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