Anxiety management

Question 1

Generalized Anxiety Management

Answer 1

• SSRIs (DOC) & Venlafaxine
• Benzos - are used at the start to produce short-term relief while the AD take 2-4 weeks. Tapered over 4-12 weeks.
• Buspirone (2nd line)
• Hydroxyzine & Pregabalin ( Alternatives)

Question 2

Panic Disorder Management

Answer 2

• SSRI (DOC) OR TCA/ MAOI if SSRI is ineffective
• Benzos- Concomitantly with AD or Monotherapy for acute relief
  NB: Alprazolam is widely used but may cause rebound anxiety, withdrawal syndrome & seizures

Question 3

Social Anxiety Management

Answer 3

• SSRI (DOC)

Question 4

Obsessive Compulsive Disorder Management

Answer 4

• Clomipramine
• Fluoxetine
• Fluvoxamine
• Paroxetine
• Sertraline
  NB: Add a BENZO or AP for highly anxious OCD pts.

Question 5

Post-traumatic Stress Disorder Management

Answer 5

• SSRI (DOC)
• Venlafaxine, TCAs & MAOIs - more AE
• Sertraline & Paroxetine (Acute management)

NB: Sertraline is also approved for long-term management

Question 6

Performance Anxiety Management

Answer 6

• B-blockers - Propranolol & Nadolol

AE: hypotension

NB: b-blockers w/ higher lipophilicity is used

Question 7

Benzodiazepine MOA

Answer 7

Binds to the GABAa receptors –> Opens Cl channel –> Cl influx

• +ve allosteric modulator –> Dec EC50
• Inc. FREQUENCY of channel opening

Question 8

GABAa receptor & the binding sites

Answer 8

• A2B2y pentameric structure
• GABA binding site = between adjacent A&B subunits
• Benzo binding site = between adjacent A&Y subunits
  NB: Benzo receptors in the CNS are BZ1 & BZ2

Question 9

Actions of Benzos

Answer 9

• Anxiety management - Clonazepam, Lorazepam, Alprazolam & Diazepam
• Sedative & hypnotic - Temazepam & Triazolam
• Anticonvulsant - Clonazepam (epilepsy), Midazolam, Lorazepam & Diazepam ( Status epilepticus)
• Muscle relaxant - Diazepam
• Alcohol withdrawal
• Anesthesia

Question 10

Pharmacokinetics of Benzos

Answer 10

• Onset of action= 30-60 mins (varying half-life)
• Lipophilic
• Rapidly & completely absorbed
• Oral

Question 11

Benzos (names) based on duration of action

Answer 11

Long acting
- Clonazepam
- Diazepam
- Flurazepam
Intermediate acting
- Alprazolam
- Lorazepam
- Oxazepam
- Temazepam
Short acting
- Midazolam
- Triazolam

Question 12

Metabolism of Benzos

Question 13

Adverse effects of Benzos

Answer 13

• Drowsiness & confusion
• Ataxia
• Cognitive impairment
• Paradoxical effects (rare)- anxiety, irritability, hostility, rage, paranoia, depression & suicidal ideation
• Dependence & withdrawal syndrome - Confusion, anxiety, agitation, restlessness, insomnia & tension

Question 14

Benzo Overdose Management

Answer 14

FLUMAZENIL (Only Benzo receptor antagonist)

• rapid onset & short duration (1hr)
• reverse CNS depressant effects
• blocks effects of Benzos & Z-drugs
• may cause seizures if benzo was used for seizure control
• may precipitate withdrawal syndrome

Question 15

Barbiturates MOA

Answer 15

• +ve GABAa receptor allosteric modulators
• Inc. DURATION of Cl- channel opening
• High dose - Directly activate Cl channels
• Block Glutamate receptors
• Inhibits voltage-activated Na & Ca channels

Question 16

Actions of Barbituates

Answer 16

CNS depression
- Low dose - Sedation
- High dose - Hypnosis, Anesthesia, Coma & Death
RESP. depression
- Suppress the Hypoxic & Chemoreceptor response to CO2
ENZYME induction
- Induce P450 enzymes

Question 17

Uses of Barbituates

Answer 17

• Anesthesia (short-acting barbiturates used IV)
  Anticonvulsants
• Phenobarbital - Tonic-clonic seizures & Status epilepticus
  Phenobarbital & Thiopental - Status epilepticus

Question 18

Adverse effects of Barbiturates

Answer 18

• Drowsiness & impaired concentration
• Paradoxical excitement
• Hypersensitivity
• Hangover
• Respiratory depression
• Pain
• Dependence & Severe withdrawal syndrome
• Poisoning- severe Resp. & central CV depression

Question 19

Non-benzodiazepine Benzodiazepine Receptor Agonists (NBBRA)/ Z-Drugs (names)

Answer 19

• Zolpidem
• Zaleplon
• Eszopiclone

Question 20

NBBRA/ Z-drugs MOA

Answer 20

• +ve GABAa receptor modulator
• Acts on BZ1
• ONLY used as hypnotics
• Little/ No tolerance & AEs - FLUMAZENIL reverses effects

Question 21

Uses of NBBRA

Answer 21

Only approved for HYPNOTICS
INSOMNIA w/
- problems initiating sleep = Zolpidem
- problems of sleep onset & maintenance = Zolpidem ER
- short term management = Zaleplon

• Minimal muscle relaxing & anti-convulsant effects

Question 22

Z-drugs properties (onset, DOA, HL & uses)

Question 23

Melatonin Receptor Agonists (Name & MOA)

Answer 23

RAMELTEON

• MT1 & MT2 agonist
• Can be used long term bc of minimal abuse potential

Question 24

Uses of Melatonin Receptor Agonist (Remelteon)

Answer 24

Insomnia characterized by difficulty with sleep onset

Question 25

Adverse effects of Melatonin Receptor Agonist

Answer 25

- Dizziness - Somnolence - Fatigue - Endocrine changes - Dec in Testosterone - Inc in Prolactin

Question 26

Orexin Receptor Antagonist (names & MOA)

Answer 26

SUVOREXANT & LEMBOREXANT - Dual OX1R & OX2R Receptor Antagonist (DORA) NB: Orexin A & B promote wakefulness by activating OX1 & OX2

Question 27

Uses of Orexin Receptor Antagonist

Answer 27

Insomnia characterized by difficulties w/ sleep onset and/or sleep maintenance

Question 28

Adverse effects & Contraindications of Orexin Receptor Antagonist

Answer 28

- Daytime somnolence - Worsening of depression/ Suicidal Ideation Contraindicated in Narcolepsy

Question 29

Beta blockers (names, uses)

Answer 29

PROPRANOLOL - Dec autonomic symptoms of specific phobias - USED to control performance anxiety (stage fright)

Question 30

Anti-histaminic (names, class, uses)

Answer 30

Doxepin (TCA) - Insomnia w/ difficulty of sleep maintenance - H1 antagonism Hydroxyzine - Symptomatic relief of anxiety - Antiemetic propertied Diphenhydramine & Doxylamine (non-prescription) - Mild types of insomnia

Question 31

5HT1A Partial Agonist (Name, uses, onset, MOA, interactions)

Answer 31

BUSPIRONE - Anxiety & GAD (2nd line) - ONLY anxiolytic properties - Onset = 2-3 weeks - MOA- same as Antidepressants - No interaction w/ alcohol or benzos or other sedative-hypnotics, rebound anxiety, withdrawal signs, dependence & less psychomotor impairment than BZ