pharmacology of sedatives and hypnotics n.
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Pharmacology of Sedatives and Hypnotics. These drugs inhibit anxiety and diminish insomnia. They make people more comfortable. These drugs also inhibit other behaviors such as sexual control, which is why they’re used for date rape.

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slide2

These drugs inhibit anxiety and diminish insomnia.

They make people more comfortable.

These drugs also inhibit other behaviors such as sexual control, which is why they’re used for date rape.

When taken in excess, they may cause sleepiness, stupor, loss of consciousness, anesthesia, or death.

slide3

Benzodiazepines

Benzodiazepines were a big discovery because they are essentially non-lethal in overdose.

Excellent treatment for anxiety, insomnia, seizures.

slide4

Benzodiazepines bind to a non-GABA site on the receptor and enhance the activity of GABA, ​but benzos do not directly activate the receptor.

This is why they’re less lethal in overdose!

Benzodiazepines may act as receptor agonists, antagonists, or inverse agonists (have opposite ​activity of agonists but are still blocked by antagonists).

slide5

Patients using benzodiazepines often become addicted.

The three signs of addiction are:

​1. Reinforcement

​2. Tolerance

​3. Withdrawal (withdrawal, rather than overdose, is what’s fatal with benzodiazepines).

slide6

Withdrawal is very dangerous because long-term benzodiazepine use desensitizes and ​down-regulates GABA receptors.

Taking away the drug leads to seizures and CNS overactivity.

Benzodiazepines are great for short-term or once-in-a-while use, but not for long-term maintenance.

slide7

Flumazenil(Romazicon) is a benzodiazepine antagonist used for rescue against overdose.

​Must be used with care because of the dangers of withdrawal.

slide9

Benzodiazepines include:

​--Alprazolam (Xanax)

​--Clonazepam (Klonopin) which is used for long-term maintenance

​--Diazepam (Valium) which is also used for long-term maintenance

​--Lorazepam (Ativan).​

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--Triazolam (Halcion)

​--Flunitrazepam (Rohypnol), also called “ruffies,” are used a recreational drug

Novel hypnotic benzodiazepines:

​--Zolpidem (Ambien)

​--Zaleplon (Sonata)

slide11

Barbiturates

Used to treat anxiety, insomnia, and seizures. Highly lethal in overdose.

May paradoxically cause pain sensitization or activation (rather than sedation).

Barbiturates bind to a non-GABA site of the GABA receptor and directly activate it.

slide12

Barbiturates exacerbate porphyria!!

Barbiturates induce their own metabolism (which is why tolerance gets worse and worse)!!

These drugs are lipid soluble.

The more lipid soluble the drug, the better it penetrates the CNS.

slide13

Barbiturates include:

​--Amobarbital (Amytal) which is also called “truth serum”

​--Pentobarbital (Nembutal)

​--Phenobarbital (Luminal).

slide14

GABA and its receptor

There is huge heterogeneity in the GABA receptor, since there are many different combinations ​of subunits.

Thus, drugs can have very different binding properties in different people.

slide15

Benzodiazepines may act as receptor agonists, antagonists, or inverse agonists (have opposite ​activity of agonists but are blocked by antagonists).

--GABA agonists are anxiolytic, anti-convulsant, and muscle relaxing.

--GABA inverse agonists are anxiogenic, pro-convulsant, arousing, spasmogenic.