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Psychiatry > Antipsychotics > Flashcards

Antipsychotics Flashcards

1
Q

Dopamine pathways and action of antipsychotic

A
  1. Mesocortical: VTA to FC->Stereotypic behaviour and cognition ->D2 blockade, may worsen negative symptoms, +5HT block increases DA (improved -ve) 2. Mesolimbic: VTA to amygdala and NAc->Limbic system ->D2 blockade, treating +ve symptoms 3. Nigrostriatal: SN to striatum->Movement’ ->D2 blockade= relative ACh excess->EPS 4. Tuberphypophyseal: VHypothalamus to median eminence->Prolactin secretion 5. CTZ->Vomiting
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2
Q

Dopamine role in schizophrenia

A
  1. Positive symptoms= ++Dopmine in mesolimbic
  2. Negative symptoms= -ve DA in mesocortical
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3
Q

NMDA R hypofunction function/role

A
  1. Mesolimbic= disinhibition by GABA, NMDA on GABA interneurons
  2. Mesocortical= -ve ++of DA postsynaptic neruons
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4
Q

Explanation of side effect origin

A
  1. Motor-> nigrostriatal
  2. Prolactin->tuberohypophyseal (loss of inhibition)
  3. Loss of pleasure->Reward of mesolimbic
  4. Antimuscarinic->balance of DA and Ach in striatum. -ve DA = ++ACh= EPS, antimuscarinic = -ve EPS + constipation, urinary retention, dry eyes
  5. Alpha adrenoR->hypotension and sedation, impotence, failure to ejaculate
  6. Serotonin 2 A antagonism->++DA and Glu at mesocortical= reduces negative symptoms. At nigrostriatal= disinhibition +DA->-ve EPS. At mesolimbic->-ve ++in DA->less positive symptoms
  7. Antihistamine->sedation and weight gain 8. Metabolic/CV risk
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5
Q

First generation typicals

A
  1. Haloperidol
  2. Flupenazine
  3. Chlorpromazine
  4. Flupentixol
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6
Q

Second generation atypicals

A
  1. Sertindole
  2. Clozepine
  3. Quetiapine
  4. Aripiprazole
  5. Amisulpride
  6. Risperidone
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7
Q

Drug with ++side effects, +effect on negative symptoms

A

Clozepine

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8
Q

Less weight gain

A
  1. Amisulpride 2. Aripiprazole 3. Asenapine 4. Sertindole
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9
Q

More sedating and weight gain, hyperlipidemia

A

Clozepine Olanzepine

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10
Q

High prolactin

A
  1. Paliperidone
  2. Risperidone
  3. First generation
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11
Q

QTc prolongation

A
  1. Sertindole
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12
Q

Orthostatic hypotension

A
  1. Risperidone 2. Paliperidone
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13
Q

Indications

A
  1. Schizophrenia and other psychotic disorders
  2. Mood disorders with/without psychosis
  3. Violent behaviour
  4. ASD
  5. Tourettes
  6. Somatoform
  7. Dementia
  8. OCD
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14
Q

Onset

A

Immediate calming effect and decrease in agitation

Thought disorder responds in 2-4 weeks

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15
Q

Rational use

A
  1. Do not combine
  2. All are equally effective, except for clozepine
  3. Atypicals are as effective and have better side effect profile
  4. Choose a drug the patient has responded to in the past or successful use in a family member
  5. Route is either daily oral or IM
  6. Duration is minimum of 6 months, usually for life.
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16
Q

Dosing

A
  1. Start at low dose, then titrate every 2-4 weeks to maximise safety and minimise side effects
17
Q

Advantages and disadvantages for clozapine

A
  1. Advantages: Most effective for treatment resistant.
    a. Does not worsen tardive symptoms
    b. 50% benefit, especially those with paranoid
  2. Disadvantages: a. Drowsy b. sedation c. hypersalivation d. tachyC e. dizziness f. EPS g. NMS h. 1% agranulocytosis i. myocarditis
18
Q

Side effects

A
  1. Anticholinergic:

Dry mouth, urinary retention, constipation, blurred vision, toxic-confusional states

  1. α-adrenergic blockade Orthostatic hypotension, impotence, failure to ejaculate
  2. Dopaminergic blockade: Extrapyramidal syndromes (dystonia, akathisia, pseudoparkinsonism, dyskinesia), galactorrhea, amenorrhea, impotence, weight gain
  3. Anti-histamine: Sedation Hematologic Agranulocytosis (clozapine)
  4. Hypersensitivity reactions: Liver dysfunction, blood dyscrasias, skin rashes, neuroleptic malignant syndrome, altered temperature regulation (hypothermia or hyperthermia)
  5. Endocrine: Metabolic syndrome
19
Q

Anticholinergic SE

A

Red as a beet Hot as a hare Dry as a bone Blind as a bat Mad as a hatter

20
Q

Counselling in clozapine

A
  1. You will need to have regular blood tests and other checks while taking clozapine to help your doctor look out for serious side effects. Before starting treatment you will need CBC w/ neutrophil count, BMI, waist circumference, Fasting lipids, Fasting sugars, HbA1C, Anticonvulsant levels if appropriate, Baseline ECG.

Most important risks are agranulocytosis, myocarditis, metabolic syndrome

  1. CV risk- we will monitor your BP, BMI, glucose, lipids, waist circumference.
  2. Recommend healthy lifestyle to avoid ++risks.
  3. Taking your antipsychotic medicine regularly is important: because stopping or taking it irregularly is associated with high risk of relapse and suicide in order to prevent an episode, rather than taking it after symptoms occur.
  4. Consider whether a regular injection may suit you better than taking tablets.
  5. It is best to avoid using illicit substances because: even intermittent use of cannabis or amphetamine markedly decreases control of psychotic symptoms regular use of illicit drugs increases risk of relapse.
  6. Make sure you understand:
    a. what extrapyramidal side effects are and what you can do about them
    b. the risk of tardive dyskinesia with long-term antipsychotic treatment.
  7. This medicine may cause drowsiness and may increase the effects of alcohol, cannabis or sleeping tablets. Do not drive or operate machinery if you are affected.
  8. You may feel dizzy on standing when taking this medicine. Get up gradually from sitting or lying to minimise this; sit or lie down if you become dizzy.
21
Q

Adverse effects of clozapine

A
  1. Common (>1%)

drowsiness (occurs in 40%), hypersalivation (can cause aspiration pneumonia), constipation (may result in obstruction, paralytic ileus and death), seizures, headache, tachycardia, hyperpyrexia (5%), hepatitis, neutropenia, vomiting, urinary incontinence, nocturnal enuresis

  1. Infrequent (0.1–1%) myocarditis (usually in the first month of initial treatment but rarely may occur when starting after a break in treatment), agranulocytosis, eosinophilia, priapism, EPSE
22
Q

Clozapine workup and follow up

A
  1. General and CV health
  2. CBC w/ neutrophil count
  3. BMI, waist circumference
  4. Fasting lipids
  5. Fasting sugars, HbA1C
  6. Anticonvulsant levels if appropriate
  7. Baseline ECG
  8. May consider CRP and troponins

Titration: frequent BP

Day 7, 14, 21: ECG, cardiac enzymes + CK, FBC, wt, BP

Weekly until 18 weeks, then monthly: FBC, BP, weight

3-6: Echo, fasting lipids, fasting glucose

6 monhts: weight, fasting lipids, fasting glucose, ECG

Annual: ECG, full physical, fasting lipis and glucose, wt

23
Q

Monitoring WCC in clozapaine

A
  1. Weekly during the first six months of clozapine administration
  2. Every other week for the second six months
  3. Every four weeks after one year, for the duration of treatment
  4. For an additional month after clozapine is stopped
24
Q

CV monitoring in clozapine

A
  1. Risk of myocarditis which can worsen rapidly
  2. This should include assessment of clinical status for subjective signs of distress, vital signs each visit, electrocardiogram at baseline, and then weekly laboratory tests including:

●Eosinophil count

●Sedimentation rate or C-reactive protein

●Troponins

25
Q

Metabolic and GIT monitoring

A
  1. Monthly lipids, glucose, BMI, BP, waist
  2. Prophylactic stool softener for constipation
26
Q

Antipsychotic metabolic monitoring

A
  1. Baseline

Wt, ht, BMI, BP

ECG, Prolactin, FBC, UEC, LFTS, fasting lipids, fasting glucose, TFTs, bHCG

  1. First 2-3 weeks: weight, BP
  2. 3, 6 months: wt, LFTs, lipids, glucose, ECG
  3. Long term 6 monthly: wt, BMI, BP
  4. Annual

Wt, BMI, BP

Full physical

FBC, UEC, LFTs, fasting lipids, fasting glucose, ECG

27
Q
A

Psychiatry (31 decks)

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