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Drugs > Benzodiazepines > Flashcards

Benzodiazepines Flashcards

1
Q

Name 8 effects of benzodiazepines?

A
  • sedation
  • anxiolysis
  • anticonvulsion
  • hypnosis
  • skeletal muscle relaxation
  • antegrad amnesia (humans)
  • reduction of dosages of other anaesthetics (e.g. propofol, barbiturates)
  • apetite stimulation
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2
Q

What is the mechanism of action of benzodiazepines?

A
  • bind to receptors that facilitate the inhibitory actions of the neurotransmitter GABA
  • antagonism of serotonin
  • diminished release or turnover of acetylcholine in the CNS
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3
Q

Where in the body do benzodiazepines mediate their mechanism of action?

A
  • limbic, thalamic, and hypothalamic levels of the CNS
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4
Q

Where are benzodiazepines metabolised and excreted?

A

metabolized in the liver to active metabolites that, after conjugation, are excreted in the urine

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5
Q

What are the major differences between diazepam and midazolam?

A

Diazepam:
- not water soluble as it is formulated in a 40% propylene glycol and 10% alcohol vehicle
- better rectal bioavailability

Midazolam:
- water soluble –> well absorbed after i.m. injection
- poor bioavailability when given rectally –> not recommended
- can be given peripherally as CRI
- shorter duration of action

Both can be given intranasally.

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6
Q

Why should diazepam be only given via a central vein?

A

Diazepam is formulated in a 40% Propylene glycol (and 10% alcohol) vehicle. Propylene glycol is an irritant to blood vessels and causes phlebitis and thrombosis after repeated or continuous administration through a peripheral vein.

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7
Q

Name adverse effects of diazepam related to its content of propylene glycol (particularly in cats)?

A

propylene glycol toxicity leading to:
- metabolic acidosis
- hyperosmolality
- neurologic abnormalities
- organ dysfunction

Diazepam infusions are therefore not recommended in cats.

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8
Q

What characteristics of diazepam and midazolam have to be kept in mind with CRI administration?

A

Diazepam:
- adsorbs to plastic (should not be stored in plastic syringer for a longer period of time, infusion lines may require precoating)
- should be protected from light

Midazolam:
- should be protected from light

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9
Q

Name undesired side effects of benzodiazepines?

A
  • aberrant behavior including excitation, irritability, and depression
  • healthy patients may demonstrate dysphoria (more likely when given as sole agent)
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10
Q

Why is oral diazepam in cats contraindicated?

A
  • oral diazepam can lead to fulminant hepatic failure (rare) via an idiosyncratic reaction resulting in acute hepatic necrosis

Successful treatment with recovery appears to be rare, but has been reported.

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11
Q

What is the proposed mechanism of liver failure after oral diazepam administration in cats?

A

idiosyncratic reaction resulting in acute hepatic necrosis

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12
Q

What is neuroleptanalgesia?

A

combination of benzodiazepines with oipiods

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13
Q

Name 2 water soluble benzodiazepines?

A
  1. Midazolam
  2. Lorazepam
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14
Q

What is the recommended sedative dose of diazepam?

A
  • IV: 0.2-0.6mg/kg
    -CRI: 0.1-1mg/kg/hr (central vein)
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15
Q

What is the recommended sedative dose of midazolam?

A
  • IV or IM: 0.1-0.4mg/kg
  • CRI: 0.1-0.5mg/kg/hr
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16
Q

What is the recommeded dose of diazepam for anticonvulsant therapy?

A
  • IV, intranasal: 0.5-1mg/kg
  • PR: 2mg/kg - can be repeated 2-3 times
  • CRI: 0.5-1mg/kg/hr (cental vein)
17
Q

What is the recommeded dose of midazolam for anticonvulsant therapy?

A
  • IV, IM, intranasal: 0.2-0.5mg/kg - can be repeated 2-3 times
  • CRI: 0.2-0.5 mg/kg/hr
18
Q

Discuss benzodiazepines role as appetite stimulans? What is the recommended dose?

A
  • especially in cats
  • effect is separate from sedation or anxiolysis
  • involves binding to benzodiazepine receptors
  • increases attraction to tastes
  • increases the amount of food consumed and the rate of consumption
  • dose: 0.005 to 0.4 mg/kg IV q24h or 1 mg orally q24h (risk of hepatic toxicity)
  • onset of action: few seconds
19
Q

What was the finding of Charalambous et al. study “Intranasal midazolam versus rectal diazepam for the management of canine status epilepticus: a multi- center randomized parallel-group clinical trial” in JVIM 2017? What were the side effects noted?

A

Intranasal midazolam is more affective than rectal diazepam:

  • IN-MDZ and R-DZP terminated status epilepticus in 70% and 20% of cases, respectively.
  • All dogs showed sedation and ataxia.
20
Q

Name the 3 most important adverse effects after a long-term benzodiazepine infusion?

A
  • dysphoric signs
  • excitatory signs
  • delayed awakening
21
Q

Name 2 possible agents to reverse benzodiazepine induced CNS depression or dysphoria, recommended dosages and their mechanism of action?

A
  1. Flumazenil
    - antagonist
    - IV: 0.01-0.02mg/kg (Alternative routes are effective, with some limitations)
    - CRI: 0.005 to 0.02 mg/kg/hr - if frequent dosing is needed
  2. Sarmazenil
    - inverse agonist
22
Q

What does SACCM state about the routine use of benzodiazepine reversal agents flumazenil and sarmazenil?

A

Neither can be recommended for routine use in stable conditions
Toxic effects generally can be managed with supportive care and administration of emetics and/or activated charcoal.

The use in critically ill patients with cardiovascular or pulmonary instability is more commonly justified

23
Q

Name 3 possible adverse effects of the reversal benzodiazepines agents (flumazenil + sarmazenil)?

A

Adverse effects:
- seizure
- Marked excitement and dysphoria
- acute benzodiazepine withdrawal

24
Q

Discuss the role of flumazenil vs. sarmazenil in hepatic enceophalopathy and the proposed pathophysiology in humans and dogs/cats?

A

Flumazenil:
- Human patients with HE have occasionally shown arousal following administration of the benzodiazepine antagonist flumazenil.
- increased endogenous benzodiazepine agonist activity may be involved in HE
- A lack of arousal in dogs and cats (endogenous benzodiazepines are not increased in this syndrome)

Sarmazenil:
- The inverse agonist sarmazenil in animal research models of both acute and chronic HE has resulted in improvement of encephalopathic signs
- consistent with increased GABAergic constitutive activity in HE, rather than an increase in endogenous benzodiazepine agonist ligands

(Sarmazenil should not be considered part of the therapeutic modality for HE)

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