Psychoses, Schizophrenia Flashcards
what are positive symptoms of schizophrenia?
thought disorders (disorganised thoughts and speech) hallucinations delusions
what causes +ve symp in schizophrenia
the OVERactvitity in mesolimbic pathway in the brain
what are -ve symptoms of schizophrenia?
social w/d
poor hygiene
apathy
catatonia (immobility)
what causes -ve symp in schizophrenia
UNDERactivity in the mesocortical pathway in the brain
what class of drugs are antipsychotic drugs?
DOPAMINE-Receptor 2 -ANTAGONIST
in what way are the second gen. of antipsychotic drugs are better than the first gen.
2nd gen. more effective than 1st gen. in treating negative symps. not just antagonising DA to suppress the OVERactivity of mesolimbic D-pathway
what are extrapyramidal symptoms
movement symptoms: tremours, akathisia (inner restlessness), dystonia, dyskinesia, parkinsonism, tardive dsykinesia
how does antipsychotic drugs cause extrapsyramidal symptoms
they are D2 anatagonist. they also inhibit D2 receptors in NIGROSTRAITAL (regulates movement) pathway
what is the other pathway that antipsyhotic drugs can effect and cause ADRs?
D2 antagnoists can also act on tuberofundibular pathway and cause hyperprolactineamia by promoting prolactin release from pituitary gland (DA acts as a prolactin inhibitor) symps: breast enlargement, sexual dysfunction, menstrual disturbances, galatorrhoea
how should antipsyhotics be stopped after taking long term (1-2 years) and why
gradually to avoid risk of actue withdrawal syndromes and rapid relapse
how long should pt be monitored for after withdrawing antipsychotics
2 years
what are the 7 advice of Royal College of Psychiatrists on doses of antipsychotics
- consider alternatives (eg adjvants, newer or 2nd gen - clozapine)
- consider risk factors (obesity, elderly>70)
- consider drug interactions
- ECG to exclude QT prolongation, repeat and reduce dose if heart affected
- increase dose slowly and once weekly
- regular pulse, BP, temp check
- high dose only for short period and review.
STOP if NO improvement after 3 months
what form admin of antipsyhotics is required during an emergency psychotic episode and should the dose be adjusted from regular PO dose, why and how often review
IM ROUTE
IM dose is LOWER than PO dose as avoids 1st pass effect in liver, more drug in the circ.
dose reviewed daily
what are the risks of using antipsychotics in elderlies?
postural hypotension
hyper/hypothermia
if dementia, increased risk of death, stroke, TIA
what are the 3 rules to follow when rx antipsych in elderly
- not recommended to treat mild-mod psychotic symps
- initial dose is HALF adult dose
- review regularly
for how long should a person try antipsychotic before determining its effectiveness
4-6 weeks
what are the risks of antipsychotics
EPSE, QT prologation (predipose to ventricular tachycardia, lead to ventricular defibrillation and sudden cardiac death
antipsyhotics drugs are also known as … what are its long term and short term indication
neuroleptics - long term to treat schizophrenia, short term as tranquiliser to clam disturbed pts, regardless of underlying causes eg severe agitating depression, anxiety, brain damage etc
what are the major types of antipsychotics
2 distinct types - 1 and 2nd generation
what is the first line trt for schizophrenia
no 1st line opetion suitable for all pts, choice based on individual pt factors
describe the predominant MOA of 1st gen antipsychotics
UN-SELECTIVELY block D2 receptors in the brain, affecting all 4 dopamine pathways -mesolimbic, mesocorticol, nigrostriatal, tuberofundibular
base on the characteristics of 1st and 2nd gen antipsychs, what factors can be used to determine treatment choice for pt
- 1st gen cause EPSE and HYPERprolactineamia –> avoid in parkinson pt
- 2nd gen cause more METABOLIC s/e –> avoid in overweight, diabetic pt
- other factors inc, sedation level, QT proplongation
three class of 1st gen antipsychs
- phenothiazines (divided into 3 gps)
- butyrophenones
- thioxanthenes
- others: pimozide (QT-P), sulpiride, loxapine (bronchospasm)
what are the 3 groups of phenothiazines?
group1: ‘promazine’ eg CHLORpromazine, LEVOpromazine, Promazine (used as sedative OTC)
group2: ‘cyazine’ eg PERIcyazine
group3: ‘phenazine/perazine’ eg FLUphenazine, PERphenazine, PROCHLORperzine, TRIFLUOperavzine
describe the level of EPSE, SEDATION, ANTIMUSCARINIC effect of 3 groups of phenothiazine
group1: MOD EPSE, antimuscarinic, MOST sedative
group2: LEAST EPSE, MOD sedative
group3: MOST EPSE, LEAST antimuscarinic, sedative
Butyrophenones are similar to gp3 of phenothiazine. name one butyrophenone
haloperidol (MOST EPSE, can cause QT-P)
name 2 thioxanthenes
- FLUpentixol - do NOT take in evening as has altering sedative and stimulating effect
- ZUCLOpenthixol - depot used in aggitated/aggresive pt, more effective in preventing relapse
2nd generation antipsychotics are also known as…
Atypical antipsychotics
MOA of 2nd gen antipsychotics
block post-synaptic D1-D4 receptors and a wide range of other receptors –> many SE
what are the two features of 2nd gen antipsychotics (SE, indication)
more metabolic SE eg weight gain, diabetes,
less EPSE
more effective at treating negative symptoms
name a few 2nd gen antipsychotics
amisulpride (most hyperprolactin)
aripriprazole (does not cause hyperprolactin)
clozapine (adranulocytosis, myocarditis, GI obstruction, MOST weight gain and diabetes)
lurasidone
olanzapine (MOST weight gain and diabetes)
quetiapine
risperisone (MOST hyperprolactin)
clozapine is the most effective atypical antipsychotic with numerous SE therefore licensed only for…
resistant schizophrenia, where unresponsive to 2 or more drugs (inc. 2nd gen) for 6-8 weeks each
what are the requirements for dose change for clozapine what happened if missed dose?
measure plasma clozapine level before change or adding a 2nd antipsychotic
if miss 2 or more doses then need to re-initiate by specialist
who should avoid taking clozapine and why
clozapine increases the risk of agranulocytosis, avoid concomitant with bone marrow suppressant eg amoinosalicylates (sulfasalazine), immunosuppressants (MTX, cytotoxics)
what are the main SE of clozapine MAG
Myocarditis, cardiomyopathy (esp 1st 2 months of trt) –> STOP e.g. tachycardia, med Hx of heart disease
Agranulocytosis, neutropenia (FBC,WBC every week for 18/52, then 2 weekly for 52/52 then monthly) REPORT SIGNS OF INF
Gastro intestinaal obstruction (concomitant drug eg hyoscine -antimusc) REPORT CONSTIPATION
what is agranulocytosis
an acute condition involving a severe and dangerous leukopenia (lowered white blood cell count), most commonly of neutrophils –> look for signs of infection/flu
fever, sore throat, mouth ulcer, rapid HR and BR, LOW BP
what is depot preparations (typically end in decanoate)
long acting, sustained release antipsychotics by IM injection every 1-4 weeks to aid compliance
how to initiate depot and switch from PO to depot
initiate - test dose as SE are prolonged (a month or longer)
switch - give PO whilest stablising on depot
antipsychotic drug side effects and monitoring in detail:
EPS
esp with group 3 phenothiazine “perazine”, haloperidol and 1st gen depot preparations. e.g parkinsonian (old), dystonia (children, abnormal move of face and body), akathisia, tardive dyskinesia (rhythmic involuntary move of tongue, face, jaw. MOST SERIOUS can be IRREVERSIBLE –> STOP at FIRST SIGN
physical health monitoring yearly
what is the first sign of tardive dyskinesia
fine vermicular movement of tongue
HYPERLACTINEAMIA (which drug, symp, monitor)
esp with risperidone, amisulpride, 1st gen Antipsychotics
breast enlargement, galactorrhoea, menstrual irregularities, sexual dysfunction, reduced bone mineral density
monitor prolactin level, endocrine function in children eg weight height sexual maturation
which antipsychotic drug does not increase prolactin level and why
aripripazole as it is a partial D2 receptor antagonist
METABOLIC SE (which drug, symp, monitor)
more common with 2nd gen hyperglycaemia (sometimes diabetes) most with CROQ clozapine, risperidone, olazapine, quetiapine weight gain (most with COW clozapine, olazapine) lipid changes (dyslipidemia) sexual dysfunction (most with haloperidol, risperidone)
CV S/E (which drug, symp, monitor)
tachycardia, arrhythmias, postural hypotension (dose related, avoid in elderly who at risk of falls, most with clozapine, chlorprmazine, lurasidone, quetiapine) , QT prolongation (most with pimozide, haloperdol) annual CV risk assess and ECG
which drug has negligible effect on QT-P
aripripazole
symptoms for neuroleptic malignant syndrome
muscle rigidity, fluctuating consciousness and BP, hyperthermia, sweating, tachycardia, loss of blood from skin- pallor (pale), urinary incontinence
neuroleptic malignant syndrome is rare but potentially fetal, how long does it lasts once discontinued?
5-7 days longer with depot
which drug can treat neuroleptic malignant syndrome
bromocriptine, dantrolene (DAagonist)
which drug is known to cause QT-P? monitoring requirement and DDI
pimozide, ECG BEFORE trt and yearly, STOP or reduce dose if prolonged. No concomitant QT drug/electrolyte imbalance drug
S/E profile of antipsychotics
- EPSE
- HYPERPROLACTINAEMIA
- WEIGHT GAIN, BGL, diabetes
- SEXUAL DYSFUNCTION
- CV RISK - QT-P, HYPOTENSION
- NEUROLEPTIC MALIGNANT SYDNMORE (FATAL)
- ANTIMUSCARINIC
- AGRANULOCYTOSIS, BLOOD DYSCRASIAS
- PHOTOSENSITIVITY
- LIVER TOXICITY (JAUNDICE)
- chlorpromazine - contact sensitisation
- pimozide - QT-P
antipsychotic drug monitoring
- FBC, UE, LFT (esp with phenothiazine)
- Lipid and weight at baseline, 3M then yearly
- Fasting blood glucose at baseline, 3M, yearly
- ECG at start (esp if CV risk factor or Hx of CVD)
- BP before starting upon dose change
Common DDI with antipsychotics
- risk of QT-P: amiodarone, quinolones, quinine, SSRI, macrolides (ACE)
- risk of EPSE (parkinsons, metoclopramide D2 agnoist)
- risk of sedation: hypnotics Zs, benzos, alcohol, opioid, antiepileptics
- risk of HYPOtension: antihypertensives, diuretics, nitrates
- risk of antimuscarnic SE: TCA, antihistamines, antimuscarnicis (hyoscine)
