Insomnia

Define insomnia

Inability to obtain adequate sleep - e.g. issues falling asleep, frequent nocturnal wakening, or early wakening.

Acute insomnia

Less than three months, often related to stressful events, change in habits, travel, pain, certain medications - treated by treating underlying issue

Chronic insomnia

Persist past three months, related to chronic pain, sleep apnoea, mood disorder, nocturia caused by diabetes

Non-drug treatment

Cognitive behavioural therapy and adjustments to sleep hygiene

Pharmacologcial management

Sedatives, hypnotics, anxiolytics - whole not curtaive cna provide short term relief.

Benzodiazepines - Short acting or long acting?

Short acting preferred as long acting can cause increased drowsiness during the day.

Benzodiazepines MOA

Act selectively on GABA-A receptors by binding allosterically - this enhances GABA effect by facilitating the openinf of GABA-activated chloride channels, leading to an influx of chloride ions into the neuron causing hyperpolarisation, thereby reducing neuronal excitability which creates a calming effect.

This decreases time taken to fall asleep and increase total sleep duration

Which GABA A subunit mediate sedative/hypnotic effects?

Alpha 1

Which GABA A subunit mediate anxiolytic effects?

Alpha 2

Benzodiazepines adverse effects

Tolerance or dependence may develop with chronic use and withdrawal can lead to rebound.

Cause excessive CNS depression - drowsiness, impaired coordination, ataxia, increased risk of falls for elderly people

Z drugs

Potentiate the inhibitory effects of GABA-A specific to Alpha 1 subunit.

Reduce sleep onset time by 5-15 minutes and increase total sleep duration by 30-60 minutes.

This selectivity leads to a more focused hypnotic effects with less muscle relaxant and anxiolytic activity.

Onset of action is rapid, short half-life, and no active metabolite therefore, less daytime sedation

Z drugs adverse effects

Lowered risk of dependance and tolerance!

Can cause sedation, dizziness, increased risk of falls, paranomias - sleepwalking, driving, eating.

Melatonin

Acts as an agonist on MT1 and MT2 receptors. Promotes sleepiness and helps regulate circadian rhythm - natural hormone.

Dual Orexin receptor antagonist - suvorexant

Orexins A and B are wake promoting neuropeptides - high during the day, fall at night. Dual Orexin receptor antagonists block Orexins A and B from binding to orexin 1 and 2 thereby reducing wakefulness

Sedating antihistamines

Inverse agonists at histamine H1 receptors - keeping H1 in its inactive state thereby reducing wakefulness and promoting sleep

Sedating antihistamines adverse effects

Broad effects - not generally recommended, tolerance and dependence develop relatively quickly, sedation, falls, confusion, next day drowsiness, dizziness and anticholinergic effects e.g. dry mouth and constipation.