Anxiety and Its Control

Question 1

Immediate Acting Antianxiety Agents

Answer 1

Benzodiazepines, Barbiturates, Alcohol, Beta Blockers (ex. Panic attacks)

Question 2

Delayed Action Antianxiety Agents

Answer 2

Antidepressant drugs, Buspirone (ex. Medical anxiety)

Question 3

Benzodiazepine Effects

Answer 3

Diazepam (Valium)
Relief of Anxiety (Tame animals), Sedation, Hypnosis (Large TI 70+) > Limited REM suppression, Amnesia, Anticonvulsant (Medically induced), Muscle Relaxant, Controls gagging and vomiting, Minimal effect on heart and respiration (Lost safety margin with combination of drugs; Exception = Midazolam - Between Benzodiazepine and Barbiturate), Treatment of alcohol withdrawal - chlordiazepoxide, May contribute to mild analgesia, Adjunct treatment in psychiatry

Question 4

Diazepam

Answer 4

(Valium); Benzodiazepine; Very Fast onset; Single dose, behavioral, 6hr, multidose, blood level up to 200; Long active metabolites; Used for antianxiety, anticonvulsant, sedation and hypnotic, muscle relaxant, amnesia; Mild respiratory depression - may be lethal when combined with other depressants, Amesia; Class D pregnancy

Question 5

Triazolam

Answer 5

(Halcion); Benzodiazepine; Fast onset; 2-3hr duration half-life; Short active metabolites; Hypnotic, Used for antianxiety, anticonvulsant, sedation and hypnotic, muscle relaxant, amnesia; Amnesia; Class X pregnancy

Question 6

Midazolam

Answer 6

(Versed); Benzodiazepine; Fast onset; 1-12hr duration; Short active metabolites; Pre-anesthesia and conscious sedation, given parenterally; Overdose can cause respiratory depression and result in death; Amnesia; Class D pregnancy; pH4 - water/lipid soluble, More efficacy binds to receptor than Diazepam, Possible platelet aggregation, Status epilepticus/Local anesthetic induced seizures, IV, IM, Intranasal, Intrabuccal

Question 7

Flurazepam

Answer 7

(Dalmane); Benzodiazepine; Inter med. onset; Multidose, Up to 100hr duration; Long active metabolites; Hypnotic (Similar to diazepam); Amnesia, Class X pregnancy

Question 8

Alprazolam

Answer 8

(Xanax); Benzodiazepine; Rapid onset; 12-15hr duration; Short active metabolites; May have antidepressant properties; Not much amnesia; Class D pregnancy

Question 9

Clonazepam

Answer 9

(Klonopin); Benzodiazepine; Slow onset; 24hr duration; Used as anticonvulsant; Partial agonist; Class D pregnancy

Question 10

Chlordiazepoxide

Answer 10

(Librium); Benzodiazepine; Inter med. onset; 5-30hr duration; Long active metabolites; Withdrawal; Minimal respiratory depression, Amnesia

Question 11

Lorazepam

Answer 11

(Ativan); Benzodiazepine; Int. (2hrs) onset; 10-18hr duration; Pre-op sedation in elderly; Mild respiratory depression; Amnesia, Class D pregnancy

Question 12

Oxazepam

Answer 12

(Serax); Benzodiazepine; Int.Slow onset; 5-13hr onset; Pre-op sedation in elderly; Mild respiratory depression; Amnesia; Class D pregnancy

Question 13

Benzodiazepine Warnings and Contraindications

Answer 13

Sedation, Amnesia, Paradoxical excitation, Allergy, Avoid use in pregnancy class - D,X, Venous thrombosis (IV - Diazepam), Increase drug metabolizing enzymes, Altered kinetics in liver or kidney failure (Black box warning), Pulmonary disease (COPD, Myesthinia gravis, Sleep Apnea), Respiratory depression - Midazolam, Narrow angle glaucoma BB, Tolerance and dependence, Drug interactions

Question 14

Benzodiazepine Drug Interactions - Physiologic Stimulants and Depressants

Answer 14

Stimulants: Nicotine, Caffiene, Methylphenidate, Amphetamine, Cocaine
Depressants: Sedatives, Anesthetics, Opiates, Neurologics (decrease Benzodiazepine safety)

Question 15

Benzodiazepine Drug Interactions - Drugs Inhibiting Metabolism of Benzodiazepines

Answer 15

Erythromycins (Midazolam, Alprazolam, Triazolam), Diltiazam and Verapamil (Substrates for CYP3A4), Azole Antifungals (Diazepam + Fluconazole = 2.5XDiazepam); Grapefruit juice (Midazolam, Alprazolam, Triazolam); Cimetidine, Oral contraceptive, Fluoxetine (SSRI); Propoxyphene, Propranolol; Isoniazd, Vaproic acid

Question 16

Smoking with Benzodiazepine

Answer 16

(Antagonizes sedation)

Question 17

Flumazenil

Answer 17

(Romazicon); Benzodiazepine Antagonist; Reverses actions (Blocks BZ receptor) (exception - Antagonizes zolpidem, Z drugs), Reverses sedation and amnesia better than respiratory depression, Relatively short acting (t1/2 =1hrs), Some use in epilepsy; 5mg/min up to 3mg/hr; May precipitate withdrawal in BZ dependent individuals or overdosed cyclic antidepressants

Question 18

Zolpidem

Answer 18

(Ambien); Hypnotic Drug; Act on BZ1 (Omega 1), Anticonvulsant, Amnesia like Triazolam, Issues with sleep driving, eating and sex; 10mg men/5mg women; Max effect in 1.6hrs, Half life in 2.5hrs, Ambien CR; Metabolized CYP3A4 in liver (Reduce in hepatic disease, elder, no active metabolites), Absorption reduced by meals; Side effects: Drowsiness, Dizziness, Allergy, Hallucinations (Combine with SSRI), Risk of dependence; Interaction reverse by Flumazenil

Question 19

ZZZ Drugs

Answer 19

Zolpidem, Zaleplon (Sonata), esZopiclone (Lunesta); Behaviorally similar to BZs; Pregnancy Class C; Flumazenil reverses;

Question 20

Buspirone

Answer 20

(Buspar); Long acting Anti-anxiety; Don’t prescribe for dental anxiety; Proposed action partial agonist at serotonin 5HT receptors, Minor antagonist action on dopaminergic receptors, Increased use in psychiatry; Min sedation, Not anticonvulsant, Little risk of dependence; Drug interaction - MAO inhibitors (hypertension), RX 5-10mg

Question 21

Melatonin agonists

Answer 21

Natural pineal hormone, OTC, Remelteon (Rozerem) - Sleep onset insomnia, MT1, MT2, MT3 agonist; Shorten sleep latency, Hormone associated with circadian rhythm, Side effects (Tasimelteon - Hetlioz - 24hr sleep-wake disorder in blind)

Question 22

Suvorexant

Answer 22

(Belsomra CIV); Orexin antagonist, Marginally effective, Hangover sleepiness, Expensive

Question 23

Phenobarbital

Answer 23

Barbiturate; 3 Partition coefficient, Slow absorption from stomach, Slow entry into CNS, 30% renal excretion, Terminate liver and kidney, Long duration of action, Anticonvulsant and sedative, Soluble in oil/water

Question 24

Pentobarbital

Answer 24

Barbiturate; 50 Partition coefficient, Rapid absorption from stomach, Rapid entry into CNS, Negligible renal excretion, Termination of action in liver; Short duration of action; Hypnotic use

Question 25

Thiopental

Answer 25

580 Partition coefficient, Rapid absorption from stomach (Not oral); Very rapid rate of entry into CNS, Negligible renal excretion, Redistribution and liver termination of action, Ultrashort duration of action, Induction anesthetic use, Moves out of brain into mass of body down concentration gradient

Question 26

Barbiturate Pharmacology

Answer 26

Hypnotics, Sedatives, Anesthetic, Muscle relaxants, Anticonvulsant, Not analgesic (May be hyperalgesic)

Question 27

Barbiturate Side Effects and Toxicity

Answer 27

Hangover, Paradoxical excitement (Inhibitory neurons more, Occurs before anesthesia), Decreased REM sleep, Dependence (Related to dose and duration - Severe withdrawl), Induce drug metabolizing enzymes of liver (P450, UGT) - Metabolic intolerance (Pharmacokinetic intolerance, Some pharmacodynamic, Less and less drug effect), Drug interactions (Sedation), Porphyria (ALA synthetase increase contraindication), Respiratory and cardiac depression (High dose), Allergies, Birth defects Class D

Question 28

Barbiturate Examples

Answer 28

Nembutal = Pentobarbital, CII, Hypnotic; Luminal = Phenobarbital, CIV, Raise seizure threshold; Pentothal = Thiopental, CIII, Through paradox excitation to anesthesia; Presate = Hexobarbital, CII, Preop Sedative that is rapid

Question 29

Selected Non-Barbiturate Sedative - Hypnotics

Answer 29

Examples: Quaaludes (CI), Glutethimide (CII), Thalidomide - Sedative, Antiinflammatory, Immunosuppressant (Apthous ulcers, leprosy, brain malignancy, major teratogen); Similar to barbiturate and toxicity

Question 30

Chloral Hydrate

Answer 30

Short, mild sedative; Metabolized to trichoral ethanol; Used in elder and children (Diazepam or antihistamines are safer); Eliminated by liver and kidney (ONE PURPOSE) - Induce hepatic enzymes P450; Drug interaction with alcohol (Micky finn); Irritation of GI tract and poor taste; Tolerance and dependence; Possibly carcinogenic; Active metabolite - Trichloroethanol, Inactive metabolite - Trichloroacetic acid

Question 31

Date Rape Drugs

Answer 31

Canada - Triazolam (Halcion); Outside US - Flunitrazepam (Rhoypnol), Ketamine (Ketalar) - sedation and analgesic and Phencylidine, TX - Gamma-Hydroxbutyrate (GHB) - Release of GH - Severe withdrawl

Question 32

Centrally Acting Muscle Relaxants (CAMRs)

Answer 32

Acts on CNS poly-snaptic reflexes, Effectiveness is proportional to sedative, Important to warn patient of drowsiness, Used with NSAID analgesic in pain, Adjunct in TMJ treatment, Large TI than barbiturates (~20) but less safe than Diazepam (~70), Similar side effect and toxicity to barbiturates, Can induce liver enzymes, Tolerance and dependence, Beers list (problem in elder)

Question 33

CAMR Examples

Answer 33

Mephenisin like - Carisoprodol (Soma), CIV; Chlorozoxazone (Paraflex); Methocarbamol (Robaxin); Pregnancy Class C Non-Mephenisn like - Orphenadrine (Norflex); Cyclobenzaprine (Flexeril) - Antihistamine like, Structurally dissimilar, Tricyclic antidepressant - Blocks reuptake of NE and 5HT; Pregnancy Class C and B

Question 34

Agents for Relief or Spasticity

Answer 34

MS or spasticity | Baclofen (Lioresal), Dantrolene (Dantrium), Tizanidine (Zanaflex)

Question 35

Baclofen

Answer 35

(Lioresal); GABA-B receptor to decrease spasticity, MS or spinal cord injury, Intrathecal (spinal) route; Side effects - CNS depression, Tolerance and dependence, Teratogenic (Pregnancy Class C), Trigeminal neuralgia, Cerebral palsy, Tardive dyskinesia, Titrated dose

Question 36

Dantrolene

Answer 36

(Dantrium); Acts in muscle - Contractile response; Used in upper spinal cord lesions that induce spasticity - Used in malignant hyperthermia; Side effects - Serious heptatoxicity, Sedation, Weakness, Respiratory depression, Diarrhea; Titrate dose, Pregnancy Class C

Question 37

Tizanidine

Answer 37

(Zanaflex); Alpha 2 agonist - Reduce cardiac tone and relax muscles, Treats spasticity associated with MS and spinal cord injury; Flutripine - alpha 2 agonist and NMDA inhibitor; May cause pQT; Side effects - Drowsiness, PROFOUND DRY MOUTH, Mydriasis, Asthenia, Dizziness, Hypotension (Orthostatic as well), Pregnancy Class C

Question 38

Natureceutical Agents with Sedative Property

Answer 38

Valarian, Kava Kava, Melatonin

Question 39

Agents with Sedation as Side Effect

Answer 39

Opiates, Anticonvulsants, Antipsychotics, Tranquilizers, Tricyclic Antidepressants, Anticholinergics, Beta receptor blockers, Diuretics, Anesthetics

Question 40

Agents Antagonizing Sedation Stimulants

Answer 40

Caffeine, Nicotine, Amphetamines, Cocaine

Question 41

CNS Depressants

Answer 41

Alcohol, Chloral Hydrate (CIV); Solvents and glues - General - Hydrocarbons; Barbiturates (CII - Phenobarbital=IV), Nonbarbiturate Sedatives (CII), Muscle relaxants - CIV, Benzodiazepines (CIV), Cannabis (CI)