Pharm for Anxiety Disorders--Craviso Flashcards
What is generalized anxiety disorder?
The presence of excessive anxiety and worry about a variety of topics, events, or activities. Worry occurs more often than not for at least 6 months, and is clearly excessive.
The person finds it difficult to control the worry.
The anxiety and worry are associated with three (or more) of the following six symptoms.
restlessness or feeling keyed up or on edge
being easily fatigued
difficulty concentrating or mind going blank
irritability
muscle tension
sleep disturbance (difficulty falling or staying asleep, or restless unsatisfying sleep)
The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
What are the 3 NT systems that are targeted by GAD drugs?
noradrenergic (antidepressants)
serotonergic (antidepressants)
GABAergic (benzodiazepines)
What is the first line pharm treatment for anxiety disorders? Why?
antidepressants, not benzodiazepines
b/c they lack the potential for abuse & dependence
**antidepressants also help comorbid disorders–depression etc.
What is the problem with non-benzos for anxiety treatment?
they take several weeks to work
**may want to start a patient on benzo + non-benzo to get them over their immediate anxiety
What is a good non-benzo to treat GAD?
Buspirone (buspar)-partial agonist @ 5-HT1A receptors
effect takes several weeks, but long-term treatment
also used for alcohol withdrawal
What are the adverse reactions to buspirone?
dizziness, light-headedness, insomnia, headache and nausea
What are antidepressants that are good to use also for anxiety?
venlafaxine (effexor)
duloxetine (cymbalta)
paroxetine (paxil)
If a patient has anxiety w/o depression…what is the best treatment?
buspirone (buspar)
What is the MOA of venlafaxine?
blocks reuptake of 5-HT and NE
What is the MOA of duloxetine?
– blocks reuptake of 5-HT and NE
What is the MOA of paroxetine ?
– blocks reuptake of 5-HT (SSRI)
F.L. is a 31-year-old male who has been employed as a bank clerk for the past six years & his job is in jeopardy b/c of his irritability and absences. Reports being tired, tense, GI problems, anxious, unable to relax.
Which meds are appropriate?
Start him on a benzo & buspirone b/c shows no signs of depression. 2 weeks on benzo & then taper down.
Aside from short-term w/ another med to treat anxiety…what is another indication for benzos?
short term treatment of situational anxiety–anxious response to a certain event
What is the MOA of benzodiazepine?
augment GABAergic neurotransmission bind to site on GABAa receptors enhance chloride conductance **increase the # of times chloride channels open when GABA is bound. Remember: GABA is inhibitory
Which benzodiazepines undergo Phase I Biotransformation of N-dealkylation?
Chloridiazepoxide (Librium)
Diazepam (Valium)
Flurazepam
**long acting
What is phase II after phase I?
3-hydroxylated compounds
happens after Phase I & then a trip to the liver
Which drugs bypass Phase 1 & 2 & go straight to the liver for glucuronidation?
Clonazepam
Triazolam
Alprazolam
**short acting
What is the t1/2 for diazepam & chlordiazepoxide?
over 100 hours!
long lived active metabolites
What are the half lives of the short acting benzos? Which are most potent?
Alprazolam (Xanax): t1/2=14 hrs **most potent Lorazepam (Ativan): t1/2=14 hrs **still quite potent Oxazepam (serax): t1/2=9 hrs **least potent
Aside from anxiety, what is another indication for lorazepam?
status epilepticus
When do you NOT want to prescribe a long-acting drug?
if someone has decreased liver function OR is elderly
What drug do you want to choose when treating alcohol-withdrawal status epilepticus?
if liver damage: lorazepam (short acting, not as hard on the liver)
if no liver damage: diazepam (better to have a longer acting drug)
What is another indication for benzodiazepines?
alcohol withdrawal b/c cross-dependence
just keep in mind hepatic insufficiency
**diazepam, lorazepam
What are adverse reactions to benzodiazepines?
dizziness and ataxia (dose-related) cognitive impairment anterograde amnesia (particularly with very short-acting) paradoxical reactions in some such as anxiety, and irritability/hostility when using clinically effective doses of long-acting benzo-diazepines – can lead to cumulative effects
**high risk for falls in the elderly who are more sensitive
What is anterograde amnesia?
can’t make new memories
If you are prescribing a benzo to an elderly person which one should you prescribe?
oxazepam is preferred b/c short acting & least potent
start on small dose & decrease dose over time b/c it will accumulate in the body
What are some serious issues w/ benzos?
CNS depression & resp depression
physical dependence w/ prolonged use
What is a benzo that is considered the date rape drug?
flunitrazepam (rohyphnol)
What can happen if you suddenly stop using benzos?
seizures
anxiety, agitation, irritability, insomnia, tremor, headache
more intense withdrawal symptoms w/ short acting & with high potency
Which drug was sung about by the Rolling Stones?
Valium (benzo) physical dependence
over-prescribed by doctors in the 60s & 70s
What are the therapeutic uses for benzos?
anxiolytics – limited, short-term use
managing alcohol and barbiturate withdrawal
anticonvulsants – e.g., lorazepam (Ativan) for terminating status epilepticus
preanesthetic adjuncts – e.g., midazolam (Versed)
muscle relaxants – diazepam (Valium)
No longer used as sedative-hypnotics – replaced by non-benzodiazepine drugs such as zolpidem (Ambien)
What is the MOA of zolpidem?
binds alpha subunit on BZ receptor
only alpha type 1, not 2, 3, or 5 or other 2!
Which of the alpha subunits are bound by benzos?
1, 2, 3, 5
2 & 3: responsible for anxiety
5: cognitive impairment
Is zolpidem (ambien) helpful for anxiety treatment?
NO b/c it doesn’t bind alpha 2 or 3.
What is the structure of BZ receptors? What do benzos bind?
BZ has 5 subunits 2 alphas, 2 betas, 1 gamma.
6 different isoforms of alpha.
some don’t have gamma.
Benzos bind b/w gamma & alpha
sometimes GABAa receptors don’t have gamma subunits & those don’t bind benzos.
What is the effect of flumazenil on GABA a receptors?
bind receptor as an antagonist
used to treat withdrawals.
What is the effect of Flumazenil (romazicon)?
non-selective competitive antagonist (blocks actions of benzodiazepines and BZ1 receptor agonists such as zolpidem)
partially or completely reverses most central effects (sedation; impairment of recall, etc.)
has no effect in the absence of benzodiazepines
When would flumazenil be used IV?
hasten recovery following use of these drugs in anesthetic and
diagnostic procedures
reverse the sedation of BZ receptor agonist overdose
What is the onset of action like for flumazenil?
Has a rapid onset of action (1-2 minutes; peak effect between
6 – 10 minutes) but a short half-life (0.7-1.3 hours)
What could happen to patients who are dependent on benzos & take flumazenil?
severe abstinence syndrome
Prior to benzos what was used to treat anxiety & insomnia?
barbiturates
What are barbiturates used for?
general anesthetics (thiopental) anticonvulsants (phenobarbital) on the street abused final exit drugs execution drugs
What is the MOA of barbiturates?
Like benzodiazepines, facilitate GABAergic inhibitory neurotransmission at GABAA receptors but:
act at a different site
increase the length of time the Cl- channel is open (more potent effect on Cl- influx than benzodiazepines
Why do barbiturates have a greater effect than benzos?
reduce glutamate-induced depolarization via AMPA and kainate receptors
depress sensory cortex, decrease motor activity
What is a panic disorder?
Sweating, trembling, palpitations, shortness of breath, choking
sensation, chest discomfort, nausea, dizziness, chills or hot flushes, fear of going crazy; individuals may confuse a panic attack with a heart attack
What are the meds used to treat panic disorders?
Antidepressants
used for long-term treatment
because effects take several weeks, can initiate treatment together with a benzodiazepine
FLUOXETINE (Prozac), PAROXETINE (Paxil) and SERTRALINE (Zoloft) – SSRIs
VENLAFAXINE (Effexor) – blocks reuptake of 5-HT and NE
OR
Benzos:
Xanax (alprazolam)
Lorazepam (Ativan)
Social anxiety disorder is treated with what?
antidepressants
Venlafaxine (effexor)
paroxetine (paxil)
How do you treat performance anxiety stage fright?
treated with the -adrenergic receptor blocker PROPRANOLOL (Inderal) to prevent palpitations, tachycardia, tremors, etc.
How do you treat OCD?
FLUOXETINE (Prozac), PAROXETINE (Paxil), SERTRALINE (Zoloft)
How do you treat PTSD?
PAROXETINE (Paxil) and SERTRALINE (Zoloft)
