Hypnotics Hupka

Front 1

we see insomnia commonly in what population?

Back 1

elderly, women

Front 2

common risk factors for insomnia?

Back 2

depression, respiratory symptoms, disability, fair to poor percieved health, widowhood.

Front 3

sleep is defined as?

Back 3

Sleep - reversible state of reduced consciousness

Front 4

define sleep latency

Back 4

inability to fall asleep

Front 5

if you are constantly fatigued post sleep you have?

Back 5

poor quality of sleep

Front 6

hypnotics therapy is aimed at doing two main things:

Back 6

initiating sleep

maintaining sleep

Front 7

Elderly adults often show similar sleep patterns to that of people with _________

Back 7

insomnia

Front 8

changes in sleep EEG patterns vary widely but two generalities exist we see:

Back 8

decreased:


amount of slow wave sleep (deep)
Total time spent in sleep

Front 9

name the 7 types of insomnia:

Back 9

transient
short term ( situation)

primary (long term)

drug induced (CNS stimulants, tolerance/withdrawal from CNS depts)


Associated with mental disorders like
Neurotic (anxiety and insomnia often co-exist) and Affective and Psychotic

Associated with physical disorders,( e.g., anginal pain, gastro-esophageal reflux)

Associated with disorders of the sleep process (e.g., sleep apnea, or restless leg)

Front 10

mainstays of hypnotic drug therapy:

Back 10

Hypnotic drug therapy should be accompanied by other non-pharmacologic intervention and should be used over short time periods only

Front 11

define a hypnotic drug

Back 11

Definition – a drug which produces drowsiness (somnolescnce) and facilitates the onset and maintenance of a state of natural sleep

Front 12

characteristics of an "ideal" hypnotic agent?

Back 12

An ideal agent would have:

Rapid onset and sufficient duration
No disturbance in normal sleep pattern
Wide margin of safety
Absence of hangover effect – no hangover.
No tolerance or physical/psychological dependence (low)
No interaction with other CNS depressant drugs**

that last one is hard to achieve*

Front 13

hypnotic drugs are ALL _______

and generally ------------------- normal sleep pattern
generally ----------------- other CNS depressants
Often have potential for -----------------

Back 13

cns depressants

alter

potentiate

abuse

Front 14

what miscellaneous drugs do we use to treat insomnia?

Back 14

Melatonin receptor agonists
Natural products
Chloral hydrate
Paraldehyde
Sodium oxybate

Front 15

mainly BDZ drugs for insomnia target which receptor?

why?

Back 15

Selective BDZ1 agonists


BDZ1 has minimal effect on sleep architecture
BDZ2 may change sleep patterns (don’t want to do that!)

**recall one of our charectersitics for ideal drugs is that we dont want to change the sleep pattern

Front 16

the gaba A chloride channel where BZD selectively bind is made up of __ subunits?

Back 16

5

Front 17

describe current day hypnotics and there effects?

Back 17

Hypnotics used most frequently today selectively bind to BDZ1
They also have a shorter duration givine less daytime sedation and hangover

Front 18

Zolpidem (Ambien) has a onset time of? duration of?

Back 18

30 min.

6-8 hrs

Front 19

name some specific BZD1 agonists?

Back 19

zolpidem ( Ambien), zaleplon (Sonata) and eszopiclone (Lunesta)

produce minimal rebound insomnia or disruption of deep sleep

Front 20

is zolpidem and pther "ZO" drugs true BZD1 agonists true BZDs?

Back 20

no. they act on a subtype of the same receptor, chemically different.

Front 21

main reason we use zolpidem?

Back 21

induce sleep

Front 22

adverse effects of BDZ1 agonists?

Back 22

Headache and drowsiness upon awakening, dizziness, NVD
Memory impairment at higher dose
Bitter aftertaste with eszopiclone
Sleep-driving (?)

Front 23

flurazepam and quzepam have LONG HALF LIVES and can induce a hangover effect, what else do they do (2) ?

Back 23

produce Less REM rebound upon withdrawal

Form active metabolites which may accumulate upon chronic use (long t1/2 of metabolites)

Front 24

tamazepam duration of action?

Back 24

immediate

Front 25

which bdz1 drugs are Safer for use in presence of liver dysfunction and in elderly patients?

Back 25

oxazepam, loraazepam

Front 26

Triazolam has a __________________
But controversy over safety
Thought to increase incidence of confusion and abnormal (disinhibited) behaviors


Also problem with _________and increased likelihood of rebound insomnia when stopping use

Back 26

fast onset, short T ½ (3-4 hours).

early morning insomnia

Front 27

dont use estzolam with?

Back 27

CYP3A4 inhibitors (ketaconazole - doc for tinea versoicolor)

Front 28

other classes used in tx of insomnia?

Back 28

Melatonin receptor agonist (Rameteon)

Front 29

which two receptors do melatonin receptor agonists hit, what are its effects on sleep?

Back 29

MT1 regulates sleep
MT2 mediates phase shifting on circadian rhythm.


Effects on sleep
decreases sleep latency (desired effect)
slight decreases in stage 3 & 4
does not help to stay asleep (duration 2-4 hrs)
No tolerance, so ok for chronic use.

USED FOR DIFFICULTY FALLING ASLEEP.

Front 30

adverse effects of ramatleon?

Back 30

Somnolence
Dizziness
Nausea
Headache
Hyperprolactinemia( melanin receptors – dopamine)


No rebound insomnia, withdrawal signs or potential for abuse

Front 31

when talking about barbiturates which 2 drugs can we use to cure insomnia?

Back 31

Secobarbital and pentobarbital have been used primarily as hypnotics because of their intermediate duration of effects
(4-6 DURATION HR)

USE THEM TO FALL ASLEEP

AMOBARB USE TO STAY ASLEEP (6-8 DURATION HR)

Front 32

duration of action of:

THIOPENTAL - AND USE?

PHENOBARBITAL- AND USE?

Back 32

THIOPENTAL IS ULTRA SHORT AND USED FOR ANESTHETIC PURPOSES.

PHENOB IS LONG ACTING (12 HRS) AND IS FOR DAY TIME SEDATION AND ANTICONVIULSANT USE, NOT DOC.

Front 33

MOA OF BARBIURATES?

Back 33

Like BDZs, enhance GABA effects
Barbiturates act at a specific receptor site on the GABA receptor-modulated ionophore
Keeps the channel open longer
Also thought to have some direct GABA agonistic properties (at higher doses)

unlike bdz they are LESS SELECTIVE IN THEIR ACTION , depress neuroexcitatory NTs (GLUTAMATE)

CNS – continuous CNS depressant
sedation
Hypnosis
Hangover: more intense with long acting agents
↓ REM phase, ↑ duration of stage 2 NREM phase → REM rebound
Hyperalgesia (not analgesics!!)
Anesthesia
Anticonvulsant

Front 34

barbiturate effect at the RESP system? CV system?

Back 34

at anesthetic or toxic dose they depress the meduallry resp center


at therapetuic dose, there is a slight decrease in BP and HR, but ar a toxic dose, we see CHF, hypoveolemic shok and cardiac arrest due to vasomotor depression.

Front 35

relationship between phenoB and the liver?

Back 35

induces p450, can lead to acute intermittent porphyria (contraindication)

Front 36

how us thiopental special in the termination of its effects?

Back 36

it gets redistributed amongst tissues.

Front 37

barb side effects in therapeutic dose?

in acute overdose?

in chronic use?

Back 37

At therapeutic dose:
Hangover effect at hypnotic dose
Drowsiness, dizziness, ↓ motor skill at sedative dose
Paradoxical hyperexcitability, confusion
Allergic dermatitis

acute overdose:


Acute overdose:
coma, decreased respiration, hypothermia, hypotension, pulmonary edema, renal or cardiovascular failure
Treatment – symptomatic support, gastric lavage, dialysis, pH alteration (phenobarb)

Lethal dose for addicts not much greater than normal individuals (little tolerance develops to lethal dose)

chronic: psyhcological, physical dependence can occur.

Front 38

why is aprupt whithdrawal of barb such a bad thing what do we see, describe the timeline of events?

Back 38

24 hrs - nervous, weak, termor, insomnia

2-3 days - NV, bp, delrium, fever, convulsions, hyperexcitable

4-7 days - cv collapse and death FATAL!!!

DAY 8= SYMPTOMS SUBSIDE.

Front 39

how would we manage withdrawal from barbs?

Back 39

Slowly wean (10 days to 3 weeks)
Substitute with phenobarbital and gradually taper off
IV diazepam to manage status epilepticus

Front 40

once again, tell me which barb to use for convulsions, which to use for induction anesthesia?

Back 40

phenoBarb, anticonvulsant

induction anesthesia - thiopental.

Front 41

chloral hydrate how does it work?

Back 41

metabolzed to tricholoroethanol by alchohol dehydrogenase, induces sleep in 30 min and lasts fr 6 hrs.

Front 42

chlorol hydrate side effects?

Back 42

GI irritation, disagreeable taste
less hangover effect, REM suppression than barbiturates
lacks marked respiratory and cardiovascular depression

Front 43

chlorol hydrate enhances tox with?

Back 43

ethanol,


Knock-out drops or “Mickey Finn” – enhanced toxic effects when combined with ethanol

Front 44

when to use cholorol hydrate?

Back 44

Safe in children & elderly patients in whom BZDs or barbiturates can induce paradoxical excitation

Front 45

STINKY SLEEP DRUG?

Back 45

PARALDEHYDE

Front 46

which drugs are known to have less resp depressive effects than barbs, but more CV depression, convuslsion and coma and death?

Back 46

glutethimide

methlpyrlon

Front 47

which drug has increased hypnotic effects when admoinistered with etoh?

Back 47

ethchloyvynol


Tertiary alcohol with hypnotic and toxic effects increased by ethanol
Widely advertised but efficacy not well established

Front 48

a breakdown product of GABA , functions as a endogenous neuromodulator, with effects on behavior and vigilance, stimulates gabaB and specfic GHB receptors?

Back 48

sodium oxybate (GHB - gamma hydroxy butyrate)

Front 49

GHB can be used for?

Back 49

cataplexy associated with narcolepsy

Thought to improve quality of nighttime sleep and thus decrease daytime sleepiness and cataplexy

May also help sleep problems associated with fibromyalg

Front 50

ghb can cause _________ there are strict guideline for its use, what are some adverse effects?

Back 50

dependency (psych and physical)


adv:

sleepwalking
Incontinence
respiratory depression and amnesia (esp. combined with alcohol or other CNS depressants).

Front 51

an antypical antidepressant, with sedative properties, sleep aid used for people who are DEPRESSED, EFFECTIVE FOR BOTH INSOMNIA AND DEPRESSION CAN EVEN BE USED TO TX INSOMNIA BROUGHT ON BY OTHER ANTIDEPRESSANT MEDICATIONS.

Back 51

trazodone.

**many antidepressants are likely to cause insomnia, even when taken in the morning, trazodone does NOT.

Front 52

OTC sleep aids, just to name a few?

Back 52

diphenhydramine ( benadryl)
doxylamine
melatonin - natural, for jetlag, helps w/ weaning off BDZ

valerian -dietary supplement.

Front 53

avoid BDZ WITH?

Back 53

pregos = teratogenic

Front 54

you want to Caution the patient that alcohol, barbiturates, non-barbiturate sedative-hypnotics, and other CNS depressants have _______ depressing effects and should not be taken in combination without specific instructions from the physician.

Back 54

ADDITIVE.

Front 55

SOME NOTES ON BARBITUATES:


After chronic administration, sudden drug withdrawal may cause _________ with increased periods of dreaming, nightmares, and insomnia


Because of their high abuse potential, duration of drug administration should be as ____ as possible.

Chronic use may increase ______ and exacerbate insomnia. ____________________ is possible.

Back 55

REM REBOUND

SHORT

ANXIETY

Physical and psychological dependence

Front 56

QUICK REVIEW DRUGS (AND CLASSES) USED TO TX INSOMNIA:

Back 56

bdz1 agonists

BARBS

MT1,2 AGONIST

CHOLORAL HYDRATE

PARAALDEHYDE

SODIUM OXYBATE (GHB)

ETHCHLORVYNOL

TRAZODONE

ANTIHISTAMINE OTC

VALERIAN HERBAL

OTC MELATONIN