Pharmacology
Central Nervous System
Neuroleptic malignant syndrome is characterised by all EXCEPT which one of the following:
Answer:
Neuroleptic malignant syndrome is characterised by:- Hyperthermia
- Fluctuating level of consciousness
- Muscle rigidity
- Autonomic dysfunction (pallor, tachycardia, labile blood pressure, sweating, and urinary incontinence)
- Raised creatinine kinase
- Leucocytosis
- Raised liver function tests
Antipsychotics
Pharmacology / Central Nervous System
Last Updated: 4th April 2019
Mechanism of Action
The first generation antipsychotic drugs act predominantly by blocking dopamine D2 receptors in the brain. First generation antipsychotic drugs are not selective for any of the four dopamine pathways in the brain and so can cause a range of side effects, particularly extrapyramidal symptoms and elevated prolactin.
The second generation antipsychotic drugs (sometimes referred to as atypical antipsychotic drugs) act on a range of receptors in comparison to the first generation antipsychotic drugs and tend to cause less extrapyramidal side effects.
There is little meaningful difference in efficacy between each of the antipsychotic drugs (other than clozapine), and response and tolerability to each antipsychotic drug varies. There is no first-line antipsychotic drug which is suitable for all patients.
Side Effects
Side effects of antipsychotic drugs are common and include:
- Extrapyramidal effects (due to blockage of dopamine receptors in the basal ganglia)
- Sedation (due to blockage of H1-receptors)
- Hyperprolactinaemia (because dopamine usually inhibits prolactin release)
- Sexual dysfunction
- Reduced bone mineral density
- Menstrual disturbance
- Galactorrhoea
- Breast enlargement/gynecomastia in men
- Cardiovascular effects
- QT-interval prolongation
- Tachycardia
- Arrhythmias
- Hypertension
- Postural hypotension
- Increased risk of stroke and VTE
- Anticholinergic effects
- Dry mouth
- Blurred vision
- Urinary retention
- Constipation
- Cutaneous flushing
- Hyperglycaemia, dyslipidaemia and weight gain
- Temperature dysregulation
- Neuroleptic malignant syndrome
- Hyperthermia
- Fluctuating level of consciousness
- Muscle rigidity
- Autonomic dysfunction (pallor, tachycardia, labile blood pressure, sweating, and urinary incontinence)
- Blood dyscrasias
Extrapyramidal Effects
Antipsychotic drugs also block dopamine receptors in the basal ganglia and this frequently results in distressing and disabling extrapyramidal side-effects.
Extrapyramidal side effects include:
- Parkinsonian symptoms (tremor, bradykinesia and rigidity)
- Dystonia (acute dystonic reactions may require treatment with antimuscarinic drugs)
- Dyskinesia
- Akathisia (motor restlessness)
- Tardive dyskinesia (rhythmic, involuntary movements of tongue, face, and jaw)
Tardive dyskinesia is the most serious manifestation of extrapyramidal symptoms; it is of particular concern because it may be irreversible on withdrawing therapy and treatment is usually ineffective. Tardive dyskinesia occurs fairly frequently, especially in the elderly, and treatment must be carefully and regularly reviewed.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
