Pharmacology of anxiolytic drugs Flashcards
What is the main tract involved in fear
Amygdala-centred circuit
What is the main tract involved in worry?
Cortico-striatal-thalamic-cortical circuit
What is the function of the amygdala?
Integrates sensor and cognitive information
Structure involved in the affect of fear?
Anterior cingulate cortex/orbitofrontal cortex
Structure involved in avoidance?
Periaqueductal gray (Fight or flight)
Structure involved in cortisol increase in fear?
Hypothalamus
Structure involved in increasing BP and HR in fear?
Locus coeruleus
Structure involved in re-experiencing of traumatic memories?
Hippocampus
What are some neurotransmitters and hormones involve din the amygdala-centred circuits?
- 5-HT
- GABA (Gamma-aminobutyric acid)
- Glutamate
- CRF (Corticotrophin releasing factor)
- Noradrenaline
- Voltage-gated ion channels
What is the main inhibitory transmitter of the brain?
GABA
What is the function of GABA in anxiety and fear?
GABA reduces the activity of neurones in the amygdala and CSTC circuit, therefore diminishing anxiety and fear levels
How does GABA decrease neuronal activity?
GABA binds to GABA binding sites
This causes opening of Cl- channels which hyper polarises the cell, making it harder for the cell to reach it’s threshold for AP
What are some drugs that affect the GABA channels?
Benzodiazepines
Barbituates
General anaesthetics
Alcohol
What is the MOA of benzodiazepines
Benzodiazepines bind to BDZ binding sites on GABA-A channels, causing it to open, allowing more Cl- to enter and therefore depressing neuronal activity
What are the pharmacological effects of benzodiazepines?
reduction in anxiety and aggression, sedation, muscle relaxation, anti-convulsant effect and anterograde amnesia
What are some examples of benzodiazepines?
- Lorazepam (Activan)
- Diazepam (Valium)
- Chlordiazepoxide (Librium)
- Alprazolam (Xanax)
- Midazolam
- Clonazepam
What are some clinical uses of benzodiazepines?
- Acute treatment of extreme anxiety
- Hypnosis
- Alcohol withdrawal
- Mania
- Delerium
- Rapid tranquilisation
- Premedication before surgery or during minor procedures
- Status epilepticus
What drug can be given in cases of benzodiazepine overdose?
Flumazenil (BDZ antagonist)
What are some side effects of benzodiazepines?
Paradoxical aggression
Anterograde amnesia
Impaired coordination
Tolerance or dependance
What are some withdrawal effects of benzodiazepines?
- Abdominal cramps
- Increased anxiety and panic attacks
- Muscle tension, chest pain, palpitations, sweating and shaking
- Blurred vision
- Depression
- Insomnia, nightmares
- Dizziness and headaches
- Nausea and vomiting
What are some possible effects of rapid benzodiazepine withdrawal?
Confusion, psychosis and convulsions
How can benzodiazepines cause tolerance?
Chronic treatment with BDZs causes a decrease in GABA receptors and so decreases the bodies response to GABA
How should withdrawal of BDZs be performed?
Withdrawing benzodiazepines should be done by switching to the equivalent dose of diazepam and then reducing the dose ever 2-3 weeks, maintaining the dose if withdrawal symptoms occur, until symptoms improve
How can SSRIs and SNRIs be used in anxiety?
Serotonin is a key neurotransmitter in the amygdala
Increasing extrecellilar serotonin causes neuroadapidve changes, causing increased neurosteroid synthesis
