Drugs for anxiety disorders Flashcards
Psychological components of anxiety:
- Tension
- Fears
- Difficulty in concentration
- Apprehension
Somatic components of anxiety:
- Tachycardia
- Hyperventilation
- Apnea
- Palpitations
- Tremor
- Sweating
Anxiety disorders incl:
- GAD
- Panic disorders
- Phobia disorders
Most common anxiety disorder:
GAD
TorF: GAD rate tends to decrease with age?
False. Increase with age. Manifestations occur initially in 20-35 y/o
What effects does GAD have on the CVS?
- Tachycardia
- HTN
What affects does GAD have on the GI system?
Increased acidity, nausea, epigastric pain
What affects does GAD have on the Neurologic Sys?
Headache, near-syncope
In GAD, abnormalities in the activities of norepinephrine, serotonin and benzodiazepine-binding systems incld:
Decreased α2-adrenoceptor receptor binding
Decreased serotonin levels in the CSF
Reduced benzodiazepine receptor binding in the LEFT
TEMPORAL LOBE.
In adults, anxiety is associated with what kind of activity in the brain?
ELEVATED cingulate cortex activity
(Cingulate cortex: A component of the limbic system, it is involved in processing emotions and behavior regulation. It also helps to regulate autonomic motor function. Furthermore, the cingulate cortex has many bilateral connections with the frontal, temporal, and occipital cortex of both hemispheres of the brain.)
In CHILDREN anxiety is associated with what activity in the brain?…..
Increased RIGHT amygdala activation
(Amygdala is the integrative center for emotions, emotional behavior, and motivation….. The amygdala may be best known as the part of the brain that drives the so-called “fight or flight” response……Amygdala, region of the brain primarily associated with emotional processes)
Which type of anxiety is defined as recurrent, unpredictable episodes of intense anxiety accompanied by marked physiologic manifestations?
Panic disorder: RECURRENT AND UNPREDICTABLE
What are the symptoms of panic disorders?
Symptoms include dyspnea, tachycardia, palpitations, headaches, dizziness, CHOKING, PARESTHESIA, nausea and bloating.
TorF: About 25% of pts w. Panic disorders also have OCD.
True
What are the panicogens(what causes the anxiety)?
Panicogens include:
CO2
Caffeine
Cholecystokinin(peptide hormone)
Sodium lactate
Yohimbine( a2 adrenergic antagonist commonly used for erectile dysfunction, athletic performance, weight loss, angina)
__________________ in the amygdala may play a role in generating FEARFUL PERCEPTIONS.
Increased pH sensitivity
Excessive activation of ______________ locus ceruleus neurons may also enhance symptoms of panic.
NOREPINEPHRINE
Binding of GABA to the GABA receptor triggers the ____________
Binding of GABA to the receptor triggers the opening of channel leading to Cl- influx (and hyperpolarization)
Binding of GABA is enhanced by BZD, resulting in ______
Binding of GABA is enhanced by BZD, resulting in a greater entry of Cl-
MOA of BZDs:
- Modulate GABA by binding to a distinct site on the a subunit and gamma subunit of the GABAA receptor
- INCREASE FREQUENCY of channel openings produced by GABA
- INCREASE AFFINITY of GABA to the GABA binding site
TorF: BZDs reduce anxiety at high doses by selectively enhancing GABAergic transmission in neurons
having the α2 subunit in their GABAA receptors.
False: BZDs reduce anxiety at LOW doses by selectively enhancing GABAergic transmission in neurons
having the a2 SUBUNIT in their GABAA receptors.
TorF: Some benzodiazepines can produce hypnosis in high doses by mediating the α2 subunit of GABAA
receptors.
False: Hypnotic effects are mediated by α1 subunit of GABAA receptor
How does BZDs mediate their muscle relaxant effects?
BZDs can relax spasticity of skeletal muscles in HIGH doses (by INCREASING PRESYNAPTIC INHIBITION in the spinal cord where α2 SUBUNIT of GABAA receptors are located)
The a1 subunit of GABA receptors are also involved in these pharmacological effects:
Anticonvulsant actions:
Effect is partially mediated by α1 subunit of GABAA receptors
Anterograde amnesia:
Mediated by α1 subunit of GABAA receptors.
What 2 mechanisms are involved in the tolerance of BZDs?
- Decreased expression of GABAA receptors at synapses.
2. Uncoupling of BZD binding site from the GABA site.
What are the SE of alprazolam on the CNS?
CNS depression
fatigue
impaired coordination, memory impairment
changes in libido or appetite
paradoxical excitation (rebound excitement)
seizures
dysarthria (motor speech disorder)
T or F: alprazolam can cause constipation?
True
CNS depression can be enhanced with concurrent use of BZDs and what other class of medications?
alcohol, psychotropics, anticonvulsants, antihistamines
TorF: alprazolam levels can be enhanced by drugs like cimetidine?
True. BZDs are potentiated by CYP3A inhibitors (e.g., cimetidine, nefazodone,
fluvoxamine, fluoxetine, paroxetine, nifedipine)
Lorazepam SE:
CNS: sedation, dizziness, transient MEMORY IMPAIRMENT, confusion, disorientation, change in appetite, headache, SLEEP APNEA
GI: nausea
Increased sedation, respiratory depression, coma and death with opioids is a SE of which BZD?
Lorazepam
TorF: alprazolam may be potentiated by probenecid, or VPA?
False. LORAZEPAM may be potentiated by probenecid or valproic acid
May be antagonized by theophylline, aminophylline
TorF: clonazepam cause amnesia
True
TorF: clonazepam can cause hyper-salivation
True
Absence seizures with valproic acid is a SE of which BZD?
Clonazepam
CNS: depression, ataxia, memory impairment, paradoxical excitement
GI: salivation changes
Neutropenia, jaundice
Are the SE of which BZD?
SE of diazepam
Buspirone is a selective partial agonist at which receptor?
Selective partial agonist at 5-HT1A receptors.
Also displays affinity for dopamine D2 and 5-HT2A receptors.
SE of Buspirone
dizziness,
headache,
nervousness,
tinnitus,
dream disturbances
Nonspecific chest pain
TorF: Both SSRIs and SNRIs may produce some increases in anxiety in the short-term that will dissipate with time.
True
Both SSRIs and SNRIs are beneficial in specific anxiety conditions such as
Generalized anxiety disorder
Phobic disorders
Obsessive-compulsive disorder (e.g., fluvoxamine)
Panic disorder (e.g., sertraline)
