14.6 Drugs that Affect sleep Flashcards
what are the three main classes of sleep affecting drugs
- Hypnotic drugs - increase sleep
- antihypotnitoc drugs - decrease sleep
- Drugs that influence circadian rhythmiticity - like melatonin
what is the primary class of hypnotic drugs, and what is their mechanism
benzodiazepines - GABAa agonists - developed to treat anxiety yet commonly prescribed to assist in sleep
what are the short term effects of benzos (4 plus general conclusion)
- increase drowsiness
- decrease time it takes to fall asleep
- reduce number of mid - night awakenings
- increase total sleep time
- good for the occasional treatment of sleeping difficulties
what are the long term effects of benzos for sleep? (5)
- tolerance develops - need higher doses
- cessation after chronic use causes insomnia which can exhasterbate the problems the drugs were initially designed to solve
- distort the normal pater of sleep - increase the duration of NREM2 and decreasing both slow wave and REM sleep
- cause next-day drowsiness and increase the incidence of traffic accidents
- chronic use substantially reduces life expectancy
explain the imidazopyridines
designed to have similar hypnotic effects to benzos but without as many side effects
- also GABAa agonists
- claimed to be less addictive
give an example of an imidazopyridine and compare it to Benzos
zolpidem
- no safer or more effective than Benzos
what did the finding that the seratonergic raphe nuclei play a role in sleep suggest?
serotonergic drugs might be effective hypnotics
what drug has been the focus of efforts to demonstrate the hypnotic effects of seratonergic drugs?
why?
5 - hydroxytryptophan (5HTP)
- chemical precursor to serotonin
- can pass through the BBB while pure serotonin cannot
is 5 HTP an effective hypotonic?
injections in cats and rats do reverse the insomnia caused by the serotonin antagonist PCPA
- appear to be of no therapeutic benefit in the treatment off human insomnia
what are the three primary classes of anthypnotics?
- cocaine derived stimulants
- amphetamine derived stimulants
- tricyclic antidepressants
what is the primary mechanism of the anti-hypnotics
promote wakefulness by boosting catecholamine activity (norepinephrine, epinephrine and dopamine) through any of the common agonist pathways
is the chronic use of antihypnotics safe?
not so much, they have a variety of adverse side effects like loss of appetite, anxiety, tremor, addiction and disturbance of normal sleep patterns
- may mask pathology causing excessive sleepiness
what is melatonin?
endogenous hormone synthesized from serotonin in the pineal gland
what is the function of the pineal gland in birds reptiles amphibians and fish?
has inherent timing properties
regulating circadian rhythms, seasonal changes in reproductive behaviour through its release of melatonin
what is the function of the pineal gland in humans and other mammals?
were not so sure
Do circulating levels of melatonin display circadian rhythmicity in humans and mammals?
what has this correlation led to?
yes, under control of the SCN, higher levels associated with darkness and sleep
- the long held belief that melatonin pays a role in promoting sleep or regulating its timing in mammals
what is the primary piece of evidence to consider when thinking about the effects of melatonin?
pinealectomy and the elimination of melatonin have little effect on sleep
-the pineal gland does play a role in the dev of mammalian sexual maturity but its functions after puberty are not at all obvious
does exogenous melatonin improve sleep?
meta analysis indicates that it has a small but statistically significant soporific (or sleep promoting) effect
does exogenous melatonin play any influence n human sleep?
yes, specifically as a chronotbiotic (or a substance that adjust the timing of internal biological rhythms)
- shifts the timing of circadian cycles n mammals
how do we believe melatonin increases sleep inn mammals?
evening melatonin - accelerating the start of the nocturnal phase of the circadian rhythm
morning melatonin - increases sleep by dealing the end of the nocturnal phase