so reorted to ca"se 2ei&ht &ain! the incidence is #ess than

2ith *a#roate

Imm"ne s'stem( ;eni&n skin rashes occ"r in /1>301 o% atients recei*in&

anticon*"#sants! inc#"din& *a#roate! carbama.eine! and #amotri&ine( Ho2e*er!

serio"s and otentia##' %ata# imm"ne reactions to anticon*"#sants are not


11/26

"ncommon( Se*ere and o%ten %ata# h'ersensiti*it' c"taneo"s reactions inc#"de

Ste*ens,

Gohnson s'ndrome and to$ic eiderma# necro#'sis( Mor, ta#it' occ"rs in abo"t

/1>)01 o% atients 2ith Ste*ens, Gohnson s'ndrome and in " to @/1 o% those

2ith to$ic eiderma# necro#'sis( In comarison 2ith &enera# medica# atients! the

risk o% de*e#oin& Ste*ens,Gohnson s'n, drome or to$ic eiderma# necro#'sis

d"rin& the %irst 3 months o% anticon*"#sant thera' is increased b' )30,%o#d %or

carbama.eine! 3/,%o#d %or #amotri&ine! and 3@,%o#d %or *a#roate

The resence o% an anti, con*"#sant,ind"ced rash sho"#d romt dr"& discontin",

ation 4Hebert and Ra#ston 300)5(

Dr"& interactions( Si&ni%icant c'tochrome P@/0 en.'me ind"ction occ"rs 2ith

carbama.eine 4CYP)A3! CYP3C! and CYP:A@5! o$carba.eine 4CYP:A@5! and

*a#roate 4CYP3C5

Side E%%ects and To$icit')( Centra# Ner*o"s S'stem

Ac"te EPSakathisia! akinesia! and d'stoniaocc"r in as man' as /01>F/1

o% atients 2ho take t'ica# antis'chotics 4Co##aborati*e orkin& =ro" on

C#inica# Tria# E*a#"ations )5( Hi&h, otenc' t'ica# antis'chotics are

associated 2ith hi&her rates o% EPS than are #o2,otenc' a&ents( Amon& the c"r,

rent#' a*ai#ab#e at'ica# antis'chotics! the hierarch' o%

EPS risk 4&reater to #esser5 is riseridone o#an.aine J .irasidone J

ariira.o#e 4estimated5 ?"etiaine c#o, .aine 4Tandon 30035(

It is a#so im, ortant to e$c#"de other ca"ses o% rest#essness that ma' mimic

akathisia in medica##' i## atients! s"ch as h'o', cemia! h'o$ia! dr"&

2ithdra2a#! ain! e#ectro#'te dist"r, bances! iron de%icienc'! and rest#ess #e&s

s'ndrome(

Sei."res( At hi&her doses! there aears to be an in, creased risk o% sei."res

associated 2ith antis'chotics(

Most o% the ear#' case reorts 2ere o% sei, ."res 2ith ch#orroma.ine( A#tho"&h

there are no con, tro##ed comarati*e st"dies to a##o2 an acc"rate assess, ment

o% re#ati*e sei."re risk! it aears that hi&h,otenc' t'ica# antis'chotics and

riseridone ha*e the #o2est rate o% sei."resB o#an.aine! ?"etiaine! and #o2,otenc' t'ica# antis'chotics ha*e an intermediate riskB and c#o, .aine has the

hi&hest risk

Sedation( Sedation is the most common sine side e%, %ect! esecia##' 2ith the

#o2,otenc' t'ica# antis'chot, ics( Amon& the at'ica# antis'chotics! the

hierarch' o% otentia# %or sedation 4&reater to #esser5 is c#o.aine ?"etiaine


12/26

o#an.aine riseridone .irasidone J ariira.o#e 4estimated5 4Tandon 30035(

Sedation is most rominent in the ear#' sta&es o% thera'! 2ith some de, &ree o%

to#erance de*e#oin& o*er time(

Ne"ro#etic ma#i&nant s'ndrome( NMS is a rare! oten, tia##' %ata#! idios'ncratic

reaction to antis'chotics(

NMS is not seci%ic to an' ne"ros'chiatric dia&nosis and has been reorted in

non>s'chiatrica##' i## indi*id"a#s 2ho 2ere treated 2ith other doamine

anta&onists s"ch as metoc#o, ramide and roch#orera.ine 4

Ma#n"trition! deh'dration! and iron de%icienc' a## aear to increase risk %or NMS(

NMS &enera##' de*e#os o*er a )>: da' eriod and #asts %or />)0 da's a%ter a

nondeot antis'chotic is dis, contin"ed( Morta#it' is hi&h! o%ten ?"oted at 301>

:01 b"t robab#' #o2er no2 beca"se o% ear#ier reco&nition( The main c#inica#

%eat"res o% NMS inc#"de h'erthermia 4:FQC5! &enera#i.ed m"sc#e ri&idit'!

menta# stat"s chan&es and a"tonomic instabi#it'( Temerat"re in h'er, thermiais &reater than :QC in the maorit' o% cases and can e$ceed @0QC! 2hich

redisoses the atient to se*ere com#ications! inc#"din& irre*ersib#e CNS and

other or, &an dama&e( M"sc#e ri&idit' is o%ten hetero&eneo"s and can be +#ead,

ie- or co&2hee#in&( A"tonomic d's%"nc, tion in NMS ma' inc#"de h'ertension!

orthostatic h'o, tension! #abi#e b#ood ress"re! tach'cardia! tach'nea!

sia#orrhea! diahoresis! skin a##or! and "rinar' inconti, nence( Ne"ro#o&ica#

d's%"nction ma' consist o% tremor! m'oc#on"s! %oca# d'stonias! d'sha&ia!

d'sarthria! oistho, ton"s! oc"#o&'ric crisis! and d'skinesias( A#tered #e*e# o%

conscio"sness ma' ran&e %rom decreased a2areness to coma( CPK #e*e#s are

o%ten e#e*ated in NMS secondar' to m"sc#e necrosis %rom ri&idit'! h'erthermia!

and ische, mia( E#e*ated CPK #e*e#s are not roo% o% NMS! beca"se the' ma'

res"#t %rom a&itation! "se o% h'sica# restraints! and intram"sc"#ar inections(

E$treme e#e*ation o% CPK 4)00!000


13/26

be trans%erred back to a s'chiatric ser*ice on#' a%ter the atient is med, ica##'

stab#e( Amon& atients 2ho reco*er %rom NMS! there ma' be a :01 risk o%

rec"rrent eisodes %o##o2in& s"bse, ?"ent antis'chotic recha##en&e! b"t the

maorit' o% a, tients 2ho re?"ire antis'chotic thera' can be ca"tio"s#' re,

treated(

A"tonomic and cardio*asc"#ar(

Amon& the at'ica# a&ents! the hierarch' %or rod"cin& h'otension 4%rom

&reatest risk to #east risk5 is c#o.aine ?"etiaine riseridone o#an.aine J

.irasidone J ariira.o#e 4estimated5

Other cardiac side e%%ects( Potentia##' %ata# m'ocarditis! cardiom'oath'! and

heart %ai#"re ha*e been reorted 2ith c#o.aine(

3( Endocrino#o&ica# and Metabo#ic=#"cose to#erance(

Pharmacoeidemio#o&ica# st"dies and case reorts re*ea# an associationbet2een the "se o% *ario"s at'ica# antis'chotics 2ith h'er'cemia! ne2,

onset t'e 3 diabetes

C"rrent #imited data reort that h'er, 'cemia has been associated 2ith a##

marketed at'ica# antis'chotics(

Diabetic ketoacidosis has been reorted in association 2ith a## at'ica# anti,

s'chotics e$cet %or .irasidone

Liids( More recent st"dies 2ith at'ica# antis'chotics ha*e demonstrated

e#e*ated ser"m tri'ceride #e*e#s in atients takin& c#o.aine! o#an.aine! and

?"etiaine 4Domon and Car&i#e 3003B =a"#in et a#( )B Me'er 300)b5! "s"a##'

eakin& in the %irst 'ear o% thera'(

H'erro#actinemia( H'erro#actinemia is re#ati*e#' common! esecia##' 2ith

hi&h,otenc' t'ica# antis', chotics and riseridone! and can res"#t in

amenorrhea or irre&"#ar menses! &a#actorrhea! &'necomastia! se$"a# d's,

%"nction! and osteoorosis(

ei&ht &ain( A## c"rrent#' marketed antis'chotics 42ith the ossib#e e$cetion o%

mo#indone! .irasidone! and ariira.o#e5 are associated 2ith 2ei&ht &ain! 2hich

ma' increase hea#th risks 4h'ertension! atherosc#erosis! t'e 3 diabetes!

cardio*asc"#ar disease! and stroke5! sti&, mati.ation! noncom#iance! imairmentin ?"a#it' o% #i%e! and socia# 2ithdra2a#( The re#ati*e roensit' to ca"se 2ei&ht

&ain amon& the at'ica# antis'chotics 4%rom &reatest to #east5 is c#o.aine

o#an.aine riseridone J ?"etiaine J ariira.o#e 4estimated5 .irasidone

4Tan, don 30035(

S'ndrome o% inaroriate antidi"retic hormone secre, tion( SIADH can occ"r


14/26

2ith t'ica# as 2e## as at'ica# antis'chotics 4and some antideressants and

anticon*"#, sants5( SIADH is characteri.ed b' a red"ced abi#it' to e$crete 2ater!

res"#tin& in e$trace##"#ar di#"tion and h'o, natremia(

Common s'mtoms inc#"de 2eakness! #ethar&'! headache! anore$ia! and 2ei&ht

&ain and ma' ro&ress to con%"sion! con*"#sions! coma! and death(

Hemato#o&ica#( Hemato#o&ica# side e%%ects o% antis'chotics inc#"de

a&ran"#oc'tosis! a#astic anemia! ne"troenia! eosinohi#ia! and

thromboc'toenia

A&ran"#oc'tosis is the most common serio"s hemato#o&ica# side e%%ect 2ith

t'ica# antis'chotics 40()15 and occ"rs more %re?"ent#' 2ith #o2,otenc'

a&ents( C#o.aine,associated a&ran"#oc'tosis occ"rs in abo"t )1>31 o%

atients! 2ith hi&hest risk in the %irst months( A 2hite b#ood co"nt #ess than

3!000mm: or an abso#"te ne"trohi# co"nt #ess than )!000mm: is an indication%or immediate cessation o% c#o.aine(

A##er&ic! dermato#o&ica#! and ohtha#mo#o&ica#( Derma, to#o&ica# ad*erse

reactions inc#"de ear#' a##er&ic rashes! hotosensiti*it'! and skin

h'eri&mentation! esecia##' 2ith ch#orroma.ine(

Se$"a#( Antis'chotics ma' ca"se se$"a# d's%"nction

Dr"& interactions( Most antis'chotic dr"&s ha*e sedat, in&! h'otensi*e!

anticho#iner&ic! antiarrh'thmic! and sei, ."re thresho#d>#o2erin& roerties(

antis'chotics ma' stron' otentiate the sedati*e e%%ects o% other CNS

deressants! and anticho#iner&ic anti, s'chotics 2i## ha*e additi*e ad*erse

e%%ects 2ith other anticho#iner&ic dr"&s(

Antis'chotics ma' &reat#' enhance the h'otensi*e e%%ects o% antih'ertensi*e

a&ents

An$io#'tics and Sedati*e,H'notics

Side E%%ects and To$icit'

)( ;en.odia.eines;en.odia.eines ha*e #on& been considered the corner, stone o%

harmacothera' %or an$iet' and insomnia( A#, ternati*es inc#"de b"sirone %or

an$iet' and the nonben, .odia.eine h'notics .o#idem! .oic#one! and

.a#e#on( These ne2er a&ents aear to ha*e m"ch #ess to#erance and ab"se

otentia# and %e2er ad*erse e%%ects than ben.o, dia.eines( Ch#ora# h'drate has

been "sed as a sedati*e, h'notic since )! b"t deendence occ"rs raid#'


15/26

and 2ithdra2a# can be %ata#(

Centra# ner*o"s s'stem( Ac"te ad*erse CNS e%%ects! in, c#"din& sedation! %ati&"e

and 2eakness! ata$ia! s#"rred seech! con%"sion! and memor' imairment! are

com, mon! esecia##' in o#der indi*id"a#s and the medica##' i##( hen "sed %or the

treatment o% insomnia! #on&,ha#%,#i%e ben.odia.eines are more #ike#' to ca"se

da'time seda, tion and co&niti*e imairment than short,ha#%,#i%e dr"&s(

A st"d' o% the co&niti*e e%%ects o% #on&,term ben.odia.eine "se in the e#der#'

demonstrated that the imairment o% memor'! at, tention! and s'chomotor

seed e*ident 2ith ac"te ben, .odia.eine "se re*erts to redr"& #e*e#s o*er

months o% thera'

Resirator'(

The resirator' deressant e%, %ects o% ben.odia.eines ma' become c#inica##'si&ni%i, cant in those 2ith ree$istin& resirator' disorders! s"ch as chronic

obstr"cti*e "#monar' disease 4COPD5 4C#arke and L'ons )FFB Mode# )F:5 or

s#ee anea 4Mende#son et a#( ))5! or those 2ith sei."re disorders 42hich a#so

can ca"se resirator' deression5(

The incidence o% resirator' deression associated 2ith ben.odia.eine

treatment o% sei."re disorder ran&es %rom )0(1 %or #ora.eam in ad"#ts

4A##dred&e et a#( 300)5 to )@1 in chi#dren treated main#' 2ith #ora.eam 4Ste2art

et a#( 30035 and 1>301 %or chi#dren treated 2ith dia.eam

Dr"& interactions( Additi*e CNS deressant e%%ects! in, c#"din& resirator'

deression! res"#t %rom the combina, tion o% ben.odia.eines and other CNS

deressants! in, c#"din& a#coho#(

To$icit'O*erdose(

;en.odia.eines ha*e a 2ide mar&in o% sa%et'B

O*erdose ma' res"#t in sedation! ata$ia! s#"rred seech! con%"sion! sei."res!

resirator' deres, sion! and coma( Treatment inc#"des remo*a# o% an' "nab,

sorbed dr"& %rom the stomach 4&astric #a*a&e or emesis5 %o##o2ed b' s"orti*ethera'( The ben.odia.eine anta&onist %#"ma.eni# can a#so be "sed b"t ma'

ca"se sei."res(

S"dden discontin"ation o% ben.odia.eines ma' res"#t in se*ere 2ithdra2a#

s'mtoms! inc#"din& an$iet'! a&ita, tion! d'shoria! anore$ia! insomnia!

s2eatin&! *omitin&! diarrhea! abdomina# crams! ata$ia! s'chosis! and sei."res(


16/26


3( Nonben.odia.eine Sedati*es 4o#idem! oic#one! and a#e#on5

o#idem! .oic#one! and .a#e#on are *er' 2e## to#erated short,ha#%,#i%e h'notics

2ith *er' %e2 dose,re#ated ad, *erse e%%ects( o#idem9s ad*erse e%%ects inc#"de

CNS 4di..iness! dro2siness! and headache5 and &astrointestina# e%%ects 4na"sea

and d'sesia5 4Haak and ;ande#o2 )5( oic#one9s ad*erse e%%ects inc#"de

bitter taste! dr' mo"th! di%%ic"#t' arisin& in the mornin&! s#eeiness! na", sea! and

ni&htmares 4A##ain et a#( ))5(

Resirator'( o#idem has been reorted to ca"se resi, rator' deression at

hi&h doses 4Ciri&notta et a#( )5( oic#one dose not aear to ha*e si&ni%icant

e%%ects on resirator' %"nction( The resirator' e%%ects o% .a#e#on are "nkno2n(To$icit'o*erdose(

S'mtoms o% intentiona# o*erdose o% .o#idem inc#"de dro2siness! *omitin&!

coma! and resirator' %ai#"re( Treatment is &enera##' #imited to s"orti*e

meas"res andor &astric #a*a&e( S'mtoms o% to$icit' raid#' s"b,

side in most cases 4=arnier et a#( )@5(

ata# o*erdose 2ith .oic#one has been reorted b"t!

as 2ith .o#idem! aears rare

:( Ch#ora# H'drate

@( ;"sirone

Psychostimulants


Methylphenidate, Amphetamines, and Pemoline

Modafinil and Atomoxetine

Cognitive Enhancers


17/26


Cholinesterase Inhibitors

NMDA Receptor Antagonists

Alternative Routes of Administration

Antideressants


Antis'chotics

Ps'chostim"#ants

Mood Stabi#i.ers

Cho#inesterase Inhibitors

Com#ementar' Medicines

Patients 2ith chronic disease ma' be esecia##' *"#nerab#e to ad*erse e%%ects%rom herba# medicines beca"se o% comromised or&an %"nction and

o#'harmac' 2ith con*entiona# a&ents(

Herba# rearations ma' contain se*era# #ant secies "sed "nder a sin, e

name 4Chand#er 30005 and ma' be ad"#terated 2ith "n#isted harmaco#o&ica#

a&ents! esticides! and hea*' meta#s! inc#"din& cadmi"m! #ead! merc"r'! or

arsenic 4Crone and ise )5( Dr"&s s"ch as anti,in%#ammator' a&ents!


18/26

steroids! di"retics! antihistamines! si#dena%i#,#ike como"nds 4oo#torton 300:5!

and ben.odia.eines ma' be intentiona##' added to the herba# rod"ct %or

therae"tic e%%ect(

Se#ected Herba# Medicines

)( ;#ack Cohosh

P"rorted "se(

Menoa"sa# s'mtoms

;#ack co, hosh binds to estro&en recetors and #o2ers #e*e#s o% #", teini.in&

hormone( It is contraindicated in re&nanc' and #actation and sho"#d be a*oided

b' 2omen 2ith estro&en,

deendent t"mors(

3( e*er%e2

P"rorted "se( Mi&raine roh'#a$is! anti,in%#ammator'Pharmaco#o&ica# e%%ects and dr"& interactions(


19/26

/( =insen&

P"rorted "se=insen& is romoted as a h'sica#! men, ta#! and se$"a# tonic!

imm"nostim"#ant! and mood enhancer(

Pharmaco#o&ica# e%%ects and dr"& interactions =insen& ossesses estro&enic

acti*it'B it is contraindicated in a, tients 2ith estro&en recetor>ositi*e breast

cancer( It ma' ca"se estro&en,re#ated b#eedin& disorders 4*a&ina# b#eedin&5 and

breast nod"#es( S'mathomimetic acti*it' ma' ca"se tach'cardia! h'ertension!

ner*o"sness! a&ita, tion! mania! and headache(

A*oid "se in atients 2ith diabetes! h'ertension! an$iet' disor, ders! and bio#ar

disorder or those "sin& estro&en thera'! antiestro&en thera'! or anticoa&"#ants(

A*oid #on&,term "se! 2hich ma' be associated 2ith +&insen& ab"se s'n, drome-B

s'mtoms inc#"de h'ertension! ner*o"sness! in, somnia! skin er"tions!

diarrhea! and tremor( A 2ith, dra2a# s'ndrome 4h'otension! 2eakness! tremor5ma' occ"r on discontin"ation( Discontin"e at #east F da's be,

%ore s"r&er'(

( Ka*a Ka*a

P"rorted "se( An$io#'ticB sedati*e

Ka*a ka*a is a#so ha##"cino&enic( Sa#e o% ka*a has been banned in man'

"risdictions beca"se o%

se*era# incidents o% %ata# heatoto$icit'( Discontin"e at #east 3@ ho"rs be%ore

s"r&er'(

F(Ma H"an& 4Ehedra5

P"rorted "se( ei&ht #oss! stim"#ant

E$cessi*e s'mathetic stim"#ation can #ead to di..iness! headache! decreased

aetite! &astro, intestina# distress! irre&"#ar heartbeat! tach'cardia! h'er,

tension! insomnia! %#"shin&! sei."res! stroke! and death(

Discontin"e at #east 3@ ho"rs be%ore s"r&er'(

( St( Gohn9s ort

P"rorted


20/26

( 8a#erian

P"rorted "se(

Sedati*e! short,term treatment o% in,somnia! an$io#'tic

Pharmaco#o&ica# e%%ects and dr"& interactions(

ithdra2a# e%%ects are simi#ar to ben.odia.eine 2ith, dra2a# and can be

mana&ed 2ith ben.odia.eines(

)0( Yohimbe! Yohimbine

P"rorted "se( Ahrodisiac! stim"#ant

Ad*erse e%%ects inc#"de insomnia! an$iet'! anic attacks! ha##"cinations!

h'ertension! tach'cardia! na"sea! and *omitin&( It sho"#d be a*oided in atients

2ith h'er, tension! s#ee disorders! an$iet' disorders! and s'chosis(

Se#ected Nonherba# N"tritiona# S"#ements

DHEA 4Deh'droeiandrosterone5

P"rorted "se( Deression! ostmenoa"sa# osteooro, sis! s'stemic #""s

er'thematos"s! erecti#e d's%"nction! m"#ti#e sc#erosis! dementia

Pharmaco#o&ica# e%%ects and dr"& interactions(

DHEA ma' ca"se 2ei&ht &ain! *oice chan&e! hirs"tism! and menstr"a#

irre&"#arities in %ema#es and &'necomastia and rostatic h'ertroh' in ma#es(

DHEA is contraindi, cated in atients 2ho ha*e #i*er d's%"nction! rostate can,

cer! or hormone,deendent diseases s"ch as estro&en, deendent breast

cancer(

=amma,H'dro$'b"t'rate 4=H;5! =amma,;"t'ro#actone! and )!@,;"tanedio#

P"rorted "se( Narco#es'! recreationa# %ast,actin& h', notic

Ad*erse e%%ects inc#"de n'sta&m"s! ata$ia! anea! sedation! di..iness! and

resira, tor' deression( Coma! brad'cardia! and death can res"#t( Ps'chiatric

side e%%ects o% =H; inc#"de ha##"cinations! de#"sions! a&itation! con%"sion! and

e"horia( =H; is a banned dr"& in man' "ris, dictions! b"t its rec"rsors!

&amma,b"t'ro#actone and )!@,b"tanedio#! are ind"stria# so#*ents and area*ai#ab#e as street dr"&s(

S,Adenos'#,L,Methionine 4SAMe5

P"rorted "se( Deression! osteoarthritis! chronic #i*er


21/26

disease

Pharmaco#o&ica# e%%ects and dr"& interactions(Ad*erse e%%ects inc#"de na"sea!

*omitin&! and diarrhea( SAMe ma' increase an$iet' and rest#essness in atients

2ith deression and mania and h'omania in a, tients 2ith bio#ar disorder(

Ps'chotroic Dr"&


22/26

monitorin& secondar' to %#"ct"atin& %#"id ba#ance in atients 2ith #i*er disease

accomanied b' as, cites 4secondar' h'era#dosteronism5(

e( Cho#inesterase inhibitors(

Donee.i# c#earance ma' be red"ced in cirrhosis! b"t there are no seci%ic

dosin& rec, ommendations %or heatic ins"%%icienc'(

Ri*asti&, mine c#earance ma' be red"ced b' 01>/1 in atients 2ith mi#d to

moderate heatic ins"%%icienc'! and dosin& sho"#d be &"ided b' monitorin&

e%%icac' and to#erabi#it'(

%( Ps'chostim"#ants(

There are no seci%ic dosin& recom, mendations %or meth'#henidate( Moda%ini#

c#earance is red"ced in heatic ins"%%icienc'! and its dosa&e sho"#d be red"ced

b' /01 in atients 2ith se*ere heatic ins"%%i, cienc'(

3( =astrointestina# ;#eedin&

Antideressants( Recent reorts ha*e raised concern re, &ardin& SSRIs and the

risk o% &astrointestina# b#eedin& 4Da#ton et a#( 300:B de Abao et a#( )5(

Serotonin #a's a ro#e in hemostasis! and there ha*e been cases o% ro, #on&ed

b#eedin& time! ecch'mosis! "r"ra! and eista$is! as 2e## as &astrointestina#!

&enito"rinar'! and intracrania# b#eedin&! in atients recei*in& SSRIs(

:( Other =astrointestina# Disorders

In &enera#! ho2e*er! ora##' administered dr"&s ma' be oor#' absorbed in the

resence o% ma#absortion s'ndromes( In atients 2ith de#a'ed &astric emt'in&

4d"e to diabetes me##it"s! atrohic &astritis! &astric cancer! '#oric stenosis!

ancreatitis! or &astric "#cer or dr"& ind"ced5! the harmacokinetic e%%ect ma' be

to s#o2 ab, sortion rate and de#a' time to onset o% the medication(

or non,enteric,coated rearations! increased &astric emt'in& is #ike#' to

increase the rate o% dr"& absor, tion! and con*erse#'! de#a'ed &astric emt'in&

2i## s#o2 the rate o% dr"& absortion(

or enteric,coated rearations! ho2e*er! red"ced &astric acidit' increases the

rate o% dr"& absor, tion beca"se disso#"tion o% the rearation 2i## occ"r in the

stomach(

;( Rena# Disease

most s'chotroics do not re?"ire drastic dosa&e ad"stment in rena# %ai#"re

2ith end,sta&e rena# disease 4ESRD5 man' rob#ems associated 2ith "se o%


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s'chotroics in atients are re#ated to comorbid i##nesses rather than to therena# %ai#"re

r"#e o% +t2o, thirds- atients 2ith rena# ins"%%icienc'! "se t2o,thirds o% the dose4e$cet %or #ithi"m and &abaentin5 "sed %or atients 2ith norma# rena# %"nction

not dia#'.ab#e most s'chotroicsJ#iohi#ic como"nds 2ith #ar&e *o#"mes o%distrib"tion

remo*ed b' dia#'sis on#' #ithi"m! &abaentin! *a#roate! toiramate! and#e*etiracetam are a(Antideressants

b( Antis'chotics

c(An$io#'tics and Sedati*e,H'notics

d( Mood Stabi#i.ers

e(Cho#inesterase Inhibitors

%( Ps'chostim"#ants

Antipsychotics

U Pregnancy:> Typical agentsNot associated 2ith an' e*idence o%

terato&enic! beha*iora#! emotiona#! or co&niti*e ab,

norma#ities(> Low-potency drugsCan ca"se neonata# tach'cardia!

&astrointestina# d's%"nction! sedation! and h'oten, sion %or a %e2 da's a%terbirth( ;est a*oided so as to minimi.e anticho#iner&ic! h'otensi*e! and anti,histaminic e%%ects(

> High-potency drugsPre%erred desite the risk o% %eta# EPS( Incidence o% %eta#EPS 4h'eracti*it'! h', erre%#e$ia! abnorma# mo*ements! tremor! hand %#ain&!and cr'in& that ma' ersist %or se*era# months5 is dose re#ated(


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> Atypical agentsIns"%%icient h"man data %or recom, mendation(

> Depot preparationsA*oid beca"se o% #on& d"ration o% action(

U ;reast,%eedin& VVVVVVVVVVVVVVVVVVVVV

Antidepressants

Pregnancy:

> TCAsNot associated 2ith e*idence o% terato&enic e%%ects(A*oid maroti#ine beca"se o% increased ma, terna# sei."re risk(Neonata# TCA 2ithdra2a# s'm, toms inc#"de sei."res! irritabi#it'!

abdomina# crams! insomnia! tach'cardia! tach'nea! andc'anosis(

> SSRIs#"o$etine not associated 2ith terato&enic e%%ects( OtherSSRIs do not aear to be terato&enic %rom #imited h"man data(

> MAOIsA*oid beca"se o% h'otensi*e e%%ects and otentia# %ordr"& and %ood interactions(

U ;reast,%eedin& VVVVVVVVVVVVVVVVVV

NOT YET INISHEDJJJJJJJJJJJJJJJJ

=enera# ="ide#ines %or Ps'chotroic Dr"&


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( Pre%er monothera' to combination thera'(

F(Se#ect estab#ished dr"&s 2ith kno2n e%%ects in re&nanc' and breast,%eedin&

(Se#ect medications %or minim"m terato&enic and beha*iora# to$icit'

(d"rin& re&nanc' monitor c#inica# resonse and dr"& #e*e#s 2here ossib#e

s#o2#' ret"rn dr"& dose to rere&nanc' #e*e#s at de#i*er'

)0( Minimi.e dr"& e$os"re %or the n"rsin& in%ant

))(treatment o% deressionconsider e#ectrocon*"#si*e thera'

Raid de*e#oments in medica# care in &enera#! and s'choharmaco#o&' in

artic"#ar! cha##en&e c#inicians to remain c"rrent 2ith ne2 a&ents! ne2 indications

%or estab#ished a&ents! and otentia# harmacokinetic and harmacod'namic

interactions in a o#'harmac' en*i, ronment! 2hich a#so inc#"des o*er,the,

co"nter and herba# rearations(


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