Lecture 20 Benzodiazepines and related drugs

What kind of drugs are benzodiazepines?

CNS depressants

what are CNS depressants?

generalized inhibition of brain function and a dose dependent continuum of neural depression.

What kind of drugs are benzodiazepines?

CNS depressants

what are CNS depressants?

generalized inhibition of brain function and a dose dependent continuum of neural depression.

what drugs fall under CNS depressants?

1. chloral hydrate
2. paraldehyde
3. bromides
4. Barbituates
5. methaqualone
6. benzodiazepines

what kind of drugs are anxiolytics and sedative - hypnotic drugs

they are CNS depressants

what drugs do anxiolytic and sedative hypnotic include?

- Barbiturates
- Benzodiazepines
- alcohol

How do all CNS depressants effect neurons?

they all reduce neuron excitability

What do anxiolytics generally produce?

a calm and relaxed state with:
- drowsiness
- mental clouding
- incoordination

what do anxiolytics induce at higher doses?

they induce sleep and are sometimes called hypnotics

what do anxiolytics do at highest doses?

induce coma and death

How do BDZ and Barbituates cause sedation and reduced anxiety?

By binding to modulatory sites on the GABA A receptor complex (the chloride channel)

is there any antidote for the BDZ?

yes flumazenil

is there any antidote for the Barbituates?

no theres no antidote

where do the z drugs act?

they act at the GABA A receptor but not at the BDZ binding site.

-Same way the barbituates dont act at the BDZ site.

what is the medical use of ambien and xanax?

only approved for insomnia

are the BDZ drugs abused?

yes but not like the barbituates. the barbituates are more dangerous and have higher addiction.

when the BDZs are abused it is usually in a poly drug use state, with other drugs.

when are the barbituates and the BDZs the most similar?

in the short acting states vs the longer acting has more differences between the drugs.

how are the BDZs useful medically?

- anxiety
- insomnia
- anticonvulsants
by adding GABA in as GABA inhibition of glutamate circuit.
- alcohol or barbituate withdrawal
if you use BDZ for chronic alcohol abuse and have developed dependence and tolerance that have severe withdrawal effects including dellerium tremmins, seizure like activity BDZ help control them

what causes seizure activity?

too much glutamate in the brain causes excitability

what are the two ways you can treat seizure activity?

- adding GABA to inhibit glutamate circuit , so taking BDZ will do that.
- sodium or calcium channel blockers.

Are the BDZ side effects worse or better than barbiturates and alcohol?

compared to alcohol and barbiturates the BDZ drugs have minimal side effects

what are the minimal side effects of the BDZs compared to barbiturates and alcohol?

- lower toxicity
- memory problems (due to clouded judgment and sedative effects) amnesia and blackouts can occur
- altered REM cycling
although they have promote sleep but they effect REM cycling
- can promote violence at higher doses chronically

what is the subunit we want to try to target in the future with BDZ in treating only insomnia?

the alpha-4 subunit of the GABA A receptor
- we have yet been able to target only the alpha-4 subunit of the GABA A receptor which is causing the anxiolytic, muscle relaxant or anticonvulsant effects

what ultimately opens the Cl- and what enhances the flow of more chloride through the channel?

the GABA ultimately opens and BDZ allows more to flow because BDZ are GABA A positive allosteric modulators

what happens if you block the GABA site but add BDZ?

It takes away the Cl- conductance

Nothing happens because you are blocking the GABA site so the channel cannot open and Cl- is not flowing out the channel.

How are the BDZ and the Barbitutes the most similar? short or long acting?

The barbituates in their long acting are more similar to the BDZ in their short acting than they are with themselves in short acting.

barbituates long acting -- more similar to --> BDZ short acting

Barbituates long acting -- very different to --> barbituates short acting

what are the longer acting BDZs used for?

hypnotics to sleep aid

how do the doses of BZD impact effect and duration of action?

- Day time relief of anxiety --> Low dose = long acting forms
- Induce sleep--> Higher dose = shorter-acting

what drugs potentiate one another?

all CNS depressants potentiate each other;
- alcohol, inhalants, opiates)

how do the CNS depressants potentiate one another?

They interfere with eachothers metabolism of and create toxicity impacting the GABA receptor Cl- potentiation (too much Cl-)

what are the dangerous effects of CNS poly drug use ?

- blackout; coma; death
-accidental overdoses and suicide -- due to --> respiratory depression

when is physical dependence more likely?

with drugs that have short duration of action. (drugs dont last long)

when is psychological dependence more likely?

when drugs have a faster onset of effects.

The faster it starts to kick in the more psychological dependence occurs

what tolerance builds faster? the barbiturates or the BDZs?

- Barbiturates tolerance develops rapidly
- BZDs tolerance develops more slowly

what makes the tolerance dangerous?

the safety margin becomes very narrow and increases risk of respiratory depression

what is withdrawal like with the barbiturates and BZDs?

- Peripheral & cognitive effects (like alcohol)
- Rebound insomnia & REM rebound
- the withdrawal effects are less likely and severe for the BZDs than the barbiturates

what has more severe withdrawal? BZDs or barbiturates?

barbiturates are more likely and severe.
- BZDs are safer than barbiturates

are barbiturates addictive? are they more addictive than BZDs?

yes barbiturates are very addictive
- BZDs are less addictive

What is usually associated with BZD abuse?

polydrug use
- those who have a history of drug or alcohol abuse are more likely to abuse BDZs