13.05.15 Psychopharmacology

EPSEs

    • Early and common

      • Parkinsonism

      • Akathesia

      • Dystonia

    • Late (years-decades), irreversible (in a third), often on withdrawal or reduced dose

      • Tardive dyskinesia

Antipsychotics

    • Receptors

      • Alpha1 NA

        • Orthostatic hypotension

        • Sedation

      • H1

        • Sedation

      • mACh

        • Reduceds EPSEs

        • Autonomic antimuscarinic effects

      • Dopamine

        • D2 receptors (Esp. D4) => Antipsychotic

    • Anti-EPSEs

      • Centrally acting antimuscarinics

        • Benzatropine, orphenadrine, procyclidine

      • May make TD worse

    • Clozapine

      • Hits D4

      • Is a potent antimuscarinic

        • But yet causes hypersalivation

        • ? Knocks out swallow reflex (so only apparent at night?)

    • Atypicals

      • All have strong anti-5-HT2 activity

      • Adverse effects:

        • Metabolic syndrome

        • Diabetes

        • Increased QT

        • Hypotension

        • Weight gain

    • Aripiprazole

      • "Dopamine stabiliser"

        • Stimulates at low [D]; Inhibits at high

      • Side-effects

        • Orthostatic hypotension

        • Seizures

        • Somnolence

      • As effective as risperidone; Not quite as good as olanzapine

Mood disorders

    • Progression

      • MAOIs

        • MAO also in GI tract => "Cheese effect" (tyramines) => Hypertensive crisis

        • Interaction with indirect sympathomimetics (epedrine etc)

      • TCAs

        • Antimuscarinic effects

        • NA uptake block => Tachycardia

        • Dangerous + no antidote

      • Atypicals

      • SSRIs

        • Half-lifes 20-30 hours, except fluoxetine (4-16 days) => Long wash-out

        • Early anxiety, agitation, nervousness

        • Beware in bipolar! => Manic symptoms

        • Increase bleeding risk cf NSAIDs, warfarin

        • P450 inhibition : Fluoxetine > Paroxetine > Citalopram/Sertraline

        • Discontinuiation syndrome: Dizziness, lethargy, nausea, headache, paraesthesia

      • SNRIs

    • Lithium has a very narrow t. window

    • Mood stabilisers are often antiepileptics (carbamazepine, valproate, lamotrigine)

Notes

    • Dopamine receptors

      • D1 = D1, D5

      • D2 = D2, D3, D4

    • Serotonin syndrome with SSRI plus MAOI/St John's Wort

    • All anticonvulsants reduce effectiveness of COCP

    • Flumazenil reverses benzo effect

    • Zopiclone is probably also addictive

    • SSRIs in anxiety disorders