CENTRAL NERVOUS SYSTEM-ANXIETY-Contd...

BARBITURATES AND OTHER SEDATIVES-ANXIETY TREATMENTS-Contd...

In general barbiturates, the derivatives of barbituric acid are reversibly depressing all excitable tissues in CNS. The barbiturates which contain a phenyl radical such as phenobarbital can be used as antiepileptics and anesthetic. Barbiturates usage for relieving anxiety is mostly replaced by benzodiazepines because of the safety issue.

Examples are,

1.Phenobarbital (Cardinal, Luminal)-Long acting

2.Pentobarbital (Nembutal)-Short acting

3.Amobarbital-Short acting

4.Thiopental-Ultra short-acting.

Mechanism:-

Barbiturates enhance the binding of GABA on its receptor by itself binding at GABA-A receptor and thereby increase the inward conduction of chloride ion into the neuronal cell and make hyperpolarised to become relaxed, and thereby produce sedation. Remember barbiturates do not bind to the benzodiazepine receptor which is adjacent to GABA receptor. But barbiturates enhances the benzodiazepine activity if given concomitantly and produce dangerous irreversible respiratory depression and coma.

Therapeutic Uses:-

1.Induction of anesthesia-Thiopental, because of its ultra-short action anesthesia can be safely induced to its first stage-induction.

2. Anticonvulsants- Phenobarbital-which because of its phenyl radical at the fifth position of the structure can effectively control the seizures.

3.Treatment of anxiety-Mostly replaced by benzodiazepines

4.Induction of hypnosis.

Route of administrations:-

1.Intravenous-I.V.

2.Oral            -P.O

3.Intra muscular-I.M.

Kinetics:-

Barbiturates are metabolized in the liver and excreted by kidneys.

Thiopental is ultra shortly acting because of its rapid redistribution to other tissues and hence its dosage should be determined accordingly.

Drug Abuse:-

Misuse of the drug would result in drug abuse and dependence. Ataxia and confusion may result. Abrupt withdrawal may give rise to serious symptoms like tremor, palpitation, restlessness, nausea, seizures, respiratory depressions, coma, and cardiac arrest.

Contraindications:-

1.Acute porphyria because barbiturates increase porphyrin a haem pigment available in red blood cells. Barbiturates interfere with the metabolism of porphyrin and produce serious consequences like mental depression.

Adverse effects:-

1.Drowsiness and depression.

2.Decreased motor control

3.Induction of cytochrome p-450 enzyme in the liver. Concomitant administration of drugs like cimetidine, ketoconazole, etc may need double dosage as they are metabolized by this enzyme.

4.Addiction.

5.Respiratory depression and coma.

6.Allergic reactions especially in patients with asthma.

ZOLPIDEM (Ambien)

Zolpidem is another newer class of drug used in anxiety.

Mostly it is a safe medicine to treat insomnia.

It is an imidazopyridine compound a nonbenzodiazepine used to treat insomnia

It is acting on the GABA-A receptor and thereby enhance the GABA activity of greater inward conductance of chloride ions into the neuronal cell and thereby make it hyperpolarised and to become inhibited.

Use

Insomnia-Sleeplessness

Side effects

1.Ataxia

2.Confusion.

CHLORAL HYDRATE

Chloral hydrate is widely used in children to produce hypnosis and sedation.

Side effects

1.Nausea and Vomiting

2.Unpleasant taste.

 

CENTRAL NERVOUS SYSTEM-ANXIETY-CONTINUE

CNS-ANXIETY-TREATMENTS-CONTD...

1.AZASPIRONES

Buspirone:-

Buspirone is an anxiolytic with minimum side effects with a slow onset of actions such as a minimum of 2 weeks to give apparent actions.

Mechanism:-

Buspirone unlike benzodiazepines and GABA it stimulates partially the serotonin (5-hydro tryptamine) 5-HT-1A receptor which by partial agonism produces calmness.

Uses

For generalized anxiety with minimum side effects because of its slow onset of action and lack of withdrawal symptoms.

Metabolism:-

The drug is metabolized in the liver and excreted by kidneys.

I have a moderate duration of action as its half-life is 11 hours maximum.

It differs from benzodiazepines by the lack of muscle relaxant action and anticonvulsant properties.

It cannot be used like diazepam for seizures and epilepsy.

Side effects:-

1.Headaches

2.Nausea

3.Vomiting

Advantages:-

1.Less sedation

2.Low drug abuse potential

3.No overdosage fatalities

4.No withdrawal symptoms

2.CARBONATES:-

Meprobamate:-

Its mechanism of action is unknown.

These medicines totally out of use in the medical field because of its serious side effects.

Side effects:-

1.Respiratory Depression-very serious

2.Hypotension

3.Shock

4.Heart Failure.