NE2 Insomnia

Sleep Hygiene: ASLEEP
• Avoid ❌
• ❌ should be the only use of the bed
• Leave ❌ out of the bedroom
• ❌ regularly and be outdoors during the day
• Early rising - avoid ❌
• Plan for bedtime

Lack of sleep
• Irritability
• ❌ sleepiness
• ❌ energy/motivation
• Physical discomfort
• Impaired ❌

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

Neurotransmitter effects:
1. Cortical arousal regulated by - (match NT to location)
❌ (locus coeruleus)
❌ pathways (brainstem)
❌ (tuberomamillary nucleus)
❌ (raphe nucleus)

2. Promote wakefulness: orexins/hypocretins (❌)

3. Sleep induced by: ❌

GABA
- Gamma-aminobutyric acid, major inhibitory neurotransmitter, decreases ❌ and therefore CNS function
- Drugs potentiating GABA ❌
1. Hypnotic (❌ properties)
2. Sedative (moderating excitement and ❌)
3. ❌ (anxiety-relieving)

Benzodiazepine receptor agonists e.g. ❌.
Indicated for acute insomnia.
• Dose related ❌ effects
• Facilitate ❌ of sleep
• Alter NREM:REM
• ❌ insomnia
• Caution in pulmonary/respiratory disease: ❌ depression risk.

Pharmacodynamics of benzos:
- ❌ modulator of GABA(A) R (most ❌ R in CNS)
- ‘❌’ inhibition
- ❌polarisation via Cl-
- makes excitation ❌ likely

Pharmacokinetics of benzos:
- Potency: hydrophobicity
- Plasma protein ❌ (less free drug concentration).. so less potency in vivo
- E.g.: ❌ - rapid onset, long acting, vs ❌ rapid onset, short acting, temazepam and triazolam very ❌ half life, nitrazepam ❌ half life
- Caution: increased potency with low ❌ (e.g. haemodilution, liver dysfunction)
- Metabolised by CYP3A4 (Caution: impaired ❌ function)

Non-benzodiazepine hypnotics: zalepon, zolpidem, zopiclone
• ❌ chemical class, similar mechanism
• Postsynaptic GABA(A) Rs - binding site ❌ from benzo site
• Increased ❌ causes hyperpolarisation
• Rapidly ❌, metabolized by liver
• Short t1/2 ~ ❌h

Unwanted effects: Incoordination, drowsiness, dizziness, confusion, amnesia

Benzos and Zs have problems as short term and long-term therapy:
❌ - affects driving, machinery operation, ❌ in elderly
❌ (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. ❌)
- Antipsychotics (e.g. ❌)

GABA ❌ are sleep promoting:
- Anxiolytics (e.g. alprazolam, ❌)

Histamine is a potent wake-promoting neurotransmitter, so ❌ at H1 receptors have sedating properties:
- ❌. Long ❌ of action = daytime drowsiness.
Unwanted effects: headache, psychomotor impairment, ❌ effects, paradoxical excitation (children, elderly)

Melatonin:
-• Produced in the ❌ gland
• Under control of circadian system (SCN)
• Late evening ❌ = arousal ❌, facilitates sleep onset
• Prescription except when supplied: for primary insomnia (adults ❌ years or older, up to ❌ weeks), by a NZ registered, trained pharmacist, in the original pack. Tablets 3mg or MR 2mg.