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308: Clinical Pharmacology and Therapeutics > Systems Bases Pharmacology for Psychiatry > Flashcards

Systems Bases Pharmacology for Psychiatry Flashcards

1
Q

SSRI examples

A

Fluoxetine

Paroxetine

Sertraline

Citalopram

Escitalopram

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2
Q

Indications for SSRIs

A

Depression

Anxiety disorders

Panic disorders

OCD

PTSD

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3
Q

Similarities between SSRIs

A

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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4
Q

Differences between SSRIs

A

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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5
Q

SSRI discontinuation syndrome

A

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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6
Q

Treatment for SSRI discontinuation syndrome

A

Reassurance and monitoring

Reintroduction of drug with tapered withdrawal

Consider alternative antidepressant of anxiolytic

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7
Q

Tricyclic antidepressants

A

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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8
Q

Examples of tricyclic antidepressants

A

Amitriptyline

Imipramine

Lofepramine

Dotheipin

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9
Q

Mechanism of tricyclic antidepressants

A

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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10
Q

Adverse effects of tricyclic antidepressants

A

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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11
Q

Overdose of tricyclic antidepressants

A

Neurological and cardiovascular effects

  • confusion
  • tachycardia/ other arrhythmias
  • hypotension
  • mydriasis

Seizure
Coma
Cardiorespiratory arrest

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12
Q

Other antidepressants

A

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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13
Q

Monoamine oxidase inhibitors

A

Selegiline: used in Parkinson’s

Prevents action of monoamine oxidase

Prevents 5HT, DA and NA being broken down

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14
Q

MOAI interactions

A

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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15
Q

Mirtazapine

A

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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16
Q

Licensed use of antipsychotics

A

Psychotic illnesses

Bipolar affective disorder

Adjunctive therapy for depressive episodes

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17
Q

Off-licence use of antipsychotics

A

Behavioural disturbance in dementia and learning disability

Conduct disorder

Personality disorder

PTSD

Anxiety disorders

18
Q

Dopamine hypothesis

A

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

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

19
Q

Serotonin hypothesis

A

Some hallucinogenic drugs have structural resemblance to serotonin

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

20
Q

Glutamate hypothesis

A

Phencyclidine- glutamate agonist that can produce schizophrenia like symptoms

Some evidence of abnormal glutamate activity in schizophrenia

21
Q

Examples of typical antipsychotics

A

Butyrophenones: haloperidol

Phenothiazines: chlorpromazine, rifluoperazine, luphenazine

Thioxanthines: flupenthixol

22
Q

Atypical antipsychotics

A

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

23
Q

Typical antipsychotics

A

Various different classes of drugs

Roughly similar efficacy

Serious neurological side-effects

  • EPS: parkinsonism, akathisia, dystonia, bradykinesia
  • tardive dyskinesia
24
Q

Dopamine receptor blockade side effects

A

Extrapyramidal side effects

Parkinsonism

Dystonias

Tardive dyskinesia

Hyperporlactinaemia

25
Q

Muscarinic (cholinergic) receptor side effects

A

CNS: dizziness, somnolence, impaired memory and cognition

Iris: blurred vision

Salivary glands: dry mouth

Heart: tachycardia

Stomach and oesophagus: dyspepsia

Colon: constipation

26
Q

Alpha adrenergic receptor side effects

A

Examples: doxazosin, clonidine, methyldopa

Orthostatic hypotension

Palpitations

Sexual dysfunction

27
Q

Clozapine

A

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

28
Q

Rapid tranquillisation

A

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

29
Q

Examples of mood stabiliser

A

Lithium

Valproate

Carbamazepine

Lamotrigine

Other anticonvulsants e.g. gabapentin

30
Q

Lithium

A

Uncertain mode of action

Second messenger inhibition of inositol

Regulation of gene expression- protein kinase C

31
Q

Lithium side effects

A

Short term

  • polydipsia and polyuria
  • nausea
  • fine tremor
  • loose stools

Long term

  • hypothyroidism
  • renal impairment
  • weight gain
  • acne
32
Q

Lithium toxicity

A

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
33
Q

Carbamazepine

A

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

34
Q

Valproate

A

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

35
Q

Benzodiazepine examples

A

Diazepam

Lorazepam

Clonazepam

Temazepm

36
Q

Differences in benzodiazepines

A

Potency

Half life

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

37
Q

Uses of benzodiazepine in psychiatry

A

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

38
Q

Issues with benzodiazepine dependency

A

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’

39
Q

Management of alcohol withdrawal

A

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
40
Q

Other anxiolytics

A

Buspirone

Pregabalin

41
Q

Buspirone

A

Partial agonist at 5HT_1a receptors

Licensed for use in GAD

May have applications in other neuro/ psych contexts e.g. parkinsons

42
Q

Pregabalin

A

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

308: Clinical Pharmacology and Therapeutics (14 decks)

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