Benzodiazepines and Z-hypnotics Flashcards
BZD common side effects
CNS: sedation, drowsiness
- do not drive/operate machinery
- take at bedtime
- do not drink alcohol (excessive sedation due to CNS depression)
CV: low BP, light-headedness
- get up slowly from sitting/lying position
GI: nausea, stomach discomfort, constipation
- take with/after food
- take adequate fiber and drink water
BZD serious side effects
- stop meds, seek medical attention
- Allergy: rashes, itch, swelling on face, eyes or lips
- Difficulty breathing
-
Tolerance/Dependence: This medication can be habit-forming when taken excessively or for a
prolonged duration. If taken at high doses or for long-term, do not stop abruptly as it may lead to withdrawal symptoms (e.g. sweating, increased heart rate, tremors, insomnia, agitation, hallucinations, fits). Need gradual dose tapering by Dr. - Amnesia: Memory loss
- Abnormal thinking, behavioural changes, or hearing/seeing things that do not exist (hallucinations)
- Disinhibition/Paradoxical reactions: Unusual excitement, irritability, or agitation
- Sleepwalking
- Confusion, slurred speech, vertigo/headache
- Fast, slow, or irregular heartbeat
- Problems with eyesight (visual disturbances)
- Hepatotoxicity: Dark brown urine, light coloured stools (pale grey/ clay-coloured), yellowing of skin and eyes
- Muscle weakness, ataxia; feeling clumsy/unsteady
- IV/IM: Propylene glycol/Polyethylene glycol toxicity more likely in renal/ paediatric patients, higher
doses.
[BZD DDIs - PD]
DDIs with alcohol
What about Z-hypnotics
BZD + Alcohol/CNS depressants
- Enhance CNS depressant effects (excessive sedation, poor concentration, slowed breathing)
- Take BZD and alcohol at least 4-6h apart
Same precaution for Z-hypnotics - may increase CNS depressant effect + complex sleep-related behaviors like sleep walking
CNS depression occurs with: alcohol, barbiturates, antipsychotics, sedatives/hypnotics/anxiolytics, antidepressants, opioids, sedating antihistamines, anticonvulsants, anesthetics
[BZD DDIs - PD]
DDIs with opioids
What about Z-hypnotics
BZD + opioids
- increased mortality due to profound CNS depression, respiratory depression, coma and death
- avoid combi, limit dose and duration (typically BZD is discontinued, as opioid is indicated for severe pain)
Same precaution for Z-hypnotics: profound sedation, respiratory depression, coma, and death
[BZD PK - metabolism]
Benzodiazepines are metabolized by CYP3A4 (EXCEPT Lorazepam)
Lorazepam undergoes phase 2 glucuronidation (no CYP enzyme interactions)
[BZD Contraindications]
- Hypersensitivity to benzodiazepines or any component of the product
- Acute narrow angle glaucoma
(IV/IM) - standby Flumazenil + ventilatory support + resuscitation equipment
- Severe respiratory insufficiency (except during mechanical ventilation) - includes unstable myasthenia gravis
- Hypersensitivity to excipients: polyethylene glycol toxicity
[Z-hypnotics Contraindications]
Contraindicated in:
- Acute narrow angle glaucoma
- Acute pulmonary insufficiency, respiratory depression, sleep apnea syndrome, COPD, marked neuromuscular respiratory weakness including myasthenia gravis
- History of known hypersensitivity
SAME AS BZD
- History of complex sleep behaviors after taking any non-BZD sedative
- Severe hepatic insufficiency
[BZD DDI]
- Probenecid
- Valproate
Probenecid and Valproate increase plasma Lorazepam concentrations (due to UGT enzyme interactions)
Require reduction in IM/IV dose of Lorazepam (50% dose reduction)
[BZD DDI]
IM Olanzapine and IM Lorazepam
IM Olanzapine and IM Lorazepam must be given 1h apart due to risk of cardiorespiratory fatality
Additional Precautions for BZD use:
- Renal and hepatic impairment
- Lower dose in mild-mod hepatic/renal impairment
- Avoid use in severe hepatic/renal impairment
Additional Precautions for BZD use:
- Children, elderly, debilitated
Children, elderly, debilitated:
- Paradoxical excitement
Elderly, debilitated:
- Beers criteria, increase risk of fall and delirium
- initiate at low end of dosage range, titrate slowly to a lower max dose (Lorazepam: initiate at 0.5mg/day, max 2mg/day)
Additional Precautions for BZD use:
- Pregnancy and breastfeeding
- Avoid unless benefits outweight risks
Additional Precautions for BZD use:
- History of substance (drug/alcohol) abuse or psychiatric disorders
- Avoid, risk of CNS depression with alcohol
Additional Precautions for BZD use:
- Abrupt discontinuation
Withdrawal effects
- Rebound anxiety, sweating, increased HR, tremors, insomnia, agitation, hallucinations, seizures
Gradual tapering required
Additional Precautions for BZD use:
- ECT
Omit BZD 12h before ECT
Also same for lithium and anticonvulsants
