GABA System, Sedative-Hypnotic & Anxiolytic Drugs - 27

Question 1

What is GABA an abbreviation for?

Answer 1

Gamma-Aminobutyric Acid

Question 2

What can drugs that target the GABA system be used for?

Answer 2

Anti-Anxiety, Sedation, Muscle Relaxation, General Anesthesia, Hypnosis (insomnia), Anti-convulsants

Question 3

What is a sedative?

Answer 3

A drug that decreases activity, moderates excitement and calms the recipient.

Question 4

What is a hypnotic?

Answer 4

A drug that produces drowsiness and facilitates the onset and maintenance of a state of sleep.

Question 5

What are examples of Anxiety Disorders?

Answer 5

Panic disorder, Agoraphobia, Social phobia, Specific phobia, Posttraumatic stress disorder, OCD, Generalized anxiety disorder.

Question 6

What areas of the brain are involved in anxiety disorders?

Answer 6

The amygdala, hippocampus, and cortex

Question 7

How can anxiety be induced/worsened?

Answer 7

Stress, lack of sleep, chemical dependency (alcohol binge)

Question 8

Why are some people more susceptible to anxiety disorders?

Answer 8

Anxiety disorders are a product of genes and environmental interactions

Question 9

Generally, how do anxiety disorders occur?

Answer 9

Over-activation in emotion centers of brain (amygdala, hippocampus, and cortex) - Caused by insufficient GABA transmission (GABA is inhibitory)

Question 10

What is the primary inhibitory neurotransmitter in the brain?

Answer 10

GABA

Question 11

How does GABA inhibit neuronal activity?

Answer 11

When it binds its receptor, it opens a Cl- channel - makes more negative/inhibits

Question 12

What do drugs that potentiate the GABA receptor do?

Answer 12

They make the Cl channel stay open longer.

Question 13

What is the precursor of GABA?

Answer 13

Glutamate

Question 14

How many subunits does the GABA receptor have?

Answer 14

5. Its a pentamers

Question 15

Where does GABA bind on its receptor?

Answer 15

At the interface of the Alpha and Beta subunits

Question 16

Where do Benzodiazepines bind the GABA receptor?

Answer 16

At the interface of the Alpha and Gamma subunit

Question 17

What effect do barbiturates have on GABAa receptors?

Answer 17

At low concentrations - keeps GABAa receptor open longer when GABA bound :
In high concentrations - directly opens the Cl channel without GABA bound

Question 18

How can barbiturates be dangerous

Answer 18

In high doses, will suppress so many neurons that will have complete CNS depression - death

Question 19

What are three common barbiturates? And their relative lipid solubilities.

Answer 19

Phenobarbital (+), Pentobarbital (++), Thiopental (+++)

Question 20

How does lipid solubility affect the drug?

Answer 20

Affects how fast they get in the CNS, and their duration of action.

Question 21

What are some therapeutic uses of barbiturates?

Answer 21

Anesthesia, anticonvulsant, anxiety/insomnia (replaced by benzos), 1 time use is acceptable (not a daily medicine)

Question 22

What effect does P450 have in the liver?

Answer 22

P450s metabolize drugs in the liver.

Question 23

What are some problems with barbiturates?

Answer 23

They induce P450’s (drug-drug interactions) : demonstrate rapid tolerance : severe withdrawals (seizures) : low margin of safety

Question 24

Why do people who have withdrawals from barbiturates have seizures?

Answer 24

The drug is having depressive effects, so the brain is compensating by overproducing excitatory neurotransmitters. When the drug is no longer there, the excitatory effects are overwhelming.

Question 25

What drugs are the most common use of overdose/euthanasia? Why?

Answer 25

Barbiturates. Low margin of safety

Question 26

How do different barbiturates differ?

Answer 26

Primarily in their speed and duration of action (pharmacokinetics)

Question 27

What would a drug like thiopental be used for? Why?

Answer 27

Because of its high lipid solubility, it would be used for intravenous anesthesia

Question 28

Would Phenobarbital have a long or short onset/duration? Why?

Answer 28

LONG : low lipid solubility : gets in slow, stays around long.

Question 29

What are the adverse effects of barbiturates?

Answer 29

People feel affected for a prolonged period : potentiate action of any other CNS depressant : physical/psychological dependence : repiratory and cardiovascular depression : Hypersensitivity (rebound)

Question 30

What drug class have largely replaced barbiturates?

Answer 30

Benzos

Question 31

What is better about benzos in comparison to barbiturates?

Answer 31

They have a larger margin of safety.

Question 32

What effects do benzodiazepines have on the GABAa receptor?

Answer 32

They promote more GABA binding - elicit more Cl channel openings

Question 33

What do Benzos NOT do that barbiturates do?

Answer 33

Benzos do NOT open Cl channels on their own

Question 34

What therapeutic uses are there for Benzodiazepines?

Answer 34

Anxiety, skeletal muscle spasm, alcohol withdrawal, seizures, sleep disorders

Question 35

What benzo would be used for Anxiety?

Answer 35

Alprazolam (Xanax)

Question 36

What benzo would be used for skeletal muscle spasms?

Answer 36

Diazepam

Question 37

What benzo would be used for seizures?

Answer 37

Diazepam

Question 38

What benzo would be used for sleep disorders?

Answer 38

Lorazepam or triazolam

Question 39

What benzo would be used for alcohol withdrawals?

Answer 39

Diazepam

Question 40

What is alprazolam used for?

Answer 40

Anxiety

Question 41

What is diazepam used for?

Answer 41

Skeletal muscle spasms, seizures, and alcohol withdrawal

Question 42

What is lorazepam/triazolam used for?

Answer 42

Sleep disorders

Question 43

What is the primary way of choosing benzodiazepines?

Answer 43

Duration of actions

Question 44

Benzodiazepines that have a long half life can be used as: | Examples?

Answer 44

Anticonvulsants and anti-anxiety agents | Diazepam (anticonvulsant) lorazepam (both)

Question 45

Drugs with a short half-life can be used for:

Answer 45

Hypnotics

Question 46

Half-life is largely determined by ______________

Answer 46

Metabolism

Question 47

What makes some benzos longer acting?

Answer 47

They may have multiple active metabolites

Question 48

Explain redistribution.

Answer 48

You give a drug the first time, and it gets absorbed into the brain (lipid soluble), but it slowly gets absorbed into the fat so it may have less of an effect than you expected. Then, you give the drug again, most of it gets absorbed into the brain, and less into the fat, so it elicits a stronger effect.

Question 49

What benzos are used in dentistry? Why?

Answer 49

Preop Sedation (midazolam) : Adjunct to local anesthetic (diazepam, midazolam) : Oral sedation (diazepam, triazolam)

Question 50

Characteristics of Midazolam

Answer 50

Short duration : Water soluble (can be mixed w/ other drugs) : IV sedation : Anterograde amnesia

Question 51

What are examples of other CNS depressants? How will they react with Benzos?

Answer 51

Opioids, barbiturates, antihistamines, alcohol : the potentiate CNS depression

Question 52

What is an example of a GABAa antagonist? Where does it bind? What effect does it have?

Answer 52

Flumazenil : binds at the benzo binding site : reverses effect of benzo

Question 53

What characteristic of a benzo or barbiturate would make it likely to give a “hangover” or rebound side effect?

Answer 53

Longer half-life

Question 54

What characteristic of a benzo/barbiturate would make it elicit withdrawal/dependence?

Answer 54

Short half-life

Question 55

What drug (barbiturates or benzos) would you need to worry about drug-drug interactions more? Why?

Answer 55

Barbiturates : increases activity of P450s

Question 56

Which drug (benzos or barbiturates) would you need to worry about causing respiratory depression? Why?

Answer 56

Barbiturates : they can activate the GABAa receptor without the presence of GABA