antipsychotics according to hesi

8/13/2019 Antipsychotics According to HESI

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Antipsychotics according to HESI

The population of the United States doubled between 1900 and 1950; during this time, the population in public mental hospitals quadrupled. The

aerage length of confinement was usuall! !ears, and the trend was definitel! toward an annual increase in clients admitted to such institutions."lient and emplo!ee in#uries caused b! combatie or abusie clients led to the common use of ph!sical restraints and client isolation.

$efore the deelopment of the antips!chotic agents, the treatment of mentall! ill clients consisted of either being isolated %i.e., hidden in cellars or

attics in their homes& or, if the! came to the attention of local authorities, being transferred to #ails or homes for the insane. 'ctual therapies usedbefore the adent of the antips!chotic agents were water or ice pac( therapies, strait#ac(ets or other ph!sical restraints, shoc( therap! with insulinor electricit!, lobotom!, and the use of a few drugs such as paraldeh!de, chloral h!drate, and the barbiturates.

The era of antips!chotics was ushered in with the release of chlorproma)ine %Thora)ine& in the earl! 1950s. "hlorproma)ine belongs to aclass of drugs referred to as phenothia)ines. 'ntips!chotics are also referred to b! the outmoded term *ma#or tranquili)ers.+ These agents bloc(

dopaminergic receptors in the "S and, while not curatie, for the first time, allowed adequate s!mptom control %Box 19-1& to ma(e communit!liing a realistic opportunit! for man! with significant ps!chosis-related conditions. The use of the antips!chotic drugs proed to be a reolutionar!

force in the ps!chiatric field. The duration of institutionali)ation has decreased from !ears to months for man! clients; other clients lie at home andare treated at communit! mental health centers. The reported incidence of in#uries has declined, and man! large public mental health facilities haeclosed.

BOX 19-1

Positive and Negative Symptoms in Schizophrenia

Clients with schizophrenia present with a wide variety of symptoms that are categorized as positive or negative. ost antipsychoticagents prod!ce an effect on the following positive symptoms" agitation# anxiety# hall!cinations# poor hygiene and dress# hyperactivity#

del!sions# paranoia# and hostility# whereas the negative symptoms of flat affect# social inade$!acy# diminished speech patterns#

%!dgment# insight# and others are !s!ally less responsive to dr!g therapy.

&he target symptoms are !sed as monitoring parameters to eval!ate the individ!al's response to the medication. &he atypical

antipsychotic dr!gs (e.g.# clozapine# risperidone# olanzapine) appear to *e more effective than older typical ne!roleptic agents againstnegative symptoms# altho!gh one analysis noted little difference in symptom control *etween the typical agent haloperidol and the

atypical olanzapine (+osenhec, et al.# /)

The antips!chotics fall into two broad categories the earlier t!pical agents, including chlorproma)ine %Thora)ine& and haloperidol %/aldol&, and thenewer at!pical agents including clo)apine %"lo)aril& and olan)apine %!prea&. 'ripipra)ole %'bilif!& represents a noel approach with dopaminergic

agonist-antagonist actiit! and is discussed separatel!. 2hile the newer at!pical agents hae largel! replaced the older t!pical antips!chotics, both

are discussed here. &a*le 19-1presents selected agents.
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Agent Chemical Class

Typical Oral

Adult Daily

Dose (mg)[*]EPS

is! TD is!

Anticholi

nergic Sedation

Cardio"ascular

is! Comment

(seeBox 19-1)

:ften effective inrefractory cases

See text for significantadverse effects# incl!ding

*one marrow s!ppression#

seiz!res# drooling

;very 1 wee, if

?7 mg)

5ow (@>

if ?7 mg)

5ow 5ow 5ow Controls positive and

negative symptoms >;PSfor doses greater than 7

mg daily

ziprasidone

(Aeodon)

Benzisoxazole 81 5ow 5ow 5ow oderate oderate

(prolonged &

interval)

Controls positive and

negative symptoms

&OE% A&T$PS#C'OT$CS

aripiprazole

(0*ilify)

Class not yet

esta*lished

1/ 5ow 5ow 5ow 5ow

oderate

oderate high Controls positive and

negative symptoms

Partial agonistantagonist

activity may explain!ni$!e profile
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WBC,


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&o!rette syndrome# antipsychotic medications have prod!ced dramatic improvement in some clients.

harmaco(ineticsA3osing

/aloperidol, li(e other t!pical antips!chotics, is well absorbed orall! and has an onset of action between 80 and 0 minutes. The onset of action after@7 administration of the lactate %immediate-release& form is within 80 minutes. /aloperidol is metaboli)ed to pharmacologicall! inactie compounds

that are eliminated in the urine and feces. The elimination half-life of haloperidol is approimatel! 40 hours. The t!pical oral adult dose ranges from0.5 mg twice dail! to 5 mg three times dail!. 3oses aboe 10 mg dail! hae questionable efficac! for most clients, but some clients ma! require 80mg dail! or more. Single doses of 4 to 5 mg @7 or intraenousl! %@B& of the immediate-release parenteral formulation of haloperidol lactate %/aldolCactate& are t!picall! used for acute management. Cower doses are often used in older or debilitated clients.

Use of long-acting haloperidol decanoate %/aldol 3ecanoate& b! @7 in#ection results in a prolonged duration of action of approimatel! 8 wee(s. Thisproduct should not be confused with the shorter-acting parenteral formulation. /aloperidol decanoate is generall! resered for circumstances where

infrequent dosing is adantageous, the client has tolerated shorter-acting dose forms, and a dail! dose has been established. This formulation is

often used for clients who do not adhere to conentional therap!. @n such circumstances, a number of ethical issues must be addressed %Box 19-/&.The t!pical dose of the decanoate formulation is 10 to 40 times the dail! oral dose administered @7 eer! : wee(s, with the dose titrated to effect.

BOX 19-8

;thical and 5egal Considerations in the Hse of Psychotropic 6r!gs

&he !se of psychotropic dr!g therapy raises a n!m*er of ethical and legal considerations. &his is partic!larly tr!e for antipsychoticdr!gs# which are associated with significant adverse effects. In many circ!mstances# the client may not *e in a position to f!lly

!nderstand the ris,s and *enefits of therapy. It is important for the mental health team to apply the principles of *iomedical ethics to eachcase.

Eo!r *asic principles of *iomedical ethics are *eneficence# nonmaleficence# a!tonomy# and %!stice descri*ed *elow"

+ene,icence-J6o good.K

L 6oes the intervention help the client@

6oes the dr!g red!ce mor*idity or mortality@ 6oes the dr!g improve symptoms@

. &onmale,icence-J6o no harm#K

L


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Is the client competent to ma,e decisions@

Is the client f!lly informed of the ris,s and *enefits of therapy@

0 1ustice" JIs it fair for everyone@K

L


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Pharmacodynamics

Mariation in dopamine receptor s!*types where antipsychotics act may *e genetically determined. Binding of atypical antipsychotics and

the li,elihood for elevations in prolactin levels (a commonly o*served effect of these agents) is proportional to the genetic mar,er for the6

receptor F6+6G (o!ng et al.# 8).


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tiss!e levels o*served with standard doses of many of the antidepressants# incl!ding the tricyclics# paroxetine# and fl!oxetine. &his mayexplain differences o*served in *oth therape!tic response and toxicity for these agents ( alhotra et al.# 8).

0dverse ;ffects

0cc!m!lation of a n!m*er of antidepressants may *e secondary to the significant variation noted in 67 activity# which is geneticallydetermined. 0mong the agents meta*olized *y this enzyme are many of the tricyclic antidepressants# incl!ding amitriptyline#

desipramine# imipramine# and nortriptyline. Cardiac dysrhythmias secondary to toxic levels of desipramine have *een correlated with67 polymorphism in exican 0mericans (Elores# 0lvarado#


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to focus and continuous arm and leg moement. @t is most commonl! obsered in !ounger clients, and ma! appear earl! in therap! %within the firstfew months&. Unfortunatel!, this motor restlessness ma! be mista(en for an increase in underl!ing ps!chosis, and result in an increase in the dose

of the offending agent. Such an action onl! seres to worsen the a(athisia.

' third acute presentation of =S is drug-induced par(insonism. This presents in a manner similar to s!mptoms seen in someone with idiopathic

ar(insonHs disease, and includes a coarse %8 c!cles per second& tremor that worsens on actiit!, shuffling gait, drooling, a mas(ed loo( to the face,and muscle rigidit!. "ommon to drug-induced par(insonism is cogwheel rigidit! where passie moement of the wrist or elbow of the affectedindiidual b! an eaminer results in ratchet-li(e or on-off-li(e moement.

Treatment of =S includes aoiding future use of the offending drug, if possible, and use of drugs with anticholinergic %specificall! antimuscarinic&properties. 'cute d!stonic reactions are er! distressing to clients. The! are t!picall! treated with a drug with antimuscarinic actiit! %e.g., @7 or @Badministration of the antihistamine, diphenh!dramine $enadr!l6&. Treatment of drug-induced par(insonism includes treatments with other longer-

acting antimuscarinics, including ben)tropine %"ogentin& and tr ihe!phenid!l %'rtane&. Unfortunatel!, these antimuscarinic agents hae their own

aderse effects, including dr! mouth, urinar! retention, constipation, and occasionall! confusion. Iefer to Chapter 1for a more completediscussion of antimuscarinic agents.

!T! is tr"at"d %ith par"nt"ra# diph"nhydra$in" &B"nadry#( and his sy$pto$s r"so#," o,"r th" n")t /"% ho+rs! H" ")pr"ss"s conc"rnthat th" h"a#th car" t"a$ %as trying to poison hi$ and h" has h"ard that dr+gs #i0" ha#op"rido# &Ha#do#( can ca+s" #ong-t"r$

$o,"$"nt pro*#"$s!

Ho% #i0"#y ar" #ong-t"r$ $o,"$"nt pro*#"$s to r"s+#t /ro$ antipsychotic +s"5

aranoid delusions are common with a number of ps!chiatric conditions, but the aderse-effect profiles of the t!pical antips!chotics are troublesomeand ma! sere to reinforce paranoid perceptions for clients who do not !et hae a full therapeutic response to the antips!chotics.

'lthough a number of long-term aderse effects ma! occur with chronic use of the t!pical antips!chotics, tardi," dys0in"sia &T'(has raised thegraest concern. This is a s!ndrome of abnormal inoluntar! muscle moements related to long-term bloc(ade of 3

4receptors. The eact

mechanism of how dopamine bloc(ade can lead to T3 is not clear, but ma! inole dopamine supersensitiit!, depletion of ?'$', neurologic

oidatie stress, or some other process %Aold*erg# &. ?enetics has also been proposed as a ris( for deeloping T3 %see the Special

"onsiderations for harmacogenetics bo onp. /28&. T3 is characteri)ed b! inoluntar! perioral moements such as lip smac(ing, lip puc(ering,

tongue darting, and #aw moements %see Box 19-8&. 'lso commonl! obsered is difficult! swallowing, and choreoathetoid %worm-li(e& moementsof the hands, arms, nec(, torso, legs, and feet. @t is more li(el! to occur with higher doses of t!pical agents for long periods of time %e.g., greaterthan months&. Significant =S earl! in therap! ma! signal increased ris( for T3. Dlder women also appear to be at higher ris( for deeloping thecondition.

'lthough there is some data that high-dose itamin = ma! offer some improement in s!mptoms, there is no reliable treatment for tardied!s(inesia. 's such, earl! identification and preention are critical.
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antipsychotics according to hesi

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