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Year 4 - Toxicology > 15 - Benzodiazepines > Flashcards

15 - Benzodiazepines Flashcards

1
Q

What are some GABAergic sedative-hypnotic drugs?

A
  • Chloral hydrate
  • Meprobamate
  • Barbiturates
  • Benzodiazepines
  • Z-drugs
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2
Q

Briefly describe chloral hydrate and meprobamate

A
  • Used historically for anxiolysis and sedation
  • 3 chloral hydrate products still marketed in Canada
  • Meprobamate and its pro-drug (carisoprodol) unavailable in Canada
  • Narrow therapeutic index compared to future GABAergic drug classes
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3
Q

Are barbiturates still used today?

A
  • Secobarbital/ amobarbital/ thiopental used for procedural sedation and anesthesia
  • Phenobarbital used for status epilepticus, refractory epilepsy
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4
Q

Can BZD overdose alone be fatal?

A

Rarely

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5
Q

Predisposing factors to BZD overdose

A
  • Age
  • Hepatic impairment
  • COPD
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6
Q

Mild CNS sx of BZD

A
  • Drowsiness or lethargy

- May appear w/in 30-60 mins of ingestion

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7
Q

Moderate CNS sx of BZD

A
  • Slurred speech
  • Amnesia and ataxia
  • May appear shortly thereafter
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8
Q

Severe CNS sz of BZD

A
  • Stupor or coma
  • May occur hours after large ingestions alone or sooner if polydrug overdose
  • Usually accompanied by hypothermia, hyporeflexia, miosis
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9
Q

Rare paradoxical reactions to BZD

A
  • Agitation

- Aggression w/ confusion (more common in elderly, especially if previous dementia)

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10
Q

Rank barbiturates, BZDs, and Z-drugs based on effect on respiration

A

Barbiturates > BZDs >/ Z-drugs

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11
Q

Respiratory depression ____ CNS depression

A
  • Parallels

- Ex: pt in stupor or coma more likely to be hypo-ventilated than pt w/ slurred speech or ataxia

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12
Q

Does level of CNS depression predict level of respiratory depression?

A
  • Not always

- Pt in coma may have normal vital signs

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13
Q

What can increase the risk of respiratory depression with BZDs?

A
  • Respiratory disease
  • Elderly
  • Concomitant opioid use
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14
Q

What is considered hypoventilation?

A

< 12 breaths/min for adults

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15
Q

CVD effects from BZDs and Z-drugs

A
  • Negligible effects generally
  • May produce significant postural hypotension or bradycardia in at-risk px
  • CV collapse rare but may occur w/ large combined alcohol or opioid overdose
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16
Q

Management of BZD overdose

A
  • Emergency and supportive measures
    • Protect airways, assist ventilation
    • Treat coma, hypotension, and hypothermia
  • Decontamination
    • Activated charcoal for poly-drug OD (limited utility in mono-drug overdose due to aspiration risk)
    • Urinary alkalinisation for barbiturates (especially phenobarbital)
17
Q

Antidote for BZD overdose

A

Flumazenil (controversial)

18
Q

What is flumazenil?

A
  • Competitive antagonist of BZ receptor
  • Reverses BZD (and Z-drug) induced CNS depression
  • Can induce BZD withdrawal
  • Re-sedation common after 1-2 hours (like naloxone)
19
Q

When is flumazenil used?

A

Ideal for BZD naive px w/ BZ only overdose

20
Q

Dose of flumazenil

A
  • 0.1-0.2 mg IV over 30 seconds

- Subsequent doses of 0.3 mg and 0.5 mg at 1 min interval up to 3 mg total

21
Q

Flumazenil contraindications

A
  • Pt is physically dependent (withdrawal)
  • Pt receiving BZ for control of seizure disorder
  • Pre-existing cardiac arrhythmia or high-risk of arrhythmia
  • Co-ingestion of agents causing seizure (theophylline, TCAs, etc.)
  • Increased intracranial pressure
  • Unreliable/ unavailable hx (w/ a mono overdose b/c rarely fatal; would potentially be putting pt at more risk)
22
Q

Ideal scenario for flumazenil use

A
  • Pure BZD overdose in non-tolerant individual who has:
    • CNS depression
    • Normal vital signs, including SaO2
    • Normal EKG
    • Otherwise normal neurologic exam
23
Q

BZD chronic use issues

A
  • Long term use of BZD has NOT been associated w/ cumulative toxicity or organ damage
  • Tolerance and dependence during continuous use and withdrawal after cessation of drug use are common clinical consequences
  • Female gender and older age are strong predictors of long-term use
  • Inappropriate use is often “long-term” use BUT “long-term” use alone is not necessarily inappropriate use
24
Q

Treating BZD dependency

A
  • Pharmacotherapy substitutions include (among others):
    • Longer acting BZD (ie: diazepam)
    • Pregabalin
    • Carbamazepine
    • Melatonin
    • Flumazenil (patch?)
  • *Gradual dose reduction +/- behavioural or psychological interventions
  • Determine gradual dose reduction regimens specific to pt
    • Switch to long-acting BZD not usually required

Year 4 - Toxicology (22 decks)

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