14.6 Drugs that Affect sleep

Question 1

what are the three main classes of sleep affecting drugs

Answer 1

1. Hypnotic drugs - increase sleep
2. antihypotnitoc drugs - decrease sleep
3. Drugs that influence circadian rhythmiticity - like melatonin

Question 2

what is the primary class of hypnotic drugs, and what is their mechanism

Answer 2

benzodiazepines - GABAa agonists - developed to treat anxiety yet commonly prescribed to assist in sleep

Question 3

what are the short term effects of benzos (4 plus general conclusion)

Answer 3

1. increase drowsiness
2. decrease time it takes to fall asleep
3. reduce number of mid - night awakenings
4. increase total sleep time
   - good for the occasional treatment of sleeping difficulties

Question 4

what are the long term effects of benzos for sleep? (5)

Answer 4

1. tolerance develops - need higher doses
2. cessation after chronic use causes insomnia which can exhasterbate the problems the drugs were initially designed to solve
3. distort the normal pater of sleep - increase the duration of NREM2 and decreasing both slow wave and REM sleep
4. cause next-day drowsiness and increase the incidence of traffic accidents
5. chronic use substantially reduces life expectancy

Question 5

explain the imidazopyridines

Answer 5

designed to have similar hypnotic effects to benzos but without as many side effects

• also GABAa agonists
• claimed to be less addictive

Question 6

give an example of an imidazopyridine and compare it to Benzos

Answer 6

zolpidem

- no safer or more effective than Benzos

Question 7

what did the finding that the seratonergic raphe nuclei play a role in sleep suggest?

Answer 7

serotonergic drugs might be effective hypnotics

Question 8

what drug has been the focus of efforts to demonstrate the hypnotic effects of seratonergic drugs?
why?

Answer 8

5 - hydroxytryptophan (5HTP)

• chemical precursor to serotonin
• can pass through the BBB while pure serotonin cannot

Question 9

is 5 HTP an effective hypotonic?

Answer 9

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

Question 10

what are the three primary classes of anthypnotics?

Answer 10

1. cocaine derived stimulants
2. amphetamine derived stimulants
3. tricyclic antidepressants

Question 11

what is the primary mechanism of the anti-hypnotics

Answer 11

promote wakefulness by boosting catecholamine activity (norepinephrine, epinephrine and dopamine) through any of the common agonist pathways

Question 12

is the chronic use of antihypnotics safe?

Answer 12

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

Question 13

what is melatonin?

Answer 13

endogenous hormone synthesized from serotonin in the pineal gland

Question 14

what is the function of the pineal gland in birds reptiles amphibians and fish?

Answer 14

has inherent timing properties

regulating circadian rhythms, seasonal changes in reproductive behaviour through its release of melatonin

Question 15

what is the function of the pineal gland in humans and other mammals?

Answer 15

were not so sure

Question 16

Do circulating levels of melatonin display circadian rhythmicity in humans and mammals?
what has this correlation led to?

Answer 16

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

Question 17

what is the primary piece of evidence to consider when thinking about the effects of melatonin?

Answer 17

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

Question 18

does exogenous melatonin improve sleep?

Answer 18

meta analysis indicates that it has a small but statistically significant soporific (or sleep promoting) effect

Question 19

does exogenous melatonin play any influence n human sleep?

Answer 19

yes, specifically as a chronotbiotic (or a substance that adjust the timing of internal biological rhythms)
- shifts the timing of circadian cycles n mammals

Question 20

how do we believe melatonin increases sleep inn mammals?

Answer 20

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