Lecture 10 - Benzos Flashcards
List some GABAergic Sedative-Hypnotic Drugs
- Chloral Hydrate
- Meprobamate
- Barbiturates
- Benzodiazepines
- Z-Drugs
BZD overdose in ____ is almost never fatal
isolation
Why are barbiturates more toxic than BZD?
have a more narrow therapeutic window
What are patient factors that predispose them to BZD overdose?
- age
- hepatic impairment
- COPD
describe sedative-hypnotic symptoms
- sedation, disinhibition, anxiolysis
- hypnosis
- anesthesia
- medullary depression
- coma
Describe the mild CNS symptoms
drowsiness or lethargy may appear within 30-60 mins of ingestion
Describe the moderate CNS symptoms
slurred speech, amnesia, ataxia, may appear shortly after the mild symptoms
Describe the severe CNS symptoms
stupor or coma may occur hours after large ingestions alone of sooner if polydrug overdose
*usually accompanied by: hypothermia, hyporeflexia, miosis
Describe the rare CNS symptoms
agitation, aggression with confusion may occur (more common in elderly)
What has the most respiratory symptoms in toxicity: barbiturates, benzos, or z drugs?
barbiturates
T or F: CNS depression always predicts respiratory depression
False: does not always predict it
i.e. patient in stupor or coma may have normal vital signs
What are risks for respiratory symptoms during toxicity?
- respiratory disease
- elderly
- concomitant opioid use
What RR defines hypoventilation?
RR < 12 breaths/minute for adults
*if patient is apneic (breathing is suspended) or cyanotic (skin is blue), death may be imminent
Which drugs are CV side effects seen in toxicity: barbiturates, BZD, or Z drugs?
barbiturates!
*negligible CVD effects from BZD and Z-Drugs
What are CV effects that are produced with toxicity (specifically with barbiturates) ?
- postural hypotension
- bradycardia
*specifically in those at risk patients (elderly with pre-existing CVD)
Cardiovascular collapse is rare, but may occur with large combined _____ or _____ overdose.
alcohol or opioid
Bullous fixed drug eruptions may occur with ______ and rarely with BZD
*idiosyncratic drug effect
barbiturates
________ is common in severe overdose and may be accompanied by ____ as the poisoning progresses
- hypothermia
- cyanosis
Which benzo’s have some studies saying that they are more toxic?
- alprazolam
- flurazepam
- temazepam
Why do Z drugs possibly have less risk?
once daily dosing
i.e. lesser dispensing quantities compared to BZD
which gender has more deaths from BZD?
male
What is the unholy trinity?
- BZD
- Opioids
- Skeletal Muscle Relaxants
*can get additive euphoric symptoms
Describe the management of the intoxicated patient
Emergency and supportive measures:
- protect airways, assist ventilation
- treat coma
- treat hypotension
- treat hypothermia
Decontamination:
- activated charcoal for poly-drug overdose (limited utility in mono-drug overdose - aspiration risk)
- Urinary alkinization for barbiturates (esp. phenobarbital)
- Antidotes: Flumazenil ? - it is controversial (it is a BZD receptor antagonist)
What is Flumazenil ?
-competitive antagonist of BZ receptor
What can Flumazenil reverse?
BZD and Z-drug induced CNS depression
What can Flumazenil induce?
BZD withdrawal
In what situation is Flumazenil ideal?
for BZ-naive patients with BZ only overdose
What is the dose of Flumazenil?
- 1-0.2 mg IV over 30 seconds
- subsequent doses of 0.3mg and 0.5mg at 1 min interval up to 3mg total
_______ is common after 1-2 hours of flumazenil ?
re-sedation
*common with naloxone as well
When should we avoid using Flumazenil?
- Patient is physically dependent (withdrawal situation)
- Patient is receiving BZ for control of seizure
- Pre-existing cardiac arrhythmia or high-risk of arrhythmia
- Coingestion of agents causing seizures (theophylline, TCAs, etc.)
- Increased intracranial pressure
- Unreliable/unavailable history
Describe the characteristics of the patient in an ideal scenario for Flumazenil
PURE benzodiazepine overdose in a nontolerant (BZD-naive) individual who has:
- CNS depression
- normal vital signs, including Saturated O2
- normal ECG
- otherwise normal neurologic examination
Has long-term use of BZD been associated with cumulative toxicity or organ damage?
nope
What are some common clinical consequences of chronic use of BZD?
Tolerance and dependence during continuous use and withdrawal after cessation of drug
What are some strong predictors of long term BZD use?
- female gender
- older age
*role for pharmacist education and risk reduction (i.e. falls and fractures)
What are some BZD/Z-drug use emerging issues that have yet to be unproven?
- infections
- pancreatitis
- dementia
- cancer
What are some pharmacotherapy substitutions for BZD?
- longer-acting BZD
- pregabalin
- carbamazepine
- melatonin
- flumazenil (patch?)
How can we treat BZD dependency?
- pharmacotherapy substitutions
- gradual dose reduction +/- behavioural or psychological interventions
Describe a gradual dose reduction of BZD?
-decrease dose by 10-25% q1-2 weeks - slower taper may be needed for final 20%
What is absolutely essential for successful discontinuation?
patient “buy-in”
