anxiolytics and hypnotic drugs Flashcards
Generalized anxiety disorder
Generalized persistent anxiety for at least 1 months duration
absence of the specific symptoms and patterns that characterize other anxiety disorders such as phobias, panic attacks or ocd
Psychological correlates include apprehensive expectation with worry fear and anticipation of misfortune to self and others, hyper attentiveness, distractibility, difficulty concentrating, insomnia, feeling on edge and impatience
Somatic correlates of anxiety
ANS arousal sweating, tachycardia and palpitations, cold clammy hands, dry mouth and lump in throat feeling, GI upset
Frequent urination and diarrhea
Voluntary Muscle activation
Jitteriness and an inability to relax
Sleep disorder- insomnia and hypersomnia
Stages of sleep
Drowsy- alpha waves
Stage 1-3 - theta waves
Stage 2- sleep spindles and k complexes
Stage 4- best sleep deep saw tooth
REM- similar to wake
Slwo wave sleep- 5HT
REM sleep- Norepinephrine and ACh
Gaba ergic synapse
Glutamate–> GABA (via GAD) the primary inhibitory NT
Vesicles and synapse
GABA B- muscle relaxer, metabotropic
GABA A- ion channel, can be deactivated by GaBA transaminase or reuptake
Closest thing to a GABA receptor is a nicotinic receptor that allows Na influx and depolarization
Where is GABA
Substantia nigra, globus pallidus, hippocampus, limic system (amygala), hypothalamus, sp cord
GABA BDZ receptor
Chloride channel
Several acting sites, alpha or beta is where GABA goes
Gamma is where benzodiazepine goes
when Gaba attaches to the receptor, it opens the channel
Cl comes in and hyperpolarizes the cell
Benzodiazepine will further open (increase more openings) to allow more Cl to come in
Ligands (drugs) of the benzodiazepine receptor (BDZ)
Agonists- BDZs, Diazepam, Zolpidem, hypnotics
Antagonists- Flumazenil (reverses agnoist action)
Busipirone
partial agonist for 5HT1A –> inhibition of adenylate cyclase and opens K channels
Also binds to dopamine receptorsw
Benzodiazepines used to treat anxiety
All end in pam or lam
Excetp Chlodiazepoxide, and clorazepate
Good separation between anxiolytic and insomnia
Z drugs are hypnotics
Role of liphilicity
Diazepam- fast onset of action (oral)
High lipid solubility- rapid absoption and entry into the brain, rapid redistribution after single dose, active metabolites change this in multi dose situation
Lorazepam- less lipophilic than diazepam, absorption and onset of action are slower, longer duration of action after single dose, no active metabolites
Quick vs slow onset- lipophilicity (diazepam vs lorazepam)
Active metabolites vs none- Diazepam vs lorazepam/oxazepam
Wide range of elimination half lives
Singel dose vs repeated administration
CNS effects
Decreased anxiety, sedation, hypnosis, muscle relaxation, anterograde amnesia, IV adminsteration, Anticonvulsant action, minimal CV and respiratory actions at therapeutic doses
Drug interactions
Produce additive CNS depression with most other depressant drugs (ethanol, sedative hypnotics and sedating antihistamines, and opioids)
Drugs that affect metabolism such as cimetidine
Clincal uses
anxiety and sleep, muscle relaxant- diazepam, seizure treatment, IV sedation and anesthesia, Alcohol withdrawal (chlordiazepoxide)
Benzodiazepine withdrawal
Anxiety, insomnia, irritability, headache, hyperacusis, hallucinations, seizures
Treatment of abuse- gradual dose reduction (switch to longer acting drugs)
Buspirone
Not related chemically or pharmacologically to the benzodiazepines
High affinity for 5HT1A receptors, less sedating than benzodiazepines
no cross tolerance with benzodiazepines, does not potentiate other sedative hypnotics and depressants nor suppress symptoms of their withdrawal
Used in the treatment of GAD
Therapeutic effect may take 1 to 2 weeks to occur
Other treatments for anxiety
SSRI and SNRI pannic attacks and GAD
Beta blockers for performance anxiety
Dimensions of insomnia
Symptoms may be mild or severe. Transient, chronic or intermittent
Cant fall asleep and or stay asleep
Daytime sequelae: tired fatigued, sleepy anxious, depressed
Whats the one drud that you can take for both anxiety and sleep
Lorazepam
Fast onset
Effects of benzodiazepines on sleep
Decreased latency to sleep Increases in stage 1 and 2 sleep Decreased time in stage 3 and 4 and REM sleep Rebound insomnia upon withdrawal Newer drugs (zolpidem) have less effects
Adverse effects of benzos for sleep
Daytime sedation, ataxia, rebound insomnia, tolerance and dependence, occasional idiosyncratic excitement and stimulation
Increased death rate associated with use
non benzodiapines sleep drugs
Zolpidem, Zaleplon, Eszopiclone
Bind to BDZ receptor on GABA receptor complex
Weak anxiolytic, muscle relaxant and anticonculsant at hypnotic dose
Stage 3 and 4 sleep preserved minro effect on REM sleep
Zolpidem typical duration of action 5-6 hrs, sustained release prep, oral spray targeted at problems of sleep initiation and sublingual tablets
Zaleplon is a hypnotic agent that is similar to zolipdem with fast oset and
Eszopiclone - approved for 6 mo
Ramelteon and Suvorexant
Ramelteon- MElotonin, not controlled, treats disrupted sleep patterns
Suvorexant- block orexin receptors - suppresses wakefulness
Suvorexant
Hypnotic approved 2014, orexin receptor (O! and 2) antagonist, orexins are neuropeptide central promotors of wakefulness through excitement of brain regions involved in arousal and attention
Hypothalamus location
barbituates (barbital)
rapidly absorbed and distruted, highly lipid soluble compounds suchas thiopental distributed rapidly to brain
Action terminated by redistribution
Can induce own metabolism adn that of other drugs
Eliminated primarily by renal excretion
Activate GABA
Sedation, hypnosis, anesthesia, anticonvulsant, respiratory depression, tolerance, lethal (opiods), physical dependence withdrawal–> seizures
Acute poisoning- stupor and coma
Additive with other CNS depressatn
hydroxyzine
sedating H1 blockeer, non perscription med contain diphenhydramine
Skeletal muscle relaxants
Drugs used to reduce muscle tone associated with spasticity related to MS injuries and other musclular skeletal disorders
Spasticity is characterized by increases in tonic stretch reflexes and flexor muscle spasms, together with a possible muscle weakness
MOA- underlying spasticity involve both the stretch reflex arc itself and higher centers in the brain
Pharmacologic treatment of spasticity targets both sites
Gabaergic agents
Diazepam- its action in reducing spasticity is at least partly mediated in the spinal cord, it can be used in pts with muscle spasm of almost any origin including local trauma, it produces sedation in most pts at the doses required to reduce muscle tone
Baclofen- GABA mimetic agent that works at GABAb receptors, this results in hyperpolarization, causing presynpatic inhibition, this can result in decreased release of excitatory transmitters such as glutamate, baclofen is at least as effective as diazepam, without as much sedaation
Tizanidine
an alpha2 adrenergic agonist that is related to clonidine, it may enhance both presynaptic and post synaptic inhibition
May have similar efficacy to diazepam and baclofen
SE- drowsiness, hypotension, dry mouth, and asthenia, interacts with ciprofloxacin and fluvoxamine
