15 - Benzodiazepines Flashcards
What are some GABAergic sedative-hypnotic drugs?
- Chloral hydrate
- Meprobamate
- Barbiturates
- Benzodiazepines
- Z-drugs
Briefly describe chloral hydrate and meprobamate
- 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
Are barbiturates still used today?
- Secobarbital/ amobarbital/ thiopental used for procedural sedation and anesthesia
- Phenobarbital used for status epilepticus, refractory epilepsy
Can BZD overdose alone be fatal?
Rarely
Predisposing factors to BZD overdose
- Age
- Hepatic impairment
- COPD
Mild CNS sx of BZD
- Drowsiness or lethargy
- May appear w/in 30-60 mins of ingestion
Moderate CNS sx of BZD
- Slurred speech
- Amnesia and ataxia
- May appear shortly thereafter
Severe CNS sz of BZD
- Stupor or coma
- May occur hours after large ingestions alone or sooner if polydrug overdose
- Usually accompanied by hypothermia, hyporeflexia, miosis
Rare paradoxical reactions to BZD
- Agitation
- Aggression w/ confusion (more common in elderly, especially if previous dementia)
Rank barbiturates, BZDs, and Z-drugs based on effect on respiration
Barbiturates > BZDs >/ Z-drugs
Respiratory depression ____ CNS depression
- Parallels
- Ex: pt in stupor or coma more likely to be hypo-ventilated than pt w/ slurred speech or ataxia
Does level of CNS depression predict level of respiratory depression?
- Not always
- Pt in coma may have normal vital signs
What can increase the risk of respiratory depression with BZDs?
- Respiratory disease
- Elderly
- Concomitant opioid use
What is considered hypoventilation?
< 12 breaths/min for adults
CVD effects from BZDs and Z-drugs
- 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
Management of BZD overdose
- 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)
Antidote for BZD overdose
Flumazenil (controversial)
What is flumazenil?
- 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)
When is flumazenil used?
Ideal for BZD naive px w/ BZ only overdose
Dose of flumazenil
- 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
Flumazenil contraindications
- 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)
Ideal scenario for flumazenil use
- Pure BZD overdose in non-tolerant individual who has:
- CNS depression
- Normal vital signs, including SaO2
- Normal EKG
- Otherwise normal neurologic exam
BZD chronic use issues
- 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
Treating BZD dependency
- 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
