Benzodiazepines -reduce anxiety and prevent panic attacks (clonazepam)

Question 1

what are BZD?

Answer 1

GABA modulators
-most frequently used sedative-hypnotics
-they have a binding site at the GABA a receptor called BDZ receptor
-important of a subunit:
a1-sedative, hypnotic
a2-anxiolytic

Via activating BDZ receptors they promote the GABA binding to its own binding site.

They do not substitute for GABA but enhance the GABA’s effects without directly activating GABA receptors or opening the associated cl- channels
-they potentiate the GABAergic inhibition by increasing the frequency of cl- channel opening events

Question 2

BDZ receptor agonists

Answer 2

Diazepam:

a positive allosteric modulator

Question 3

BDZ receptor antagonists

Answer 3

Flumazenil:

a neutral allosteric modulator, it occupies the BDZ receptors and inhibits agonist binding

Question 4

BDZ receptor inverse agonists

Answer 4

beta- Carbolines:

they are negative allosteric modulators inhibiting GAB binding at its own receptor thereby causing anxiety and seizures

Question 5

Pharmacological actions of BDZ

Answer 5

1. anxiolytic (sedative)
2. hypnotic
3. premaedication BEFORE general anesthesia
4. antiepileptic
5. central skeletal muscle relaxant
6. amnesia
7. panic attacks
8. Endoscopy
9. alcohol withdrawal

Question 6

BDZ used as anxiolytics

Answer 6

1. Chlordiazepoxide
2. Diazepam (centrally acting mm relax, epileptic acute state,alcohol withdrawal, endoscopy)
3. Clonazepam (panic attacks, absent seizures chronically)
4. Oxazepam
5. Lorazepam (epileptic state)

6.Alprazolam (tetracyclic) (panic attacks)

Question 7

BDZ used as Hypnotics

Answer 7

1. Nitrazepam
2. Flunitrazepam

3.Lorazepam

4. Midazolam
5. Triazolam (tetracyclic)

Question 8

BDZ: pharmacokinetics

Answer 8

• are lipophilic drugs with good oral bioavailability >80%
• they are distributed very well crossing the blood-brain barrier and the placenta
• they bind extensively to plasma proteins (60-95%) without important clinical consequences
• they are metabolized in the liver (have acive metabolites) and excreted in urine.

Question 9

BDZ: metabolism

Answer 9

1. Diazepam type:
   active metabolites with long half life (30-90hrs), they can be accumulated
   -diazepam, chlordiazepoxide

2.Triazolam type (tetracyclic BDZs):
active metabolites with short half life only
-triazolam,alprazolam

3.Oxazepam type:
no active metabolites they are conjugated directly
-oxazepam, lorazepam

Question 10

BDZ: side effects

Answer 10

• sedation
• mild dependance and tolerance
• anterograde amnesia- cant learn new information
• in elderly: confusional states, aggresion, violence (paradox effects)
• no sexual disturbance
• they are relatively safe drugs, they depress the CV and resp functions usually only in case of underlying disease after adminstration of high doses
• in case of intoxication give FLUMAZENIL
• with alcohol or too rapid IV use it can be dangerous

Question 11

Z compounds

Answer 11

non- BDZ but BDZ agonist GABAergic hypnotics:

Zopiclone
Zolpidem
Zaleplone -has a 1/2life of 1hr and decreases sleep latency but has little effect on total sleep time. Amnestic effects less common and favourable in pts who have sleeping difficulty

• Prefer BDZ receptors with a1 subunits
• less muscle relaxing, anxiolytic and antiepileptic effects
• they cause minor effects on sleep patters and the risk of the develop of tolerance and dependance is lower than with the use of BDZ