neuro: schizophrenia Flashcards
antipyschotic meds, aka
neuroleptics
- Generally tranquilize without impairing consciousness and without causing
paradoxical excitement
indications for antipsychotics
- schizo and related psychoses
- acute mania
- short-term adjunctive mgmt of severe anxiety or psychomotor agitation, violent behaviour
other uses:
- antiemetic in palliative care (chlorpromazine, haloperidol, prochlorperazine)
- adjunct treatment for major depression (quetiapine, aripiprazole)
- irritability a/w autism disorder (risperidone)
- motor tics and adjunctive treatment in choreas and Tourette’s syndrome (haloperidol)
- intractable hiccups (haloperidol)
antipyschotics for schizo
relieve sx of psychosis such as thought disorder, hallucinations and delusions
- less effective in apathetic withdrawn patients
is long-term treatment necessary after first episode of psychosis?
yes, prevent illness from becoming chronic
a person who is maintaining well on antipyschotic may relapse if
treatment is withdrawn inappropriately
- relapse is often delayed for several weeks after cessation of treatment
- adipose tissues act as depot resesrvoir after chronic regular usage of antipsychotics: antipsychotics store in fat cells then diffuse back into bloodstream after treatment cessation and until depletion
methods to overcome poor treatment adherance
- IM long-acting injections
- Community Psychiatric Nurse
- Patient and Family (Caregiver) Education
central dopamine systems is composed of the following 4 tracts
- mesolimbic tract
- mesocorticol tract
- nigrostriatal tract
- tuberoinfundibular tract
mesolimbic tract
common moa for all antipsychotics: blockade of the dopamine receptors in this tract
- overactivity in this region is responsible for the pos sx
mesocorticol tract
responsible for higher-order thinking and executive functions
- dopamine blockade or hypofunction in this region results in neg sx
nigrostriatal tract
modulates body movement
- dopamine blockade in this region causes EPSE
tuberoinfundibular tract
dopamine blockade in this region of the anterior pituitary leads to hyperprolactinemia
- unopposed secretion of prolactin into blood stream: can cause osteoporosis, sexual dysfunction, gynecomastia
d2 antagonism
improve +sx
se: EPSE, hyperprolactinemia
5ht1a agonism
anxiolytic
5ht2a antagonsim
antidepressant effects? improve -sx?
5ht2c antagonism
se: weight gain
h1 antagonism
se: sedation/weight gain
a1 antagonism
orthostasis, sedation
m1 antagonism
memory dysfunction, peripheral anticholinergic effects
IKr antagonism
qtc interval prolongation: pro-arrhythmic
adequate trial
at optimal therapeutic doses, at least 2-6 weeks
- clozapine trial req up to 3months
- additional augmentation trial of up to 8-10weeks req if another antipsychotic is added to clozapine
long-acting injectables
IM Risperidone microspheres, IM Paliperidone prolonged release suspension, IM Aripiprazole LAI, IM
Haloperidol decanoate, IM Flupenthixol Decanoate, IM Zuclopenthixol decanoate
consider clozapine in those
treatment-resistant ie. failed >= 2 adequate trials of diff antipsychotics, at least 1 should be a SGA
routine _____ monitoring is req for pt on clozapine
hematological: FBC monthly - risk of agranulocytosis
precautions to antipsychotic use
Cardiovascular disease
QTc prolongation (contraindicated)
ECG required esp. if physical exam identifies cardiovascular
risk factors, or if there is personal history of cardiovascular
disease, or if patient is being admitted as inpatient.
PD: EPSE worsened by antipsychotics
Epilepsy & conditions predisposing to seizures
Depression
Myasthenia gravis
Prostatic hypertrophy
Angle-closure glaucoma
Severe respiratory disease
History of jaundice
Blood dyscrasias, esp. for Clozapine
Elderly with Dementia - increased risks for mortality and stroke
which antipsychotics must be taken w food
lurasidone, ziprasidone
which SGA better in terms of metabolic profile
ziprasidone, aripiprazole, brexiprazole
lurasidone also q good
which SGA worst in terms of metabolic profile
clozapine, olanzapine
mgmt of side effects: dystonia (muscle spasms eg. oculogyric crisis, torticollis)
risks:
- high potency antipsychotics eg. haloperidol
- neuroleptic-naive patients
- young males
onset: within mins (if im/iv) or hrs (if PO)
IM anticholinergics eg. benztropine, diphenhydramine
mgmt of side effects: pseudo-parkinsonism (tremors, rigidity, bradykinesia, salivation)
risks:
- elderly females
- those with previous neurological damage eg. head injury or stroke
onset: days or weeks
decr antipsychotic dose or switch to SGA
+ anticholinergics PRN eg. benzhexol or benztropine
mgmt of side effects: akathisia (restlessness)
risks: high potency antipsychotics > risp > olan > quet/cloz
onset: hrs to weeks
decr antipsyhotic dose or switch to SGA
or clonazepam low dose prn
or propranolol 20mg TDS, max 160mg/d
- anticholinergics generally unhelpful
mgmt of side effects: tardive dyskinesia (orofacial moements eg. lip chewing, tongue protrusion, pelvic thrusting)
risks: FGA>SGA, those who develop acute EPSEs when inisitated on FGA, WORSENS W ANTICHOLINERGIC DRUGS
onset: months/years to develop, 50% irreversible
discontinue any anticholinergics, decr antipsychotic or switch to SGA (clozapine possibly effective), or reversible inhibitor of vesicular monoamine transporter 2 (VMAT2) valbenazine 40-80mg/d, or clonazepam PRN
mgmt of side effects: hyperprolactinemia
risks: FGA, pali>risp> other SGA
decr FGA dose, dopaine agonist (eg. amantadine, bromocriptine), or switch to aripiprazole
mgmt of side effects: metabolic
risks: olan/cloz (high), cpz/quet/risp (moderate), ari,lura,zip,halo (low)
lifestyle modification: diet or exercise, treat dm w metformin, treat hld, switch to lower risk agents
mgmt of side effects: cv, orthostatic hypoTN
risks: cpz, cloz > risp, pali, quet > olan, zip, ari, sulpride
switch to lower risk agents
- get up slowly from sitting or lying position
mgmt of side effects: qtc proongation
thio>cpz>zip>halo>ilo?qut?risp?olan
high doses, IV halo, hypoK, IHD, female
switch to lower risk agent:
- >440ms for male
- >470ms for female
mgmt of side effects: VTE/PE
low potency>SGA>FGA> high potency, air
manage emergent DVT
mgmt of side effects: sedation
switch to lower risk agent (risp, pali,zip,ari)
mgmt of side effects: seizure
switch to high potency agents eg halo
mgmt of side effects: neuroleptic malignant syndrome - muscle rigidity, fever, incr ck
IV dantrolene 50mg TDS, oral dopamine agonist eg. amantadine, bromocriptine
switch to SGA
pt on quet
eye exam every 6 months
clozapine impt but rare adr
agranulocytosis: decr absolute neutrophil and WBC count
- ANC<1.5x10^9/L
- WBC <3x10^9/L
weekly counts for the first 6 months then every 2 weeks for next 6 months then weekly
- sg: weekly for first 18 weeks then monthly
monitoring parameters
BMI, waist circumference, fasting blood sugar/HbA1c, lipid panel, plasma prolactin, bp, EPSE, WBC and ANC, ECG
ziprasidone need to monitor
ECG, qt prolongation
antipyschotics for breastfeedign
olanzapine, quetiapine
- pt on clozapine should continue on the drug and not breastfeed
antipyschotics for renal impairment
oral aripiprazole preferred
- avoid sulpride and amisulpride
antipyschotics for hepatic impairment
sulpride, amisulpride preferred
elderly
Avoid drugs with high propensity for a1-adrenergic blockade
(orthostatic hypotension eg. cloz) or anticholinergic side effects (constipation,
urinary retention, delirium); start low go slow; simplify regime; avoid
adverse interactions; avoid long T½ drugs
- Precaution: FGAs and SGAs reported to incr mortality and CVAs
dementia patients
pregnancy
Olanzapine, Clozapine, to watch for gestational diabetes
antipsychotics may worsen what disease condition
parkinson’s
cbz and cloz
agranulocytosis
time course of treatment response
Early improvements
- 1st week: decr agitation, aggression, hostility
- 2-4 weeks: decr paranoia, hallucinations, bizarre behaviors + improved organization in thinking
Late improvements
- 6-12 weeks: decr delusions, negative Sxs may improve
- 3-6 months: cognitive Sxs may improve (with SGAs)
FGA and SGA moa
d2 antagonist in mesolimbic dop tract, improve + sx
SGA only moa
5ht2a anta may improve mood sx and possibly also - sx
SGA: -ines
clozapine, olanzapine, quetiapine: relatively more sedating, more weight gain
SGA: -ones or -piprazoles
risperidone, lurasidone, ziprasidone, aripiprazole: relatively less sedating, less weight gain
IM rapid acting
IM haloperidone or olanzapine
IM long actign
IM haloperidol deconate, 4-weekly dose of 200mg
