In addition to benzodiazepines, already mentioned, the following are also used as anxiolytics:
– Non Benzodiazepine
– Non – sedating anxiolytic
– Onset of action slow
– No hypnotic, anti convulsant or muscle relaxant properties
Mechanism of Action:
Act as partial agonist at brain 5-HT1A receptors
– Rebound anxiety after sudden cessation of high doses
– Minimal abuse liability.
–Rapidly absorbed orally, undergoes Ist pass metabolism
-Active metabolites are formed after hydroxylation & dealkylation
-Active metabolite (I-PP) has alpha2 ADRENERGIC action in CNS
– t ½ of Buspirone is 2-4 hrs.
- no rebound anxiety
- no withdrawal symptoms
- minimal abuse liability
- cause less psychomotor impairment than benzodiazepines and do not effect driving skills
- does not potentiate effects of sedatives/hypnotics of ethanol and TCAs
- elderly people do not appear to be more sensitive to its actions
Onset of action is delayed. It takes about 7 days. In generalized anxiety disorders, although action is comparable to benzodiazepines, so may be used. It does not interact with other CNS depressants except ethanol.
Acts by inhibiting presynaptic receptors, increasing serotonin.
Less troublesome than benzodiazepines
– GI distress
– Dose dependent pupillary constriction
– Monoamine oxidase inhibitors antidepressants + Buspirone increase B.P
– Macrolyte antibiotics (Erythromycin [enzyme inhibitor], Ketoconazole) increase plasma levels
– Rifampin decrease plasma level
Imadazopyridine derivative- (Non BDZ)
Mechanism of action:
Binds with benzodiazepine receptor (omega 1)
Facilitates GABA mediated neuronal inhibition
– Has minimal anti Convulsant & muscle relaxant properties
– Affects sleep pattern & respiration at higher doses.
– Metabolized in liver, t ½ is 1-5 – 3-5 hrs.
- Improves sleep
- Increases sleep time
- Tolerance is less
- Short term insomnia –usually administered for short term effect which persists for 4-5 days, after 1-2 doses drug is stopped and effect persists for about a week
- In chronic insomnia, with initial doses, chances of rebound insomnia are there when drug is discontinued
- Patients suffering from obstructive apnea are not given as may increase hypoxia.
- Patients of respiratory distress, COPD, cardiac patients are not administered as aggravate.
Available as biphasic formulation, which provides sustained drug levels.
-First hypnotic, trichloroethanol.
It is one of the oldest hypnotic, used since 18th century.
Present is liquid form, irritant to skin and gastric mucosa, producing a burning sensation when taken orally.
It is converted to trichloroethanol in liver.
It is occasionally used in children and elderly undergoing painful diagnostic procedures.
Onset of action occurs within 5-10 minutes. Duration of action is about 4 hours.
-High P. Protein binding & displace oral anticoagulant.
May be used for dental extraction but not preferred.
- Forms active metabolite trichloroacetic acid, which is cardio toxic
- Idiosyncratic reaction occurs in some individuals and person shows disorientation and incoherent and paranoid behavior.
Urochloric acid is excreted in urine, which is the third metabolite.
Has muscle relaxant activity and blocks inter-nuncial neurons in spinal cord.
It is not used now because of abuse liability and hypnotic actions, safer drugs are available
– Cyclic ether, a polymer of acetaldehyde. It has a strong aromatic smell and disagreeable taste. If given orally, it causes burning sensation, irritation of mouth, throat and stomach. After oral administration, it is rapidly absorbed and sleep occurs within 10-15 minutes. It is never administered I/V and never in plastic syringe, as is corrosive.
-70-80% is metabolized in liver, 20-30% is exhaled from lungs.
Thus, if liver is compromised, alternative route is used.
- In retention enema, via rectum
- Also given in delirium tremors
– Selectively bind to benzodiazepines receptors
– Rapid onset & shorter duration (short half life).
– Not antagonized by flumazenil
– Effective for management of patients who woke up early in sleep cycle.
Has longer half life than Zaleplon.
Is associated with less dizziness, less insomnia and drowsiness.