Anxiolytics and Sedative Hypnotic Drugs

GABAa Receptor

when GABA binds to GABA binding site or when BZDs bind to their site between the alpha and gamma subunits it opens the Cl channel, negative Cl ions depolarize neuron so doesn’t fire, decreases anxiety

alpha subunit effects

• a1= sedation

• a2 & a3= anxiolytic and muscle relaxation (for seizures)

• a5= cognitive SE

Benzodiazepines Drugs

Alprazolam (Xanax)

Chloradiazepoxide (Librium)

Clonazepam (Klonopin)

Clorazepate (Tranxene)

Diazepam (Valium)

Lorazepam (Ativan)

Oxazepam (Serax)

Clonazepam:Alprazolam:Lorazepam:Diazepam = 0.25: 0.5 : 1 : 5

BZD Pharmacodynamics and Pharmacokinetics

BZDs bind to a lot of the alpha units, but increasing dose doesn’t have a linear relationship with increasing CNS effects (older barbiturates do), however combining with other depressants like opioids can make the curve more linear and dangerous (BBW)

BZDs are lipophilic (especially diazepam) so quickly crosses into brain and distributes quickly

BZDs are sedating so withdrawal effects are stimulating (jittery, anxious, etc)

Most BZDs go through phase 1 metabolism so concentration increases if liver disease

Oxazepam, temazepam, and lorazepam go through conjugation so not affected by liver (Out of The Liver)

Amphetamine blocks DA and NE reuptake, cocaine also blocks DA reuptake, this combo increases NE and DA too much (sedation and ataxia)

Non-BZD Hypnotics

Z drugs (CYP3A4 metabolism)

• Zolpidem (Ambien)- multiple formulations, unlike BZDs bind selectively to a1 so primarily sedation effects, however also binds to a5 at high doses, also be careful with accumulation in elderly and hepatic impairment, females have slower metabolism than males

• Eszopiclone (Lunesta)

• Zaleplon (Sonata)

Other Agents

these treat insomnia by causing sedation

melatonin induces sleep and orexin is wake promoting neuropeptide

Ramelteon (Rozerem) and Tasimelteon are melatonin like

Surovexant (Belsomra) blocks orexin