QuestionSBA
QuestionChoice
This patient has recently started clozapine for his schizophrenia and has now developed pyrexia, general malaise, and symptoms of pharyngitis. Clozapine is associated with a relatively high risk of agranulocytosis and neutropenia within the first few months of treatment. They are therefore at risk of neutropenic sepsis.
 

 Unfortunately we do not know this patients neutrophil count yet although, given his risk factors, he should be started on intravenous antibiotics within one hour of recognition of signs of sepsis. As patients with neutropenia cannot mount the normal immune response to infection that others can, they can look and feel completely well for some time, with relatively normal observations, before rapidly becoming unwell and deteriorating. It is therefore important to have a high index of suspicion and treat aggressively early
33178
a
Start broad spectrum intravenous antibiotics
QuestionChoice
This patient has recently started clozapine and so is at risk of agranulocytosis and neutropenia (black box warning). We do not have his blood results back but, given he has developed new pyrexia with general malaise, he must be treated as suspected neutropenic sepsis
33179
b
Hourly observations for further temperature spikes
QuestionChoice
This patient has recently started clozapine and so is at risk of agranulocytosis and neutropenia (black box warning). We do not have his blood results back but, given he has developed new pyrexia with general malaise, he must be treated as suspected neutropenic sepsis
33181
d
Prescribe a 10 day course of penicillin V
QuestionChoice
This patient is at risk of agranulocytosis and neutropenia and has signs and symptoms of possible sepsis so reassurance is not a safe option, and he requires urgent treatment
33180
c
Reassure
QuestionChoice
Nasendoscopy is an excellent way to assess pathology within the nasal passage, larynx, and vocal cords. If epiglottitis or supraglottitis were suspected in this patient, then urgent referral to ENT would be warranted with help from anaesthetics for airway support. This patient is not showing signs of airway obstruction e.g. drooling, stridor, hoarse voice, or respiratory distress and so epiglottitis is unlikely
33182
e
Refer to ENT for nasendoscopy
Concept
Chapter
# Summary



# Typical antipsychotics

- Also known as 'first-generation' antipsychotics, these not only act as antagonists to D2 receptors but also on cholinergic, adrenergic and histaminergic receptors. The most commonly used medication in this class is **Haloperidol**, though other examples include Chlorpromazine and flupentixol. 
- Side effects can therefore be grouped according to receptor blockade (see below).

### Dopamine D2 Receptor Blockade:

1. **Extrapyramidal Symptoms (EPS):**
   - **Acute Dystonia:** Involuntary muscle contractions causing spasms.
   - **Akathisia:** Restlessness and an inability to sit still.
   - **Parkinsonism:** Tremors, rigidity, and bradykinesia (slowed movements).
   - **Tardive Dyskinesia:** Involuntary, repetitive movements, especially of the face.

2. **Hyperprolactinemia:**
   - Elevated levels of prolactin, leading to:
     - Menstrual irregularities in women.
     - Gynecomastia (breast enlargement) in men.
     - Sexual dysfunction in both genders.

### Other Receptors:

1. **Histamine H1 Receptor Blockade:**
   - **Sedation:** Drowsiness and sleepiness.

2. **Alpha-1 Adrenergic Receptor Blockade:**
   - **Orthostatic Hypotension:** A sudden drop in blood pressure upon standing, leading to dizziness or fainting.

3. **Muscarinic Receptor Blockade:**
   - **Anticholinergic Effects:**
     - Dry mouth.
     - Constipation.
     - Blurred vision.
     - Urinary retention.


# Atypical antipsychotics

- Also known as 'second-generation' antipsychotics, these are D2, D3 and 5-HT2A antagonists, with less overspill into other receptors. 
- As effective as typical antipsychotics (even slightly better at negative symptoms), and have a more favourable side effect profile with reduced extrapyramidal effects, but increased metabolic side-effects. 
- They are 1st line for new-onset psychosis. Examples include risperidone, quetiapine, olanzapine, aripiprazole and clozapine (see below). 

### Dopamine Receptor Blockade:

1. **D2 Receptor Blockade:**
   - **EPS (Extrapyramidal Symptoms):**
     - Atypicals generally have a lower risk of causing EPS compared to typicals.
     - Lower risk of tardive dyskinesia.

### Serotonin Receptor Blockade:

1. **5-HT2A Receptor Blockade:**
   - **Lower Risk of EPS:** Atypicals have a reduced risk of causing EPS due to serotonin receptor blockade.

### Other Receptors:

1. **Histamine H1 Receptor Blockade:**
   - **Sedation:** Although less common than with typicals, some atypicals can cause drowsiness.

2. **Alpha-1 Adrenergic Receptor Blockade:**
   - **Orthostatic Hypotension:** Some atypicals may cause a drop in blood pressure upon standing.

3. **Muscarinic Receptor Blockade:**
   - **Anticholinergic Effects:**
     - Generally less pronounced compared to typicals.
     - Mild dry mouth, constipation, or blurred vision.

### Metabolic Effects:

1. **Weight Gain:**
   - **Common Side Effect:** Atypical antipsychotics, in general, have a higher risk of causing weight gain compared to typicals.
   - **Varying Degrees:** The degree of weight gain can vary among different atypicals.

2. **Dyslipidemia and Glucose Metabolism:**
   - **Increased Risk:** Some atypicals are associated with an increased risk of dyslipidemia and impaired glucose metabolism.

3. **Prolactin Elevation:**
   - **Variable:** Some atypicals may elevate prolactin levels, leading to menstrual irregularities and sexual dysfunction.

### Other side effects:

1. **Seizures:**
   - **Low Risk:** Generally, atypicals have a lower risk of lowering the seizure threshold compared to typicals.

2. **QT Prolongation:**
   - **Potential Risk:** Some atypicals may have a mild effect on the QT interval, but the clinical significance varies.

3. **Increased risk of VTE and stroke in elderly**

### Monitoring

* Weight should be measured at the start of therapy, then weekly for the first 6 weeks, then at 12 weeks, at 1 year, and then yearly.
* Fasting blood glucose, HbA1c, and blood lipid concentrations should be measured at baseline, at 12 weeks, at 1 year, and then yearly. 
* Prolactin concentrations should also be measured at baseline.
* Before initiating antipsychotic drugs, an ECG may be required, particularly if there are cardiovascular risk factors (e.g. high blood pressure), if there is a personal history of cardiovascular disease, or if the patient is being admitted as an inpatient.
* Blood pressure monitoring before starting therapy, at 12 weeks, at 1 year and then yearly during treatment and dose titration of antipsychotic drugs.

# Clozapine

- Clozapine is an atypical antipsychotic that is indicated if there is failure of treatment of 2 other antipsychotic medication, known as treatment-resistant schizophrenia.
- Treats both positive and negative symptoms, slightly more effective than other antipsychotics.
- Important side effects include: **agranulocytosis**, neutropenia, reduced seizure threshold, myocarditis, slurred speech (due to hypersalivation), constipation (most common cause of mortality when related to clozapine use).

### Monitoring

- Due to its unique and potentially serious side effect profile, monitoring while on clozapine is very important.
- Patients should have weekly FBC (to look at white cell counts) for the first 18 weeks of treatment then fortnightly for up to one year, and then monthly.
- Blood lipids and weight should be measured at baseline, every 3 months for the first year, and then yearly.
- Fasting blood glucose should be tested at baseline, after one months’ treatment, then every 4–6 months.


# Neuroleptic Malignant Syndrome

Neuroleptic Malignant Syndrome (NMS) is a rare, but potentially life-threatening, idiosyncratic reaction to antipsychotic medications, particularly those that block dopamine receptors. It typically occurs as a response to the introduction or an increase in the dosage of neuroleptic medications.

### Clinical Features

1. **Hyperthermia:**
   - Profound elevation of body temperature is a hallmark feature.
   
2. **Altered Mental Status:**
   - Fluctuating levels of consciousness, ranging from confusion to catatonia.

3. **Autonomic Dysregulation:**
   - Dysautonomia characterized by fluctuations in blood pressure, tachycardia, and diaphoresis.

4. **Rigidity:**
   - Generalized muscle stiffness, often described as "lead-pipe" rigidity.

### Differential Diagnosis

- **Malignant Hyperthermia** - a rare, genetic condition triggered by certain medications, often during anaesthesia.

- **Serotonin Syndrome** similar to NMS but associated with serotoninergic medications. Presents with hyperthermia, autonomic dysregulation, and altered mental status.

### Investigations 

- Bloods:
	- FBC - Monitoring for potential leukocytosis or signs of infection.
   - **Creatine Kinase (CK) Levels:**  Markedly elevated CK levels are often observed due to muscle breakdown.
   - Renal and Liver Function Tests: monitoring organ function due to the potential systemic effects.
   
### Management

1. **Discontinuation of Causative Agent:**
   - Immediate cessation of the implicated neuroleptic medication.

2. **Supportive Care:**
   - Aggressive cooling measures to address hyperthermia, including cooling blankets and IV fluids to prevent renal failure.

3. **Benzodiazepines:**
   - Administering benzodiazepines to manage agitation and muscle rigidity.

4. **Dantrolene:**
   - Consideration of dantrolene, a skeletal muscle relaxant, in severe cases.

5. **Intensive Monitoring:**
   - Continuous monitoring of vital signs, fluid balance, and laboratory parameters.
1783
1965
Antipsychotics
Topic
18
Psychiatry
Start broad spectrum intravenous antibiotics
6636
Clozapine treatment increases the risk of agranulocytosis which si treated with broad spectrum intravenous antibiotics.
A 35-year-old man is currently detained in a psychiatric unit under section 3 of the mental health act after an acute deterioration of his schizophrenia two months ago, for which he was started on clozapine. He complains of a two-day history of a sore throat and general malaise. On examination his respiratory rate is 16, oxygen saturations are 100% on room air, heart rate 95, blood pressure 118/65, temperature 38.0°C. He looks well, and has an erythematous oropharynx with no purulent discharge and no deviation of his uvula. 

Routine bloods and blood cultures have been taken.


Which of the following is the best next step in the management of this patient?
a