Agranulocytosis

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

2. 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. Death from toxaemia and septicaemia. Psychotropics drugs which can cause agranulocyctosis include Clozapine, CPZ,antiepileptics, antidepressants mitazapine and Imipramine. Signs and symptoms of Agranulocyctosis

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. 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. Summary

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 one’s (Chlorpromazine, Haloperidol), and some atypicals (Olanzapine, Quetiapine and Clozaril most significant). • Monoamine Oxidase Inhibitors-Moclobemide

17. Change to less anticholinergic drug. Reduce combination therapy. Stop offending drug. Treatment