Z drugs Flashcards
What are the indications for Z-drugs?
Insomnia
Give examples of Z-drugs
Zopiclone
Zolpidem
What is the pharmacodynamic of Z-drugs?
Non-benzodiazepine hypnotics
Interacts with the GABABZ receptor complex
GABABZ is responsible for some of the pharmacological properties of benzodiazepenes including, sedation, anti-anxiety, muscle relaxant and anticonvulsant
What is the pharmacokinetic of zolpidem?
Bioavailability = rapidly absorbed from GI tract
Protein binding = 92.5 +/- 0.1
Half-life = 2.5-2.6
Metabolism = Hepatic - CYP3A4, CYP1A2, CYP2C9 mainly
Excretion = Kidneys
What is the pharmacokinetic of zopiclone?
Bioavailability = rapidly absorbed after oral administration
Protein binding = ~45%
Half-life = 5 hours (range = 3.8-6.5 hours)
Metabolism = Hepatic via decarboxylation, demethylation and side chain oxidation
Excretion = Unknown
What is the typical dosing of zopiclone?
Adults = 7.5mg OD at bedtime
Elderly = if essential use reduced dose - initially 3.75mg OD at bedtime
What is the typical dosing of zolpidem?
Adults = 10mg OD at bedtime
Elderly + debilitated patients = if essential use reduced dose - 5mg OD at bedtime
What are the contraindications of Z-drugs?
- marked neuromuscular respiratory weakness
- respiratory failure
- myasthenia gravis
- OSA
- pregnancy and breastfeeding (risk of neonatal respiratory depression and withdrawal symptoms)
- severe hepatic impairment
- psychotic illness
What are the cautions of Z-drugs?
- chronic pulmonary insufficiency (increased risk of respiratory depression)
- the elderly (avoid if possible due to increased risk of adverse effects including falls and fractures)
- Hx of drug or alcohol abuse (manufacturer advises extreme caution)
- muscle weakness
- psychiatric illness inc. depression
- hepatic and renal impairment (reduce dose, avoid if severe)
What are the GI adverse effects of Z-drugs?
Dry mouth
Abdo pain
N+V
Diarrhoea
What are the psychiatric adverse effects of Z-drugs?
Anterograde amnesia
Impaired cognition and concentration
Depression
Suicidal ideation and attempt
Anxiety
Psychosis and behavioural abnormalities
Restlessness
Agitation
Irritability
Aggression
Delusion
Anger
Nightmares
Hallucinations
Inappropriate behaviour
What are the neurological adverse effects of Z-drugs?
Confusion
Dizziness
Hallucination
Headache
Sleep disorders
Ataxia
Falls
Muscle weakness
Respiratory depression
Decreased level of consciousness
What should you advice people of Z-drugs about performing skilled task e.g., driving?
MHRA advises that people on zolpidem should:
- not drive, operate machinery, or work at heights until at least 8 hours after taking zolpidem
The manufacturer advises that the risk of psycomotor impairment (including impaired driving ability) is increased if:
- zopiclone is taken within 12 hours of performing activities requiring mental alertness
- a dose higher than the recommended dose is taken
- zopiclone is co-administered with alcohol, other CNS depressants or drugs that increase the blood levels of zopiclone
Apart from performing skilled tasks, what other advice does the MHRA give for people of zolpidem?
- only take 10mg of zolpidem at bedtime and not take it again the same night (people with liver impairment and the elderly should take no more than 5mg of zolpidem a night)
- not take zolpidem with alcohol, illicit drugs, or other CNS suppressants
How does the blood concentration of zolpidem differ between men and women?
Studies have shown that women tend to have higher blood concentrations of zolpidem and greater impairment of driving ability the following morning than men
The US Food and Drugs Administration recommend dosing for women at half that for men.
