Psychoses, Schizophrenia

Question 1

what are positive symptoms of schizophrenia?

Answer 1

thought disorders (disorganised thoughts and speech)
hallucinations
delusions

Question 2

what causes +ve symp in schizophrenia

Answer 2

the OVERactvitity in mesolimbic pathway in the brain

Question 3

what are -ve symptoms of schizophrenia?

Answer 3

social w/d
poor hygiene
apathy
catatonia (immobility)

Question 4

what causes -ve symp in schizophrenia

Answer 4

UNDERactivity in the mesocortical pathway in the brain

Question 5

what class of drugs are antipsychotic drugs?

Answer 5

DOPAMINE-Receptor 2 -ANTAGONIST

Question 6

in what way are the second gen. of antipsychotic drugs are better than the first gen.

Answer 6

2nd gen. more effective than 1st gen. in treating negative symps. not just antagonising DA to suppress the OVERactivity of mesolimbic D-pathway

Question 7

what are extrapyramidal symptoms

Answer 7

movement symptoms: tremours, akathisia (inner restlessness), dystonia, dyskinesia, parkinsonism, tardive dsykinesia

Question 8

how does antipsychotic drugs cause extrapsyramidal symptoms

Answer 8

they are D2 anatagonist. they also inhibit D2 receptors in NIGROSTRAITAL (regulates movement) pathway

Question 9

what is the other pathway that antipsyhotic drugs can effect and cause ADRs?

Answer 9

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

Question 10

how should antipsyhotics be stopped after taking long term (1-2 years) and why

Answer 10

gradually to avoid risk of actue withdrawal syndromes and rapid relapse

Question 11

how long should pt be monitored for after withdrawing antipsychotics

Answer 11

2 years

Question 12

what are the 7 advice of Royal College of Psychiatrists on doses of antipsychotics

Answer 12

1. consider alternatives (eg adjvants, newer or 2nd gen - clozapine)
2. consider risk factors (obesity, elderly>70)
3. consider drug interactions
4. ECG to exclude QT prolongation, repeat and reduce dose if heart affected
5. increase dose slowly and once weekly
6. regular pulse, BP, temp check
7. high dose only for short period and review.
   STOP if NO improvement after 3 months

Question 13

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

Answer 13

IM ROUTE
IM dose is LOWER than PO dose as avoids 1st pass effect in liver, more drug in the circ.
dose reviewed daily

Question 14

what are the risks of using antipsychotics in elderlies?

Answer 14

postural hypotension
hyper/hypothermia
if dementia, increased risk of death, stroke, TIA

Question 15

what are the 3 rules to follow when rx antipsych in elderly

Answer 15

1. not recommended to treat mild-mod psychotic symps
2. initial dose is HALF adult dose
3. review regularly

Question 16

for how long should a person try antipsychotic before determining its effectiveness

Answer 16

4-6 weeks

Question 17

what are the risks of antipsychotics

Answer 17

EPSE, QT prologation (predipose to ventricular tachycardia, lead to ventricular defibrillation and sudden cardiac death

Question 18

antipsyhotics drugs are also known as … what are its long term and short term indication

Answer 18

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

Question 19

what are the major types of antipsychotics

Answer 19

2 distinct types - 1 and 2nd generation

Question 20

what is the first line trt for schizophrenia

Answer 20

no 1st line opetion suitable for all pts, choice based on individual pt factors

Question 21

describe the predominant MOA of 1st gen antipsychotics

Answer 21

UN-SELECTIVELY block D2 receptors in the brain, affecting all 4 dopamine pathways -mesolimbic, mesocorticol, nigrostriatal, tuberofundibular

Question 22

base on the characteristics of 1st and 2nd gen antipsychs, what factors can be used to determine treatment choice for pt

Answer 22

1. 1st gen cause EPSE and HYPERprolactineamia –> avoid in parkinson pt
2. 2nd gen cause more METABOLIC s/e –> avoid in overweight, diabetic pt
3. other factors inc, sedation level, QT proplongation

Question 23

three class of 1st gen antipsychs

Answer 23

1. phenothiazines (divided into 3 gps)
2. butyrophenones
3. thioxanthenes
4. others: pimozide (QT-P), sulpiride, loxapine (bronchospasm)

Question 24

what are the 3 groups of phenothiazines?

Answer 24

group1: ‘promazine’ eg CHLORpromazine, LEVOpromazine, Promazine (used as sedative OTC)
group2: ‘cyazine’ eg PERIcyazine
group3: ‘phenazine/perazine’ eg FLUphenazine, PERphenazine, PROCHLORperzine, TRIFLUOperavzine

Question 25

describe the level of EPSE, SEDATION, ANTIMUSCARINIC effect of 3 groups of phenothiazine

Answer 25

group1: MOD EPSE, antimuscarinic, MOST sedative group2: LEAST EPSE, MOD sedative group3: MOST EPSE, LEAST antimuscarinic, sedative

Question 26

Butyrophenones are similar to gp3 of phenothiazine. name one butyrophenone

Answer 26

haloperidol (MOST EPSE, can cause QT-P)

Question 27

name 2 thioxanthenes

Answer 27

1. FLUpentixol - do NOT take in evening as has altering sedative and stimulating effect 2. ZUCLOpenthixol - depot used in aggitated/aggresive pt, more effective in preventing relapse

Question 28

2nd generation antipsychotics are also known as...

Answer 28

Atypical antipsychotics

Question 29

MOA of 2nd gen antipsychotics

Answer 29

block post-synaptic D1-D4 receptors and a wide range of other receptors --> many SE

Question 30

what are the two features of 2nd gen antipsychotics (SE, indication)

Answer 30

more metabolic SE eg weight gain, diabetes, less EPSE more effective at treating negative symptoms

Question 31

name a few 2nd gen antipsychotics

Answer 31

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)

Question 32

clozapine is the most effective atypical antipsychotic with numerous SE therefore licensed only for...

Answer 32

resistant schizophrenia, where unresponsive to 2 or more drugs (inc. 2nd gen) for 6-8 weeks each

Question 33

what are the requirements for dose change for clozapine what happened if missed dose?

Answer 33

measure plasma clozapine level before change or adding a 2nd antipsychotic if miss 2 or more doses then need to re-initiate by specialist

Question 34

who should avoid taking clozapine and why

Answer 34

clozapine increases the risk of agranulocytosis, avoid concomitant with bone marrow suppressant eg amoinosalicylates (sulfasalazine), immunosuppressants (MTX, cytotoxics)

Question 35

what are the main SE of clozapine MAG

Answer 35

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

Question 36

what is agranulocytosis

Answer 36

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

Question 37

what is depot preparations (typically end in decanoate)

Answer 37

long acting, sustained release antipsychotics by IM injection every 1-4 weeks to aid compliance

Question 38

how to initiate depot and switch from PO to depot

Answer 38

initiate - test dose as SE are prolonged (a month or longer) | switch - give PO whilest stablising on depot

Question 39

antipsychotic drug side effects and monitoring in detail: | EPS

Answer 39

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

Question 40

what is the first sign of tardive dyskinesia

Answer 40

fine vermicular movement of tongue

Question 41

HYPERLACTINEAMIA (which drug, symp, monitor)

Answer 41

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

Question 42

which antipsychotic drug does not increase prolactin level and why

Answer 42

aripripazole as it is a partial D2 receptor antagonist

Question 43

METABOLIC SE (which drug, symp, monitor)

Answer 43

``` 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) ```

Question 44

CV S/E (which drug, symp, monitor)

Answer 44

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

Question 45

which drug has negligible effect on QT-P

Answer 45

aripripazole

Question 46

symptoms for neuroleptic malignant syndrome

Answer 46

muscle rigidity, fluctuating consciousness and BP, hyperthermia, sweating, tachycardia, loss of blood from skin- pallor (pale), urinary incontinence

Question 47

neuroleptic malignant syndrome is rare but potentially fetal, how long does it lasts once discontinued?

Answer 47

5-7 days longer with depot

Question 48

which drug can treat neuroleptic malignant syndrome

Answer 48

bromocriptine, dantrolene (DAagonist)

Question 49

which drug is known to cause QT-P? monitoring requirement and DDI

Answer 49

pimozide, ECG BEFORE trt and yearly, STOP or reduce dose if prolonged. No concomitant QT drug/electrolyte imbalance drug

Question 50

S/E profile of antipsychotics

Answer 50

1. EPSE 2. HYPERPROLACTINAEMIA 3. WEIGHT GAIN, BGL, diabetes 4. SEXUAL DYSFUNCTION 5. CV RISK - QT-P, HYPOTENSION 6. NEUROLEPTIC MALIGNANT SYDNMORE (FATAL) 7. ANTIMUSCARINIC 8. AGRANULOCYTOSIS, BLOOD DYSCRASIAS 9. PHOTOSENSITIVITY 10. LIVER TOXICITY (JAUNDICE) 11. chlorpromazine - contact sensitisation 12. pimozide - QT-P

Question 51

antipsychotic drug monitoring

Answer 51

1. FBC, UE, LFT (esp with phenothiazine) 2. Lipid and weight at baseline, 3M then yearly 3. Fasting blood glucose at baseline, 3M, yearly 4. ECG at start (esp if CV risk factor or Hx of CVD) 5. BP before starting upon dose change

Question 52

Common DDI with antipsychotics

Answer 52

1. risk of QT-P: amiodarone, quinolones, quinine, SSRI, macrolides (ACE) 2. risk of EPSE (parkinsons, metoclopramide D2 agnoist) 3. risk of sedation: hypnotics Zs, benzos, alcohol, opioid, antiepileptics 4. risk of HYPOtension: antihypertensives, diuretics, nitrates 5. risk of antimuscarnic SE: TCA, antihistamines, antimuscarnicis (hyoscine)