Lecture 10 - Benzos Flashcards by Sam Myers

List some GABAergic Sedative-Hypnotic Drugs

Chloral Hydrate
Meprobamate
Barbiturates
Benzodiazepines
Z-Drugs

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BZD overdose in ____ is almost never fatal

isolation

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Why are barbiturates more toxic than BZD?

have a more narrow therapeutic window

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What are patient factors that predispose them to BZD overdose?

age
hepatic impairment
COPD

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describe sedative-hypnotic symptoms

sedation, disinhibition, anxiolysis
hypnosis
anesthesia
medullary depression
coma

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Describe the mild CNS symptoms

drowsiness or lethargy may appear within 30-60 mins of ingestion

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Describe the moderate CNS symptoms

slurred speech, amnesia, ataxia, may appear shortly after the mild symptoms

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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

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Describe the rare CNS symptoms

agitation, aggression with confusion may occur (more common in elderly)

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What has the most respiratory symptoms in toxicity: barbiturates, benzos, or z drugs?

barbiturates

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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

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What are risks for respiratory symptoms during toxicity?

respiratory disease
elderly
concomitant opioid use

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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

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Which drugs are CV side effects seen in toxicity: barbiturates, BZD, or Z drugs?

barbiturates!

*negligible CVD effects from BZD and Z-Drugs

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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)

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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?

0. 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"