Pharm for Anxiety Disorders--Craviso

Question 1

What is generalized anxiety disorder?

Answer 1

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.

Question 2

What are the 3 NT systems that are targeted by GAD drugs?

Answer 2

noradrenergic (antidepressants)
serotonergic (antidepressants)
GABAergic (benzodiazepines)

Question 3

What is the first line pharm treatment for anxiety disorders? Why?

Answer 3

antidepressants, not benzodiazepines
b/c they lack the potential for abuse & dependence
**antidepressants also help comorbid disorders–depression etc.

Question 4

What is the problem with non-benzos for anxiety treatment?

Answer 4

they take several weeks to work

**may want to start a patient on benzo + non-benzo to get them over their immediate anxiety

Question 5

What is a good non-benzo to treat GAD?

Answer 5

Buspirone (buspar)-partial agonist @ 5-HT1A receptors
effect takes several weeks, but long-term treatment
also used for alcohol withdrawal

Question 6

What are the adverse reactions to buspirone?

Answer 6

dizziness, light-headedness, insomnia, headache and nausea

Question 7

What are antidepressants that are good to use also for anxiety?

Answer 7

venlafaxine (effexor)
duloxetine (cymbalta)
paroxetine (paxil)

Question 8

If a patient has anxiety w/o depression…what is the best treatment?

Answer 8

buspirone (buspar)

Question 9

What is the MOA of venlafaxine?

Answer 9

blocks reuptake of 5-HT and NE

Question 10

What is the MOA of duloxetine?

Answer 10

– blocks reuptake of 5-HT and NE

Question 11

What is the MOA of paroxetine ?

Answer 11

– blocks reuptake of 5-HT (SSRI)

Question 12

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?

Answer 12

Start him on a benzo & buspirone b/c shows no signs of depression. 2 weeks on benzo & then taper down.

Question 13

Aside from short-term w/ another med to treat anxiety…what is another indication for benzos?

Answer 13

short term treatment of situational anxiety–anxious response to a certain event

Question 14

What is the MOA of benzodiazepine?

Answer 14

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

Question 15

Which benzodiazepines undergo Phase I Biotransformation of N-dealkylation?

Answer 15

Chloridiazepoxide (Librium)
Diazepam (Valium)
Flurazepam
**long acting

Question 16

What is phase II after phase I?

Answer 16

3-hydroxylated compounds

happens after Phase I & then a trip to the liver

Question 17

Which drugs bypass Phase 1 & 2 & go straight to the liver for glucuronidation?

Answer 17

Clonazepam
Triazolam
Alprazolam
**short acting

Question 18

What is the t1/2 for diazepam & chlordiazepoxide?

Answer 18

over 100 hours!

long lived active metabolites

Question 19

What are the half lives of the short acting benzos? Which are most potent?

Answer 19

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

Question 20

Aside from anxiety, what is another indication for lorazepam?

Answer 20

status epilepticus

Question 21

When do you NOT want to prescribe a long-acting drug?

Answer 21

if someone has decreased liver function OR is elderly

Question 22

What drug do you want to choose when treating alcohol-withdrawal status epilepticus?

Answer 22

if liver damage: lorazepam (short acting, not as hard on the liver)
if no liver damage: diazepam (better to have a longer acting drug)

Question 23

What is another indication for benzodiazepines?

Answer 23

alcohol withdrawal b/c cross-dependence
just keep in mind hepatic insufficiency
**diazepam, lorazepam

Question 24

What are adverse reactions to benzodiazepines?

Answer 24

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

Question 25

What is anterograde amnesia?

Answer 25

can’t make new memories

Question 26

If you are prescribing a benzo to an elderly person which one should you prescribe?

Answer 26

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

Question 27

What are some serious issues w/ benzos?

Answer 27

CNS depression & resp depression

physical dependence w/ prolonged use

Question 28

What is a benzo that is considered the date rape drug?

Answer 28

flunitrazepam (rohyphnol)

Question 29

What can happen if you suddenly stop using benzos?

Answer 29

seizures
anxiety, agitation, irritability, insomnia, tremor, headache
more intense withdrawal symptoms w/ short acting & with high potency

Question 30

Which drug was sung about by the Rolling Stones?

Answer 30

Valium (benzo) physical dependence

over-prescribed by doctors in the 60s & 70s

Question 31

What are the therapeutic uses for benzos?

Answer 31

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)

Question 32

What is the MOA of zolpidem?

Answer 32

binds alpha subunit on BZ receptor

only alpha type 1, not 2, 3, or 5 or other 2!

Question 33

Which of the alpha subunits are bound by benzos?

Answer 33

1, 2, 3, 5
2 & 3: responsible for anxiety
5: cognitive impairment

Question 34

Is zolpidem (ambien) helpful for anxiety treatment?

Answer 34

NO b/c it doesn’t bind alpha 2 or 3.

Question 35

What is the structure of BZ receptors? What do benzos bind?

Answer 35

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.

Question 36

What is the effect of flumazenil on GABA a receptors?

Answer 36

bind receptor as an antagonist

used to treat withdrawals.

Question 37

What is the effect of Flumazenil (romazicon)?

Answer 37

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

Question 38

When would flumazenil be used IV?

Answer 38

hasten recovery following use of these drugs in anesthetic and
diagnostic procedures
reverse the sedation of BZ receptor agonist overdose

Question 39

What is the onset of action like for flumazenil?

Answer 39

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)

Question 40

What could happen to patients who are dependent on benzos & take flumazenil?

Answer 40

severe abstinence syndrome

Question 41

Prior to benzos what was used to treat anxiety & insomnia?

Answer 41

barbiturates

Question 42

What are barbiturates used for?

Answer 42

general anesthetics (thiopental)
anticonvulsants (phenobarbital)
on the street abused
final exit drugs
execution drugs

Question 43

What is the MOA of barbiturates?

Answer 43

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

Question 44

Why do barbiturates have a greater effect than benzos?

Answer 44

reduce glutamate-induced depolarization via AMPA and kainate receptors

depress sensory cortex, decrease motor activity

Question 45

What is a panic disorder?

Answer 45

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

Question 46

What are the meds used to treat panic disorders?

Answer 46

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)

Question 47

Social anxiety disorder is treated with what?

Answer 47

antidepressants
Venlafaxine (effexor)
paroxetine (paxil)

Question 48

How do you treat performance anxiety stage fright?

Answer 48

treated with the -adrenergic receptor blocker PROPRANOLOL (Inderal) to prevent palpitations, tachycardia, tremors, etc.

Question 49

How do you treat OCD?

Answer 49

FLUOXETINE (Prozac), PAROXETINE (Paxil), SERTRALINE (Zoloft)

Question 50

How do you treat PTSD?

Answer 50

PAROXETINE (Paxil) and SERTRALINE (Zoloft)