anxiolytics and hypnotic drugs

Question 1

Generalized anxiety disorder

Answer 1

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

Question 2

Somatic correlates of anxiety

Answer 2

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

Question 3

Stages of sleep

Answer 3

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

Question 4

Gaba ergic synapse

Answer 4

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

Question 5

Where is GABA

Answer 5

Substantia nigra, globus pallidus, hippocampus, limic system (amygala), hypothalamus, sp cord

Question 6

GABA BDZ receptor

Answer 6

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

Question 7

Ligands (drugs) of the benzodiazepine receptor (BDZ)

Answer 7

Agonists- BDZs, Diazepam, Zolpidem, hypnotics

Antagonists- Flumazenil (reverses agnoist action)

Question 8

Busipirone

Answer 8

partial agonist for 5HT1A –> inhibition of adenylate cyclase and opens K channels

Also binds to dopamine receptorsw

Question 9

Benzodiazepines used to treat anxiety

Answer 9

All end in pam or lam
Excetp Chlodiazepoxide, and clorazepate

Good separation between anxiolytic and insomnia

Z drugs are hypnotics

Question 10

Role of liphilicity

Answer 10

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

Question 11

CNS effects

Answer 11

Decreased anxiety, sedation, hypnosis, muscle relaxation, anterograde amnesia, IV adminsteration, Anticonvulsant action, minimal CV and respiratory actions at therapeutic doses

Question 12

Drug interactions

Answer 12

Produce additive CNS depression with most other depressant drugs (ethanol, sedative hypnotics and sedating antihistamines, and opioids)

Drugs that affect metabolism such as cimetidine

Question 13

Clincal uses

Answer 13

anxiety and sleep, muscle relaxant- diazepam, seizure treatment, IV sedation and anesthesia, Alcohol withdrawal (chlordiazepoxide)

Question 14

Benzodiazepine withdrawal

Answer 14

Anxiety, insomnia, irritability, headache, hyperacusis, hallucinations, seizures

Treatment of abuse- gradual dose reduction (switch to longer acting drugs)

Question 15

Buspirone

Answer 15

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

Question 16

Other treatments for anxiety

Answer 16

SSRI and SNRI pannic attacks and GAD

Beta blockers for performance anxiety

Question 17

Dimensions of insomnia

Answer 17

Symptoms may be mild or severe. Transient, chronic or intermittent

Cant fall asleep and or stay asleep

Daytime sequelae: tired fatigued, sleepy anxious, depressed

Question 18

Whats the one drud that you can take for both anxiety and sleep

Answer 18

Lorazepam

Fast onset

Question 19

Effects of benzodiazepines on sleep

Answer 19

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

Question 20

Adverse effects of benzos for sleep

Answer 20

Daytime sedation, ataxia, rebound insomnia, tolerance and dependence, occasional idiosyncratic excitement and stimulation

Increased death rate associated with use

Question 21

non benzodiapines sleep drugs

Answer 21

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

Question 22

Ramelteon and Suvorexant

Answer 22

Ramelteon- MElotonin, not controlled, treats disrupted sleep patterns

Suvorexant- block orexin receptors - suppresses wakefulness

Question 23

Suvorexant

Answer 23

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

Question 24

barbituates (barbital)

Answer 24

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

Question 25

hydroxyzine

Answer 25

sedating H1 blockeer, non perscription med contain diphenhydramine

Question 26

Skeletal muscle relaxants

Answer 26

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

Question 27

Gabaergic agents

Answer 27

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

Question 28

Tizanidine

Answer 28

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