Pharmacology
Central Nervous System
Which of the following is NOT an anticholinergic effect of amitriptyline:
Answer:
Adverse effects include:- Anticholinergic effects
- Dry mouth
- Blurred vision
- Dilated pupils
- Urinary retention
- Constipation
- Absent bowel sounds
- Pyrexia
- Myoclonic twitching
- Confusion
- CNS effects
- Drowsiness
- Coma
- Convulsions
- Pyramidal signs
- Rigidity
- Delirium
- Respiratory depression
- Ophthalmoplegia
- Cardiovascular effects
- Sinus tachycardia
- Prolonged PR/QRS/QT
- ST/T wave changes
- Heart block
- Vasodilatation
- Hypotension
- Cardiogenic shock
- Ventricular fibrillation/tachycardia
- Hepatic impairment
- Narrow-angle glaucoma
Tricyclic Antidepressants
Pharmacology / Central Nervous System
Last Updated: 7th June 2022
Mechanism of Action
Tricyclic antidepressants (TCAs) e.g. amitriptyline block the reuptake of both serotonin and noradrenaline, although to different extents. TCAs have similar efficacy to selective serotonin reuptake inhibitors (SSRIs) but are more likely to be discontinued because of side effects; toxicity in overdosage is also a problem. SSRIs are less sedating and have fewer antimuscarinic and cardiotoxic effects than TCAs, and hence are usually considered first line for depression.
Contraindications
TCAs should be avoided in:
- Acute porphyrias
- Arrhythmias or heart block
- Manic phase of bipolar disorder
- Immediate recovery period after myocardial infarction
- Severe liver disease
- Concomitant therapy with an MAOI
- Prostatism
- Narrow angle glaucoma or other cause of increased intraocular pressure
Interactions
Concomitant therapy with other sedating drugs or alcohol may have a synergistic sedative effect.
Concomitant therapy with antihistamines and antipsychotics may have a synergistic antimuscarinic effect.
There is an increased risk of ventricular arrhythmias when TCAs are given with antiarrhythmics.
There is an increased risk of serotonin syndrome when TCAs are given with serotonergic drugs or dopaminergic drugs.
TCAs may enhance or reduce the anticoagulant effect of warfarin.
Side Effects
Adverse effects include:
- Anticholinergic effects
- Dry mouth
- Blurred vision
- Dilated pupils
- Urinary retention
- Constipation
- Absent bowel sounds
- Pyrexia
- Myoclonic twitching
- CNS effects
- Drowsiness
- Coma
- Convulsions
- Pyramidal signs
- Rigidity
- Delirium
- Respiratory depression
- Ophthalmoplegia
- Cardiovascular effects
- Sinus tachycardia
- Prolonged PR/QRS/QT
- ST/T wave changes
- Heart block
- Vasodilatation
- Hypotension
- Cardiogenic shock
- Ventricular fibrillation/tachycardia
- Hepatic impairment
- Narrow-angle glaucoma
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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 |
