Sedatives & Hypnotics (Anxiolytics) Flashcards
What are the clinical features of anxiety disorders?
- Psychological components >> Negative emotions: worry, nervousness, unease >> Arousal >> Lack of concentration >> Insomnia
- Physical symptoms >> Tachycardia >> Shortness of breath >> Nausea >> Gastric acid hypersecretion >> Trembling
- Biochemical basis of anxiety states
» Central and peripheral noradrenergic / adrenergic activation -> the “Flight or Fight” response
» Stress response -> Hypothalamus – pituitary – adrenal (HPA) axis -> secretion of stress hormones (cortisol)
What are the clinical features of generalised anxiety disorder (GAD)?
- Excessive, uncontrollable worry over everyday matters
- Interferes with daily functioning
- Has both psychological and physical symptoms
- Diagnosed when present for at least 6 months
- Most common cause of disability in the workplace
What is the therapeutic principle of anxiolysis?
- CNS depressant:
» Sedative -> causes sedation, relaxation
» Hypnotic -> induces drowsiness and sleep, may have amnestic effects
» Anxiolytic -> reduces anxiety
*These actions are closely related. The same drug can have more than one action depending on dose. - Doses
» Low dose -> anxiolytic and sedative effects
» Higher doses -> hypnotic
» Even higher doses -> can cause anesthesia, used for surgery
Benzodiazepines and their clinical uses
MOA: benzodiazepines potentiate GABA actions by increasing the frequency of the GABA channel opening.
Names of drugs that are benzodiazepines:
- Used as anxiolytics/sedatives: e.g. diazepam, lorazepam
- Used as hypnotics: e.g. diazepam, triazolam, temazepam
- Used as pre-anesthetics: e.g. diazepam, midazolam
- May also have anti-convulsant effects: e.g. diazepam
Duration of action of benzodiazepines
Long-acting:
- diazepam
Intermediate-acting:
- lorazepam
- temazepam
Short-acting
- midazolam
- triazolam
Unwanted effects of benzodiazepines
- Acute toxicity / overdose:
- Severe respiratory depression, especially when used concurrently with alcohol
- Treatment: flumazenil, a benzodiazepine antagonist - Side effects:
- Drowsiness, confusion, amnesia
- Impaired muscle co-ordination (impairs manual skills) - Tolerance and dependence:
- Depends on frequency of use. Tolerance develops faster for epilepsy (drug is used more frequently) than for use to induce sleep.
- Dependence can develop. Withdrawal effects include disturbed sleep, rebound anxiety, tremor and convulsions.
- Important to withdraw gradually.
- Has abuse potential.
What are some examples of non-benzodiazepines?
- Barbiturates: e.g. phenobarbital
- Busipirone
- Zolpidem
- Propanolol
What are the characteristics of zolpidem?
- Potentiates GABAA mediated Cl- currents at the same site as benzodiazepines.
- Has good hypnotic effect: primarily used to treat insomnia
- Not as effective as anxiolytics
What are characteristics of buspirone?
- Serotonin 5-HT1A receptor partial agonist. Also binds dopamine receptors.
- Indicated for GAD but anxiolytic effects take 1-2 weeks.
- Lacks anticonvulsant and muscle relaxant properties
What are the characteristics of barbiturates?
- Potentiates GABAA mediated Cl- currents, but at a site distinct from benzodiazepines.
- Use as a sedative-hypnotic has been replaced by benzodiazepines as it tends to develop tolerance and dependence.
- Severe withdrawal symptoms.
- Flumazenil not effective.
- At anesthetic doses, phenobarbital can directly open Cl- channels as well as block Na+ channels.
What are the duration of action of non-benzodiazepines?
Long-acting (1-2 days)
- Anticonvulsant: phenobarbital
Short-acting (3-8 hours)
- Sedative and hypnotic: pentobarbital and amobarbital
Ultrashort (20 mins)
- IV induction of anesthesia: thiopental
Benzodiazepines are more likely to cause respiratory depression than barbiturates. T/F?
False. Benzodiazepines have stronger sedation, disinhibition and anxiolysis properties that promote possible selective anticonvulsant and muscle-relaxing activity
What are the characteristics of pregabalin?
- GABA analogue increases synaptic GABA
- > GABA receptor mediated Cl- currents resulting in hyperpolarization.
- Also acts on voltage-gated Ca2+ channels
- Used to treat GAD, also has anticonvulsant effects
- May cause worsening of suicidal thoughts.
What are the characteristics of hydroxyzine?
- First generation antihistamine, with activities on serotonergic and α-adrenergic receptors.
- Anxiolytic effects attributed to the antagonism of serotonin 5-HT2 receptors.
- Has low addictive potential compared to BZDs and barbiturates.
- Also helps with itching.
What are the characteristics of propanolol?
- Beta-adrenergic receptor antagonist
- Used for treating performance anxiety and social phobias.
- Reduces physical symptoms associated with adrenergic activation.
- Contraindicated in patients with asthma and heart conditions
