Anti-Anxiety Drugs Flashcards
What are 5 prototypic anti-anxiety/panic drugs
Alprazolam, Diazepam, oxazepam, buspirone, fluvoxamine
What are some important general principles concerning benzodiazepines (general uses)? What property makes a benzo a good anxiolytic? What can happen with a small increase in serum concentration? What is the ideal dosing rate? Why? What are some other side effects? What causes them to work less well? What are they used for?
They can function as sedative hypnotics, anticonvulsants, muscle relaxants, and anxiolytics.
While most benzos are equally anti-anxiety, A longer half life makes them a better anxiolytic.
They should ideally be take in multiple doses throughout the day b/c this prevents sedation (early intoxication) which is followed by reemergent anxiety (withdrawal)
Can cause problems with menstruation, prevent ovulation
Don’t work as well in heavy smokers.
Used for GAD and some panic disorders.
What is the administration, half-life, time to peak concentration (absorption) of diazepam (valium)? What is its distribution like? Protein binding? Biotransformation?
This compound is absorbed relatively rapidly following oral administration
and reaches a peak concentration in about 1 hr., with a half-life of 43 hrs. It has active
metabolites with half-lives of up to 100 hrs. However, this drugs undergoes extensive
redistribution due to its lipophillic nature. That is, it has an initially rapid and preferential
accumulation in brain, where it causes its central effects, and then redistributes out of the
brain (half-life of 1 hour) into body tissues, where its half-life is approximately 1.5 days. This drug is highly plasma protein bound, and has a complex biotransformation that
occurs in three steps: desmethylation followed by hydroxylation followed by conjugation
(glucuronidation).
What are two other benzos used as anxiolytics? What is their absorption, half-life, biotransformation, and when are they used?
alprazolam (xanax)- absorption is intermediate and t1/2 of about 12 hours. Undergoes hydroxylation followed by glucuronidation.
oxazepam- absorbed slowly (hours to peak [ ]), t1/2 of about 8 hours, used for elderly patients due to shorter duration of action. Undergoes only glucuronidation.
What is the mechanism of benzodiazepines?
Benzos potentiate the effects of GABA, which is the principal inhibitory NT in the brain. There are two classes of GABA receptors, GABA-A (fast inhibitory) and GABA-B (slow inhibitory), and Benzos act preferentially to GABA-A. GABA-A is a ligand gated ion channel that is selectively permeable to Chloride. When GABA binds to the receptor, Chloride enters the cell causing hyperpolarization. Benzos bind to the receptor away from the active site. When GABA then binds at the active site, more chloride enters than normally would making it even harder to depolarize the cell.
What is the mechanism of buspirone? What advantages does it have over benzos? What disadvantages? What is its halflife? Bioavailability? Protein binding? Cross tolerance with benzos?
It is a very selective partial agonist of the serotonin receptors known as 5-HT-1A. While the complete mechanism isn’t clear, these receptors are widespread throughout the brain including areas involved in anxiety. They seem to inhibit the dorsal raphe nucleus just like benzos do. It is important that they’re a partial agonist.
It is advantageous in that it does not cause sedation or dependence/tolerance/withdrawal. Both of these qualities make it ideal for elderly patients. However, it does not do well in treating severe anxiety with panic attacks or with OCD or ADHD.
Halflife is 2.5 hours. Poor bioavailability. Highly protein bound. No cross tolerance.
What drugs should be used for panic anxiety and OCD?
Benzos don’t work for panic anxiety and OCD.
Some antidepressents such as imipramine and phenelzine, as well as the SSRIs work for panic disorder.
The SSRI fluvoxamine has been approved for OCD.
What is fluvoxamine useful for? How long does it take to reach steady state levels? What should it not be used with? Why? What are 2 side effects?
Useful for depression, OCD, and ADHD
7 days to reach steady state
Should not be used with MAOIs or Diazepam (or high levels of alprazolam) b/c it interferes with oxidative benzo biotransformation (but not glucoronidation). CAn elevate levels of Carbamazepine.
Can unmask underlying mania and maybe induce seizures in susceptible individuals.
What is a possible theory as to how serotonin is involved in anxiety and depression and how a partial 5-HT-1A agonist can be used to treat both anxiety and depression?
5-HT excess leads to anxiety. It then leads to a down regulation of receptors which doesn’t work. 5-HT deficiency leads to depression. It then leads to an upregulation of receptors which doesn’t work. Since there is an excess of 5-HT in anxiety, a partial agonist will work as an antagonist, blocking receptors and working less effectively, thus treating the excess. With depression, since there is a deficiency, the partial agonist will act as an agonist, thus treating the deficiency.
Which side effects are more common with buspirone and which with alprazolam?
Nausea, dizziness, and headache more common with buspirone. Decreased concentration, drowsiness, and fatigue are much less common with buspirone, making it ideal for elderly patients.
