Trial.PDF Antipsychotic Drug Information

Pimozide FDA approved for Tic disorder Augmentation in trichotillomania Delusional disorder Reduced paranoid ideation in paranoid PD Clozapine Prevalence of resistant schizophrenia on clozapine = 25 to 40% Steps to manage: o Stop substance o Psychosocial intervention o...

Pimozide FDA approved for Tic disorder Augmentation in trichotillomania Delusional disorder Reduced paranoid ideation in paranoid PD Clozapine Prevalence of resistant schizophrenia on clozapine = 25 to 40% Steps to manage: o Stop substance o Psychosocial intervention o Augmentation Dose: Starting 12.5 once daily or twice daily Increase 25 to 50 mg every day to 300 mg divided twice or three times a day Max dose 900mg, minimum effective 150mg, response between them Plasma level 350 – 420ng/ml (we were asked about the unit in OSCE not only level) Targe dose: 300 mg, UK 450 mg (this can usually be achieved in 2 to 3 weeks) Male Female Smoker 550mg 450mg Non-smoker 350mg 250mg Lower dose: o Elderly o Female o Medically ill o Non-smoker o Whom taking enzyme inhibitors (2D6, 3A4 and 1A2) Restarting Clozapine: Table from Maudsley 13th (old) edition Worth mentioning that Maudsley 14th (old) edition changed the approach to restarting Clozapine titration from 12.5mg after 48 hours of discontinuation If you want to stop alone over 12 to 16 weeks If you want to stop by cross titration over 6 to 8 weeks Bushra Hijan, 2024 Initial work-up: Physical examinations, CBC, LFT, urea and electrolyte, lipids, glucose/HBA1C Consider troponin, CRP, beta-natriuretic peptide, ESR (as baseline for further test) ECG to screen for evidence of past MI or ventricular abnormality (before starting, one month after starting, every 6 months) ECHO if clinically indicated Monitoring: For Metabolic Syndrome: Maudsley 13th (old) edition Drug-drug interactions: Including, but not limited to: § Carbamazepine Any drug that may cause § Phenytoin agranulocytosis or bone § Propylthiouracil marrow suppression § Sulfonamide § Captopril Increases risk of seizure, confusion, movements disorders Lithium CI in history of NMS Carbamazepine Increase risk of agranulocytosis Increases risk of seizure – increases clozapine concentration Clomipramine which in turn lowers seizure threshold Benzodiazepine Respiratory depression and cardiac arrest Barbiturate 1A2 inducer ¯ clozapine level Paroxetine May precipitate clozapine-induced neutropenia Depots, sertindole, Discontinued before starting clozapine pimozide, and ziprasidone ­ clozapine level Enzyme inhibitors Risperidone, Fluoxetine, Paroxetine, Fluvoxamine TCA, SSRI, depakine, cimetidine and erythromycin Smoking ¯ clozapine level via induction of 1A2 Caffeine ­ clozapine level via inhibition of 1A2 Pregnancy and Lactation: Category B Not recommended during breast-feeding Advantages of Clozapine: No sexual side effects Low impact on prolactin & low EPS Minimal impact QTc Bushra Hijan, 2024 Side effects: Important numbers: o Seizure risk with clozapine ¾ 5% at 600mg o Myocarditis risk with clozapine ¾ 5/100.000 or 0.05% o Trial of clozapine before maximum achieved is 6 to 12 months Neutropenia/ agranulocytosis o Agranulocytosis with clozapine ¾ 3/1000 or 0.3% (with some resources mentioning 0.7%) Clozapine induce myoclonus ¾ 1. Decrease the next dose, and 2. Add antiepileptic Clozapine-induce tonic-clonic seizure ¾ 1. Stop clozapine for 1day, then 2. Resume it in half of previous dose 3. Add antiepileptic Paliperidone and Risperidone Continue oral dose for 3 to 4 weeks after starting LAi to reach steady state then taper it over 1 to 2 weeks No more advantage of increasing risperidone long acting more than 50mg and if the patient needed higher dose, switch to paliperidone LAi 150mg Olanzapine in CATIE study Causes EPS and cognitive impairment Was best for hostility Bushra Hijan, 2024 Ziprasidone Agonist and antagonist of 5HT1A (all other SGA block 5HT2A / Aripiprazole in partial agonist 5HT1A) The only antipsychotic the works as SNRI Half-life = 7 hours (shortest among SGA) Should be taken with food ¾ increase absorption Side effects: Least to ­ weight Most SGA to cause EPS, followed by Aripiprazole Moderately ­ QTc Antipsychotics Side Effects Sedation Not time limited Hyperprolactinmenia Produced by anterior pituitary gland Prolactin production inhibited by dopamine Levels: Normal level in male 5 – 15 ng\ml Normal level in female 5 – 25 ng\ml Suspect prolactinoma if prolactin level is >118 ng\ml Antipsychotic (dopamine blockade agent) = ↑ prolactin level: Clinical picture: Prolactinoma causes headache, blurred vision, sexual dysfunction Low prolactin level ↓ Libido (L-L) Hyperprolactinemia = Erectile dysfunction & anorgasmia (E-E) Bushra Hijan, 2024 Extra-Pyramidal Symptoms Most among SGA: 1. Ziprasidone ® 2. Aripiprazole ® 3. Risperidone/ Paliperidone Least among SGA: 1. Clozapine ® 2. Quetiapine ® 3. Olanzapine Medications associated with dose related akathisia and parkinsonian symptoms: 1. Olanzapine 2. Ziprasidone Treatment of EPS: 1. Decrease the dose 2. Add medications like anticholinergic 3. Switch to another medication that has less probability to case EPS Akathisia Acute dystonia 2‫ ب‬+ 2C ‫ﻛﻠﻨﺎ ﻧﻤﻮت ﻓﻲ اﻟﺒﻨﺰ‬ Propranolol Benzodiazepine ¾‫اﻟﺒﻨﺰ‬ Benztropine Diphenhydramine ¾‫ﻧﻤﻮت‬ Clonidine Clonazepam ¾‫ﻛﻠﻨﺎ‬ Clonazepam Tardive Dyskinesia Prevalence: 20 – 30% in patient with long term use of antipsychotics 3 – 5% in young patients receiving antipsychotics annually Risk factors: Extreme of age (children and elderly) Being female Mood disorders Cognitive impairment Onset: After prolonged to antipsychotics 4 weeks from withdrawal of oral antipsychotics 8 weeks from withdrawal of depot antipsychotics Prognosis: 5 – 40% eventually remit 50 – 90% of all mild cases will remit Treatment: Valbenazine ¾ VMAT inhibitor, FDA approved Reserpine and tetrabenazine (FDA for Huntington's chorea) ¾ contraindicated in patient with depression as both will increase risk of suicide Clonazepam (better than amantadine) Amantadine Buspirone and vitamin E Deutetrabenazine ¾ FDA approved for TD and Huntington's chorea in 2017 Treatment of Rabbit Syndrome: Bushra Hijan, 2024  MCQ – Antipsychotics Q: Which antipsychotic cause retrograde ejaculation: Thioridazine NB: Medications that can cause Priapism: Q: Thioridazine serious side effect: 1. Risperidone (A) Respiratory depression 2. Clozapine (B) Thyroid storm 3. Trazodone (C) Cardiotoxicity 4. Thioridazine (D) Severe hypotension 5. Chlorpromazine 6. Molindone Q: Which one is more cardio-toxic than others: (A) Chlorpromazine (B) Thioridazine (C) Trifluoperazine (D) Clozapine Q: Schizophrenia on clozapine develops seizures. What to avoid in treating seizure: (A) Sodium valproate (B) Carbamazepine ¾ with clozapine may increase the risk of neutropenia/ agranulocytosis (C) Gabapentin (D) Topiramate (E) Lamotrigine Q: Dystonia most common in: (A) Elderly (B) Children (C) Young men (D) Young women Q: Antipsychotics raise prolactin concentrations up to: (A) 10 times (B) 20 times (C) 30 times (D) 40 times Q: Normal concentrations (5 to 25 ng/mL in women and 5 to 15 ng/mL in men) fluctuate during the day, peaking during sleep. Exercise and emotional stress can increase it, what is it: (A) Cortisol (B) Testosterone (C) Prolactin (D) Estrogen Q: Hyperprolactinemia can be predisposed by: (A) Traumatic childhood experiences (B) Separation from parents (C) Living with an alcoholic father (D) All of the above (E) None of the above Q: Minimum effective dose of haloperidol in 1st episode schizophrenia: (A) 0.5mg (B) 2mg – 4mg if multiple episode (C) 5mg (D) 10mg Q: Weight gain with risperidone more common with: (A) Children (B) Adults Bushra Hijan, 2024 Q: Minimum effective dose of quetiapine in multiple episode schizophrenic patient: (A) 150mg (B) 300mg – 150mg if single episode (C) 450mg (D) 600mg Q: 31-year-old female recently diagnosed with schizophrenic & you decided to start her on Risperidone, what is the starting dose: (A) 1mg/day (B) 2mg/day ¾ minimum effective if single episode (C) 3mg/day (D) 4mg/day ¾ minimum effective if multiple episode Q: Which one is most sedating antipsychotic: (A) Chlorpromazine (B) Thioridazine (C) Haloperidol (D) Trifluoperazine (E) Perphenazine Q: Most common drug related reasons for discontinuation of risperidone is/are: (A) EPS (B) Dizziness (C) Somnolence (D) Nausea (E) All of the above Q: The first 2 injections of Paliperidone long-acting injection should be in the: (A) Deltoid muscles (B) Gluteal muscles Q: Treatment can cause sensitivity to temperature extremes: (A) Risperidone (B) Paliperidone (C) Olanzapine (D) Quetiapine Q: The rate of agranulocytosis with typical antipsychotics is: (A) 1/100 (B) 1/1000 (C) 1/10,000 (0.01%) = to ECT mortality rate & priapism from trazodone Q: Vampire syndrome (eye lens brown deposition, photosensitivity, grey blue skin) occurs with: (A) Chlorpromazine ¾ which is most sedating and causes priapism (B) Haloperidol (C) Thioridazine (D) Quetiapine Q: Patient taking chlorpromazine develop parkinsonism symptoms should be treated by: ‼ (A) Amantadine (best answer) (B) Benztropine NB: For parkinsonian symptoms: amantadine, benztropine, & diphenhydramine Kaplan 12th edition 595 Q: Patient diagnosed with schizophrenia single episode in full remission for 3 years, he is on Olanzapine 5mg, what to do: (A) Decrease the olanzapine gradually then stop (B) Keep with same dose (C) Reduce it to 2.5 and keep it for the life Bushra Hijan, 2024 Q: Which of the following antipsychotics has the highest affinity on Histamine (H1) receptors? (A) Olanzapine (B) Quetiapine (C) Clozapine (D) Ziprasidone Q: Regarding akathisia management, what to do first: (A) Give propranolol (B) Decrease dose Q: 40 YO male patient on risperidone 1mg developed akathisia, the reason: (A) Dose of medication (B) Age of patient (C) Gender NB: the risk factors (middle age, female, high dose of 1st generation) Q: Post-injection delirium sedation syndrome (PDSS) occurs with injection of which antipsychotics: (A) Risperidone (B) Olanzapine (C) Haloperidol (D) Zuclopenthixol (E) Paliperidone Q: Rate of PDSS in the previous medication is: (A) Less than 10% (around 90% happened in 1st hour so observe for 3hr then discharge) (B) 3% (C) 5% (D) 10% Q: Which of the following is not risk factor for increasing QTc: (A) Female (B) Extreme age (C) Hypocalcemia (D) Hypomagnesemia (E) Hypokalemia (F) Hyponatremia (G) Ampicillins (H) Erythromycin (I) Diphenhydramine (J) Methadone Bushra Hijan, 2024