Pharmacology of Anxiety Flashcards
Pathophysiology
Norepinephrine is produced in the __ __ in __ ___
o Projections to the cerebral cortex (__), nucleus accumbens (__), HPA (__) and spinal cord (__ tone).
o Afferents from the __, __ gyrus, __ (activated by fear→ norepinephrine) go to the locus coeruleus.
o In anxiety, there is a dysfunction of the __ feedback to the locus coeruleus.
Pathophysiology
Norepinephrine is produced in the locus coeruleus in rostral pons
o Projections to the cerebral cortex (concentration), nucleus accumbens (motivation), HPA (cortisol) and spinal cord (sympathetic tone).
o Afferents from the hypothalamus, cingulate gyrus, amygdala (activated by fear→ norepinephrine) go to the locus coeruleus.
o In anxiety, there is a dysfunction of the negative feedback to the locus coeruleus.
GABA: inhibitory neurotransmitter. When GABA binds to GABA receptors→ increase flow through chloride channels→ hyperpolarization.
Subtypes of GABA-Agonists:
§ Benzodiazepine I: throughout the brain, but high concentrations in the __. Mediates __ and __
§ Benzodiazepine II: high concentrations in __ and spinal cord. Mediates __ __
GABA: inhibitory neurotransmitter. When GABA binds to GABA receptors→ increase flow through chloride channels→ hyperpolarization.
Subtypes of GABA-Agonists:
§ Benzodiazepine I: throughout the brain, but high concentrations in the cerebellum. Mediates anxiolysis and sedation
§ Benzodiazepine II: high concentrations in striatum and spinal cord. Mediates muscle relaxations
T/F: first line treatment for anxiety would be midazolam or lorazepam
false.
Benzodiazepines
Mechanism: stimulates benzodiazepine receptors → increases inhibitory function of GABA → reduced anxiety
Common in clinical practice due to being extremely effective and having rapid onset.
However, tolerance will develop (increased doses required) and withdrawal can occur (seizures)
Side effects: impaired cognition, sedation, impaired coordination → DO NOT TAKE WITH ALCOHOL
Overdose: lethal by respiratory depression. Antidote is flumazenil (competitively inhibits Benzo site)
Examples: midazolam (shortest), lorazepam, diazepam, chlordiazepoxide, clonazepam (longest)
NOTE: First-line for chronic anxiety is NOT benzodiazepines (SSRIs and SNRIs are first line)
first line therapies for GAD
first line therapies for SAD
first line therapies for panic disorder
first line therapies for OCD
Symptoms: motor immobility (catalepsy or stupor), excessive purposeless motor activity (not related to external stimuli), extreme negativism (gegenhalten), peculiarities of voluntary movement (posturing), echolalia or echopraxia
Associated with:
Schizophrenia
Depression
Bipolar disorder
Medical conditions (MS, uremia, ketoacidosis)
WHAT IS THIS? What is the treatment?
catatonia. Treatment: GABA-A Agonist (benzo) are remarkably fast and effective treatment
