NE2 Insomnia

Sleep Hygiene: ASLEEP • Avoid [blank_start]alcohol, caffeine and nicotine[blank_end] • [blank_start]Sleep (and sex)[blank_end] should be the only use of the bed • Leave [blank_start]laptops, TVs and paperwork[blank_end] out of the bedroom • [blank_start]Exercise[blank_end] regularly and be outdoors during the day • Early rising - avoid [blank_start]sleeping in and daytime naps[blank_end] • Plan for bedtime

Lack of sleep • Irritability • [blank_start]Daytime[blank_end] sleepiness • [blank_start]Low[blank_end] energy/motivation • Physical discomfort • Impaired [blank_start]cognitive function[blank_end]

Insomnia - “Repeated inability to initiate and maintain sleep.” - Transient, [blank_start]2-3[blank_end] days - likely cause [blank_start]acute[blank_end] situational or environmental stress (shift work, jet lag) - Short term, <[blank_start]3[blank_end] weeks - likely cause [blank_start]ongoing[blank_end] personal stress - Long term, >3 weeks - likely causes psychiatric illness, behavioural, medical reasons

Neurotransmitter effects: 1. Cortical arousal regulated by - (match NT to location) [blank_start]Noradrenaline[blank_end] (locus coeruleus) [blank_start]Cholinergic[blank_end] pathways (brainstem) [blank_start]Histamine[blank_end] (tuberomamillary nucleus) [blank_start]Serotonin[blank_end] (raphe nucleus) 2. Promote wakefulness: orexins/hypocretins ([blank_start]peptide neurotransmitters[blank_end]) 3. Sleep induced by: [blank_start]GABA, melatonin and galanin[blank_end]

GABA - Gamma-aminobutyric acid, major inhibitory neurotransmitter, decreases [blank_start]neuronal excitability[blank_end] and therefore CNS function - Drugs potentiating GABA [blank_start]transmission[blank_end] 1. Hypnotic ([blank_start]sleep inducing[blank_end] properties) 2. Sedative (moderating excitement and [blank_start]calming[blank_end]) 3. [blank_start]Anxiolytic[blank_end] (anxiety-relieving)

Drag and drop pharmacotherapies people take for insomnia into the right boxes.

Benzodiazepine receptor agonists e.g. [blank_start]triazolam, temazepam[blank_end]. Indicated for acute insomnia. • Dose related [blank_start]hypnotic[blank_end] effects • Facilitate [blank_start]onset and duration[blank_end] of sleep • Alter NREM:REM • [blank_start]Rebound[blank_end] insomnia • Caution in pulmonary/respiratory disease: [blank_start]respiratory and CV[blank_end] depression risk.

Pharmacodynamics of benzos: - [blank_start]Positive allosteric[blank_end] modulator of GABA(A) R (most [blank_start]abundant[blank_end] R in CNS) - ‘[blank_start]tonic[blank_end]’ inhibition - [blank_start]hyper[blank_end]polarisation via Cl- - makes excitation [blank_start]less[blank_end] likely Pharmacokinetics of benzos: - Potency: hydrophobicity - Plasma protein [blank_start]binding[blank_end] (less free drug concentration).. so less potency in vivo - E.g.: [blank_start]Diazepam[blank_end] - rapid onset, long acting, vs [blank_start]midazolam[blank_end] rapid onset, short acting, temazepam and triazolam very [blank_start]short[blank_end] half life, nitrazepam [blank_start]long[blank_end] half life - Caution: increased potency with low [blank_start]albumin[blank_end] (e.g. haemodilution, liver dysfunction) - Metabolised by CYP3A4 (Caution: impaired [blank_start]hepatic[blank_end] function)

Non-benzodiazepine hypnotics: zalepon, zolpidem, zopiclone • [blank_start]Different[blank_end] chemical class, similar mechanism • Postsynaptic GABA(A) Rs - binding site [blank_start]distinct[blank_end] from benzo site • Increased [blank_start]Cl- influx[blank_end] causes hyperpolarisation • Rapidly [blank_start]absorbed[blank_end], metabolized by liver • Short t1/2 ~ [blank_start]1-6[blank_end]h Unwanted effects: Incoordination, drowsiness, dizziness, confusion, amnesia

Benzos and Zs have problems as short term and long-term therapy: [blank_start]Sedation, drowsiness, muscle relaxation[blank_end] - affects driving, machinery operation, [blank_start]falls[blank_end] in elderly [blank_start]Abusable[blank_end] (rapid onset, short duration, high potency) and dependence risks.

Alternate medications for sleep (off label use): ACh, NA, 5-HT, and DA promote wakefulness, so antagonists of these can be sedating: - Antidepressants (e.g. [blank_start]amitriptyline, mirtazapine, doxepin[blank_end]) - Antipsychotics (e.g. [blank_start]quetiapine[blank_end]) GABA [blank_start]agonists[blank_end] are sleep promoting: - Anxiolytics (e.g. alprazolam, [blank_start]clonazepam[blank_end]) Histamine is a potent wake-promoting neurotransmitter, so [blank_start]antagonists[blank_end] at H1 receptors have sedating properties: - [blank_start]Promethazine, diphenhydramine[blank_end]. Long [blank_start]duration[blank_end] of action = daytime drowsiness. Unwanted effects: headache, psychomotor impairment, [blank_start]antimuscarinic[blank_end] effects, paradoxical excitation (children, elderly) Melatonin: -• Produced in the [blank_start]pineal[blank_end] gland • Under control of circadian system (SCN) • Late evening [blank_start]rise[blank_end] = arousal [blank_start]declines[blank_end], facilitates sleep onset • Prescription except when supplied: for primary insomnia (adults [blank_start]55[blank_end] years or older, up to [blank_start]13[blank_end] weeks), by a NZ registered, trained pharmacist, in the original pack. Tablets 3mg or MR 2mg.