Schizophrenia👻 Flashcards

Question

Side effects to antipsychotics: hyperprolactinaemia

Answer 1

• All antipsychotics increase prolactin Dose related • Some asymptomatic, but should treat regardless due to effects on sexual function, breast growth/milk, amenorrhoea (lack of periods), breast cancer and BMD (bone mineral density) (osteoporosis) • Treat: switch to alternative or add aripiprazole • Some evidence for dopamine agonists but can worsen schizophrenia symptoms Most common with Risperidone, Paliperidone,, Amisulpride / sulpiride, Haloperidol Can add aripiprazole as it lowers prolactin but it is another antipsychotic so have to be careful

Answer 2

• QT interval involves de and re-polarising of the heart for pumping action QT interval prolongation is a risk factor for ventricular arrhythmias and TdP Causes: • Some people have QT prolongation syndromes from birth • Drugs can also cause it: • Can be dose related and additive when >1 drug used • Other psychotropic/non-psychotropics implicated • ECGs essential, limits 440ms (men), 470ms (women) • If QT interval prolonged: switch/reduce dose and refer to cardiology!! Most common: Haloperidol, Quetiapine, Amisulpride

Answer 3

Anticholinergic effects, particularly clozapine and 1st generation typicals Photosensitivity - especially chlorpromazine (use sunscreen) Sedation - problem with most except aripiprazole, risperidone, amisulpride Neutropenia Postural hypotension and tachycardia (clozapine, quetipine) Lower seizure threshold (important for epileptics) Hyponatraemia • Neuroleptic malignant syndrome - rare but could be fatal Due to rapid changes in dopamine blockade (starting & stopping, changing etc) Watch out for rigidity, hyperthermia, tachycardia, sweating, fluctuating consciousness, raised Creatinine Kinase STOP antipsychotic and initiate specialist treatment

Answer 4

Regularly record response to treatment including changes in symptoms/behaviour • Regularly screen for and record management of side effects to antipsychotic treatment • Investigations for antipsychotic treatment (see also individual drug SmPCs) - Weight - Waist circumference - Pulse and BP - Fasting BMs and HbA1c - Lipids - Prolactin levels - Assessment of movement disorders, adherence nutrition and exercise - An ECG at baseline (only if specified in SmPC, personal history of CVD, inpatient admission or physical examination reveals CV risk factor (e.g. HTN)) • "The secondary care team (mental health team) should maintain responsibility for monitoring service users' physical health and the effects of antipsychotic medication for at least the first 12 months or until the person's condition has stabilised, whichever is longer. Thereafter, the responsibility for this monitoring may be transferred to primary care under shared care arrangements."

Answer 5

Reduced hospitalisation and mortality Helps the adherence Stable levels When to use? • May be useful in cases where avoiding covert non-adherence is a priority • If the patient is refusing to take oral medication, explore preventable reasons first • Some patients may prefer to use depots: could support adherence in long term treatment BUT we must stress need to visit clinics or have home visits for injections Zuclopenthixol, flupentixol, haloperidol, fluphenazine (typicals - all decanoate) Olanzapine embonate, paliperidone palmitate, aripiprazole, risperidone (atypicals) • Little to choose between typical depots in efficacy • Possibly less EPSE with atypicals, but issues with risperidone and olanzapine • Start with a test dose for typicals (See Task on Blackboard) (has oil so may be allergy) • Start dose low and go slow • Injections into gluteal/deltoid muscle (See individual SmPCs) • Use longest possible dose interval - Paliperidone available as 3 monthly injections Cons: Some (eg risperadone) must be kept in the fridge so hard to administer & has delayed kinetics (takes a while to get into blood, weeks) Olanzapine has 1 in 1000 risk of severe overdose reaction (over sedated etc) so patients who get this must stay in clinic for 3hrs after

Answer 6

Antipsychotic polypharmacy: more than one agent prescribed Very common • NICE: Do not initiate combined antipsychotic medication, except for short periods (eg, when changing medication) Limited evidence of benefit - Large increases in risk of side effects, drug-drug interactions and non-adherence • Cautious use of two drugs only advocated in treatment resistant illness, e.g. clozapine therapy augmented with another antipsychotic (e.g. amisulpride) (in severe illness) • HOWEVER - this assumption is now being questioned though not enough evidence to change practice at present

Answer 7

Used in treatment resistant schizophrenia Patient has already tried two other antipsychotics for sufficient duration and dose, one of which is atypical and still not had a response Lowers mortality significantly Reduces risk of suicide & death Titrate up. Retitration may also be needed from 0 if missed doses as suddenly going back to dose before can cause cardiovascular collapse and death. Three different brands, do not switch between them Monitoring needed to avoid neutropenia TASKS: • Danger symptoms and signs • Who can prescribe and dispense • What needs monitoring and how often • Dose titration (see right) • When to test clozapine plasma levels • Missed doses of clozapine - risks and what to do

Answer 8

• Many patients with mental illness smoke cigarettes - Nicotine may be a gateway to using other psychoactive substances • Benefits for mental health if patients do stop smoking, but timing important • Aromatic hydrocarbons (NOT NICOTINE) responsible for drug interactions. Not in NRT. - Induction of CYP1A2 - Clozapine, olanzapine, duloxetine, TCAs and benzodiazepine (BZD) levels fall by as much as 50% if smoking (haloperidol 20%) - On stopping smoking clozapine serum levels can increase by 50-72%. Really dangerous. - Levels take time to rise - Monitor levels and/or adjust dose accordingly • Caffeine also competes with clozapine at CYP1A2, causing clozapine levels to rise by 14-47% (lots of variability between individuals)(4-5 cups / day) - Excessive caffeine intake can cause restlessness, insomnia and may worsen psychosis - Caffeine also antagonises the effects of BZDs and 'Z drug' hypnotics Patients must report changes in smoking habit / caffeine intake

Answer 9

Metabolic syndrome Myocarditis Hypersalivation Neutropenia & agranulocytosis VE, sedation, infection Constipation

Answer 10

• Patient advice for those with mental illness can be seen as a challenge • Non-pharmacological methods important treatment • Tailor drug treatment for schizophrenia to individual patient - Compare first generation 'typicals' with second generation 'aypicals' - Consider patient age, social history, metabolic and cardiovascular health • Prescribing advice: selecting and initiating the right treatment, do not delay clozapine if indicated • Education: depots do not guarantee adherence, minimise dual antipsychotic therapy, importance of monitoring • Patient advice: drug choice, initiation and important side effects

Answer 11

MOA: Typical antipsychotics are primarily D2 (dopamine) receptor antagonists. Leading to decreased dopamine neurotransmission. Atypical antipsychotics are D2 receptor antagonists plus effects on serotonin (5-HT2A, 5HT1, 5-HT2C) receptors. Newer second generation agents that produce fewer extrapyramidal actions Effects: Typical antipsychotics reduce dopaminergic neurotransmission, especially in the mesolimbic pathway. Atypical antipsychotics modulates both dopaminergic and serotonergic neurotransmission Other comments: Typical antipsychotics are used for symptom control. They have higher risk of extrapyramidal side effects (EPS). Atypical antipsychotics have a lower risk of EPS, but metabolic side effects. Also used for symptom control

Answer 12

Ability to Cross the BBB (1 slide/minute) Chemical structure properties promoting BBB penetration: Lipophilic: Highly lipophilic – favours passive diffusion across lipid-rich BBB. Molecular weight: 312.4 g/mol – small enough (<400–500 Da) for passive transport. pKa = 7.4: Mostly non-ionised at physiological pH – enhances membrane permeability. Hydrogen bonding: Acceptors: 4 Donors: 1 (Well within the recommended max of 5 donors & 10 acceptors) Efflux transporter evasion: Not a significant substrate for P-glycoprotein – avoids being pumped out of CNS. 2. Pharmacology and Pathophysiology Justification (2 slides/minutes) Schizophrenia Pathophysiology: Linked to hyperdopaminergic activity in the associative striatum → causes positive symptoms (e.g. delusions, hallucinations). Negative symptoms may be due to serotonin-dopamine imbalance or prefrontal cortex dysfunction. Olanzapine Pharmacodynamics: Second-generation (atypical) antipsychotic. D2 receptor antagonist: Blocks dopamine in striatum. Reduces positive symptoms (e.g. delusions, hallucinations). 5HT2A receptor antagonist: Improves negative symptoms (e.g. withdrawal, flat affect). Reduces extrapyramidal side effects (compared to typical antipsychotics). Monitoring Requirements Baseline & ongoing monitoring includes: Metabolic monitoring: Weight/BMI & lipids: baseline, every 3 months (first year), then yearly. Fasting glucose: baseline, 1 month, then every 4–6 months. HbA1c: at 3 months, then annually. Vital signs: BP, pulse. Annual blood tests: FBC, LFTs, renal function (eGFR, urea, electrolytes). Mental health follow-up: adherence, side effects, response. CV risk assessment: at least annually. Relevant Patient Advice: Onset: May take days to weeks for therapeutic effect. Drowsiness: Caution with driving/operating machinery (especially early). Photosensitivity: Avoid prolonged sunlight at high doses. Administration: Orodispersible tablet can dissolve on tongue or be dispersed in water/milk/juice. Side effects: Report hypersomnia, appetite increase, sexual dysfunction. Missed dose: Take as soon as remembered unless near next dose – never double up. Overdose action: 111 if drowsy, abnormal movement, dizziness, gait issues. 999/A&E if seizures, breathing issues, irregular heartbeat. Lifestyle advice: Minimise alcohol, offer smoking cessation. ✅ Advantages Effective for positive symptoms – improves function and work attendance. Mood stabilisation & productivity increase. First-line treatment for schizophrenia (NICE guidelines). ❌ Disadvantages Adherence challenge – patient may resist taking medication. Metabolic side effects – weight gain, glucose intolerance. Not curative – symptom control only; long-term condition.

Answer 13

1. Ability to Cross the BBB Key Molecular Properties of Haloperidol: Molecular weight: 375.9 Da ✅ (well under 500 Da) LogP: 3.7 ❌ (slightly above ideal range of 1.5–2.5, but still crosses BBB due to high lipophilicity) Hydrogen bond acceptors: 5 ✅ (≤10) Hydrogen bond donors: 1 ✅ (≤5) Polar surface area: 40.5 Å² ✅ (≤90 Å²) ✅ Conclusion: Haloperidol meets most BBB-crossing criteria and can efficiently pass through the lipid membrane despite a higher LogP. Pathophysiology of Schizophrenia: Mesolimbic pathway (D2 hyperactivity) → positive symptoms (e.g. hallucinations, delusions). Mesocortical pathway (D1 hypoactivity) → negative and cognitive symptoms. Haloperidol Pharmacology: Typical (first-gen) antipsychotic. Mechanism: Competitively blocks post-synaptic D2 receptors in the brain. Effect: Inhibits dopamine neurotransmission in mesolimbic pathway → reduces positive symptoms. High D2 binding affinity: Strong dopamine blockade for symptom control. 🧠 Note: Does not significantly help with negative or cognitive symptoms and may worsen them due to dopamine blockade in mesocortical areas. Monitoring and Follow-up Physical health: Weight, waist circumference, pulse, and blood pressure. Blood tests: Lipids, prolactin levels. Cardiac safety: Baseline ECG (due to QT prolongation risk). Dose strategy: Use lowest effective dose. Titrate gradually and review frequently. Relevant Patient Advice Adherence: Take exactly as prescribed. Missed dose: Take next scheduled dose, do not double up. Common side effects: Muscle stiffness or tension Drowsiness, dizziness → avoid driving or operating machinery Vision problems Low blood pressure → risk of falls Report worsening symptoms or serious side effects promptly. ✅ Advantages Effective in acute psychosis: Rapid control of positive symptoms. Multiple administration routes: Oral, intramuscular, intravenous. Titration flexibility: Individualised dosing possible. Cost-effective: Cheap and effective at low doses. Broad clinical use: Especially for emergency management. ❌ Disadvantages Extrapyramidal side effects (EPSEs): Tremors, rigidity, dystonia. QT prolongation: Risk of cardiac arrhythmias. Caution in elderly: Risk of cerebrovascular events (NICE guidance). Severe adverse effects: Neuroleptic Malignant Syndrome (NMS) Sedation and cognitive dulling

Answer 14

A. Likely Causes of Sexual Dysfunction Common side effect of flupentixol and other antipsychotics. Negative symptoms of schizophrenia (e.g. apathy, social withdrawal). Secondary depression. Emotional blunting as a side effect. Importance of a sensitive, non-judgmental conversation in a safe environment. B. Flupentixol – Mechanism & Sexual Dysfunction Mechanism of Action: Dopamine antagonist at D1 and D2 receptors (mesolimbic/mesocortical). Moderate 5HT2 antagonist – may help with negative symptoms. Depot formulation = long-acting, intramuscular injection. Mechanism of Sexual Dysfunction: D2 blockade in tuberoinfundibular pathway → ↑ prolactin → ↓ libido/arousal/orgasm. Hyperprolactinaemia is a key cause. Flupentixol is a prolactin-elevating antipsychotic (like haloperidol, risperidone). Other Common Side Effects: Fatigue, dry mouth, dizziness, constipation, insomnia. C. Management Strategies Assess medication adherence – missed doses can worsen side effects. Consider switching to aripiprazole (lower risk of sexual dysfunction). CBT or psychological support for coping and communication. Smoking cessation: 15+ cigarettes/day may induce CYP1A2, altering drug metabolism. Consider trial of sildenafil or tadalafil for erectile dysfunction (after risk assessment). ——————————————— A LIKELY TO BE Reduced libido (loss of sexual desire) and or Erectile dysfunction as is a common side effect of antipsychotic medication and in particular fllupentixol. Could also be.. Negative symptoms of schizophrenia (emotional withdrawal, apathy, reduced intrest in raltionships) Depressive symptoms as a secondary issue Other side effect from flupentixol, like emotional blunting wihc could affect his relationship It will be important to have an open and sensitive discussion with the pt in a safe environment, ensuring he is comfortable. B. Mechanism of action of flupentixol: Flupentixol is an antipsychotic medication which mainly functions as a dopamine receptor antagonist. It mainly blocks D2 receptors in the mesolimbic and mesocortical pathways but it is a powerful antagonist at both D1 and D2 receptors (unlike haloperidol-d2 antagonist only-extra info). It has less affinity at D3 and D4. By inhibiting these receptors, the medication reduces the intensity of the symptoms. Depot means it is administered intramuscularly and releases drug overtime, it is a long-acting antipsychotic. (In addition to its effects on dopamine receptors, Flupentixol decanoate also exhibits moderate antagonistic activity at serotonin (5-HT2) receptors. This dual action on both dopamine and serotonin receptors contributes to its antipsychotic efficacy and may mitigate some negative symptoms and cognitive deficits How does it cause the side effect of sexual dysfunction? The mechanism is mainly due to dopamine receptor antagonism which decreases the libido. Blockade of dopamine D2 receptors in the tuberoinfundibular pathway by antipsychotics may decrease the libido, impair arousal, and impair orgasm indirectly, by leading to elevated prolactin levels. Hyperprolactinemia is a major cause of sexual dysfunction and some antipsychotics like haloperidol,risperidone are classed as prolactin-elevating antipsychotics. Flupentixol is also under this class. Other side effects include fatigue,dry mouth, dizziness,constipation, insomnia etc C. Assess and ensure adherence Missed doses or poor adherence can contribute to worsening side effect Could consider an alternative medication like ariprazole, which is an atypical antipsychotic which has a lower risk for contributing to sexual dysfunction. Could also recoment the patient to attent CBT and other forms of counselling Tell the pt to consider smoking cessation as he smokes 15+ cigs a day which can impact metabolism of antipsychotic drugs by induceing cyp1a2. We could also consider trialing sildenafil or taladafil?

Answer 15

Clozapine and Constipation Adverse Effect: Clozapine has potent anticholinergic properties → reduces gastrointestinal motility. Can lead to severe or life-threatening constipation, including bowel obstruction, paralytic ileus, and intestinal ischemia. Patient Risk Minimisation Strategies: Routine monitoring for bowel habits and signs of GI slowdown (e.g. abdominal pain, bloating, no bowel movement >48 hrs). Encourage: High-fibre diet Adequate hydration Regular physical activity Use stool softeners or laxatives prophylactically (e.g. lactulose or macrogols). Educate patient to report any changes early. Clozapine – Smoking, Dosing & Plasma Levels Smoking Impact: Smoking induces CYP1A2, the main enzyme metabolising clozapine. Starting smoking → ↓ plasma clozapine levels → reduced efficacy. Stopping smoking → ↑ plasma clozapine levels → increased risk of toxicity. Patient Advice: Inform prescriber immediately before any change in smoking status. May require dose adjustment if smoking habits change. Missed Doses: Clozapine has a narrow therapeutic window. Missing >48 hours of doses may lead to loss of tolerance → increased risk of seizures or myocarditis if restarted at full dose. Restart at lower dose and titrate slowly under supervision. Advice: Take doses consistently at the same time daily. Contact clinical team if doses are missed for over 48 hours. Neutropenia and Agranulocytosis Adverse Effect Summary: Life-threatening blood dyscrasias: Neutropenia: ↓ neutrophil count Agranulocytosis: near-total absence of granulocytes → high infection risk Risk highest in first 18 weeks of treatment. Risk Minimisation Strategies: Mandatory blood monitoring: Weekly for 18 weeks, then every 2 weeks until 1 year, then monthly if stable. Patient education to report: Sore throat, fever, flu-like symptoms. Do not initiate or continue without valid blood test result. Clozapine should be immediately stopped if neutrophil count drops below safe threshold.

Schizophrenia👻 Flashcards

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