3002MSC Pharmacology Tutorial Week 8 Tutor PDF

Week 8 Tutorial CNS Pharmacology  CNS review  Tutorial readings: AMH Drug treatment of Schizophrenia and Major Depression  Tutorial  Week Questions and case study questions 6 Case study MCQ assessment review  https://www.youtube.com/watch?v=PU RvJV2SMso  Structural     change...

Week 8 Tutorial CNS Pharmacology  CNS review  Tutorial readings: AMH Drug treatment of Schizophrenia and Major Depression  Tutorial  Week Questions and case study questions 6 Case study MCQ assessment review  https://www.youtube.com/watch?v=PU RvJV2SMso  Structural     changes in the CNS Cortical atrophy Enlargement of the cerebral ventricles Develop Dementia Ongoing neurodegeneration  Glutamate excitotoxicity  Neurochemical  theories Dopamine theories  Dopamine releasers (amphetamine) and agonists (apomorphine)  Glutamate theory – NMDA antagonists  5-HT – LSD 5HT2A receptor agonist  All produce acute schizophrenic syndrome  Typical vs Atypical antipsychotics  How do they differ?     Receptor profile Incidence of extrapyramidal effects Efficacy in treatment resistant groups Efficacy against negative symptoms  D2 Receptor antagonists      Chlorpromazine Fluphenazine Haloperidol Flupenthixol Zuclopenthixol  Block α, H1, M, 5-HT2 receptors  Takes days/weeks to be effective  Oral and depot injectable forms  Cannot be taken with alcohol, depressant activity combined with medication  Behavioural effects      Apathy Reduced initiative Few emotions Slow to respond to external stimuli Reduced aggression Adverse effects  Catalepsy  Prolactin secretion   Extrapyramidal disturbances        Gynaecomastia, lactation Parkinsonian symptoms: rigidity, tremor, akinesia Akathisia: motor restlessness Dystonic reactions (Facial grimacing, muscle spasm of neck) Oculogyric crisis (Eyes roll back, orbital muscle spasm) Opisthotonos (Back/Neck arch severely) Tardive dyskinesia https://www.youtube.com/watch?v=lHC_QNg9cE0  Side effects  α block – hypotension  H1 block – sedation  M block – dry mouth, blurred vision, urinary retention  5-HT block – hypothermia and weight gain  Amilsulpiride – Selective D2 receptor block  Respiridone – Selective D2 and 5-HT2A receptor block  Clozapine – Blocks D2,, 5-HT2A, M and H receptors      Useful in patients failing to respond to conventional neuroleptic drugs D1 + D2 Receptor antagonists 1% neutropenia Metabolic syndrome Cardiomyopathy https://www.youtube.com/watch?v=zIR48Mb3W0  Bi-polar    Uni-polar – depression only    Oscillates between depression/mania Reactive depression (75%) - Stress Endogenous depression (25%) - Familial Monoamine theory of depression  Depression caused by deficient monoaminergic (NA/5-HT) transmission in the CNS  Imipramine, amitriptyline, clomipramine, doxepin, nortriptyline  Block uptake of NA and 5-HT and block α2 receptors  Increased 5-HT elevates mood  Increased NA encourages motor activity  Side effects occur through blocking of H, α, M and 5-HT receptors  Phenelzine,   tranylcypromine Irreversible inhibition Bind both isoenzymes  2-6 Weeks for improvement  Regulates free interneuronal levels of NA/5-HT  Important for inactivation of ingested and endogenous amines  Rapid increase in 5-HT > NA > DA in CNS  Similar changes in peripheral tissues and plasma  Do not increase sympathetic stimulation of heart or blood vessels Increased motor activity  Euphoria and excitement  Block muscarinic α - receptors   Fluoxetine, paroxetine, fluvoxamine, citalopram, sertraline  Blocks 5-HT > NA uptake    As effective as TCA’s Delay of 2-4 weeks for therapeutic effects Side effects     Nausea, vomiting anorexia, insomnia (Take medication in the morning) Sexual dysfunction, increased aggression/violence Inhibits cytochrome P450 enzymes in liver therefore many drug interactions Withdrawal effects (decrease dose over time)  CNS synapse serotonin increases, therefore hyperstimulating serotonin receptors and causing    Mental state changes (confusion, hypomania, agitation) Myoclonus/clonus, hyper-reflexia, tremor, incoordination Shivering, sweating, fever, diarrhoea  Remove drugs Not taking enough drug (dose)  Not taking drug at all – compliance  Cause of depression not addressed  Alcohol consumption  Other drugs which increase CYP enzyme in liver therefore increasing metabolism   Strategies?  Changing from one medication to another usually requires a week free of anti-depressants