Anxiolytic drugs and central muscle relaxants

Question 1

Classification and what are they used for?

Answer 1

Anxiolytic drugs are used to control symptoms of severe anxiety by relaxing the patient and even provision of hypnosis at high doses.

1. Benzodiazepines
2. Diphenilmethane (Hydroxyzine)
3. Other anxiolytics (buspirone)

Question 2

Pharmacokinetics of anxiolytic drugs?

Answer 2

1. Benzodiazepine : Good oral absorption, lipophilic hence able to penetrate the CNS. Liver metabolism into inactive and sometimes active metabolites (e.g: Diazepam). Half life of the drug is the combination of the activity of the parent drug and the active metabolites.
2. Hydroxyzine : Oral and IM administration used, liver metabolism with excretion in the feces (via the bile).
3. Buspirone : Oral administration, liver metabolism and excretion is both the urine/feces.

Question 3

What are the pharmacodynamics of the benzodiazepines ?

Answer 3

BDZ’s act as agonists for the GABA receptors, increasing the frequency by which their channels allow the passage of chlorine ions, causing hyper polarisation and inhibition of the action potential. BDZ’s also reduce the quantity of GABA required to open the channel. “Flumazenil” is the antagonist that prevents bindning of BDZ’s to GABA receptors.

Question 4

What are the pharmacodynamics of the buspirones ?

Answer 4

Slow onset of action, not used for acute treatments of anxiety. Its actions are regulated by “serotonin 5-HT1a receptor” by acting as a receptor agonist. Its main effect is to treat with general anxiety disorder (GAD).

Question 5

What are the pharmacodynamics of the Hydroxyzines ?

Answer 5

Histamine H1 receptor “inverse agonist” (meaning it blocks the receptors functions, unlike simple agonist) to produce anti-histamine and sedative effects (reduction of agitation).

Question 6

Therapeutic uses for the BDZ’s?

Answer 6

There are 5 therapeutic uses for BDZ’s :
1. Anxiety disorders (social anxiety disorders, phobias, generalised anxiety disorder). Low tolerance effect of BDZ’s.

2. Sleep disorders :Reducing the latency of sleep onset and increasing REM sleep.
3. Amnesia : Conscious sedation during unpleasant procedures, allowing patient to be compliant with instructions.
4. Seizures : Termination of epileptic episodes.
5. Muscular disorders : Treatment of skeletal muscle spasms.

Question 7

Therapeutic uses for Buspirone?

Answer 7

Treatment of General anxiety disorder, not used for acute treatment of anxiety. Provides short term anxiety relief.

Question 8

Contraindications for the use of the anxiolytic drugs?

Answer 8

• BDZ’s : pregnancy as it may cross the BPB and depress the CNS in the fetus.
• Buspirone : Acute attacks and epilepsy (lacks properties of BDZ’s - used to treat seizures and epileptic attacks)
• Hydroxyzine : Pregnancy

Question 9

Adverse effect of anxiolytic drugs?

Answer 9

• BDZ’s : Cognitive impairments, drowsiness and confusion.
• Buspirone : Dizziness and headache
• Hydroxyzine : Dizziness, headache and xerostomia.