Pharm-Sedative Hypnotics/anxiolytics/ethanol

Front 1

What are anxiolytics?

Back 1

deacrease anxiety

Front 2

What are sedatives?

Back 2

decrease activity, alertness, intellectual performance, responsiveness; produce "calming" effects; usually non-specifically releive anxiety

Front 3

What are hypnotics?

Back 3

produce drowsiness, shorten sleep onset and reduce nocturnal wakening

Front 4

What are anesthethics?

Back 4

cause a state of charct. analgesia, LOC, absence of arousal in respone to noxious stimuli

Front 5

What ia common characteristic of all sedative/hypnotics?

Back 5

All "gemeral" CNS depressants, capable of producing dose-dependent CNS depression to medullary depression, coma and death. EXCEPT BDZ!!

Front 6

What are the pharmaco properties of BDZ?

Back 6

1. high lipid/water partition coefficeint, bind 70-90% with plasma protien
2. are redistributed and helps terminate the action of some
3.completely absorbed orally, some IM or IV
4. Metabolized by liver before excreted

Front 7

What are the drugs of BDZ and relative half lifes?

Back 7

Long (>1day): Flurazepam,chlordiazepoxide, clorazepate, diazepam
Interm (6-24hrs): temazepam, estazolam
Short (<6hrs): trazolam, zolpidem

Others: lorazepam, midazolam, alprazolam, clonazepam,

Front 8

What is the mechanism of action of BDZ?

Back 8

Positive allosteric modulators of GABA-operated Chloride channels (GABAa receptors). Site distinct from barbituate site
***4 different a units that bind BDZ

Front 9

Where are the locations of the a subunits that bind the BDZ in the body?

Back 9

a1-a3 bind in the CNS
a1=cortex and thalamus=sedation and amnesia
a2=limbic system and hippocampus= anxiolytic affect
a3= reticular formation, thalamus=LOC

Front 10

Overall effect of BDZ?

Back 10

To increase synaptic inhibitions, no effect on Chloride channel conductance in the absence of GABA

Front 11

Whar are the pharm/clinic properties of BDZ?

Back 11

1. All work in CNS
2. not work lower than brainstem so little cardiorespiratory sx
3.Not analgesic
4.assoc with tolerance and dependence

Front 12

What are the CNS effects of BDZ?

Back 12

anxiolytic effects, sedation, muscle relazation, anticonvulsant, hypnosis, retrograde amnesia, ataxia, confusion,stupor

Front 13

What does the intensity of withdrawal depend on for BDZ?

Back 13

2 things:
1. dose of drug daily: higher the more severe
2. the half life of the drug: the longer the less severe

Front 14

What are the SE of BDZ?`

Back 14

1. excessive sedation and impaired motor perfomance
2. additive effects of other CNS depressants can be lethal with alcohol
3. adversley affect breathing
4. disinhibition reactions=hypomanic or hostile behavior

Front 15

What drugs are used for insomnia of the BDZ

Back 15

1. BDZ
*Common drugs:
a:Flurazepam (long half-life)-little hangoer, impaired driving after
b: Temazepam (interm half), sense of refreshing sleep without hangover, but still impaired drive in AM
c: Estazolam &Triazolam (short half 2-3hrs) SE of waking early and being anzious during the day, one dose tolerance with rebound?
2. Non-BDZ:
a1 subunit selective is Zolpidem (ambien); short half 1-2hrs, zaleplon (sonata) shorter to allow reuse, eszopiclone (lunesta)

Front 16

What are the BDZ used for anxiety?

Back 16

1. with prominent autonomic signs use: alprazolam, clonazepam, lorazepam (other tx AD)
2. generalized or non-specific syndromes use: any BDZwith long half; (alternative buspirone

Front 17

What drugs are used as pre-anesthetic meds?

Back 17

Midzolam (Versed)IM or Lorazepam (ativan)Im or IV.

Front 18

What are the other uses of BDZ?

Back 18

1. Clonazepam=absence seizures
2. Lorazepam=emergent status epilepticus
3. also suppress dangerous symptoms from withdrawal from CNS depressants (ethanol)
4. Diazepam=muscle spasticity
5. Lorazepam=antiemetic

Front 19

What us flumazenil?

Back 19

A BDZ antagonist=binds the same site on the GABA receptor but produces no effect on its own;
q

Front 20

What is the use of flumazenil

Back 20

1.to quickly reverse the sedative effects of BDZ after general anesthesia or after proceduces
2. rvs toxicity due to or suspected BDZ OD

Front 21

What are the Cautions with Flumazenil?

Back 21

1. may precipitate withdrawal in dependent people
2.short half life (1hr) mayneed repeated for a long half life BDZ

Front 22

What is Buspirone?

Back 22

BUSPAR
anxiolytic but not a sedative-hypnotic; not related to BDZ

Front 23

What is the mechanism of Buspirone?

Back 23

Does not interact with GABA-gated Cl-channels;
Action is partial agonist activity at 5-HT1a receptor

Front 24

What are the pharmacokinetics of Buspirone?

Back 24

well absorbed orally,
low bioavailabitlity
Eliminated by liver metab

Front 25

What are the clinica effects of Buspirone?

Back 25

1. less effective than BDZ in tx of severe anxiety, but not promote sleep. Anxiolytic take 1-2 wks
2. Appears not to produce rebound anxiety upon withdrawal

Front 26

What are the SE of Buspirone?

Back 26

well tolerated, free of tolerance, dependence, withdrawal problems

Front 27

What are the common CNS properties to all NON-BDZ sedative hypnotics?

Back 27

1. Progressive, dose-related CNS depression; dec cognitive/motor-> dec. inhibition and/or frank excitement-> to sleep and LOC without analgesia->coma->severe respiratory depression and cardiovascular collapse 2 to hypoxia

Front 28

What are the properties of tolarnce for all non BDZ sed-hypnotics?

Back 28

*rapidly to all CNS depressant effect xlethal respiratory and cardio
*Cross-tolerance btwn members of this group

Front 29

What is the tx of acute intoxication with all non-bdz sed. hypnotics?

Back 29

1. support ox and cardio fucntion
2. eliminate any unabsorbed drug and accelerte clearnce
3. get rid of BDZ if a mixed toxi with flumazenil

Front 30

What are the properties of Barbituates?

Back 30

*half: 8-48 hrs x for ones as anticonvulsants that are longer
*short acting=thiopental used for anesthesia are very lipid solubel ad duration is 10min.
*Can cause hyperalgesia so can interfere with hypnotic effects!
**Powerful induction of microsomal enzymes (pheonobarbital good at this)

Front 31

What is the mechanism of action of barbituates?

Back 31

*Low dose: potentiate GABAergic transmission by prolonging duration of GABA-induced openings of receptors
*High dose: promote Cl- influx thru GABA gated channel in the absence of GABA. less pronounced with anticonvulsants
*Very high: exert non-specific depressant effects by perturnng lipid membrence lie other anesthetics

Front 32

What is the mechanism of metabolims of ethanol?

Back 32

alchol dehydrogenas (RLS) then by aldehyde dehydrogenase
**Acetaaldehyde depletes hepatic glutathione and causes lipid peroxidation and damage.
***Zero-order kinetcis, blood concentrationlinear with time

Front 33

What are the important facts of ethanol?

Back 33

1. Alcohol inc. GABAa rec/Cl-funtcion and has other neuro effects
2.disrupts normal sleep pattern, exacerbates sleep apnea
3. produces cutaneous vasodilation, but overall inc. vasoconstriction, esp in coronary and cerebral beds and can inc. BP
4. dec. release of ADH and oxytoci from Ant. pituitary

Front 34

What are the hallmarks of physical dependence/withdrawal from ethanol?

Back 34

1. Very severe dependece, with DT as the most serious withdrawl sndrome that can be lethal

Front 35

How do you treat alchohol withdrawal?

Back 35

1. Give BDZ
2. rehydrate, check electrolytes
3. anticonvulsant= carbamazepine for seizure component only

Front 36

What is the pharm. tx of alcoholism?

Back 36

1.counseling+drugs+rehab
2. Disulfiram ("aversive")
3. Naltrexone
4. Acamrpsate A
5. Anti-depresants, buspirone
6. Ondansetron

Front 37

What is Disulfiram?

Back 37

binds aldehyde dehydrogenase leads to dangerous SE when drinking the smallest amount

Front 38

What is Naltrexone

Back 38

Opiate receptor antagonist, stops pleasurable aspects of alcohol

Front 39

What is AcamprosateA

Back 39

reduces rate of relapse after detox by attenuating the craving

Front 40

What are the beneficial uses of Alchohol?

Back 40

1. Small amts to reduce cornoary areter dz by inc. HDL/LDL ratio; promoting relaxation and good nutrition
2. Tx poisening with methanol or ethylene glycol: dec. the amount of formaldehyde in body by competitively bind the alchohol dehydrogenase

Front 41

What are the "other" sedative-hypnotics?

Back 41

1. Antihistamines- OTC sleep aids: diphenhydramine; hydroxyzine (iM ) as preanesthetic med for sedative, antimuscarinic, and antiemetic (not anymore b/c of midazolam)
2. meprobamte, chloral hydrate, drugs still perscribed for anxitey or insomnia but should not because of dependence issues

Front 42

What are the Barbituates?

Back 42

phenobarbital
secobarbital
thiopenthal
butalbital