Agranulocytosis

1
Agranulocytosis

• A acute condition involving a severe and
  dangerous leukopenia. The absence of Granulocytes

2
Signs and symptoms of Agranulocyctosis

• Death from toxaemia and septicaemia.
• Psychotropics drugs which can cause
  agranulocyctosis include Clozapine,
  CPZ,antiepileptics, antidepressants mitazapine
  and Imipramine.

• History of exposure to causative agents.
• Sudden or gradual onset.
• Condition begins with sore throat, fever, and
  often rigors.
• Rapidly advancing necrotic ulceration in the
  throat and mouth.

3
Diagnosis

• Complete blood count
• Neutrophil count below 500
• Need to exclude other pathologies with similar
  presentation e.g. aplastic anaemia

4
Treatment

• Cease the offending agent.
• Close monitoring and serial blood counts.
• Advice on significants of fever.
• Urgent treatment of infection with antibiotic.
• Supportive treatments.

5
Clozapine

• Clozapine clearly and substantially reduces
  overall mortality in schizophrenia, largely
  because of a reduction in the rate of suicide.
• Given to treatment-refractive persons.

6
Clozapine

• Atypical antipsychotic drugs differ from
  traditional antipsychotic agents in their ability
  to act as dopamine receptor and serotonin
  receptor blockers. This simultaneous blocking may
  account for the increased efficacy of these drugs
  in improving the negative symptoms of
  schizophrenia.

7
Clozapine

• Clozapine can cause serious, life-threatening
  adverse effects of agranulocyosis.
• In the UK, the risk of death from
  agranulocytosis, is 1 in 10,000 patients exposed
  to clozapine.
• Risk is well managed by the approved clozapine
  monitoring system.

8
Clozapine

• Clozapine has been associated with myocarditis
  and cardiomyopathy.
• Risk of death from either of these causes is
  estimated by the data to be 1 in 1300.
• Myocarditis seems to occur within 6 to 8 weeks of
  starting clozapine.
• Due to risk of agranulocytosis clozaril should
  not be combined with Carbamazepine.

9
Clozapine

• Clozapine can induce neutropenia which generally
  occurs early in treatment. White cell counts are
  normal to begin with but then fall precipitantly.
• Often this occurs in first 18 weeks of treatment
  and 3/4 by the end of the first year.
• Risk factors include Afro-Caribbean,the young and
  those with low baseline WCC.

10
Summary

• Overall mortality appears to be lower for those
  on Clozapine than in schizophrenia as a whole.
• Risk of fatal agranulocytosis is less than 1 in
  10,000 patients treated.

• Risk of pulmonary embolism is estimated to be
  around 1 in 4500 patients.
• Risk of fatal myocarditis or cardiomyopathy may
  be as high as 1 in 1300 patients.

11

• Careful monitoring is essential especially during
  the first 3 months of treatment.
• Reference The Maudsley Prescribing Guidelines 9th
  Edition.

12
Anticholinergics Effects

• Dry mouth, blurred vision, urinary retention, and
  constipation.

13
Caution

• Beware cognitive impairment and GI obstruction.

14
Action of Anticholinergics

• Anticholinergics block nerve impulses in the
  parasympathetic nervous system or counteract the
  effects of acetylcholine.
• Effects include dilation of the pupils,dry mouth,
  quickening of heart rate, reduction in gastric
  juice secretion, and retention of urine.

15
Anticholinergics

• This effect can be exacerbated by other
  anticholinergic drugs such as antihistamines or
  anti psychotics.

16
Causative Agents in Psychiatry

• Tricyclic antidepressants
• Anticholinergic medication for movement
  disorders.
• Antipsychotic mainly older ones
  (Chlorpromazine, Haloperidol), and some atypicals
  (Olanzapine, Quetiapine and Clozaril most
  significant).
• Monoamine Oxidase Inhibitors-Moclobemide

17
Treatment

• Change to less anticholinergic drug.
• Reduce combination therapy.
• Stop offending drug.