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5BBM0218 Physiology and Pharmacology of CNS > L13: Anxiolytics & Hypnotics > Flashcards

L13: Anxiolytics & Hypnotics Flashcards

1
Q

what do anxiolytic medications treat?

A
  • treat anxiety
  • including psychological symptoms such as nervousness, and physiological symptoms such as palpitations, sweating, and sleeplessness.
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2
Q

what are some examples of physiological and psychological symptoms of anxiety?

A
  • Examples of psychological symptoms: Nervousness, worry, fear
  • Examples of physiological symptoms: Palpitations (rapid heartbeat), sweating, insomnia
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3
Q

What is considered abnormal anxiety, and what are the long-term treatments for anxiety?

A
  • Abnormal anxiety is when anxiety occurs without any apparent/relevant stimulus
  • Long-term treatments for anxiety often involve the use of antidepressants
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4
Q

What do hypnotic medications treat, and what specific symptoms do they target?

A
  • hypnotic medications treat insomnia -characterized by the inability to fall asleep and stay asleep.
  • they specifically target sleep disturbances and help improve sleep quality
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5
Q

How are anxiety and insomnia related, and how are they treated?

A
  • anxiety can lead to sleep disturbances and insomnia
  • both conditions treated with CNS depressant medications, and the choice of dose determines whether the medication acts as an anxiolytic (low dose) or a hypnotic (higher dose).
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6
Q

What are GABAa receptors, and what is their most common configuration?

A

GABAa receptors are receptors for the neurotransmitter gamma-aminobutyric acid (GABA) in the brain and central nervous system.
- most common configuration = 2 alpha, 2 beta, and 1 gamma subunit - forming a pentameric structure

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7
Q

How do barbiturates work as a treatment, and what is their mechanism of action?

A
  • Barbiturates ↑ amount of time GABA channels are open, allowing more Cl- to enter the cell
  • they act as positive allosteric modulators, enhancing the functional response of GABA receptors
  • At high concentrations, they can also directly activate glycine receptors & block other receptors, including nAChR, 5-HT receptors, and AMPA and kainate receptors.
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8
Q

Why are barbiturates not commonly used as treatments?

A
  • barbiturates have a higher risk of overdose, & no specific antidote available
    (not commonly used as treatments, except in cases of epilepsy and general anesthesia)
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9
Q

How do positive allosteric modulators differ from negative allosteric modulators?

A
  • Positive allosteric modulators (PAM) ↑ the binding of agonists to their receptors at lower concentrations, enhancing functional response of the receptors
    Negative allosteric modulators (NAM) ↓ binding of agonists to their receptors, ↓ the functional response of the receptors
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10
Q

How do benzodiazepines and Z-drugs work as treatments?

A
  • They are positive modulators of GABAa receptors
  • They enhance the effect of GABA by ↑ its affinity to the receptor.
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11
Q

Where do benzodiazepines bind in the GABAa receptor?

A
  • Benzodiazepines specifically bind at the beta-gamma interface of GABAa receptors, specifically at subunits a1, a2, a3, and a5
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12
Q

What is the mechanism of action of benzodiazepines and Z-drugs?

A
  • they stabilize binding site of GABA, ↑ the receptor’s sensitivity to GABA.
  • this leads to enhanced inhibitory effects in the brain, resulting in reduced anxiety and sedation
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13
Q

How can the effects of benzodiazepines be reversed?

A
  • Flumazenil is a competitive antagonist at the benzodiazepine binding site
  • can be used to reverse the effects of benzodiazepines & Z-drugs in case of overdose/unwanted sedation.
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14
Q

What are the uses of short-acting benzodiazepines and Z-drugs?

A
  • Short-acting benzodiazepines and Z-drugs like zolpidem, clonazepam, and temazepam are used as hypnotics (to treat insomnia)
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15
Q

What are the uses of longer-lasting benzodiazepines?

A
  • Longer-lasting benzodiazepines like diazepam and chlordiazepoxide are used as anxiolytics (to reduce anxiety)
  • also used in the treatment of alcohol dependence.
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16
Q

How do benzodiazepines and barbiturates act as anxiolytics?

A

Benzodiazepines & barbiturates ↑ the amount of time GABA channels are open, allowing more Cl- into the cell.
- act as PAM of GABAa receptors, enhancing the functional response.
- At ↑ concentrations, barbiturates can also act as direct agonists at glycine receptors and block other receptors

17
Q

How do benzodiazepines work at GABAa receptors?

A
  • BZDs are positive modulators of GABAa receptors, stabilizing the binding site of GABA.
  • they ↑ the affinity of GABA to the receptor, leading to enhanced inhibitory effects
  • BZDs bind specifically at the alpha 1, 2, 3, and 5 subunits of GABAa receptors
18
Q

What are Z drugs?

A

are a class of drugs used as hypnotics to treat insomnia

19
Q

How do Z-drugs work?

A
  • act at the gamma-alpha interface of GABAa receptors.
  • have a different chemical structure to BZDs but produce similar hypnotic effects
20
Q

What are some risks associated with the use of benzodiazepines and barbiturates?

A
  • can lead to tolerance buildup over time, requiring higher doses for the same effect
  • tolerance to these drugs can lead to heightened anxiety levels due to increased activity of excitatory neurons
21
Q

why can abrupt withdrawal from BZDs & barbiturates be dangerous?

A
  • causing seizures due to the imbalance of excitatory and inhibitory inputs
22
Q

How are benzodiazepines used to treat alcohol dependence?

A
  • Alcohol increases inhibitory inputs in the brain, leading to the upregulation of excitatory receptors.
  • When alcohol is withdrawn, the brain is left with an excess of excitatory receptors, causing heightened anxiety levels.
  • BZDs gradually introduced to replace alcohol & then reduced to downregulate the number of excitatory receptors, helping with alcohol withdrawal & dependence
23
Q

What are 5-HT1A receptors?

A
  • 5-HT1A receptors are metabotropic G protein-coupled receptors
  • except for 5HT3 (a ligand-gated ion channel)
24
Q

How do 5-HT1A work?

A
  • they ↑ serotonergic drive & are autoinhibitory receptors on the presynaptic membrane to decrease further 5-HT release
  • Buspirone = commonly used 5-HT1A receptor agonist for anxiety treatment
25
Q

How do beta-adrenoreceptor antagonists (e.g., propranolol) work for anxiety?

A
  • reduce the physical symptoms of anxiety.
  • block action of norepinephrine at beta-adrenoreceptors - leading to ↓ heart rate and blood pressure, which helps to alleviate anxiety symptoms
26
Q

What role do antihistamines play in anxiety treatment?

A
  • act as antagonists at centrally acting H1 receptors
  • by blocking action of histamine at these receptors, antihistamines can help reduce anxiety symptoms.

5BBM0218 Physiology and Pharmacology of CNS (17 decks)

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