Anxiety & Insomnia🫣💤 Flashcards

Question

Benzodiazepines & insomnia

Answer 1

• Half-life important in selecting treatment, and in developing risks Shorter half life: lorazepam (10-20), oxazepam (4-15), temazepam (8-22) (most sedating) Longer half life: diazepam (20-100), clonazepam (35), nitrazepam (15-38) • Mechanism of action - see Dr Mike Harte's lectures • Risk of tolerance and dependence, withdrawal reactions greater if shorter half life, higher dose, prolonged use and higher potency - Lorazepam and clonazepam are potent benzodiazepines (tolerance & dependants) • Become more harmful in overdose when taken with other CNS depressants/alcohol/opiods • Plasma levels of BZDs affected by certain CYP3A3/4 enzyme inducers (eg antifungals) and inhibitors (eg microlides) • ADRs sedation/drowsiness (driving), confusion, falls, amnesia, aggression, disinhibition, tolerance, dependence and abuse Patient counselling important: driving/operating machinery, issuing prescriptions - Extreme caution in the elderly, previous addiction • BZDs have been used to treat anxiety for over 40 years - Diazepam, lorazepam, oxazepam, (clonazepam used, not recommended) • NOT recommended for panic disorder or social anxiety disorder, but suitable for GAD crisis • However, some evidence for persistent/severe anxiety in short courses (max. 4 weeks) at lowest effective dose, with some benefiting from long term treatment • Diazepam a suitable choice in anxiety (relatively lower potency = reduced risk of dependence) , avoid lorazepam and clonazepam Disadvantages: May not feel restored / refreshed after Rebound insomnia common: after stopping treatment, insomnia may be worse than before (more difficult getting / staying asleep / waking up early) Risk factors: shorter acting agents, higher doses, prolonged treatment Rebound insomnia can increase the likelihood of drug dependence • BZDs are the most widely prescribed hypnotic agents - temazepam, nitrazepam • Use shorter or longer acting agents depending on symptom presentation - Longer acting increases risk of 'hangover' effect • They can reduce stage 3 and 4 non-REM sleep (slow wave sleep) / nightmares • Extreme caution in the elderly, previous addiction

Answer 2

• Long term treatment may result in: Tolerance (even after 3-14 days!) Psychological and physical dependence Withdrawal reactions upon treatment cessation (anxiety, depression, flu-like symptoms, nightmares, muscle pain and weakness, poor concentration) • NICE - do not prescribe for more than 1 month • Patient and medication related risk factors eg past drug dependance, higher potency, longer duration of use, short half life, higher dose • Symptoms of dependence mimic overdose: unsteadiness, drowsiness, speech disorder, nystagmus • Withdrawal from BZDs: Successful withdrawal from treatment may take months, especially for long term users Switch patients on short/intermediate acting treatments to diazepam (useful liquid preparation) Reduce dose gradually as abrupt withdrawal can be dangerous, e.g. 10% every 2 weeks Slow withdrawal does not eliminate ADRs - psychological therapy may help - When withdrawal symptoms emerge, slow/halt titration, slight dose increase may be necessary

Answer 3

• Zopiclone (longer acting for waking up at night/ early) , Zoplidem (shorter, for when struggling to get to sleep) - little difference in efficacy between 'Z drugs' • Shorten stage 1 sleep, but increase stage 2, little effects on stage 3/4 • Stimulate activity at GABA, receptor in a similar way to BZDs (see Mike Harte's lecture) • Appear just as effective as BZDs, but may also be possible to produce rebound insomnia, tolerance/dependence and neuropsychiatric reactions • Similar cautions to BZD - withdrawal reactions, driving/operating machinery, prescriptions • Need to withdraw gradually if prolonged use • NICE Technology Appraisal TA77 If patients fail to respond to one 'Z drug' do not offer another (same is true for BZDs)

Answer 4

• Enforce practical prescribing of BZD and Z drugs • Patient counselling r.e. appropriateness of BZD and Z drugs • Patient counselling r.e. alternative treatments • Education r.e. effectiveness & tolerance/dependence with BZD/Z drugs

Answer 5

available OTC are sedating histamines, such as Diphenhydramine (e.g., Benadryl, Nytol) Promethazine (e.g., Phenergan) These antihistamines cause drowsiness by blocking histamine H1 receptors in the brain, making them effective for short-term sleep aid use. However, they should be used cautiously due to potential side effects like daytime drowsiness, cognitive impairment, and drug interactions. Sedating Antihistamines: Diphenhydramine, promethazine Block histamine (H1) receptors, inducing drowsiness. Pros OTC availability, effective for short-term use, non-habit forming. Cons Tolerance development, daytime drowsiness, cognitive impairment, drug interactions with valproate. Benzodiazepines: Temazepam, Lorazepam, Diazepam Enhance GABA activity, promoting sedation and muscle relaxation. Pros Potent sedative effect, fast-acting, useful for severe insomnia. Cons High risk of dependence, withdrawal effects, increased sedation when combined with valproate, cognitive impairment. Non-Benzodiazepine Z-Drugs Zolpidem, Zopiclone, Eszopiclone Selectively target GABA receptors to induce sleep with less hangover effect. Pros Less daytime drowsiness than benzodiazepines, effective for short-term use. Cons Can still cause dependence, may lead to sleepwalking or memory issues, interactions with CNS depressants. Melatonin Receptor Agonists Melatonin, Ramelteon Regulate circadian rhythm and promote sleep onset. Pros Helps regulate sleep-wake cycle, non-habit forming. Cons Less effective for severe insomnia, potential for dizziness and headache. Antidepressants (Sedating Types) Trazodone, Mirtazapine, Amitriptyline Affect serotonin and histamine receptors, inducing drowsiness. Pros Can be useful for insomnia with depression or anxiety, long duration of action. Cons Weight gain, daytime sedation, drug interactions, risk of worsening cognitive effects when combined with valproate. Risks to consider due to HS background Drug Interaction with Valproate Increased sedation, dizziness, and cognitive impairment with CNS depressants (e.g., benzodiazepines, sedating antihistamines). Higher Risk of Side Effects More pronounced dry mouth, dizziness, and gastrointestinal discomfort. Respiratory Depression Risk CNS depression from sedatives combined with valproate may suppress breathing in rare cases. Liver Metabolism Effects Valproate affects liver enzymes, altering drug metabolism and increasing side effects (especially for sedating antihistamines and some antidepressants). Pregnancy Concerns Valproate is harmful during pregnancy, requiring specialist consultation before considering sleep medications. Additions from EBL: Benzodiazepines Pros Effective for short-term insomnia; Relieves anxiety; Fast onset; Can be highly effective for sleep. Cons Risk of dependence and tolerance; Cognitive impairment; Withdrawal symptoms; Daytime sedation; Increased risk of falls. Non-Benzodiazepines (Z-drugs) Pros Lower risk of dependence than benzodiazepines; Fewer cognitive side effects; Effective for short-term use. Cons Risk of abuse; Unusual sleep behaviors (sleepwalking, etc.); Cognitive and motor side effects; Rebound insomnia. Melatonin Pros Non-habit forming ; Mimics natural sleep-wake cycle; Generally safe; Effective for circadian rhythm issues. Cons Limited effectiveness for chronic insomnia; Not effective for anxiety or stress-related insomnia; Mild side effects.

Answer 6

COUNSELLING POINTS 1.Take at the same time everyday - usually at night 2. Keep hydrated - 6-8 glasses of water daily 3. Maintain consistent salt intake - can affect lithium levels 4. Carry your lithium card! MONITORING REQUIREMENTS • Lithium levels must be checked weekly after starting or changing dose until they're stable. Then must be checked every 3 months to ensure levels remain within therapeutic range (0.4-0.8 mmol/L) • Toxicity risk if levels exceed 1.2 mmol/L • Kidney and thyroid function checked every 6 months • Also —> U&Es, weight, ECG DRUG INTERACTIONS AND LIFESTYLE ADVICE • Avoid NSAIDS, diuretics, ACE-inhibitors, antipsychotics and steroids antidepressants, • Avoid excess alcohol and caffeine • Avoid taking lithium during first trimester as it can cause birth detects • Avoid stopping the medication abruptly - talk with your prescriber first SIGNS OF TOXICITY Contact your doctor immediately if you experience: • severe nausea, vomiting, diarrhoea • blurred vision or difficulty focusing • tremors or muscle weakness • drowsiness, confusion, or siurred speech -›Typcially due to dehydration, overdose or sudden salt intake changes

Anxiety & Insomnia🫣💤 Flashcards

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