-
BZDs & newer hypnotics vs. older sedative hypnotics
greater margin of safety/therapeutic index
-
required for sedative hypnotic activity of BZDs
substituent in the 7 position such as a halogen or nitro group
-
-
chlordiazepoxide
alcohol withdrawl syndromes
-
clonazepam
- convulsion
- panic disorder
- muscle relaxation
-
-
Diazepam
- status epilepticus
- most commonly used
-
triazolam
early morning insomnia
-
Pharmacologic properties of BZDs
- no general anesthesia
- increases sedative effects of other CNS depressants
-
Sedation and hypnotic effects of BZDs
- decreases latency
- increases time of non-REM sleep
- decreases duration of NREM sleep
- decrease duration of REM sleep
-
sedation and hypnosis with BZDs
- cause sedation and hypnosis as dose increases
- GABAa
-
Muscle relaxation with BZDs
neuromuscular blockade at very high doses
-
Anterograde amnesia with BZDs
preanesthetic medication or diagnostic/operative prodecure
-
Anticonvulsant BZDs
- clonazepam
- lorazepam
- diazepam
-
peripheral effects of BZDs
coronary vasodilation
-
Mechanism of action for BZD
- binds alosteric site on GABAa receptor
- increases frequency of channel opening events
-
Difficult to differentiate anxiolytic properties of BZSs from sedative hypnotic properties because...
drus which control anxiety are also sedatives
-
impairment of motor performance with BZDs
- lightheadedness
- lassitude
- incoordination
- ataxia
- mental slowing
-
Abuse and dependance with BZDs
- less problematic than with barbituates and alcohol
- dependance is reported
-
chronic use and abrupt withdrawl of BZDs
- rebound anxiety
- insomnia
- agitation
- panic, paranoia, myalgia, muscle twitches, convulsions
-
Interactions of BZDs with other drugs
- ethanol increases absorption of BZDs
- BZDs + valproate = psychosis
-
4 classifications of BZDs
- ultra short acting BZDs
- short acting
- intermediate acting
- long acting
-
short acting BZDs T1/2 =
less than 6 hours
-
intermediate acting BZDs T1/2 =
6-24 hours
-
long acting BZDs T1/2 =
greater than 24 hours
-
intermediate acting BZDs
- alprazolam
- chlordiazepoxide
- lorazepam
- oxazepam
- temazepam
-
short acting BZDs
triazolam
-
long acting BZDs
- clorazepate
- diazepam
- flurazepam
-
BZDs with no active metabolites
oxazepam and lorazepam
-
Buspirone
- partial 5HT agonist
- affinity with D2 receptors
- selective anxiolytic effects
- slow onset of action
- no rebound anxiety or withdrawl symptoms
-
Zolpidem, Zaleplon, Eszopiclone
- selectively bind alpha 1 subtype of GABAa
- antagonized by flumazenil
- minimal muscle relaxing and anticonvulsant effects
- rapid onset
- less tolerance and dependance
-
zaleplon for
those awake early
-
dose reductions of sleep aids in patients with...
- hepatic dysfunction
- elderly patients
- pt. taking cimetidine or rifampin
-
Flumazenil
- competative antagonist of BDZs
- rapid action, short half life
- extensive 1st pass metabolism (less than 25% passes)
-
Taper off BDZs at
10% or less per day over 10 to 14 days
-
Barbituates
- non-selective CNS depressants
- cause unconsciousness at high doses
- narrower margin of safety
- limited use
-
Factors affecting onset and duration of barbituate actions
- lipid solubility
- tissue redistribution and affinity for plasma proteins
- liver enzyme metabolism
- renal excretion
-
barbituates in order of duration of action long to short
- phenobarb
- amobarb
- pentobarb
- secobarb
- thiopental
-
Pharmacological properties of Barbituates and sleep
- decrease REM time
- prolonged use causes rebound insomnia, restlessness, anxiety and nightmares
-
pharmacological properties of barbituates in anesthesia
thiobarbiturates and shortacting oxybarbiturates used for anesthesia
-
anticonvulsant properties of barbiturates
- phenobarb has selective anticonvulsant action
- generalized tonic-clonic seizures
-
barbiturates and respiration
depression of medullary respiratory center
-
barbiturates and cardiovascular system
- decreased cardiac output
- decreased renal plasma flow
- increased total peripheral resistence
-
barbiturates and GI
decreased GI muscle tone
-
barbiturates and uterus
- decreased force and frequency of contractions
- fetal respiratory suppression
-
mechanism of action for barbiturates
- increase duration of GABA gated CL channel openings
- GABA mimetic and high concentrations
- inhibit excitatory AMPA receptors
-
Adverse effects of Barbiturates
- CNS depression
- overt excitement
- hypersensitivity
-
contraindications of barbiturates
- acute intermittent porphyria
- pulmonary insufficiency
- cardiovascular disease
-
uses of barbiturates
- sedative/hypnotic
- anesthetics
- anticonvulsants
- hyperbilirubinemia and kernicterus
-
Chloral hydrate
- short acting sedative hypnotic
- does not affect REM
- less hangover than BDZs or barbs
-
Glutethimide and methyprylon
- methyprolon = shroter duration of action
- significant anticholinergic effects
-
Meprobamate
- anxiolytic agent
- causes widespread CNS depression
- anticonvulsant action
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