Sedative, hypnotics, and anxiolytics (part 2)

Question 1

GABAb receptor

Answer 1

metabatropic receptors
Gi/o - Couple receptor (inhibitory)
Heterodimers
Location: brain,Limbic system
Inhibitory:
Presynaptic –> decrease Ca conductance
Postsynaptic –> increase K conductance

Question 2

Agonists of GABAb receptor

Answer 2

Baclofen - skeletal muscle relaxant
Gamma-hydroxybutyric acid - ccentral nervous system depressant

Question 3

Antagonists of GABAb receptor

Answer 3

Phaclofen, saclofen, and 2-hydroxysaclofen

Question 4

Xyrem (sodium oxybate)

Answer 4

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

Question 5

Gamma-Hydroxybutyric acid

Answer 5

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

Question 6

Ramelteon (rozerem)

Answer 6

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

Question 7

Tasimelteon (Hetlioz)

Answer 7

Melatonin agonists
high affinity for MT1 and MT2 melatonin receptors
treatment of non-24-hour sleep wake disorder in blind individuals
Orphan product registration

Question 8

Suvorexant (belsomra)

Answer 8

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

Question 9

FDA required label change for all sleep disorder drugs

Answer 9

Required all drugs used for sleep disorder to have label about sleep related behavior like sleep walking, sleep driving, sleep cooking and eating

Question 10

Trazodone

Answer 10

Antidepressant
hypnotic-unlabeled/investigational use

Question 11

Antihistamines (OTC Drugs)

Answer 11

Diphenhydramine
Doxylamine
Pyrilamine

Question 12

Herbal natural sedative-hypnotics

Answer 12

Tryptophan - dietary supplement
Melatonin - sleep disturbances
Valerian - herb for insomnia hepatotoxicity has been noted

Question 13

Sedative-hypnotics overdose

Answer 13

causes: suicide and suicide gesture, drug abuse
signs and symptoms
- depressed respiration, blood pressure, reflexes, hypothermia
Treatment
- flumazenil for benzo and z-hypnotics

Question 14

Anxiety

Answer 14

Fear or apprehension of something dreadful

Question 15

when to get Treatment of anxiety

Answer 15

when it interferes with normal life
when it interferes with part of another disorder

Question 16

Symptoms of anxiety

Answer 16

a loop of different emotions at different times
Sense of dread, shaky, feel faint, wobbly legs, rapid heart rate

Question 17

Types of anxiety

Answer 17

Generalized anxiety disorder
panic disorder
social anxiety
obsessive compulsive disorder
post traumatic stress disorder
anxiety associated with other medical issues

Question 18

Drug and disease induced anxiety

Answer 18

Drug:
-cocaine, beta agonists, psychostimulants (caffeine), corticosteroids
Disease:
-CHF,COPD,Diagnosis of terminal diseases
Withdrawal
- antidepressants, anxiolytics, Drugs of abuse, Cell phone/ social media

Question 19

Nuerotransmitters and anxiety NE

Answer 19

Norepinephrine (NE)
over active locus coeruleus release NE and this stimulates autonomic nervous system
then Projects to the amygdala (fear center)

Question 20

Neurotransmitters and anxiety GABA

Answer 20

GABAergic system
- normally counteracts/balances stimulatory effects of excess NE

Glutamate is converted to GABA by Glutamic acid decarboxylase in the CNS

Question 21

Neurotransmitters and anxiety serotonin

Answer 21

may refelct tone at multiple receptors/SSRIs have efficacy
partial agonist of 5HT1a receptors effective
may involve amygdala and balance with NE

Question 22

DRUG TREATMENT

Answer 22

Benzodiazepines (quick acting, effective)

Antidepressants (SSRIs, SNRIs, TCAs, take weeks); new breakthrough: ketamine (nasal spray esketamine, very quick acting)

Buspirone (BuSpar)

Beta Blockers

Question 23

Buspirone (BuSpar)

Answer 23

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)

Question 24

Propranolol (inderal)

Answer 24

• 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

Question 25

miscellaneous anxiolytics

Answer 25

Hydroxyzine (vistaril)
-Histamine H1 antagonist

Clonidine (catapres)
-Alpha2 agonist
-used: panic attacks, anxiety associated with withdrawal

Question 26

Investigational anxiolytics

Answer 26

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