4.5 Pharmacology of anxiolytics and sedative hypnotics Flashcards
Where are the GABAb receptor located?
- Brain
- Limbic system
How does GABAb receptor have inhibitory effects on the pre- and post- synapses?
- Presynaptic: decrease Ca2+ conductance
- Postsynaptic: Increase K conductance
What drug is a GABAb receptor agonist?
Xyrem (sodium oxybate salt of GHB)
What are the two classes of Xyrem and what are their uses?
- C1: illicit use
- C3: Medical use (liquid)
Who is xyrem available to?
Available only to prescribers enrolled in xyrem pt success program
What does the use of xyrem w concomitant stimulant lead to?
- Decrease excessive daytime sleepiness
- Increase daytime wakefulness
What effect does GHB have on the CNS?
Can cause CNS depression
What is the severity of GHB’s CNS depression dependent on?
Dose dependent
What is an issue regarding GHB for sleep?
Pts often awaken spontaneously and require another dose in middle of night
What are acute SE/AEs of GHB?
- CNS depression: dizziness, drowsiness, coma
- Loss of consciousness and reflexes
- Amnesia
- N/V, headache
- Seizures
- Death
What is GHB used as and why?
Used only as supportive tx bc there is no antagonist to counteract effects
What drugs are melatonin agonist?
- Ramelteon (rozerem)
- Tasimelteon (hetlioz)
What is the MOA of ramelteon (rozerem)?
High affinity for MT1 and MT2 melatonin receptors
Why is ramelteon’s (rozerem) MOA the way it is?
- MT1 and MT2 melatonin receptors are on suprachiasmatic nucleus (SCN) which serves as “master clock” by regulating circadian rhythms
How is ramelteon (rozerem) metabolized?
CYP1A2 substrate
What is ramelteon (rozerem) used for?
Tx of insomnia characterized by difficulty w sleep onset
Does ramelteon (rozerem) have abuse potential?
- Non-controlled substance sleep aid
- No abuse, withdrawal, or dependency
What is a risk for ramelteon (rozerem)?
Negligible risk for next day “hangover” effects
What is the MOA of tasimelteon (hetlioz)?
High affinity for MT1 and MT2 melatonin receptors (same as ramelteon)
What is tasimelteon (hetlioz) used for?
Tx of non 24 hr sleep wake disorder
What is special about tasimelteon (hetlioz)?
It is an orphan drug
Where is the oxerin/hypocretin system located?
Hypothalamus
What is the MOA of suvorexant (belsomra)?
- High affinity antagonist for OX1 and OX2 orexin receptors
- Decrease arousal and attention via receptors in locus coeruleus and raphe
- Produce rewarding stimuli via receptors that modulate mesolimbic projections between VTA and nucleus accumbens
What is suvorexant (belsomra) used for?
Tx of insomnia
What is a possible SE with suvorexant (belsomra)?
Morning impairment likely/possible (use lowest dose possible)
What did the FDA require for labeling on all sleep disorder drugs?
Include:
- Sleep driving
- Cooking and eating food and making phone calls while sleeping
What is tryptophan?
A 5HT precursor dietary supplement
What is an issue w tryptophan?
- Withdrawn from market
- Caused eosinophilia-myalgia syndrome
What is melatonin?
A nutraceutical
What is melatonin used for?
Insomnia, sleep disturbances
What is a SE w melatonin?
Drowsiness
What is lemon balm?
A sedative herb
What is a caution w lemon balm?
Use w caution in pts w thyroid problems
What is valerian?
A sedative herb
What is valerian used for?
Insomnia
What has been noted w valerian use?
Hepatotoxicity
What is chamomile?
A mild sedative herb
What are cautions w chamomile?
- Avoid use in pts w a ragweed allergy
- Use w caution in pts using P450 substrates
What is kava kava?
A sedative herb
What is kava kava used for?
Insomnia
What is a possible problem w kava kava?
Possibly hepatotoxic
What is the incidence and severity of sedative hypnotics overdose?
- Incidence: commonly encountered in emergency room
- Benzos or z-hypnotics in combination w other agents
What are causes of sedative hypnotics overdose?
- Suicide and suicide attempts
- Drug abuse
What are s/sxs of sedative hypnotics overdose?
- Depressed respiration
- Decreased BP and reflexes
- Hypothermia
What are txs for sedative hypnotics overdose?
- Supportive tx: flumazenil for benzos or z-hypnotics
- Maintain respiration
- Maintain CV function
When should tx for anxiety be considered?
- Interferes w normal life
- Interferes w another disease
What drugs can induce anxiety?
- Cocaine
- Beta agonists
- Psychostimulants like caffeine
- Corticosteroids
What diseases can induce anxiety?
- CHF
- COPD
- Diagnosis of terminal disease
Withdrawal of what meds can induce anxiety?
- Antidepressants
- Anxiolytics
- Drugs of abuse
What neurotransmitters can cause anxiety?
NE and serotonin
How does NE cause anxiety?
- Overactive locus coeruleus releases NE -> stimulates autonomic nervous system -> projects to amygdala (fear center)
- Dysregulated in GAD and other anxiety disorders
How is the GABAergic system involved in controlling/causing anxiety?
- Normally counteracts/balances stimulatory effects of excess NE
- Hypothesis is reduced GABAergic signaling causes anxiety
How is serotonin involved in anxiety?
May involve amygdala and balance w NE
Which serotonin targeting drugs have efficacy in GAD, panic disorder, OCD, social anxiety?
- Drugs that target multiple receptors/SSRIs
- Partial agonists of 5HT1A receptors effective
What are the drug txs for anxiety?
- Benzos (quick acting, effective)
- Antidepressants (SSRIs, SNRIs, TCAs: take weeks; ketamine nasal spray: new breakthrough, very quick acting)
- Buspirone (buspar)
- BBs
What is the pharmacological profile of buspirone (buspar)?
- Partial agonist on brain for 5HT1A receptors
- Moderate affinity for brain dopamine D2 receptors
What is buspirone’s (buspar) onset of action compared to benzos?
Longer (adaptive response)
What is the abuse potential of buspirone (buspar)?
- Low abuse potential
- Little to no withdrawal
What are uses of buspirone (buspar)?
- GAD, social anxiety, comorbid depression
- Adjunct use w OCD, PTSD
What is buspirone (buspar) not good for?
Panic disorders (use benzos instead)
What are propranolol’s use?
- Social anxiety: decreased peripheral sxs of anxiety
- PTSD nightmares
What are monitoring parameters of propranolol?
Monitoring CV:
- HR
- BP
What are SEs of propranolol?
- Hallucinations
- Vivid dreams
- Lethargy
- Impotence
What meds are misc anxiolytics?
- Hydroxyzine (vistaril): histamine H1 antagonist
- Clonidine (catapres): alpha2 agonist
