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Nervous System > GABA System, Sedative-Hypnotic & Anxiolytic Drugs - 27 > Flashcards

GABA System, Sedative-Hypnotic & Anxiolytic Drugs - 27 Flashcards

1
Q

What is GABA an abbreviation for?

A

Gamma-Aminobutyric Acid

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2
Q

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

A

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

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3
Q

What is a sedative?

A

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

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4
Q

What is a hypnotic?

A

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

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5
Q

What are examples of Anxiety Disorders?

A

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

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6
Q

What areas of the brain are involved in anxiety disorders?

A

The amygdala, hippocampus, and cortex

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7
Q

How can anxiety be induced/worsened?

A

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

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8
Q

Why are some people more susceptible to anxiety disorders?

A

Anxiety disorders are a product of genes and environmental interactions

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9
Q

Generally, how do anxiety disorders occur?

A

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

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10
Q

What is the primary inhibitory neurotransmitter in the brain?

A

GABA

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11
Q

How does GABA inhibit neuronal activity?

A

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

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12
Q

What do drugs that potentiate the GABA receptor do?

A

They make the Cl channel stay open longer.

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13
Q

What is the precursor of GABA?

A

Glutamate

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14
Q

How many subunits does the GABA receptor have?

A
  1. Its a pentamers
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15
Q

Where does GABA bind on its receptor?

A

At the interface of the Alpha and Beta subunits

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16
Q

Where do Benzodiazepines bind the GABA receptor?

A

At the interface of the Alpha and Gamma subunit

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17
Q

What effect do barbiturates have on GABAa receptors?

A

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

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18
Q

How can barbiturates be dangerous

A

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

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19
Q

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

A

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

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20
Q

How does lipid solubility affect the drug?

A

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

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21
Q

What are some therapeutic uses of barbiturates?

A

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

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22
Q

What effect does P450 have in the liver?

A

P450s metabolize drugs in the liver.

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23
Q

What are some problems with barbiturates?

A

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

24
Q

Why do people who have withdrawals from barbiturates have seizures?

A

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.

25
Q

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

A

Barbiturates. Low margin of safety

26
Q

How do different barbiturates differ?

A

Primarily in their speed and duration of action (pharmacokinetics)

27
Q

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

A

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

28
Q

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

A

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

29
Q

What are the adverse effects of barbiturates?

A

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

30
Q

What drug class have largely replaced barbiturates?

A

Benzos

31
Q

What is better about benzos in comparison to barbiturates?

A

They have a larger margin of safety.

32
Q

What effects do benzodiazepines have on the GABAa receptor?

A

They promote more GABA binding - elicit more Cl channel openings

33
Q

What do Benzos NOT do that barbiturates do?

A

Benzos do NOT open Cl channels on their own

34
Q

What therapeutic uses are there for Benzodiazepines?

A

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

35
Q

What benzo would be used for Anxiety?

A

Alprazolam (Xanax)

36
Q

What benzo would be used for skeletal muscle spasms?

A

Diazepam

37
Q

What benzo would be used for seizures?

A

Diazepam

38
Q

What benzo would be used for sleep disorders?

A

Lorazepam or triazolam

39
Q

What benzo would be used for alcohol withdrawals?

A

Diazepam

40
Q

What is alprazolam used for?

A

Anxiety

41
Q

What is diazepam used for?

A

Skeletal muscle spasms, seizures, and alcohol withdrawal

42
Q

What is lorazepam/triazolam used for?

A

Sleep disorders

43
Q

What is the primary way of choosing benzodiazepines?

A

Duration of actions

44
Q

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

Examples?

A

Anticonvulsants and anti-anxiety agents

Diazepam (anticonvulsant) lorazepam (both)

45
Q

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

A

Hypnotics

46
Q

Half-life is largely determined by ______________

A

Metabolism

47
Q

What makes some benzos longer acting?

A

They may have multiple active metabolites

48
Q

Explain redistribution.

A

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.

49
Q

What benzos are used in dentistry? Why?

A

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

50
Q

Characteristics of Midazolam

A

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

51
Q

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

A

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

52
Q

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

A

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

53
Q

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

A

Longer half-life

54
Q

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

A

Short half-life

55
Q

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

A

Barbiturates : increases activity of P450s

56
Q

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

A

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

Nervous System (10 decks)

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