Hypnotics Flashcards
How many GABA receptors are there that hypnotics act on?
BZ1 BZ2 and BZ3
Which GABA receptor is responsible for their sedative effects?
BZ1
Which GABA receptor is responsible for myorelaxant and anticonvulsant effects?
BZ2
Which GABA receptor is responsible for anxiolytic effects?
BZ3
Which GABA receptor do Z-drugs primarily bind to?
BZ1
How do benzos work?
enhance the effect of GABA
Positive allosteric modulators of the GABA-A receptor
activation of benzodiazepine receptors causes a conformational change to a central pore, allowing chloride ions to enter the neuron. The influx of the chloride anion results in hyperpolarization of the neuron, resulting in CNS depression
benzodiazepines increase the frequency of the GABA-A receptor Cl– channel opening in the presence of GABA. In the absence of GABA, benzodiazepines have no effects on GABA-A receptor function
What are benzos divided into?
Hypnotics - short half life
Anxiolytics - long half life
What makes up the structure of the benzodiazepine receptor?
Protein comprised of 5 transmembrane subunits (2 alpha, 2 beta and 1 gamma)
What subunits form the binding site for GABA?
alpha and beta
Which subunits form a binding site for benzos?
alpha and gamma
How are most benzos metabolised?
Hepatic CYP3A4 and CYP2C19
How is lorazepam metabolised?
direct glucuronidation without CYP450 metabolism
What are side effects of benzos?
numbed emotions, confusion state, depression
drowsiness, reduced alertness, headache, dizziness
diplopia
muscle weakness
fatigue, ataxia
What is the half life of diazepam?
20-100 hours
What is the half life of clonazepam
18-50 hours
What is the half life of chlordiazepoxide?
5-30 hours
What is the half life of nitrazepam
15-38 hours
What is the half life of temazepam
8-22 hours
What is the half life of lorazepam
10-20 hours
What is the half life of alprazolam
10-15 hours
What is the half life of oxazepam
6-10 hours
What is the half life of zopiclone
5-6 hours
What is the half life of zolpidem
2 hours
What is the half life of zaleplon
2 hours
How should benzos be withdrawn?
reduce 5-10% every 2 weeks
Which benzo produces a less severe withdrawl?
diazepam
Give the equivalent doses to 1mg lorazepam:
1. Lormetazepam
2. Diazepam
3. Nitrazepam
4. Temazepam
5. Chlordiazepoxide
6. Oxazepam
7. Clonazepam
- Lormetazepam 1mg
- Diazepam 10mg
- Nitrazepam 10mg
- Temazepam 20mg
- Chlordiazepoxide 25mg
- Oxazepam 30mg
- Clonazepam 0.5mg
What are the physical features of benzo withdrawal?
Stiffness
Weakness
GI disturbance
Paraesthesia
Flu-like symptoms
Visual disturbance
What are the psychological features of benzo withdrawal?
Anxiety
Insomnia
Nightmares
Depersonalisation
Decreased memory and concentration
Delusions and hallucinations
Depression
How do benzos affect chloride channels compared to barbiturates?
Benzos increase the frequency of chloride channels
Barbiturates increase the duration of chloride channel opening
What type of drug class if zopiclone?
cyclopyrrolone
What are contraindications of zopiclone?
Unstable myasthenia gravis
Respiratory failure
Severe OSA
iS ZOPICLONE safe in breastfeeding?
No as passes through the milk in high quantities
What are side effects of zopiclone?
metallic taste
heartburn
lightening of sleep on withdrawal
What are side effects of zolpidem?
drowsiness
fatigue
depression
falls
amnesia
What receptors does melatonin work?
MT1 MT2 and MT3
How does daridorexant work?
dual orexin receptor antagonist, acting on both orexin 1 and orexin 2 receptors and equipotent on both. The orexin neuropeptides act on orexin receptors to promote wakefulness
Do orexin receptor antagonists alter the proportion of sleep stages?
no
When are orexin receptor antagonists controindicated?
narcolepsy
What are the side effects of orexin receptor antagonists?:
headache
somnolence
