Download CNS Depressants/Antianxiety Agents

CNS Depressants/Antianxiety Agents
Dr. Peter Winsauer
I.
CNS depressants
A.
Barbiturates
1.
Classification according to their rate of onset and duration of
action
a)
Ultrashort-acting barbiturates
1)
Thiopental – t1/2 = 12 hr. (duration of induction 5-8
min)
2)
Thiamylal
3)
Methylhexital – t1/2 = 4 hr.
b)
Short- to intermediate-acting barbiturates
1)
Secobarbital (Seconal) – t1/2 = 15-40 hr.
2)
Pentobarbital (Nembutal) – t1/2 = 15-50 hr.
c)
Long-acting barbiturates
1)
Phenobarbital (Luminal) – t1/2 = 80-120 hr.
2.
Pharmacokinetics
a)
Rate of distribution depends on their lipid solubility.
b)
Metabolism can be altered by induction of hepatic enzymes.
3.
Mechanism of action
a)
Bind to a specific site on GABAA receptors
b)
c)
4.
Facilitate the actions of GABA
Can activate the GABAA receptor directly at large
concentrations
Clinical uses
a)
Induction of anesthesia
b)
Treatment of some forms of epilepsy
5.
B.
Adverse effects
a)
CNS depression (i.e., sedation)
b)
Respiratory depression
c)
Tolerance
d)
Dependence
e)
Abuse
6.
Drug interactions
a)
Additive effects with other CNS depressants
b)
Induction of hepatic enzymes can accelerate metabolism of
other drugs.
Benzodiazepines
1.
Classification according to their rate of onset and duration of
action
a)
Short-acting
1)
Midazolam (Versad) – t1/2 = 2 hr.
2)
Triazolam (Halcion) – t1/2 = 3 hr.
b)
Intermediate-acting
1)
Lorazepam (Ativan), t1/2 = 14 hr.
2)
Oxazepam (Serax), t1/2 = 8 hr.
3)
Temazepam (Restoril), t1/2 = 11 hr.
4)
Alprazolam (Xanax), t1/2/= 12 hr.
5)
Chlordiazepoxide, t1/2 = 10 hr.
c)
Long-acting
1)
Flurazepam, t1/2 = 74 hr.
2)
Diazepam, t1/2 = 43 hr.
3)
Clonazepam, t1/2 = 23 hr.
2.
Pharmacokinetics
a)
Metabolism can result in the formation of active
metabolites.
3.
Mechanism of action
a)
Bind to a specific site on the GABAA receptor
b)
Facilitate the actions of GABA
c)
Do NOT activate the GABAA receptor directly
4.
Clinical uses
a)
Anxiolytic effects
b)
Sedative effects
c)
Muscle relaxant effects
d)
Anticonvulsant effects
e)
Induction of anesthesia
Adverse effects
a)
CNS depression (i.e., sedation)
b)
Anterograde amnesia
c)
Respiratory depression
d)
Tolerance
e)
Dependence
f)
Abuse potential
Drug interactions
a)
Additive effects with other CNS depressants
5.
6.
II.
Anxiety
A.
Types of anxiety disorders
1.
Generalized anxiety disorder—persistent state of heightened
anxiety with increased levels of motor tension and autonomic
hyperactivity
2.
B.
III.
Panic disorder—recurrent, discrete periods of sudden and intense
fear or discomfort accompanied by autonomic arousal
Treatment of anxiety disorders
1.
Benzodiazepines
a)
Immediate anxiolytic effects
b)
Alprazolam—only benzodiazepine marketed for panic
disorder
2.
Buspirone
a)
Serotonin agonist
b)
Long latency to obtain anxiolytic effects
c)
Not effective in treating panic disorder
d)
Adverse effects include headache, dizziness and nausea
3.
Antidepressants—first choice for treatment of panic disorder
a)
SSRIs
b)
Tricyclic antidepressants
c)
MAO inhibitors
4.
Beta blockers—used to prevent performance anxiety
Insomnia
A.
Causes of insomnia
1.
Stress or emotional upset
2.
Aging
3.
Medical and psychiatric illness
4.
Drugs/Alcohol
5.
Sleep cycle disruption (jet lag)
B.
Treatment of insomnia
1. Benzodiazepines
a)
Triazolam – t1/2 = 3 hr.
b)
Flurazepam – t1/2 = 74 hr.
c)
Temazepam (Restoril) – t1/2 = 11 hr.
2. Non-benzodiazepines that bind to the BZ1 site
d)
Zolpidem (Ambien) – t1/2 = 2 hr.
e)
Zaleplon (Sonata) – t1/2 = 1 hr.
f)
Eszopiclone (Lunesta)
3. Chloral Hydrate – SHOULD NOT BE USED!
4. Antidepressants
5. Antihistamines – e.g., hydroxyzine