Anxiety Drugs

Question 1

Drug classes to treat anxiety?

Answer 1

Benzodiazepines
Azapirones
Serotonin Specific Reuptake Inhibitors (SSRI)
Serotonin & NE Reuptake Inhibitors
Antihistamines

Question 2

MOA of BDZs?

Answer 2

BDZ’s bind to specific sites which are separate from but adjacent to the receptor for GABA. BDZ receptors are found in CNS & location parallels GABA neurons. Binding of BDZs enhances the affinity of GABA receptors, resulting in more frequent opening of adjacent Cl- channels resulting in hyper polarization and inhibition of neuronal firing

Question 3

What are the 2 BDZ receptors?

Answer 3

BZ1- assoc w/ sleep
BZ2- assoc w/ memory, motor, sensory & cognitive function (muscle relaxation, ataxia, emotional behavior, anxiolytic effects

Question 4

BDZ Pharmacokinetics

Answer 4

BDZ are lipid soluble and taken up rapidly in the brain and other perfused organs. They then get redistributed to tissue less well perfused. They do cross the placenta & get secreted into breast milk

Question 5

BDZ Metabolism

Answer 5

undergo hepatic metabolism to water soluble compounds for elimination

Question 6

Short Acting BDZ

Answer 6

Lasts 3-8 hours

Oxazepam- good for elderly & those w/ hepatic disease. Has no active metabolites

Question 7

Intermediate BDZ

Answer 7

Lasts 3-8 hours
Lorazepam- good for elderly & those with hepatic disease
Alprazolam

Question 8

Long Acting BDZ

Answer 8

Lasts 1-3 days
Chlordiazepoxide
Diazepam
Clorazepate- prodrug, must be converted to active metabolite

Question 9

Adverse effects of BDZ

Answer 9

Drowsiness & confusion
Ataxia
Cognitive Impairment
Potentiate alcohol & other CNS depressants
Tolerance is common w/ BDZ

Question 10

What is a BZD Antagonist?

Answer 10

FLUMAZENIL- binds to specific sites, where it competitively antagonizes the binding and allosteric effects of BDZ’s
Indications: suspected BDZ overdose, reverse sedative effects administered during anesthesia

Question 11

Buspirone

Answer 11

Actions are mediated by serotonin receptors (5HT1a). 5HT1a are mostly somatodendritic auto receptor that are coupled to G proteins regulating k+ membrane channel. Increase opening- hyperpolarizes the neuron and decreases firing
Buspirone is a partial agonist
Has a slow onset (2 weeks)
No physical dependence/ withdrawal syndrome

Question 12

SSRI MOA?

Answer 12

Selectively inhibit the reuptake of serotonin at the transporter. By blocking neurotransmitter removal serotonin concentration increases in the synaptic cleft

Question 13

SSRI Drugs

Answer 13

Paroxetine- social anxiety disorder
Sertaline- used in PTSD
Escitalopra
SSRI's don't have physical dependence and do not potentiate CNS depression of alcohol. 
SSRI's have a delayed onset

Question 14

SSRI Adverse Reactions

Answer 14

CNS- insomnia, tremor
CV- palpitations, hypotension, vasodilation
GI- anorexia
GU- loss of libido, sexual dysfunction

Question 15

SSRI Drug Interactions

Answer 15

MAOI’s can cause fatal reactions. If pt taking MAOI’s and switch to SSRI’s wait 14 days before starting. Get “serotonin syndrome”- hyperthermia, muscle rigidity, myoclonus, rapid changes in mental status

Question 16

SNRI MOA

Answer 16

blocks serotonin & NE reuptake transporters

Question 17

What is Venlafaxine?

Answer 17

SNRI
Used to general anxiety disorder
Adverse: Similar to SSRI; can also cause hypertension
DO NOT abruptly discontinue- slowly titrate the pt off the drug

Question 18

Antihistamines MOA

Answer 18

Antagonist at H1 receptors located in hippocampus and cortex

Question 19

Antihistamine Agents

Answer 19

Piperazine derivative
Hydroxyzine HCL
Hydroxyzine Pamoate
Used to General Anxiety Disorder
Adverse: Sedation. Do not combine w/ alcohol

Question 20

Drugs to treat Insomnia

Answer 20

Benzodiazepines

Miscellaneous

Question 21

Short Acting Hypnotic BDZs

Answer 21

last 3-8 hours
Midazolam- used as preanesthetic and intraoperative medication. Given as an oral syrup
Triazolam-Used to induce sleep in patients w/ recurring insomnia
tolerance develops in a few days
withdrawal results in rebound insomnia

Question 22

Intermediate BDZ’s

Answer 22

Lasts 10-20 hours
Temazepam
Estazolam- useful in pt who experience frequent wakening, peak sedative effect occurs 2-3 hours after oral dose

Question 23

Long Acting BDZ’s

Answer 23

Lasts 1-3 days
Quazepam
Flurazepam- significantly reduces sleep-induction time, decreases number of wakening, increase duration of sleep

Question 24

Contraindication of BDZ

Answer 24

Patient’s with obstructive sleep apnea b/c they decrease muscular tone in upper airway and exaggerate the impact of the episodes of apnea
Do not combine w/ alcohol

Question 25

Zolpidem

Answer 25

MOA: Binds to BZ1 receptor subtype at GABA -Cl channel receptor complex
Advantage- does not effect different stages of sleep like BDZs, minimal rebound insomnia, little or no tolerance
Releases 5 or 10 mg immediately and then the rest is released 3 hours later to maintain sleep. effect lasts 7-8 hours

Question 26

Zaleplon

Answer 26

MOA- binds to BZ1 receptor subtype at the GABA-Cl channel receptor complex
Little or no tolerance occurs

Question 27

Eszopiclone

Answer 27

MOA: binds to BZ1 receptor subtype at GABA-Cl channel receptor complex
Exhibits minimal rebound insomnia- helps to sleep longer
Little/ no tolerance approved for long term

Question 28

Ramelteon

Answer 28

Melatonin receptor agonist for the treatment of insomnia. For pt w/ difficultly w/ sleep onset
affinity for Melatonin MT1 &MT2 (promotion of sleep)
no affinity for GABA-A-BDZ= no anxilyic, muscle relaxant, amnesic effects

Question 29

Suvorexant

Answer 29

MOA- blocks the binding of wake-promoting neuropeptides orexin A and orexin B to receptor OX1R and OX2R.