Foods - most cheeses, red wine, yeast production, liver, broad bean pons, fermented sausage Tyramine Hypersensitive effect Drugs - serotonin syndrome (don't combine with SSRIs) - adrenaline and noradrenaline - L-dopa

Systems Bases Pharmacology for Psychiatry Flashcards by Holly O'Flanagan

SSRI examples

Fluoxetine

Paroxetine

Sertraline

Citalopram

Escitalopram

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Indications for SSRIs

Depression

Anxiety disorders

Panic disorders

OCD

PTSD

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Similarities between SSRIs

Indications

Mechanism of action

Delayed onset of action (10-14 days)

Efficacy

Relative safety in overdose

Advisability of prolonged course

Interactions

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Differences between SSRIs

Half life: paroxetine shortest (20 hours), fluoxetine longest (2-4 days)

Propensity to cause discontinuation syndrome f stopped abruptly

Side effect profiles: fluoxetine causes agitation most commonly

Individual differences: people are different

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SSRI discontinuation syndrome

Occurs in cessation of SSRI especially when abrupt

Symptoms

agitation and anxiety
dizziness, balance problems
nausea, diarrhoea
flu like symptoms

Commonest with paroxetine

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Treatment for SSRI discontinuation syndrome

Reassurance and monitoring

Reintroduction of drug with tapered withdrawal

Consider alternative antidepressant of anxiolytic

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Tricyclic antidepressants

Indications similar to SSRIs although not as widely used outside of depression

Efficacy in major depression similar to SSRIs

Rarely used first line nowadays due to adverse effects and overdose risk

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Examples of tricyclic antidepressants

Amitriptyline

Imipramine

Lofepramine

Dotheipin

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Mechanism of tricyclic antidepressants

Bind to NA and 5HT reuptake inhibitors, increasing monoamine levels in synaptic cleft

Also have pronounced anticholinergic (antimuscarinic) effects

TCA properties are variable

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Adverse effects of tricyclic antidepressants

Anticholinergic effects

dry mouth
constipation
urinary retention
cognitive effects

Other adverse effects

psychotropic effects (agitation, nightmares)
sexual dysfunction
akathisia
muscle twitches
cardiac arrhythmias

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Overdose of tricyclic antidepressants

Neurological and cardiovascular effects

confusion
tachycardia/ other arrhythmias
hypotension
mydriasis

Seizure
Coma
Cardiorespiratory arrest

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Other antidepressants

Venlafaxine: SNRI

more pronounced dose-response effect than other antidepressants
particularly effective for mixed anxiety and depression
side effects: headache, nausea, hypertension, discontinuation syndrome

Duloxetine: SNRI
- without concerns such as hypertension

Moclobemide: monoamine oxidase inhibitor
- usually reserved for treatment resistant depression or atypical depression

Reboxetine: highly selective NA reuptake inhibitor
- recent controversy over pharma data

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Monoamine oxidase inhibitors

Selegiline: used in Parkinson’s

Prevents action of monoamine oxidase

Prevents 5HT, DA and NA being broken down

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MOAI interactions

Foods
- most cheeses, red wine, yeast production, liver, broad bean pons, fermented sausage

Tyramine

Hypersensitive effect

Drugs

serotonin syndrome (don’t combine with SSRIs)
adrenaline and noradrenaline
L-dopa

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Mirtazapine

Noradrenergic and specific seratonergic antidepressant

Acts at alpha 2 receptors (antagonist)

‘Cuts the break cable’ on serotonin and noradrenaline release

Doesn’t effect sexual dysfunction

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Licensed use of antipsychotics

Psychotic illnesses

Bipolar affective disorder

Adjunctive therapy for depressive episodes

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Off-licence use of antipsychotics

Behavioural disturbance in dementia and learning disability

Conduct disorder

Personality disorder

PTSD

Anxiety disorders

Dopamine hypothesis

Dopaminergic drugs (particularly amphetamine) can produce symptoms very similar to those of schizophrenia

Dopamine- blocking drugs have antipsychotic properties (D2 receptor blockade)

Serotonin hypothesis

Some hallucinogenic drugs have structural resemblance to serotonin

Some newer antipsychotic drugs (especially clozapine) act at serotonin receptors

Glutamate hypothesis

Phencyclidine- glutamate agonist that can produce schizophrenia like symptoms

Some evidence of abnormal glutamate activity in schizophrenia

Examples of typical antipsychotics

Butyrophenones: haloperidol

Phenothiazines: chlorpromazine, rifluoperazine, luphenazine

Thioxanthines: flupenthixol

Atypical antipsychotics

Different mechanism of action: some newer drugs not as specific for D2 receptors, also act on serotonin system

Less propensity to cause EPS

Exampels: risperidone, olanzapine, quetiapine, aripiprazole

Typical antipsychotics

Various different classes of drugs

Roughly similar efficacy

Serious neurological side-effects

EPS: parkinsonism, akathisia, dystonia, bradykinesia
tardive dyskinesia

Dopamine receptor blockade side effects

Extrapyramidal side effects

Parkinsonism

Dystonias

Tardive dyskinesia

Hyperporlactinaemia

Muscarinic (cholinergic) receptor side effects

CNS: dizziness, somnolence, impaired memory and cognition Iris: blurred vision Salivary glands: dry mouth Heart: tachycardia Stomach and oesophagus: dyspepsia Colon: constipation

Alpha adrenergic receptor side effects

Examples: doxazosin, clonidine, methyldopa Orthostatic hypotension Palpitations Sexual dysfunction

Clozapine

Reserved for treatment resistant cases Most effective antipsychotic Problems with haematological side-effects necessitate blood test monitoring (granulocytosis) (neutropeanic sepsis) Acts on range of neurotransmitter systems (including D4 receptors and serotonin system) Low propensity to cause EPS Hypersalivation and hypotension may occur

Rapid tranquillisation

For acute agitation/ aggression where risk of harm to self or others Oral first IM - antipsychotics: haloperidol or olanzapine - benzodiaepines: lorazepam or midazolam Treat underlying cause - delirium- infection

Examples of mood stabiliser

Lithium Valproate Carbamazepine Lamotrigine Other anticonvulsants e.g. gabapentin

Lithium

Uncertain mode of action Second messenger inhibition of inositol Regulation of gene expression- protein kinase C

Lithium side effects

Short term - polydipsia and polyuria - nausea - fine tremor - loose stools Long term - hypothyroidism - renal impairment - weight gain - acne

Lithium toxicity

Narrow therapeutic index Coarse tremor, nausea and vomiting, ataxia and cerebellar signs, confusion Precipitants - salt depletion, dehydration (e.g. diarrhoea) - drug interactions: thiazides, NSAIDs - deteriorating renal function

Carbamazepine

Antimanic but less effective than lithium Major problems with drug interactions Induces liver enzymes so reducing levels of other agents Other agents in turn alter CBZ metabolism

Valproate

Effect on inhibition of Ca and Na channels Enhances inhibitory GABA Reduces excitatory glutamate Equal efficacy to Li in acute mania Ease of use Improved tolerability Weight gain Teratogenic - plus developmental disorders

Benzodiazepine examples

Diazepam Lorazepam Clonazepam Temazepm

Differences in benzodiazepines

Potency Half life Duration of action e.g. lorazepam short acting , clonzepam longer acting

Uses of benzodiazepine in psychiatry

Hypnotics Anxiolytics Minor tranquillisers: role in acute tranquillisation Management of alcohol withdrawal Also anticonvulsant and muscle relaxant Bind to BZP site of GABA A receptor GABA is main inhibitory neurotransmitter in CNS

Issues with benzodiazepine dependency

Tolerance Withdrawal: abrupt withdrawal can precipitate acute delirium, rarely psychosis, convulsions Other withdrawal symptoms: nausea, hyperacusis, dizziness and imbalance, tinnutis, depersonalisation Avoid lengthy prescriptions Tapered withdrawal using 'diazepam equivalents'

Management of alcohol withdrawal

Reducing regimen of benzodiazepines Vitamin supplementation - oral - intramuscular/ intravenous Additional aids to maintain absitence - acamprostate: reduces cravings - naltrexone: reduces cravings/ enjoyment via opioid receptors - disulfiram (antabuse): induces servere reaction of alcohol consumed

Other anxiolytics

Buspirone Pregabalin

Buspirone

Partial agonist at 5HT_1a receptors Licensed for use in GAD May have applications in other neuro/ psych contexts e.g. parkinsons

Pregabalin

Binds to and modulates voltage gated calcium channels in CNS Originally developed for use in neuropathic pain but has a growing role in anxiety and panic disorder, also in partial seizures