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CNS > L40 Anxiolytic drugs > Flashcards

L40 Anxiolytic drugs Flashcards

0
Q

What are the different types of anxiety? (7)

A
  • General anxiety disorder: an ongoing state of anxiety with no clear reason
  • Social anxiety disorder: fear of social interactions
  • Phobias
  • Panic disorder: sudden attacks of overwhelming fear
  • Post-traumatic stress disorder: associated with recall of traumatic event
  • Obsessive compulsive disorder: compulsive behaviour driven by irrational anxiety
  • Body dysmorphic disorder: anxiety caused by distorted view of body/appearance
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1
Q

What is anxiety?

A
  • anticipation of fear in the absence of external stimuli
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2
Q

What is the first line interventions for anxiety patients?

A
  • Drug therapy is NOT recommended for first line treatment
  • For general anxiety disorder:
    1st line= education and monitoring; 2nd line= self-help and group cognitive behavioural therapy; 3rd line= high intensity psychological interventions/ pharmacological intervention

-For Obsessive compulsive disorder and body dysmorphic disorder:
1st line= cognitive behavioural therapy; and pharmacological intervention is considered if no improvement

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3
Q

What are the types of pharmacological interventions? (6)

A
  • antidepressants: onset of action is delayed
  • benzodiazepines: act quickly but induce dependence
  • 5-HT1a receptor agonists: onset of action is delayed
  • some anti-epileptic drugs, eg gabapentin, pregabalin, tiagabine and sodium valproate (can be effective in treating general anxiety disorder)
  • beta adrenoceptor antagonists
  • anti-psychotics
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4
Q

What is the important property of anxiolytics?

A
  • they can become sedative and even hypnotics if they are in a high concentration!!
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5
Q

What drugs are anxiolytic, sedative and hypnotic?

A
  • Benzodiazepines, zopicolone related drugs, barbiturates

* barbiturates require careful dosage= can be fatal

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6
Q

What drugs are anxiolytic?

A
  • antidepressants, buspirone, beta adrenoceptor antagonists
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7
Q

What drugs are hypnotic?

A
  • anti-histamines, chloral hydrate, sodium oxybate
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8
Q

Anti-depressants

A
  • generally first drug class to try
  • there is a delay for onset of action so NOT GOOD for patients with severe depression
  • Selective serotonin reuptake inhibitors are commonly used: eg. sertraline, citalopram, fluoxentine
    OR
  • Serotonin–norepinephrine reuptake inhibitors could be useful
  • MAO inhibitors/ tricyclic antidepressants are not used commonly due to their severe side effects
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9
Q

Benzodiazepines

A
  • eg nitrazepam
  • SHOULD NOT routinely be used to treat anxiety but may be useful in patients with acute and severe symptoms in short term (4 WEEKS MAX!)
  • CANNOT combine with alcohols= respiratory depression
    SIDE EFFECTS: drowsiness, confusion, amnesia (a partial loss of memory)
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10
Q

Benzodiazapines: Loprazolam

A
  • half life: 6-12 hours

- exerts both hypnotic and anxiolytic properties

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11
Q

Benzodiazapines: nitrazepam

A
  • half life: 16-40 hours

- exerts hypnotic and anxiolytic effects

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12
Q

Benzodiazapines: diazepam

A
  • half life: 20-40 hours

- exerts anxiolytic and anticonvulsant effects

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13
Q

Why don’t we use benzodiazepines for prolonged period of time?

A
  • because common to develop tolerance and physical dependence

Tolerance: repeated use reduces effectives
= it is more commonly seen in anti-convulsant action but may occur when apply as anxiolytic. Not really seen when used in hypnotic actions

Physical dependence: can cause anxiety, tremor, dizziness, weight loss and sleep disturbances when withdrew

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14
Q

Mechanism of action of benzodiazepines

A
  • binds to GABAa receptors (like alcohols)
  • enhance affinity for GABA binding so increase the probability of channel opening.
  • so can fire MORE inhibitory signals out
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15
Q

Structure of GABAa receptor structure

A
  • 5 subunits: 2 alpha, 2 beta and 1 gamma

- there are several different subtypes for alpha, beta and gamma subunits

16
Q

Which subunits of GABAa receptors are sensitive to benzodiazepines?

A
  • alpha 4 and alpha 6 receptors are INSENSITIVE to benzodiazepines
  • gamma 2 required for benzodiazepines sensitivity
  • alpha 1 receptor induce sedation and amnesia
  • alpha 2, 3 benzodiazepines are anxiolytic
  • most abundant combination of GABAa receptors= alpha1beta2gamma2
17
Q

What are benzodiazepine antagonists?

A
  • eg. Flumazenil
  • Reverse actions of benzodiazepine, for example patients who have extreme drowsiness after benzodiazepines or after overdose
18
Q

What are barbiturates?

A
  • eg phenobarbitone
  • potentiate GABAa receptors but they are non-selective which means can also bind to other ligand-gated ion channels eg inhibit NMDA receptors
  • was commonly used before benzodiazepines
  • produces tolerance and dependence
  • produce anaesthesia and death in overdose
    SO NOT RECOMMENDED to prescribe
19
Q

What is the mechanism of action for barbiturate?

A
  • binds to GABAa receptors at site distinct from benzodiazepine binding sites
  • low conc= prolongs openings produced by GABA; high conc= opens channels even in absence of GABA
    (Depress neurones to such extent that can cause death! As lots of GABA action)
20
Q

How do the 5-HT1A agonists work?

A
  • eg buspirone, ipsapirone, gepirone
  • they are 5-HT1A receptor partial agonists
  • have less sensation and more motor coordination than benzodiazepines
  • side effects: drowsiness, dizziness, headaches (less than benzodiazepines)
21
Q

Buspirone

A
  • doesn’t show tolerance/ physical dependence
  • ineffective against panic attacks/ severe anxiety
  • only license for short-term use, although therapeutic actions take days/ weeks to develop
  • long term effectiveness is not proven
  • may INCREASE anxiety initially
22
Q

What are the adaptive changes when there’s a repeated buspirone exposure?

A
  • 5HT1a receptors are somatodendritic autoreceptors on serotonergic neurones in raphe nucleus (autoreceptors: exert negative feedback on the neurones)
  • 5HT1a receptors desensitise on repeated exposure so enhances 5HT release = more AP released= achieved anxiolytic effect
  • that’s why it takes a while to work as take time for neurones to become desensitised
23
Q

What are the other anxiety treatments?

A

1)beta adrenoceptor antagonists
- they remove the peripheral symptoms of anxiety but DO NOT treat anxiety eg palpitations, tremors, by blocking peripheral receptors
2) anti-psychotics eg olanzepine, risperidone
- maybe useful in some cases, eg general anxiety disorder/ post-traumatic stress disorder
- greater incidence of side effects
= NOT a recommended treatment

CNS (15 decks)

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