Agranulocytosis
A acute condition involving
a severe and dangerous
leukopenia. The absence of
Granulocytes
Signs and symptoms of
Agranulocyctosis
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.
Diagnosis
Complete blood count
Neutrophil count below 500
Need to exclude other pathologies with
similar presentation e.g. aplastic anaemia
Treatment
Cease the offending agent.
Close monitoring and serial blood counts.
Advice on significants of fever.
Urgent treatment of infection with
antibiotic.
Supportive treatments.
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.
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.
Clozapine
Clozapine can cause serious, lifethreatening 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.
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.
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.
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.
Careful monitoring is essential especially
during the first 3 months of treatment.
Reference The Maudsley Prescribing
Guidelines 9th Edition.
Anticholinergics Effects
Dry mouth, blurred vision,
urinary retention, and
constipation.
Caution
Beware cognitive impairment and GI
obstruction.
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.
Anticholinergics
This effect can be exacerbated by other
anticholinergic drugs such as
antihistamines or anti psychotics.
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 InhibitorsMoclobemide
Treatment
Change to less
anticholinergic drug.
Reduce combination
therapy.
Stop offending drug.