BDZ

Question 1

Benzodiazepams

Answer 1

“pams”, “lams”

MOA: allosteric modulator
-Bind to allosteric site to GABAA receptors
-increased affinity of GABAA receptor for GABA
-Potentiation of GABAergic inhibition of neuronal activity

Pharmacological Effects:
-sedative-hypnotic**
-anxiolytic
-anticonvulsants
-muscle relaxant (CNS effect)

Use:
-Insomnia
-Anesthesia
-Anxiety disorders
-Seizures (eg, status epilepticus)
-Essential tremor, Spasticity

AEs:
-drowsiness
-“confusion”, especially common in the elderly
-anterograde amnesia
-psychomotor impairment
-substance use disorder (including tolerance, withdrawal)
*predictable consequences of increased GABAergic responses

PK:
-routes of metabolism
(BDZ –> Metabolites (active/inactive) –> Conjugates –> Urine)
-Metabolism of all BDZs ends with glucuronidation (glucuronide conjugates are inactive)

Lorazepam, Oxazepam, Temazepam (LOT, Outside the Liver):
-“skip” phase I
-safer in some patients:
-1) pts taking drugs that inhibit CYP 3A4, 2C19
-2) elderly patients
-3) patients with liver disease

Biological half-life:
-BDZs differ in their biological half-life
-has important implications for indications and AEs effects of BDZs
-does not correlate with route of metabolism

Question 2

Treatment Principles of BDZs

Answer 2

-same BDZs used for insomnia and anxiety
-selection primarily based on PK differences
-duration of therapy:
–use BDZs for the shortest possible time!
–If BDZ has been used for >1month, taper dose gradually to avoid rebound insomnia or anxiety
*rebound effects more common with short t1/2 BDZ
-Consider age and hepatic function of patients

Question 3

Flumazenil

Answer 3

Benzodiazepine Antagonist

MOA:
-competitive antagonist at the BDZ binding site

Use:
-antidote to treat BDZ overdose
-used in anesthesiology to reverse effects of BDZs

Question 4

Zolpidem, Zaleplon, Eszopiclone

Answer 4

Z-compounds: Novel BDZ receptor agonists

MOA:
-Bind to allosteric site on GABAa receptors
-Increased affinity of GABAA receptor for GABA
-Potentiation of GABAergic inhibition of neuronal activity

Use:
-Sleep-onset and sleep maintenance insomnia

AEs:
-Fewer AEs than BDZ

Question 5

Z-Compounds vs. BDZ

Answer 5

-Fewer deleterious effects on sleep cycle
-Only used for the treatment of insomnia (lack significant anxiolytic, muscle relaxant, anticonvulsant effects in therapeutic doses)
-Less psychomotor impairment, anterograde amnesia, tolerance, physical dependence, rebound insomnia
—but these can still occur
-Approved for long-term use (zolpidem, eszopiclone)