Goals of therapy
3
- Promote patient’s ability to fall asleep, maintain sleep, and awaken refreshed
- Use med for as short a time as possible
- Use minimal dose with least amount of side-effects
Benzodiazepines
7
- Alprazolam (Xanax)
- Estazolam (ProSom)
- Flurazepam (Dalmane)
- Lorazepam (Ativan)
- Quazepam (Doral)
- Temazepam (Restoril)
- Triazolam (Halcion)
Benzodiazepines MOA?
3
MOA
1. Selectively acts on polysynaptic neuronal pathways throughout the CNS
- Enhance the effects of GABA (an inhibitory neurotransmitter) in the CNS
- Insomnia
- -Facilitate the effects of GABA in the ascending reticular activating system
Benzos are divided into which three categories?
- Short acting
- Intermediate acting
- Long acting
Which drugs are in each category:
1. Short acting 1
- Intermediate acting 2
- Long acting 2
- Triazolam (Halcion)
- Temazepam (Restoril)
- Estazolam (ProSom)
- Flurazepam (Dalmane)
- Quazepam (Doral)
Benzo Adverse events
3
- Drowsiness
- Impaired motor function
- Prolonged use
- Physical dependency
Benzos
- Drug interactions? 2
- Contraindications? 3
- Interactions
- Caution with alcohol
- Low-dose contraceptives - Contraindications
- Acute narrow-angle glaucoma
- Preg X
- Lactation
Benzodiazepine Receptor Agonists (BRA)
- Developed why?
- Half life?
- Has greater receptor specificity of the what?
- to improve the safety profile of barbiturate-type compounds
- Have short half-life
5 hours - GABAa BZ complex
Benzodiazepine Receptor Agonists (BRA): Drugs in this category?
3
Drugs
- Eszopiclone (Lunesta)
- Zolpidem (Ambien)
- Zaleplon (Sonata)
Eszopiclone (Lunesta)
MOA?
Interacts with GABA receptors located near benzodiazepine receptors
BRAs: Dosage
- Start with?
- Can be started or increased to?
- Elderly dosing?
- Start at 2mg immediately before bed
- Can be started or increased to 3mg to aid in sleep maintenance
- Elderly
Start 1mg to help fall asleep
2mg for sleep maintenance
Eszopiclone (Lunesta)
- Adverse affects? 3
- Contraindications? 1
- Preg cat?
- Adverse events
- HA
- Dry mouth
- Dizziness - Contraindications
- Hypersensitivity - Preg C
Zolpidem (Ambien, Ambien CR)
- MOA?
- Dosage? 2
- MOA
Modulates the GABA receptors to suppress neurons - Dosage
- 5-10mg PO qhs
- Extended release - 25-12.5mg PO qhs
Zolpidem
- Adverse affects? 3
- Contraindications? 1
- Preg?
- Adverse events
- Morning drowsiness
- Hangover
- HA - Contraindications
- Hypersensitivity - Preg C
Zaleplon (Sonata)
- MOA?
- Dosage?
- Start at?
- Range from?
- MOA
Interacts with GABA-BZ omega 1 receptor - Dosage
Start: 10mg PO qhs
Range 5-20mg qhs
Zaleplon
- Adverse affects? 3
- Contraindications? 1
- Preg?
- Adverse Events
- Back or chest pain
- Migraine
- Constipation - Contraindications
- Hypersensitivity - Preg C
Most commonly used classes of OTC sleep-inducing agents?
Specific agent?
Antihistamines
Diphenhydramine (Benadryl)
Antihistamines: Diphenhydramine (Benadryl) 1. MOA? 2. Dosage? 3. Adverse affects? 2
- MOA
Unknown, but acts as a CNS depressant - Dosage
- 25-50mg qhs - Adverse Events
- Excessive daytime drowsiness
- Impaired psychomotor function
Antidepressants
3
Newer agents? 2
- Imipramine (Tofranil)
- Amitriptyline hydrochloride (Elavil)
- Nortriptyline (Pamelor)
Newer agents
- Nefazodone hydrochloride (Serzone)
- Venlafaxine (Effexor)
Doxepin (Silenor)
- MOA?
- Dosage?
- Adverse effects? 4
- MOA
Increases synaptic concentrations of serotonin and norepinephrine in the CNS - Dosage
- 3-6mg within 30 min of bedtime - Adverse Events
- Drowsiness
- Dizziness
- Constipation
- Blurred vision
Doxepin (Silenor)
- Contraindications? 2
- BBW?
- Preg cat?
- Contraindications
- Glaucoma
- Urinary retention - Black Box Warning
- Suicide thinking/behavior - Preg C
Trazodone
MOA? 3
Dosage?
MOA
- Inhibits reuptake of serotonin
- Causes adrenoreceptor subsensitivity
- Induces change in 5-HT presynaptic receptor adrenoreceptors
Dosage
50-100mg before bedtime
Trazodone
- Adverse affects?
- Contraindications? 2
- Preg cat?
- BBW?
- Adverse Events
- Dizziness
- drowsiness - Contraindications
- Use of MAO inhibitors
- Patients receiving linezolid or IV methylene blue - Preg C
- Black box warning
Suicidal thoughts
Amitriptyline (Elavil)
- MOA?
- Dosage?
- Adverse affects? 3
MOA
1. Increases synaptic concentration of serotonin and/or norepinephrine in CNS
- Dosage
25-50mg at bedtime - Adverse Events
- Sedation
- Dizziness
- HA
Amitriptyline
- Contraindications? 2
- Preg cat?
- BBW?
- Contraindications
- History of MI
- MAOIs - Preg C
- Black box warning
Suicidal thoughts
Melatonin Agonist? 1
Ramelteon (Rozerem)
Ramelteon (Rozerem)
- MOA?
- Dosage?
- Adverse effects? 3
- Contraindications? 1
- Preg cat?
- MOA
Potent, selective agonist of melatonin receptors MT1 and MT2 within the suprachiasmic nucleus of the hypothalamus - Dosage
8mg daily within 30 min of bedtime - Adverse Events
- Somnolence
- HA
- Fatigue - Contraindications
Fluvoxamine (Luvox) - Preg C
Orexin Receptor Antagonist?
Suvorexant (Belsomra)
Suvorexant (Belsomra)
- MOA?
- Dosage?
- MOA
Blocks binding of wake-promoting neuropeptides orexin A and orexin B to receptors OZ1R and OX2R - Dosage
10mg once daily within 30min of bedtime (max 20mg)
Suvorexant
- Adverse effects? 3
- Contraindications? 1
- Preg cat?
- Adverse Events
- Drowsiness
- HA
- Abnormal dreams - Contraindications
Narcolepsy - Preg C
- First line for narcopelsy?
- MOA?
- Adverse affects? 3
- Preg cat?
- Modafinil (Provigil)/Armodafinil (Nuvigil)
- MOA: not well understood, but may increase dopaminergic signaling
- Adverse Events
- HA
- Nausea
- Nervousness
- Dry mouth - Preg C
- Narcolepsy second line?
- MOA?
- Common side effects?
- Preg cat?
- BBW? 2
- Dextroamphetamine
- MOA: not well understood, but stimulates CNS activity; blocks reuptake and increases release of norepinephrine and dopamine in extraneuronal space (sympathomimetic)
Dose: 10mg daily - Side-effects common
- HTN
- Anorexia
- Addiction - Preg C
Black Box
-High abuse potential
-Cardiac events
REM Sleep Behavior Disorder
- First line therapy?
- MOA?
- SE? 3
- Melatonin (First-line therapy)
- MOA: Prepares the body for sleep
Doses: 0.5-10mg PO qhs - Side-effects
- Abnormal heartbeat
- Dizziness
- fatigue
Movement Disorder
Dopaminergic agents? 3
MOA?
- Pramipexole (Mirapex)
- Ropinirole (Requip)
- Rotigotine (Neupro)
stimulation of postsynaptic dopamine D2-type receptors within the caudate putamen in the brain
- Dopaminergic agents SE? 2
2. Preg cat?
- Adverse Events
- Nausea
- Lightheadedness - Preg C
Movement disorder Anticonvulsants 1. Which drug? 2. MOA? 3. Adverse effects? 3 4. Preg cat?
- Gabapentin (Neurontin)
- MOA
Thought to reduce presynaptic GABA release
–Dosage
Initial: 300mg daily 2 hours before bed - Adverse Events
- Fatigue
- Dizziness
- Blurred vision - Preg C