lecture _3 agents used to manage schizophrenia june 2014

8/18/2019 Lecture _3 Agents Used to Manage Schizophrenia June 2014

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Post Basic PsychiatricNursing Programme

Psychopharmacology

Managing

SchizophreniaPresenter:Novlette Mattis-Robinson

(R.Ph, BPharm. , MP!P!"#

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• Psychotropic agents used to manageschizophrenia and other psychoticand neurologic illnesses

• Previously called “Tranquilizers” –somnolence, relaxation, sedation

• Other Names -

–Neuroleptics

–Dopamine Antagonists

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• The !rst antipsychotic agents "ereintroduced in the early to mid #$%&'s –rau"ol!a al(aloid, reserpine and the

Phenothiazines )*hlorpromazine+• eserpine "as prolematic ut the

*hlorpromazine "as very impressive

•

.ntipsychotics have reduced thenumer o/ hospital eds occupied ypatients diagnoses "ith 0chizophrenia1

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• The ma2or use – treat 0chizophrenia

• .lso used to treat .gitation and

Psychosis associated "ith psychiatricand 3 or organic disorders1

• They have little or no ause potential– not classi!ed as controlledsustances1

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• The actual cause is uncertain

• 4ultiple theories that provide partial

explanations Theories include5

– 6opamine hypothesis

–

7enetics – Neurodevelopmental

– Psychosocial

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• opamine %heory

– Postulates that dopamine hyperactivity inthe rain is responsile /or psychotic

symptoms – Other neurotransmitters involved are %-

hydroxytryptamine )0erotonin 3 %-8T+ and7lutamate

• enetic %heory – 8istory in !rst –degree relative – #& 9 ris(

– 8istory in oth parents – ris( : to ;&9

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• Neuro/evelopmental

– Occurs as a result o/ utero disturancesduring pregnancy )eg1 complications,

neonatal hypoxia+1 0tudies have lin(edprenatal conditions to : ris( o/schizophrenia1

– uences )stress,

poor interpersonal s(ills, /amily con>icts+

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• No (no"n cure exist /or 0chizophrenia

•%reatment )ptions – Psychotherapy

– Pharmacotherapy

•.ntipsychotic 4edications – Typical or ?irst 7eneration

–.typical or 0econd 7eneration

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• Phenothiazines – e1g1 *hlorpromazine

• @utyrophenones – e1g1 8aloperidol

• Thioxanthenes - e1g1 Auclopenthixol

• 6ienzoxazepines - e1g1 Boxapine

• 6ihydrolindoles - e1g1 4olindone

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• 6iphenylutylpiperidines – e1g1 Pimozide

• @enzamides – e1g1 0ulpride

• Thienoenzodiazepines – e1g1Olanzapine

• 6ienzothiazepines – e1g1 Cuetiapine

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• *hlorpromazine - B.7.*TDB

• ?luphenazine - 4O6


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• Mechanism of Action – Primarily through loc(ade o/ 6opamine

receptors

– Other receptors are involved )see diagram+• Ecacy

– Fhen in equivalent dose )equipotent+,eGcacy is similar

– Typical .ntipsychotics are usually aseHective as .typicals /or +ve symptomsut less eHective /or –ve symptoms

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• Potency – *lassi!ed y their potency /or the

dopamine receptors ($# )high,

moderate, lo"+ – 8igh potency agents have higher aGnity

/or $ and are associated "ith higher ris(/or


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• $/verse "2ects

–Dopamine Receptor Blockae

•

8yperprolactinemia• Par(insonism

– Alpha –arenergic !lockae

• Postural hypotension

• Orthostatic hypotension

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• Muscarinic Receptor Blockae – .nticholinergic eHects )dry mouth,

constipation, lurred vision, urine retention+

– Thioridazine is the most potentantimuscarinic phenothiazine+

• "istamine Receptor Blockae

– 0edation – Dncreased appetite )may cause "eight gain+

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• #$"ER E%%E&$'

– @loc(ade o/ norepinephrine reupta(e

– @loc(ade o/ serotonin receptors

– Dnhiition o/ gro"th hormone release)thin( aout use in children+

– Dmpairment o/ mechanisms related to

temperature regulation

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• Neurological

– 0edation

–


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• Enocrine

– 4enstrual irregularities

– 7alactorrhoea

– 6ecreased glucose tolerance

• "aematological

– .granulocytosis

• "epatic

– *holestatic Iaundice

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"0%R$P'R$M&$1S'NR)M" ("PS#

• esults /rom the loc(ade o/ postsynaptic dopamine receptors on thenigrostriatal tract o/ the rain –

imalance in cholinergic anddopaminergic systems1

• ?our );+ categories o/


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$cute ystonia – .normal involuntary movements

especially around mouth, 2a", /ace, and

nec(1 – eactions characterized y pain/ul muscle

spasms, !xed up"ard gaze, nec( t"isting,arching o/ the ac( and clenched 2a"s

)trismus and laryngospasm+

– Jsually occurs "ithin the !rst KL hrs o/starting antipsychotic therapy

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• $cute ystonia cont4/

–8igh potency antipsychotics are moreli(ely to produce these reactions

– Treatment –anticholinergics e1g1@enztropine, antihistamine e1g16iphenhydramine

–Parenteral therapy is pre/erred toinitiate therapy

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$5athisia

• . su2ective /eeling o/ motor

restlessness "here the patientcannot sit or lie still

• The patient o/ten paces and

ecome agitated and 3 oraggressive

• . compulsion to e in motion

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$5athisia cont4/

• 4ay occur days to "ee(s a/ter

therapy• Treatment – decrease dose o/

antipsychotic agent, s"itch to

lo" potency agent, usePropranolol L& – M& mg daily

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"0%R$P'R$M&$1S'NR)M" ("PS#

Par5insonism

•*haracterised y tremor, rigidity anda(inesia or rady(inesia

•Occurs "ee(s to months a/ter therapyand more common in elderly /emales

•

Treatment – anticholinergic agents eg1@enztropine L mg and Trihexiphendyl Lmg

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"0%R$P'R$M&$1S'NR)M" ("PS#

%ar/ive ys5inesia

• *haracterized y a rhythmic involuntarymovement o/ the tongue, lips, 2a", /ace,

extremities and sometimes the trun(• Occurs months to years a/ter therapy

egan and may e irreversile

• Protrusion o/ tongue, puc(ering o/mouth, che"ing motions, lip smac(ing,puGng o/ chee(s

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"0%R$P'R$M&$1S'NR)M" ("PS#

%ar/ive ys5inesia

• 4ore common in "omen and personsolder than %& yrs

• Persons "ith rain damage and mooddisordes are at higher ris(s

• Treatment – prevention, early diagnosis

and mgt1 @enzodiazepines e1g1 6iazepam,lithium and *aramazepine may help

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N"*R)1"P%& M$1&N$N%S'NR)M" (NMS#

• Bi/e threatening

• 0ymptoms – hyperpyrexia )#&K ?+,agitation, stupor, s"eating, respiration

– these usually develop rapidly over aL; – KL hr period

• Ba results – increased F@*, *P, liver

enzymes and renal shutdo"n• *an miss 6x in early stages )high

potency agents mostly+

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"0%R$P'R$M&$1S'NR)M" ("PS#

• Management – discontinue thedrugs immediately and startsupportive care 3 measures

• Supportive measures – monitorvitals, renal output, (eep patient cool

• There is no (no"n treatment

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"0$MP1"S )+ $%'P&$1$N%&PS')%&S

• .ripiprazole - .@DBD?

• *lozapine - *BOA.DB

•Olanzapine - AP


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• .merican Psychiatric .ssociation ).P.+recommends using an .typical !rst)


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• 6epends on patient's previousexperiences

• .dverse eHects

• 4edical condition )concomitant+

• 4edication interactions

• Patients pre/erence

• *ost

• 6osage /orm availale

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$N%&PS')%&S• .ssists "ith many aspects o/ thin(ing

and emotions

• @y themselves do not allo" mostpatients to /unction /ully in society

– Dntensive training in social s(ills

• 6opamine hypothesis does not account/or all the pathology o/ 0chizophrenia)"ee(s required to attain Tx ene!ts+


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enerally

– 8ighly lipid solule

– 8ighly protein ound )$L - $$9+

– Barge volume o/ distriution

– =ariale @ioavailaility

– elatively short plasma hal/ li/e )#&-L& hrs+

– 4etaolites may e /ound in urine "ee(sa/ter last dose o/ drugs )drugs hidden intissues+


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+our (8# classical si/e e2ects y "hich the agents are compared

–0edation )lo" potency agents+

–8ypotension

–


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• These agents have a greater aGnity/or the %8TL receptors

• *lassi!cation as .typical is ased on

three clinical oservations –


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R"+"R"N"S

• 0huster, Ioel5 Psychopharmacologicagents, emington, The 0cience andPractice o/ Pharmacy, L#st

lecture _3 agents used to manage schizophrenia june 2014

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