anxiolytics

Question 1

Benzodiazapenes

Answer 1

1. Alprazolam
2. Chlorazepate
3. Diazepam
4. Flurazepam
5. Lorazepam
6. Midazolam
7. Oxazepam
8. Temazepam
9. Triazolam
10. Flunitrazepam**date rapists

azepam, azolam, azepate

Question 2

Benzodiazepine antagonist (antidote)

Answer 2

Flumazenil

Question 3

Benzodiazepine-related Drugs - Newer Hypnotics (Z-drugs)

Answer 3

1. Eszopiclone
2. Zol[idem
   * pi*

Question 4

Barbiturates

Answer 4

1. Pentobarbital
2. Phenobarbital
3. Thiopental
   * barbitol and pental, al*

Question 5

Melatonin receptor agonists

Answer 5

Ramelteon

Question 6

5HT Receptor Agonist (Non-sedating Anxiolytic)

Answer 6

Buspirone

Question 7

B-blocker

Answer 7

Propanolol

Question 8

Other

Answer 8

Diphenhydramine (Benadryl)
Ethanol
Hydroxyzine (Vistaril)
Propofol (anesthetic)

Question 9

Date rape drug

Answer 9

Flunitrazepam

Question 10

Benzodiazepine Sedative-Hypnotic

Answer 10

1. Flurazepam*
2. Temazepam*
3. Triazolam*
4. Midazolam*

Question 11

Benzodiazepene anxiolytic

Answer 11

Alprazolam*
Clorazepate*
Diazepam*
Lorazepam*
Oxazepam*

Question 12

Other anxiolytic agents

Answer 12

Beta blocker and 5-Ht agonist propaolol and buspirone

Question 13

CNS depressants sedative hypnotics

Answer 13

Barbiturates
Pentobarbital*
Phenobarbital*
Thiopental*

Melatonin agonist
Ramelteon*

Antihistamines
Hydroxyzine*
Diphenhydramine*

Alcohols
Ethanol*

Question 14

Linear slope (higher doses no plateou lead to anesthesia, coma, death)

Answer 14

barbiturates and ethanol

Question 15

Non linear slope, reaching plateua, safer

Answer 15

Benzodiazepense and newer hypnotics

Question 16

Therapeutic uses of sedative hypnotics

Answer 16

1. Relief of anxiety
   a. primary
   b. Secondary anxiety states (e.g., acute myocardial infarction, GI ulcers, etc.)
2. Relief of insomnia
   3) Sedation and amnesia - before and during medical and surgical procedures
3. Treatment of epilepsy and seizure states

5) Control of ethanol or other sedative-hypnotic withdrawal states
6. Muscle relaxation

Question 17

Pharmakokinetics benzos

Answer 17

Absorption
Good by oral route

Metabolism: Liver

Question 18

inactive water soluble, rapid metab, short duration, less cum effects)

Answer 18

Lorazepam

oxazepam

Question 19

Weakly active, short lived matabs, short duration, little clin use

Answer 19

Alprozolam

triazolam

Question 20

Long lived active metabs, useful clinically

Answer 20

All the rest (ie diazepam)

Question 21

Metabolism influence of age benzos

Answer 21

In the elderly (>65) hepatic processing slows for some reactions

Increase in age:

• Decreased lean body mass
• Increased Vd for many lipid soluble drugs
• Decreased rate of elimination (Ve)

(oxazepam and lorazepam) are not influenced by age (Ke is age independent)

(diazepam) will be influenced by age (Ke is age dependent)

Question 22

MOA benzos

Answer 22

Potentiate effects of GABA at the GABAA receptors (chloride ion channels)

• ***1.Increase the frequency of opening and conductance of the Cl- channels
• Bind to BZ sites between α1 and γ2 subunits to facilitate channel opening

2. Influx of chloride ion

Increased membrane hyperpolarization and overall neuronal inhibition

4. Potentiate GABAergic inhibition at all levels of the neuraxis

Question 23

Sides and toxicity benzos

Answer 23

1.Drowsiness and sedation
Mental confusion and impaired judgment

2.Ataxia – Diminished motor coordination

*3.Respiratory depression – dose related
Can be lethal if combined with other depressants

*4.Anterograde amnesia – Used as date
rape drugs (e.g., flunitrazepam)

*5.Tolerance (sedative effects)
Most clinical efficacy studies~ 12-14 days; ‘short-acting agents’

• 6.Dependence – physical & psychological
  7. Dizziness, headache, nausea (uncommon

Question 24

Abrupt withdrawal benzos

Answer 24

Restlessness
Anxiety
Nervousness
Irritability
Insomnia
Headache
GI distress
Seizures
*opp of what used to treat
solve by slow titration dose and using long acting

Question 25

Contraindication benzos

Answer 25

1. Pregnancy 2. Elderly 3. Substance abuse a concern (though used in management of withdrawal) 4. Sleep disorders - Patients with sleep apnea, narcolepsy, etc. 5. When alertness is required

Question 26

Drug interactions of benzos, additive CNS depression*

Answer 26

Ethanol, opioids, anticonvulsants, phenothiazine, antihistamines, tricyclic antidepressants

Question 27

therapeutic use of benzos*

Answer 27

Anxiolytic - relief of anxiety (e.g., GAD) | Sedative/hypnotic – relief of insomnia

Question 28

MOA flumazenil (benzo antag)

Answer 28

Competitive inhibitor that binds to the BZ receptor | Can reverse the effects of benzodiazepines

Question 29

matab flumazenil

Answer 29

``` Rapid absorption (usual route – i.v.) Hepatic metabolism, Short duration (~ 2hr) ```

Question 30

Effects and uses for flumazenil

Answer 30

Effects Generalized CNS arousal Anxiogenic Uses Terminate benzodiazepine-induced sedation Diagnosis and treatment of benzodiazepine toxicity CNS depression (coma) in hepatic encephalopathy

Question 31

Benzo related newer hypnotics (moa, clin use and all)

Answer 31

Clinical Use: Newer sedative agents indicated for management of insomnia NOT a benzodiazepine (chemically) – novel structures Mecanism of Action: Selectively bind to BZ receptors on GABAA receptor and act as an agonist (only bind alpha1 subunit isoforms) Rapidly acting Short duration (t½ ~ 2-3 hr) – inactive metabolites Longer lasting effects in the elderly Similar effects as benzodiazepines Antagonist – flumazenil

Question 32

Clinical uses of barbiturates

Answer 32

1. Anesthesia (thiopental) 2. Sedative / hypnotic Largely replaced by the benzodiazepines Used in combination with other agents 3. Anticonvulsant (phenobarbital) 4. Medically induced coma (pentobarbital)

Question 33

MOA barbiturates

Answer 33

1.**Increase the duration of the GABA-gated chloride channel opening Bind to at a different site(s) from the benzodiazepine binding sites on GABAA receptors 2.Resulting in increased: Membrane hyperpolarization Neuronal inhibition

Question 34

Ramelteon (all)

Answer 34

Sedative agent - Indicated for management of insomnia Effective in inducing sleep onset – especially used in patients with difficulties falling asleep (very little influence on sleep architecture) *Mechanism of Action: Melatonin receptors agonist MT1 (sleep onset) ** MT2 (circadian pattern) Metabolism: Extensive first that forms an active metabolite with longer half-life   Minimal abuse liability, as regular use does not result in dependence; not a controlled substance

Question 35

Buspirone (All)

Answer 35

NON-sedating anxiolytic Causes less psychomotor impairment than benzodiazepines and does not affect driving skills Delayed onset of therapeutic response – not suitable for management of acute anxiety states and panic disorders No amnesia, no muscle relaxant properties *Mechanism of Action: Partial agonist at 5HT1A receptors Metabolism: Half-life is 2-4 h, extensive first-pass metabolism Minimal abuse liability Adverse effects: Nonspecific chest pain, tachycardia, palpitations, dizziness, nervousness, tinnitus, GI distress

Question 36

function of 5-Ht1A receptor

Answer 36

Activation of the 5-HT1A receptor reduces neuronal excitability, firing frequency and 5-HT release.

Question 37

Beta blockers

Answer 37

NOT an anxiolytic, but diminishes some of the somatic manifestations of anxiety (stage fright, performance anxiety)

Question 38

Anti histamines

Answer 38

Used as mild sedative/relaxant for multitude of procedures | Anxiolytic via a sedative action – common to most antihistamines

Question 39

Alcohol

Answer 39

Anxiolytic via a sedative action | Ethanol is probably the oldest and most commonly used anxiolytic