Sedative, hypnotics, and anxiolytics (part 2) Flashcards
GABAb receptor
metabatropic receptors
Gi/o - Couple receptor (inhibitory)
Heterodimers
Location: brain,Limbic system
Inhibitory:
Presynaptic –> decrease Ca conductance
Postsynaptic –> increase K conductance
Agonists of GABAb receptor
Baclofen - skeletal muscle relaxant
Gamma-hydroxybutyric acid - ccentral nervous system depressant
Antagonists of GABAb receptor
Phaclofen, saclofen, and 2-hydroxysaclofen
Xyrem (sodium oxybate)
C-I –> illicit use and C-III medical use
Used to help sleep disorder
available only to prescribers enrolled in the xyrem patient success program
concerns due to possible abuse and misuse
Gamma-Hydroxybutyric acid
STREET NAME: “liquid ecstasy”, “georgia home boy”, liquid x
CNS depression (dizziness, drowsiness,coma) –> dose dependent
Acute effects: loss of consciousness and reflexes, amnesia, N/V, headache, seizure, death
Ramelteon (rozerem)
Melatonin agonist
high affinity for MT1 and MT2 melatonin receptors
receptors located in SCN and serve as the master clock by regulating circadian rythms
CYP1A2 substrate
treatment of insomnia characterized by difficulty with sleep onset
NO ABUSE, WITHDRAWAL, or dependency
Tasimelteon (Hetlioz)
Melatonin agonists
high affinity for MT1 and MT2 melatonin receptors
treatment of non-24-hour sleep wake disorder in blind individuals
Orphan product registration
Suvorexant (belsomra)
Orexin receptro antagonists
high affinity antagonist for OX1 and OX2 receptors located in the hypothalamus
reduce rewarding stimuli via receptors between the VTA and the nucleus accumbens
Treatment of insomnia
scheduled CIV
FDA required label change for all sleep disorder drugs
Required all drugs used for sleep disorder to have label about sleep related behavior like sleep walking, sleep driving, sleep cooking and eating
Trazodone
Antidepressant
hypnotic-unlabeled/investigational use
Antihistamines (OTC Drugs)
Diphenhydramine
Doxylamine
Pyrilamine
Herbal natural sedative-hypnotics
Tryptophan - dietary supplement
Melatonin - sleep disturbances
Valerian - herb for insomnia hepatotoxicity has been noted
Sedative-hypnotics overdose
causes: suicide and suicide gesture, drug abuse
signs and symptoms
- depressed respiration, blood pressure, reflexes, hypothermia
Treatment
- flumazenil for benzo and z-hypnotics
Anxiety
Fear or apprehension of something dreadful
when to get Treatment of anxiety
when it interferes with normal life
when it interferes with part of another disorder
Symptoms of anxiety
a loop of different emotions at different times
Sense of dread, shaky, feel faint, wobbly legs, rapid heart rate
Types of anxiety
Generalized anxiety disorder
panic disorder
social anxiety
obsessive compulsive disorder
post traumatic stress disorder
anxiety associated with other medical issues
Drug and disease induced anxiety
Drug:
-cocaine, beta agonists, psychostimulants (caffeine), corticosteroids
Disease:
-CHF,COPD,Diagnosis of terminal diseases
Withdrawal
- antidepressants, anxiolytics, Drugs of abuse, Cell phone/ social media
Nuerotransmitters and anxiety NE
Norepinephrine (NE)
over active locus coeruleus release NE and this stimulates autonomic nervous system
then Projects to the amygdala (fear center)
Neurotransmitters and anxiety GABA
GABAergic system
- normally counteracts/balances stimulatory effects of excess NE
Glutamate is converted to GABA by Glutamic acid decarboxylase in the CNS
Neurotransmitters and anxiety serotonin
may refelct tone at multiple receptors/SSRIs have efficacy
partial agonist of 5HT1a receptors effective
may involve amygdala and balance with NE
DRUG TREATMENT
Benzodiazepines (quick acting, effective)
Antidepressants (SSRIs, SNRIs, TCAs, take weeks); new breakthrough: ketamine (nasal spray esketamine, very quick acting)
Buspirone (BuSpar)
Beta Blockers
Buspirone (BuSpar)
Partial agonist on brain 5HT1a receptors
Moderate affinity for brain dopamine D2 receptors
longer onset of action than BZD (adaptive response)
Low abuse potential
USES: GAD, Social Anxiety, or Comorbid Depression, Adjunct use with OCD, PTSD, not good for panic disorders(BZD is much faster)
Propranolol (inderal)
- uses (may need test dose initially)
social anxiety, PTSD- nightmares - decreased peripheral; symptoms of anxiety
Monitor: heart rate, blood pressure
Side effects: hallucination, vivid dreams, lethargy, impotence
miscellaneous anxiolytics
Hydroxyzine (vistaril)
-Histamine H1 antagonist
Clonidine (catapres)
-Alpha2 agonist
-used: panic attacks, anxiety associated with withdrawal
Investigational anxiolytics
Serotonin receptor antagonist
- 5HT3 - ondansetron (Zofran)
- 5HT2- Ketanserin (unavailable in the US)
GABA uptake blockers - Tiagabine (Gabitril)
Partial Benzodiazepine receptor agonists
Glutamatergic agents
- NDMA receptor modulators: d-cycloserine, memantine
- mGluR5 antagonist: fenobam
- mGluR2/3 agonists: LY354740
