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40 Cards in this Set
- Front
- Back
Panic Disorder:
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A panic attack is an acute, discrete period of intense
fear and discomfort associated with a number of somatic and cognitive symptoms that include: heart palpitations, sweating, trembling, shortness of breath, sensations of choking, chest pain, nausea, dizziness, tingling, chills or blushing, hot flashes. |
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Panic Disorder is diagnosed when
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a person has experienced at
least two unexpected panic attacks and develops persistent worry about subsequent attacks or changes his/her behavior to avoid attacks. |
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Social Anxiety Disorder (SAD):
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characterized by marked and
persistent anxiety in social situations, including performances and public speaking. |
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Generalized Anxiety Disorder (GAD):
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a period of anxiety
and worry of > 6 months duration accompanied by multiple associated symptoms. Need to rule out other anxiety disorders. |
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Obsessive-Compulsive Disorder (OCD):
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Obsessions are recurrent,
intrusive thoughts, images, ideas or impulses perceived as being inappropriate, grotesque or forbidden. Compulsions are repetitive behaviors or mental acts that are performed to alleviate the anxiety |
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Post-traumatic stress disorder (PTSD):
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Acute Stress Disorder refers to anxiety and behavioral disturbance (eg. nightmares) after an
extreme trauma (near-death experience, rape, witnessing a murder, etc). If symptoms and behaviors persist for >1 month and if features are associated with functional impairment, it is now considered PTSD |
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Panic Disorder Theories
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suggest that in anxiety disorders, there is an alteration in the
normal “stress response” The stress response is the coordinated reaction to threatening stimuli and involves: • Avoidance Behavior • Increased vigilance and alertness • Activation of SNS • Activation of HPA axis, ultimately releasing cortisol from adrenals |
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hippocampus and amygdala,
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two areas that are part of the limbic system
that help to regulate the body’s normal response to stress, tightly regulate control of the HPA axis. |
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Theory of Anxiety
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Inappropriate activation of the amygdala and subsequent activation of HPA axis has been associated with some anxiety
disorders. |
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The hippocampus
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normally decreases HPA responses by a negative
feedback mechanism as cortisol levels rise. With chronic stress cortisol receptors in hippocampus may downregulate or die resulting in a decline in the negative feedback pathway resulting in further dysregulation of the HPA axis by the amygdala |
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Theory summed up
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So, the combination of hyperactivity of the amygdala and under-activity of the hippocampus may underlie some of the etiology of anxiety disorders.
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Neurotransmitter involvement
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NE, 5-HT and GABA
There is a complex interaction between 5-HT, GABA and NE neurons in anxiety disorders as SSRIs and SNRIs are effective for chronic treatment of most anxiety disorders. |
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NE,
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In animal models, stress results in elevation of NE in amygdala and
hypothalamus and an elevation of ACTH release. Stress-induced NE release facilitates a number of anxiety-like behavioral responses in animal models. |
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5-HT
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Stress results in decreased 5-HT in hypothalamus. 5-HT1A knockout mice are used as a model of anxiety.Full or partial 5-HT1A
agonists have utility in treatment of certain types of anxiety disorders. |
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GABA
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Agents (eg. Benzodiazepines) that potentiate effects of GABA on GABA-A
receptors are very effective in reducing stress responses. |
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FDA-approved agents for GAD
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Alprazolam*
Buspirone Duloxetine Escitalopram Paroxetine Venlafaxine |
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FDA-approved agents for SAD
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Paroxetine
Fluvoxamine Sertraline Venlafaxine |
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FDA-approved agents for OCD
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Clomipramine
Fluoxetine Fluvoxamine Paroxetine Sertraline |
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FDA-approved agents for PANIC
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Alprazolam*
Clonazepam* Paroxetine Sertraline Venlafaxine |
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FDA-approved agents for PTSD
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Paroxetine
Sertraline |
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Off-label or general use in various anxiety disorders
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Beta blockers
Other benzodiazepines (diazepam*, oxazepam) |
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Buspirone
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(Buspar) for GAD
5-HT1A partial agonist may also act as a partial agonist of D2 receptors. No sedation does not possess anticonvulsant or muscle-relaxant properties |
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Buspirone Pharmacokinetics, Adverse Effects, Interactions:
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administered twice daily; onset of anxiolytic effect
may require 2 weeks Metabolized primarily by CYP 3A4. CNS: dizziness (12%); drowsiness (10%); headache (6%); hostility or agitation GI: N/V Nonselective MAO inhibitors |
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Sedatives
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are agents that reduce anxiety and exert a calming effect
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Hypnotics
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are agents that produce drowsiness and encourage the onset and maintenance of
sleep. |
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Most common FDA-approved agents for insomnia
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Benzodiazepines
Estazolam Flurazepam Lorazepam* Quazepam Temazepam Other Eszopiclone* Zalepion Zolpidem* Diphenhydramine Doxylamine |
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Mechanism of Action (Barbiturates, Benzodiazepines, non-benzodiazepines,)
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target the
GABA-A receptor.(a ligand-gated Cl- channel.) Upon binding the Cl- channel opens to produce hyperpolarization of the cell.decreasing activity of the neurons on which it resides. |
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GABA-A receptors
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are hetero-pentamers comprised of 3 different subunits (a, b and
g) that form the Cl- channel. subunits have heterogeneity as well in that there are at least 5 a and at least 3 b subunits that allow for a number of combinations in channel structure to exist. Benzodiazepines activate GABA-A receptors comprised of all the a subunits (1-5), newer hypnotics selectively activate only GABA-A receptors comprised of a1 subunits. |
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Barbiturates***
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Amobarbital
Secobarbital Butabarbital Pentobarbital Phenobarbital FDA-approved agents for insomnia ***Insomnia is no longer an accepted use of barbiturates; safer benzodiazepines and the newer hypnotics have mostly replaced this indication. |
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Barbiturates Mechanism of Action that contribute to barbiturates’ ability
to produce general anesthesia and more CNS depression than benzodiazepines |
act
as positive allosteric modulators of the GABA-A receptor.When GABA is present they increase the duration of GABA channel openings. high concentrations may directly open GABA-A channels. may also block excitatory amino acid AMPA receptors, reducing effects of glutamate. |
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benzodiazepines and newer non-benzodiazepine hypnotics (eg. Zolpidem) MOA
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act as allosteric modulators of the GABA-A channel by increasing the frequency of
GABA channel openings, making channels more sensitive to the effects of GABA |
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Barbiturates Indications
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Insomnia (not recomended); preoperative anxiety; sedation induction
(surgical procedures); sedation maintenance (surgery); some for seizure disorders |
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Barbiturates Pharmacokinetics
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Phenobarbital: Very long T1/2 of 50-120, metabolized CYP 2C9, inducer of many enzymes, Short acting with duration of 1-4 hrs.
Amobarbital: IV or IM only; 10-12 hr duration. Butabarbital: oral, 6-8 hr duration. 45-60 min onset. Complete metabolism in liver, excreted by kidney as metabolites. |
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Barbiturates Adverse Effects/Toxicity:
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• CNS deoression
• Respiratory depression • CV depression • Tolerance • Cross-tolerance to ethanol • Physical dependence: o Withdrawal symptoms: • All are teratogens, Pregnancy Category D |
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Barbiturates Pharmacodynamic Interactions:
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CNS depressants: antihistamines, alcohol, opiates, tricyclic antidepressants,
phenothiazines, anticonvulsants |
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Benzodiazepines Pharmacokinetics:
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Phase I metabolism that results in active metabolites,
some with very long T1/2. These metabolites may then undergo Phase II conjugation reactions and then be eliminated by urinary excretion. |
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Benzodiazepines Adverse Effects/Toxicities:
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• CNS effects: euphoria, drowsiness, amnesia, sleep driving, sleep walking, binge
eating while asleep, impaired judgment, diminished motor skills • CV depression • Respiratory depression • Daytime sedation with longer T1/2 agents if used for insomnia. • Tolerance after use of >1-2 weeks • Physical dependence (similar to barbiturates) |
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Benzodiazepines Adverse Effects/Toxicities: cont
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• Rebound insomnia may result if used for more than 1-2 weeks
• Shorter T1/2 drugs have more withdrawal symptoms after chronic use • Toxicities in overdose are less severe than with barbiturates, but still dangerous. • All agents mentioned are Pregnancy Category D and considered teratogens. |
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Benzodiazepines Pharmacodynamic Interactions
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• CNS depressants
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Top 200 Benzodiazepine Agents:
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• Diazepam (Valium, generic, Diastat rectal gel)
• Lorazepam (Ativan, generic) • Alprazolam (Xanax XR, Niravam ODT, generic) • Clonazepam (Klonopin, generic) |