• describe anxiety and the associated neurotransmitters;
• describe symptoms of anxiety, including somatic and psychological symptoms;
• describe its pathophysiology;
• outline the mechanisms of action of common anxiolytic agents;
• explain the mechanism of action of benzodiazepines;
• explain the connection between anxiety, phobia and panic disorder.
Jo had been asked to give a seminar as part of her final-year project. She was anxious to perform well and spent one month preparing for the presentation. During the preparation period, she was irritable, restless and had difficulty in concentrating; she also complained of diarrhea. Jo asked some of her friends if they would listen to her practise, prior to the final presentation. But as the day of the practise presentation approached, Jo became very tense, pale and sweaty. She felt increasingly apprehensive and uncomfortable, was unable to talk properly as her mouth was dry and she was very aware that her heart was beating rapidly (tachycardia). She visited her doctor to ask for help as she felt unable to carry on with her normal duties in life.
What is the likely diagnosis of Jo’s symptoms?
Jo is showing symptoms of anxiety. Many symptoms of anxiety are observed in our fear response to unpleasant or threatening stimuli. In anxiety states these symptoms occur independently of the usual fear-provoking stimuli. So an anxiety disorder is a condition in which a state of anxiety persists without any obvious reason.
List the symptoms of anxiety.
Symptoms of anxiety can include: breathlessness, palpitations (increased awareness of the heart beat, or an irregular heart rhythm), dry mouth, difficulty in swallowing, flatulence, nausea, diarrhea, tachycardia, dizziness, blurred vision, sleep disturbance, sweating, tension, irritability, restlessness, apprehension, depression, worry, fear. Some patients also report chest pain or chest constriction.
Outline the somatic and psychological symptoms evident in this case.
Somatic symptoms presented in this case are: dry mouth, tachycardia and sweating. Psychological symptoms are: tension, apprehension, irritability, restlessness and difficulty in concentrating. The symptoms usually result from overactivity in part of the autonomic nervous system or increased tension in skeletal muscles.
Which neurotransmitters are mainly associated with anxiety?
The neurotransmitters GABA (gamma-aminobutyric acid) and serotonin (5-HT) are mainly associated with anxiety disorders. In addition the sympathetic component of responses observed in anxiety, which stimulates a dry mouth, tachycardia, sweating and so on, involves the neurotransmitter noradrenaline.
What is the explanation for Jo’s tachycardia (increase in the heart rate)?
Jo’s tachycardia is due to the activation of the sympathetic nervous system to prepare the body for ‘fight or flight’. Stimulation of sympathetic nerves supplying the heart releases noradrenaline, which increases both the rate and force of cardiac muscle contraction via beta-1-receptor (β1-receptor) activation.
Which other conditions could be confused with anxiety?
Other conditions that could be confused with anxiety include endocrine disorders such as thyroid problems and hypoglycaemia, autonomic disorders, drug/alcohol misuse and other CNS disorders such as panic disorder.
What could the doctor prescribe for Jo?
Treatment of anxiety disorders involves the use of anxiolytic preparations such as benzodiazepines. The ‘fight or flight’ symptoms can be controlled by sympathetic β-adrenoceptor antagonists, such as propranolol. Non-pharmacological behavioural therapy is also successfully used in the treatment of anxiety disorders.
What are anxiolytics? Your answer should cover the major subdivisions of this class of drug.
Anxiolytics are a group of drugs that reduce the symptoms of anxiety mentioned earlier. They are among the most frequently prescribed drugs and can be divided into two subgroups: benzodiazepines and non-benzodiazepines.
By giving an example of a benzodiazepine, explain the mechanism of action of the named agent in anxiety.
Benzodiazepines (BZDs), such as diazepam or alprazolam, act on neuronal benzodiazepine receptors (located adjacent to GABA receptors) in the CNS. Stimulation of these receptors leads to increased inhibition at postsynaptic neurones mediated by GABA. This inhibition results in depression in the limbic and subcortical areas of the brain. Benzodiazepines thus cause sedation and muscle relaxation.
Diazepam can also be used as a muscle relaxant and has anticonvulsant activity when given intravenously. Alprazolam possesses antidepressant properties in addition to its anxiolytic actions.
What are the main concerns associated with the use of benzodiazepines?
A major problem associated with benzodiazepines is the development of tolerance, a gradual increase in the dose needed to elicit the therapeutic effect and dependence in chronic use. Following the cessation of treatment, the patient may suffer from rebound anxiety and insomnia. Withdrawal from benzodiazepines also occasionally causes bizarre visual disturbances.
Explain the mechanism of action and usual daily dosage of an anxiolytic agent which does not belong to the benzodiazepine class.
Non-benzodiazepines, such as buspirone, may be used to treat anxiety. Buspirone is an agonist at 5-HT1A receptors. It has been suggested to act by inhibiting the neuronal firing via these receptors which in turn reduces serotonin turnover in the CNS. The anxiolytic action of this agent may take days or weeks to develop, but there are less troublesome side effects. The exact mechanism of action of buspirone in reducing anxiety is not yet known. The usual daily dosage is from 15 to 30 mg, used in divided dosages.
Can anxiety develop into a phobic state and/or a panic disorder?
Yes, anxiety could develop into a phobic state. A phobic state is defined as anxiety/fear triggered by a single stimulus or set of stimuli that would not normally be of concern. A panic disorder involves sudden and unpredictable episodes of acute anxiety, with feelings of fear and terror, usually accompanied by severe physical symptoms. The tendency to panic disorder may be genetically transmitted. A change in levels of lactic acid or carbon dioxide in the blood may play a part in this disorder.
• Anxiety disorder is a condition in which a state of anxiety persists without any obvious reason.
• The symptoms usually result from overactivity in part of the autonomic nervous system or increased tension in skeletal muscles.
• Somatic symptoms of anxiety are: breathlessness, palpitations (increased awareness of the heart beat, or an irregular heart rhythm), tachycardia, dry mouth, difficulty in swallowing, flatulence, nausea, diarrhea, dizziness, blurred vision, sleep disturbance, sweating.
• Psychological symptoms are: tension, irritability, restlessness, apprehension, depression, worry, fear.
• The neurotransmitters GABA and serotonin (5-HT) are mainly associated with anxiety disorders. In addition the sympathetic component of responses is mediated by noradrenaline.
• Treatment includes: non-pharmacological therapies, such as psychological approaches, and pharmacological treatment, use of anxiolytic preparations, such as benzodiazepines, non-benzodiazepines, such as buspirone, and β-adrenoceptor antagonists such as propranolol.