Flashcards in 32: Anxiolytics and Sedative Hypnotics Deck (56):
sensory and motor function, cognition, short-term memory, speech, etc..
area of brain that encloses the 3rd ventricle
integration of sensory relays
temperature, appetite, emotional and hormonal regulation
bridge between cerebrum/diencephalon and the brainstem
the thalamus and hypothalamus are part of the...
the pons, medulla oblongata, and reticular formation are part of the...
involved in control of respiration and cardiovascular function (vasomotor center)
pons and medulla oblongata
control of consciousness, arousal and alertness
planning and coordination of motor movements and motor patterns including maintenance of balance and posture
caudate nucleus and putamen
basal ganglia =
primarily involved in control of motor activites
amygdala, hippocampus, cingulate gyrus, prefrontal cortex, hypothalamuc, thalamic nuclei, mamillary bodies,, etc...
primarily involved in control of emotional and behavioral activity
ex: stress responses, fear, mood control, etc
formation of tight junctions between endothelial cells on CNS capillaries
selective filter - prevents many substances from entering the brain and the spinal cord, especially polar and lipophobic compounds
excitatory or inhibitory: Acetylcholine
excitatory or inhibitory: DA, NE, 5HT
mostly inhibitory, but the overall effect is often general excitation of the brain (disinhibition)
excitatory or inhibitory:GABA
excitatory or inhibitory: glycine
excitatory or inhibitory: glutamate
excitatory or inhibitory: aspartate
excitatory or inhibitory: substance P
excitatory nt involved in spinal pain processing
excitatory or inhibitory: endogenous opiods (endorphins, enkephalins and dynorphins)
excitatory - inhibit pain sensation
decreased neuronal excitability
agents that are mainly used to treat anxiety states and sleep disorders
selective depressants/ sedative hypnotics include...
non-selective/ general depressants include..
exert a calming effect or sedation with concomitant relief or anxiety at relatively low doses
depressant effects on psychomotor and cognitive functions
agents that produce drowsiness adn encourage the onset and maintenance of a state of sleep
general hypnotic effects
1) more rapid onset of sleep
2) increased duration of stage 2 NREM sleep
3) decreased duration of REM and stage 4 NREM sleep
overwhelming and continuous worrying about life events
symptoms include anxiousness, nervousness, apprehension, fear, panic, mental disintegration
linear slope drugs (barbiturates and alcohols) at doses higher than needed for hypnosis may lead to a state of ...
at even higher doses: depression of respiratory and vasomotr centers in the medulla resulting in coma and death
non-linear slope drugs (benzodiazepines) are generally safer to use than linear because...
reach plateau in CNS depression
greater dose increments are needed to achieve hypnosis
what is required for benzodiazepine sedative-hypnotic activity?
electronegative substituent in the 7 position is required for sedative-hypnotic activity
where are benzodiazepines meatabolized?
liver via P450s, mainly CYP3A4 + glucoronidation
which benzos are inactive water-soluble glucornides with metabolism? weakly active? active?
inactive = lorazepam and oxazepam
weakly active = alprazolam and triazolam
long-lived = all the rest
what 4 pharmacodynamic changes occur with aging?
1. >65 hepatic processing slows
2. decreased lean body mass
3. increased Vd for many lipid soluble drugs
4. decreased rate of elimination
which benzos are affected by age? which are not?
oxazepam and lorazepam are not influenced by age
diazepam is age dependent
increase the frequency of opening and conductance of the GABA Cl- channels ---> inhibition
binds to BZ sites to facilitate channel opening
side effects and toxicity of benzodiazepines:
-drowsiness and sedation
- respiratory depression
- anterograde amnesia
- tolerance and dependence
date rape drug
flunitrazepam -- anterograde amnesia
contraindications for benzodiazepines
- substance abuse
- sleep disorders
- required alertness (surgery, driving, etc)
major drug interaction for benzodiazepines
additive CNS depression
with ethanol, opiods, etc...
therapeutic uses for benzodiazepines
anxiolytic (relief of anxiety) and sedative hypnotic ( relief of insomnia)
competitive inhibitor that binds to the BZ receptor ----> REVERSE the effects of benzodiazepines
uses for flumazenil
- terminate benzodiazepine-induced sedation
- diagnosis and treatment of benzodiazepine toxicity
MOA of the Z drugs
selectively bind to BZ receptros on GABA and act as an agonist only to alpha1 subunits
clinical uses for barbiturates
- medically induced coma
3+4 = phenobarbital
which of the discussed drugs are NO active metabolites?
slow meatbolism of the barbiturates by the lier
MOA of barbiturates
increase the duration of the GABA-gated chloride channel opening
MOA barbiturates v. benzos
barbiturates: increase duration
benzos: increase frequency
melatonin receptor agonist
MT1 - sleep onset
MT2- circadian pattern
does using ramelteon have a dependence risk for sleeping?
regular use does not result in dependence - not a controlled substance
causes less psychomotor impairment than benzodiazepines and does not affect driving skills
but delayed response is not suitable for acute anxiety or panic
partial agonist at 5HT 1a receptors
(autoreceptors - activation of 5HT1a receptor reduces neuronal excitability, firing frequency and 5HT release)
adverse effects buspirone
nonspecific chest pain
not an anxiolytic, but diminishes some of the somatic manifestations of anxiety (stage fright, performance anxiety)