Class: Benzodiazepine

Kinetics:

Ultra short acting (t1/2 < 2 hours)

Completely absorbed--lipophilic

Protein bound

Metabolized by P450 (CYP3A4): except temazepam, oxazepam, and lorazepam

MOA: Bind to modulatory site on GABA_A receptor and increase channel opening (therefore help GABA inhibit neuronal activity)

Side Effects:

Common: Daytime sedation, drowsiness, weakness, psychomotor incoordination, anterograde amnesia, HA, blurred vision, vertigo, n/v/d

Overdose: respiratory depression, somnolence, confusion, apnea, hypotension, slurred speech, coma

Other: anaphylaxis, facial angioedema, complex sleep behaviors

Tolerance and dependence

Abrupt withdrawal = increased anxiety, dizziness, tremor, and hyperreflexia

Interactions:

Medical conditions: hepatic disease, COPD, obstructive sleep apnea

Other CNS depressants: anesthesia, opioids, alcohol

CYP3A4 inhibitors: erythromycin, clarithromycin, ritonavir, itraconazole, ketoconazole, nefazodone, grapefruit

Age--reduced clearance

Avoid long-acting benzodiazepines (flurazepam, quazepam)

Class: Benzodiazepine

Kinetics:

Ultra short acting (t1/2 < 2 hours)

Completely absorbed--lipophilic

Protein bound

Metabolized by P450 (CYP3A4): except temazepam, oxazepam, and lorazepam

MOA: Bind to modulatory site on GABA_A receptor and increase channel opening (therefore help GABA inhibit neuronal activity)

Uses:

Preanesthesia

Reduces anxiety and apprehension

Synergy for smooth and rapid induction

Counteract anesthesia adverse effects

Side Effects:

Common: Daytime sedation, drowsiness, weakness, psychomotor incoordination, anterograde amnesia, HA, blurred vision, vertigo, n/v/d

Overdose: respiratory depression, somnolence, confusion, apnea, hypotension, slurred speech, coma

Other: anaphylaxis, facial angioedema, complex sleep behaviors

Tolerance and dependence

Abrupt withdrawal = increased anxiety, dizziness, tremor, and hyperreflexia

Interactions:

Medical conditions: hepatic disease, COPD, obstructive sleep apnea

Other CNS depressants: anesthesia, opioids, alcohol

CYP3A4 inhibitors: erythromycin, clarithromycin, ritonavir, itraconazole, ketoconazole, nefazodone, grapefruit

Age--reduced clearance

Avoid long-acting benzodiazepines (flurazepam, quazepam)

Class: Benzodiazepine

Kinetics:

Short acting (t1/2 = 2.9 h)

Completely absorbed--lipophilic

Protein bound

Metabolized by P450 (CYP3A4): except temazepam, oxazepam, and lorazepam

MOA: Bind to modulatory site on GABA_A receptor and increase channel opening (therefore help GABA inhibit neuronal activity)

Use: Hynoptic (insomnia)

Reduce sleep latency--make it easier to fall asleep

Increase total sleep time

Side Effects:

Common: Daytime sedation, drowsiness, weakness, psychomotor incoordination, anterograde amnesia, HA, blurred vision, vertigo, n/v/d

Overdose: respiratory depression, somnolence, confusion, apnea, hypotension, slurred speech, coma

Other: anaphylaxis, facial angioedema, complex sleep behaviors

Tolerance and dependence

Abrupt withdrawal = increased anxiety, dizziness, tremor, and hyperreflexia

Interactions:

Medical conditions: hepatic disease, COPD, obstructive sleep apnea

Other CNS depressants: anesthesia, opioids, alcohol

CYP3A4 inhibitors: erythromycin, clarithromycin, ritonavir, itraconazole, ketoconazole, nefazodone, grapefruit

Age--reduced clearance

Avoid long-acting benzodiazepines (flurazepam, quazepam)

Class: Benzodiazepine

Kinetics:

Intermediate acting (t1/2 = 6-24 hours)

Completely absorbed--lipophilic

Protein bound

Metabolized by P450 (CYP3A4): except temazepam, oxazepam, and lorazepam

MOA: Bind to modulatory site on GABA_A receptor and increase channel opening (therefore help GABA inhibit neuronal activity)

Use: Antianxiety

Side Effects:

Common: Daytime sedation, drowsiness, weakness, psychomotor incoordination, anterograde amnesia, HA, blurred vision, vertigo, n/v/d

Overdose: respiratory depression, somnolence, confusion, apnea, hypotension, slurred speech, coma

Other: anaphylaxis, facial angioedema, complex sleep behaviors

Tolerance and dependence

Abrupt withdrawal = increased anxiety, dizziness, tremor, and hyperreflexia

Interactions:

Medical conditions: hepatic disease, COPD, obstructive sleep apnea

Other CNS depressants: anesthesia, opioids, alcohol

CYP3A4 inhibitors: erythromycin, clarithromycin, ritonavir, itraconazole, ketoconazole, nefazodone, grapefruit

Age--reduced clearance

Avoid long-acting benzodiazepines (flurazepam, quazepam)

Class: Benzodiazepine

Kinetics:

Intermediate acting (t1/2 = 6-24 hours)

Completely absorbed--lipophilic

Protein bound

Metabolized by P450 (CYP3A4): except temazepam, oxazepam, and lorazepam

MOA: Bind to modulatory site on GABA_A receptor and increase channel opening (therefore help GABA inhibit neuronal activity)

Uses:

Alcohol withdrawal-induced symptoms

Preanesthetic

Reduce anxiety and apprehension

Synergy for rapid and smooth induction

Counteract adverse anesthesia effects

Side Effects:

Common: Daytime sedation, drowsiness, weakness, psychomotor incoordination, anterograde amnesia, HA, blurred vision, vertigo, n/v/d

Overdose: respiratory depression, somnolence, confusion, apnea, hypotension, slurred speech, coma

Other: anaphylaxis, facial angioedema, complex sleep behaviors

Tolerance and dependence

Abrupt withdrawal = increased anxiety, dizziness, tremor, and hyperreflexia

Interactions:

Medical conditions: hepatic disease, COPD, obstructive sleep apnea

Other CNS depressants: anesthesia, opioids, alcohol

CYP3A4 inhibitors: erythromycin, clarithromycin, ritonavir, itraconazole, ketoconazole, nefazodone, grapefruit

Age--reduced clearance

Avoid long-acting benzodiazepines (flurazepam, quazepam)

Class: Benzodiazepine

Kinetics:

Intermediate acting (t1/2 = 6-24 hours)

Completely absorbed--lipophilic

Protein bound

Metabolized by P450 (CYP3A4): except temazepam, oxazepam, and lorazepam

MOA: Bind to modulatory site on GABA_A receptor and increase channel opening (therefore help GABA inhibit neuronal activity)

Uses:

Anticonvulsant

Antianxiety

Side Effects:

Common: Daytime sedation, drowsiness, weakness, psychomotor incoordination, anterograde amnesia, HA, blurred vision, vertigo, n/v/d

Overdose: respiratory depression, somnolence, confusion, apnea, hypotension, slurred speech, coma

Other: anaphylaxis, facial angioedema, complex sleep behaviors

Tolerance and dependence

Abrupt withdrawal = increased anxiety, dizziness, tremor, and hyperreflexia

Interactions:

Medical conditions: hepatic disease, COPD, obstructive sleep apnea

Other CNS depressants: anesthesia, opioids, alcohol

CYP3A4 inhibitors: erythromycin, clarithromycin, ritonavir, itraconazole, ketoconazole, nefazodone, grapefruit

Age--reduced clearance

Avoid long-acting benzodiazepines (flurazepam, quazepam)

Class: Benzodiazepine

Kinetics:

Intermediate acting (t1/2 = 6-24 hours [10-24])

Completely absorbed--lipophilic

Protein bound

Metabolized by P450 (CYP3A4): except temazepam, oxazepam, and lorazepam

MOA: Bind to modulatory site on GABA_A receptor and increase channel opening (therefore help GABA inhibit neuronal activity)

Use: Hypnotic (insomnia)

Reduce sleep latency--make it easier to fall asleep

Increase total sleep time

Side Effects:

Common: Daytime sedation, drowsiness, weakness, psychomotor incoordination, anterograde amnesia, HA, blurred vision, vertigo, n/v/d

Overdose: respiratory depression, somnolence, confusion, apnea, hypotension, slurred speech, coma

Other: anaphylaxis, facial angioedema, complex sleep behaviors

Tolerance and dependence

Abrupt withdrawal = increased anxiety, dizziness, tremor, and hyperreflexia

Interactions:

Medical conditions: hepatic disease, COPD, obstructive sleep apnea

Other CNS depressants: anesthesia, opioids, alcohol

CYP3A4 inhibitors: erythromycin, clarithromycin, ritonavir, itraconazole, ketoconazole, nefazodone, grapefruit

Age--reduced clearance

Avoid long-acting benzodiazepines (flurazepam, quazepam)

Class: Benzodiazepine

Kinetics:

Intermediate acting (t1/2 = 6-24 hours)

Completely absorbed--lipophilic

Protein bound

Metabolized by P450 (CYP3A4): except temazepam, oxazepam, and lorazepam

MOA: Bind to modulatory site on GABA_A receptor and increase channel opening (therefore help GABA inhibit neuronal activity)

Use: Antianxiety

Side Effects:

Common: Daytime sedation, drowsiness, weakness, psychomotor incoordination, anterograde amnesia, HA, blurred vision, vertigo, n/v/d

Overdose: respiratory depression, somnolence, confusion, apnea, hypotension, slurred speech, coma

Other: anaphylaxis, facial angioedema, complex sleep behaviors

Tolerance and dependence

Abrupt withdrawal = increased anxiety, dizziness, tremor, and hyperreflexia

Interactions:

Medical conditions: hepatic disease, COPD, obstructive sleep apnea

Other CNS depressants: anesthesia, opioids, alcohol

CYP3A4 inhibitors: erythromycin, clarithromycin, ritonavir, itraconazole, ketoconazole, nefazodone, grapefruit

Age--reduced clearance

Avoid long-acting benzodiazepines (flurazepam, quazepam)

Class: Benzodiazepine

Kinetics:

Intermediate acting (t1/2 = 6-24 hours)

Completely absorbed--lipophilic

Protein bound

Metabolized by P450 (CYP3A4): except temazepam, oxazepam, and lorazepam

MOA: Bind to modulatory site on GABA_A receptor and increase channel opening (therefore help GABA inhibit neuronal activity)

Use: Antianxiety

Side Effects:

Common: Daytime sedation, drowsiness, weakness, psychomotor incoordination, anterograde amnesia, HA, blurred vision, vertigo, n/v/d

Overdose: respiratory depression, somnolence, confusion, apnea, hypotension, slurred speech, coma

Other: anaphylaxis, facial angioedema, complex sleep behaviors

Tolerance and dependence

Abrupt withdrawal = increased anxiety, dizziness, tremor, and hyperreflexia

Interactions:

Medical conditions: hepatic disease, COPD, obstructive sleep apnea

Other CNS depressants: anesthesia, opioids, alcohol

CYP3A4 inhibitors: erythromycin, clarithromycin, ritonavir, itraconazole, ketoconazole, nefazodone, grapefruit

Age--reduced clearance

Avoid long-acting benzodiazepines (flurazepam, quazepam)

Class: Benzodiazepine

Kinetics:

Intermediate acting (t1/2 = 6-24 hours [11])

Completely absorbed--lipophilic

Protein bound

Metabolized by P450 (CYP3A4): except temazepam, oxazepam, and lorazepam

MOA: Bind to modulatory site on GABA_A receptor and increase channel opening (therefore help GABA inhibit neuronal activity)

Use: Hypnotic (insomnia)

Reduce sleep latency--make it easier to fall asleep

Increase total sleep time

Side Effects:

Common: Daytime sedation, drowsiness, weakness, psychomotor incoordination, anterograde amnesia, HA, blurred vision, vertigo, n/v/d

Overdose: respiratory depression, somnolence, confusion, apnea, hypotension, slurred speech, coma

Other: anaphylaxis, facial angioedema, complex sleep behaviors

Tolerance and dependence

Abrupt withdrawal = increased anxiety, dizziness, tremor, and hyperreflexia

Interactions:

Medical conditions: hepatic disease, COPD, obstructive sleep apnea

Other CNS depressants: anesthesia, opioids, alcohol

CYP3A4 inhibitors: erythromycin, clarithromycin, ritonavir, itraconazole, ketoconazole, nefazodone, grapefruit

Age--reduced clearance

Avoid long-acting benzodiazepines (flurazepam, quazepam)

Class: Benzodiazepine

Kinetics:

Long acting (t1/2 > 24 hours)

Completely absorbed--lipophilic

Protein bound

Metabolized by P450 (CYP3A4): except temazepam, oxazepam, and lorazepam

MOA: Bind to modulatory site on GABA_A receptor and increase channel opening (therefore help GABA inhibit neuronal activity)

Uses:

Alcohol withdrawal-induced symptoms

Anticonvulsant

Antianxiety

Side Effects:

Common: Daytime sedation, drowsiness, weakness, psychomotor incoordination, anterograde amnesia, HA, blurred vision, vertigo, n/v/d

Overdose: respiratory depression, somnolence, confusion, apnea, hypotension, slurred speech, coma

Other: anaphylaxis, facial angioedema, complex sleep behaviors

Tolerance and dependence

Abrupt withdrawal = increased anxiety, dizziness, tremor, and hyperreflexia

Interactions:

Medical conditions: hepatic disease, COPD, obstructive sleep apnea

Other CNS depressants: anesthesia, opioids, alcohol

CYP3A4 inhibitors: erythromycin, clarithromycin, ritonavir, itraconazole, ketoconazole, nefazodone, grapefruit

Age--reduced clearance

Avoid long-acting benzodiazepines (flurazepam, quazepam)

Class: Benzodiazepine

Kinetics:

Long acting (t1/2 > 24 hours [74])

Completely absorbed--lipophilic

Protein bound

Metabolized by P450 (CYP3A4): except temazepam, oxazepam, and lorazepam

MOA: Bind to modulatory site on GABA_A receptor and increase channel opening (therefore help GABA inhibit neuronal activity)

Use: Hypnotic (insomnia)

Reduce sleep latency--make it easier to fall asleep

Increase total sleep time

Side Effects:

Common: Daytime sedation, drowsiness, weakness, psychomotor incoordination, anterograde amnesia, HA, blurred vision, vertigo, n/v/d

Overdose: respiratory depression, somnolence, confusion, apnea, hypotension, slurred speech, coma

Other: anaphylaxis, facial angioedema, complex sleep behaviors

Tolerance and dependence

Abrupt withdrawal = increased anxiety, dizziness, tremor, and hyperreflexia

Flurazepam ONLY: nightmares, garrulousness (excessive talking), irritability, tachycardia, sweating

Interactions:

Medical conditions: hepatic disease, COPD, obstructive sleep apnea

Other CNS depressants: anesthesia, opioids, alcohol

CYP3A4 inhibitors: erythromycin, clarithromycin, ritonavir, itraconazole, ketoconazole, nefazodone, grapefruit

Age--reduced clearance

Avoid long-acting benzodiazepines (flurazepam, quazepam)

Class: Benzodiazepine

Kinetics:

Long acting (t1/2 > 24 hours [39])

Completely absorbed--lipophilic

Protein bound

Metabolized by P450 (CYP3A4): except temazepam, oxazepam, and lorazepam

MOA: Bind to modulatory site on GABA_A receptor and increase channel opening (therefore help GABA inhibit neuronal activity)

Use: Hypnotic (insomnia)

Reduce sleep latency--make it easier to fall asleep

Increase total sleep time

Side Effects:

Common: Daytime sedation, drowsiness, weakness, psychomotor incoordination, anterograde amnesia, HA, blurred vision, vertigo, n/v/d

Overdose: respiratory depression, somnolence, confusion, apnea, hypotension, slurred speech, coma

Other: anaphylaxis, facial angioedema, complex sleep behaviors

Tolerance and dependence

Abrupt withdrawal = increased anxiety, dizziness, tremor, and hyperreflexia

Interactions:

Medical conditions: hepatic disease, COPD, obstructive sleep apnea

Other CNS depressants: anesthesia, opioids, alcohol

CYP3A4 inhibitors: erythromycin, clarithromycin, ritonavir, itraconazole, ketoconazole, nefazodone, grapefruit

Age--reduced clearance

Avoid long-acting benzodiazepines (flurazepam, quazepam)

Class: BZ receptor agonist

MOA: Selective action at BZ receptor; hypnotic effect without anxiolytic, muscle relaxant, or anticonvulsant effects

Kinetics:

CYP3A4 metabolism

Half life = 2.5 h, Duration of effect = 6-8 h

Food decreases absorption (take on empty stomach)

Use: Reducing sleep latency and increasing total sleep time

Side effects:

Drowsiness, amnesia, dizziness, headache, GI

Brief psychotic reactions (sleep eating)

NO tolerance, rebound insomnia, or impaired psychomotor performance

Class: BZ receptor agonist

MOA: Selective binding to BZ receptor (GABA receptor complex)

Kinetics:

Metabolized by CYP3A4

Excreted in urine

Half life = 1 h

**Caution in liver and renal failure**

Use: Sleep-onset insomnia

Reduces sleep latency, but does NOT increase total sleep time or reduce nighttime awakening

Side effects: Few!

Headache, somnolence, dizziness

Interactions:

Cimetidine- 3A4 inhibitor

Rifampin- 3A4 inducer

Class: Non-benzodiazepine hypnotic

MOA: Binds to GABA-A/benzodiazepine receptors

Kinetics:

CYP3A4 metabolism

Half life = 3.5-6.5 h

Use: Insomnia (did not specify what kind)

Side effects:

Sedation, dizziness, dose-dependent amnesia, hyper-excitability

Class: Non-benzodiazepine hypnotic

MOA: Binds to GABA-A/benzodiazepine receptor; active stereoisomer of zopiclone

Kinetics:

Metabolized by CYP3A4

Half-life 5-6 h

Caution in elderly patients or hepatic dysfunction

Use: Reduce time to sleep onset, waking time after sleep onset, and number of awakenings; increase total sleep time and sleep quality

OK for long term use (6 months)

Side effects:

Somnolence, unpleasant taste, headache, dry mouth

Interactions:

CYP3A4 inhibitors: fluvoxamine, nefazodone, clarithromycin

Class: Benzodiazepine receptor antagonist

MOA: Binds with high affinity to specifc sites on GABA_A receptor, where it competitively antagonizes binding and allosteric effects of BZs and other ligands

Kinetics:

Hepatic metabolism

Half life = 1 h

Duration of action 30-60 min

Uses:

Benzodiazepine overdose

Reversal of benzodiazepine sedation

Side effects:

Cutaneous vasodilation, headache (cerebral vasodilation), CONVULSION!!!!

Modest anticonvulsant efffect at high dose, but can't use it this way because it actually induces seizures in certain patients

Important not to give for BZ overdose when BZ's are used for seizure treatment

Class: Barbituate

MOA: Enhance action of GABA, but bind to a different site than BZs and have less specific action

Kinetics:

Long-acting (half life = 100 h)

Lipophilic; wide distribution

Hepatic metabolism and renal excretion

Induce P450 enzymes

Uses:

Sedation

Antagonize unwanted stimulant effects of ephedrine, dextroamphetamine, theophylline, etc.

Anticonvulsant

Side effects:

Tolerance, abuse, dependance, withdrawal

Peripheral nervous system: Reduced autonomic transmission and nicotinic excitation

Respiration: depress respiratory drive and mechanisms; cause cough, sneeze, hiccup, and laryngospasm

Cardiovascular: Decrease BP and CV reflexes

GI: decreased contractility

Coma and medullary depression

Drowsiness, impaired judgment, vertigo, n/v/d, euphoria, irritability

Paradoxical excitement

Hypersensitivity

Contraindicated in patients with porphyria

Class: Barbituate

MOA: Enhance action of GABA, but bind to a different site than BZs and have less specific action

Kinetics:

Long-acting (half life = 53-118 h)

Lipophilic; wide distribution

Hepatic metabolism and renal excretion

Induce P450 enzymes

Uses:

Sedation

Antagonize unwanted stimulant effects of ephedrine, dextroamphetamine, theophylline, etc.

Anticonvulsant

Side effects:

Tolerance, abuse, dependance, withdrawal

Peripheral nervous system: Reduced autonomic transmission and nicotinic excitation

Respiration: depress respiratory drive and mechanisms; cause cough, sneeze, hiccup, and laryngospasm

Cardiovascular: Decrease BP and CV reflexes

GI: decreased contractility

Coma and medullary depression

Drowsiness, impaired judgment, vertigo, n/v/d, euphoria, irritability

Paradoxical excitement

Hypersensitivity

Contraindicated in patients with porphyria

Class: Barbituate

MOA: Enhance action of GABA, but bind to a different site than BZs and have less specific action

Kinetics:

Intermediate-acting (half life = 15-50 h)

Lipophilic; wide distribution

Hepatic metabolism and renal excretion

Induce P450 enzymes

Uses:

Insomnia and anxiolytic (sometimes, but BZs safer)

Side effects:

Tolerance, abuse, dependance, withdrawal

Peripheral nervous system: Reduced autonomic transmission and nicotinic excitation

Respiration: depress respiratory drive and mechanisms; cause cough, sneeze, hiccup, and laryngospasm

Cardiovascular: Decrease BP and CV reflexes

GI: decreased contractility

Coma and medullary depression

Drowsiness, impaired judgment, vertigo, n/v/d, euphoria, irritability

Paradoxical excitement

Hypersensitivity

Contraindicated in patients with porphyria

Class: Barbituate

MOA: Enhance action of GABA, but bind to a different site than BZs and have less specific action

Kinetics:

Intermediate-acting (half life = 28 h)

Lipophilic; wide distribution

Hepatic metabolism and renal excretion

Induce P450 enzymes

Uses:

Insomnia and anxiolytic (sometimes, but BZs safer)

Side effects:

Tolerance, abuse, dependance, withdrawal

Peripheral nervous system: Reduced autonomic transmission and nicotinic excitation

Respiration: depress respiratory drive and mechanisms; cause cough, sneeze, hiccup, and laryngospasm

Cardiovascular: Decrease BP and CV reflexes

GI: decreased contractility

Coma and medullary depression

Drowsiness, impaired judgment, vertigo, n/v/d, euphoria, irritability

Paradoxical excitement

Hypersensitivity

Contraindicated in patients with porphyria

Class: Barbituate

MOA: Enhance action of GABA, but bind to a different site than BZs and have less specific action

Kinetics:

Intermediate-acting (half life = 25 h)

Lipophilic; wide distribution

Hepatic metabolism and renal excretion

Induce P450 enzymes

Uses:

Insomnia and anxiolytic (sometimes, but BZs safer)

Side effects:

Tolerance, abuse, dependance, withdrawal

Peripheral nervous system: Reduced autonomic transmission and nicotinic excitation

Respiration: depress respiratory drive and mechanisms; cause cough, sneeze, hiccup, and laryngospasm

Cardiovascular: Decrease BP and CV reflexes

GI: decreased contractility

Coma and medullary depression

Drowsiness, impaired judgment, vertigo, n/v/d, euphoria, irritability

Paradoxical excitement

Hypersensitivity

Contraindicated in patients with porphyria

Class: Barbituate

MOA: Enhance action of GABA, but bind to a different site than BZs and have less specific action

Kinetics:

Short-acting (half life = 3-8 h)

Lipophilic; wide distribution

Hepatic metabolism and renal excretion

Induce P450 enzymes

Uses:

IV anesthesia

Side effects:

Tolerance, abuse, dependance, withdrawal

Peripheral nervous system: Reduced autonomic transmission and nicotinic excitation

Respiration: depress respiratory drive and mechanisms; cause cough, sneeze, hiccup, and laryngospasm

Cardiovascular: Decrease BP and CV reflexes

GI: decreased contractility

Coma and medullary depression

Drowsiness, impaired judgment, vertigo, n/v/d, euphoria, irritability

Paradoxical excitement

Hypersensitivity

Contraindicated in patients with porphyria

Class: GABA receptor agonist

MOA: Metabolized to trichloroethanol, which has barbituate-like effects on GABA_A receptor channels

Kinetics:

Works within 30 minutes, lasts 6 hours

Uses:

Hypnotic (induce sleep)

Sedation for children undergoing uncomfortable procedures

Side effects:

Unpleasant taste, epigastric distress, n/v

Hepatic damage and withdrawal with long term use

Interactions: warfarin (displaces warfarin from plasma proteins)

Class: Melatonin receptor agonist

MOA: Selective for MT1 and MT2 receptors; regulate circadian rhythm and sleep onset

Use: Induce sleep

Side effects:

Headache, dizziness, somnolence

Class: Typical antipsychotic (low potency); phenothiazine

MOA: D₂ dopamine receptor antagonist

Kinetics:

Highly lipophilic

Typical half life = 20-40 h

Metabolized by P450

Uses:

Positive symptoms of schizophrenia

Antiemetic

Pruritis

Side Effects:

Sedation: +++

EPS: ++

Hypotension: ++/+++

Autonomic effects (block M receptor)

Block α adrenoceptor

Corneal or lens pigmentation

Jaundice

Agranulocytosis

Class: Typical antipsychotic (low potency); phenothiazine

MOA: D₂ dopamine receptor antagonist

Kinetics:

Highly lipophilic

Typical half life = 20-40 h

Metabolized by P450

Uses:

Positive symptoms of schizophrenia

Antiemetic

Pruritis

Side Effects:

Sedation: +++

EPS: +

Hypotension: ++

Autonomic effects (block M receptor)

Block α adrenoceptor

Urticaria, dermatitis, photosensitivity, epithelial keratopathy, opacity of eye

Agranulocytosis

Class: Typical antipsychotic (low potency); phenothiazine

MOA: D₂ dopamine receptor antagonist

Kinetics:

Highly lipophilic

Typical half life = 20-40 h

Metabolized by P450

Uses:

Positive symptoms of schizophrenia

Pruritis

Side Effects:

Sedation: +++

EPS: +

Hypotension: ++

Autonomic effects (block M receptor)

Block α adrenoceptor

QT prolongation

Pigmentary retinopathy

Agranulocytosis

Class: Typical antipsychotic (high potency); phenothiazine

MOA: D₂ dopamine receptor antagonist

Kinetics:

Highly lipophilic

Typical half life = 20-40 h

Metabolized by P450

Uses:

Positive symptoms of schizophrenia

Antiemetic

Pruritis

Side Effects:

Sedation: +

EPS: ++++

Hypotension: +

Urticaria, dermatitis, photosensitivity, epithelial keratopathy, opacity of eye

Class: Typical antipsychotic (high potency); phenothiazine

MOA: D₂ dopamine receptor antagonist

Kinetics:

Highly lipophilic

Typical half life = 20-40 h

Metabolized by P450

Uses:

Positive symptoms of schizophrenia

Antiemetic

Pruritis

Side Effects:

Sedation: ++

EPS: ++

Hypotension: +

Urticaria, dermatitis, photosensitivity, epithelial keratopathy, opacity of eye

Class: Typical antipsychotic (high potency); phenothiazine

MOA: D₂ dopamine receptor antagonist

Kinetics:

Highly lipophilic

Typical half life = 20-40 h

Metabolized by P450

Uses:

Positive symptoms of schizophrenia

Antiemetic

Pruritis

Side Effects:

Sedation: +

EPS: +++

Hypotension: +

Urticaria, dermatitis, photosensitivity, epithelial keratopathy, opacity of eye

Class: Typical antipsychotic (high potency); thioxanthene

MOA: D₂ dopamine receptor antagonist

Kinetics:

Highly lipophilic

Typical half life = 20-40 h

Metabolized by P450

Uses:

Positive symptoms of schizophrenia

Side Effects:

Sedation: +/++

EPS: ++++

Hypotension: ++

Class: Typical antipsychotic (high potency); butyrophenone

MOA: D₂ dopamine receptor antagonist

Kinetics:

Highly lipophilic

Typical half life = 20-40 h

Metabolized by P450

Uses:

Positive symptoms of schizophrenia

Tourette's syndrome

Side Effects:

Sedation: +

EPS: ++++

Hypotension: +

Class: Typical antipsychotic (high potency); benzapine

MOA: D₂ dopamine receptor antagonist

Kinetics:

Highly lipophilic

Typical half life = 20-40 h

Metabolized by P450

Uses:

Positive symptoms of schizophrenia

Side Effects:

Sedation: +

EPS: ++

Hypotension: +

Class: Typical antipsychotic (high potency)

MOA: D₂ dopamine receptor antagonist

Kinetics:

Highly lipophilic

Typical half life = 20-40 h

Metabolized by P450

Uses:

Positive symptoms of schizophrenia

Side Effects:

Sedation: ++

EPS: ++

Hypotension: +

Class: Atypical antipsychotic; benzapine

MOA: D₂ dopamine receptor partial agonist; 5-HT2A antagonist

Kinetics:

Highly lipophilic

Typical half life = 20-40 h

Metabolized by CYP3A4 and CYP2D6

Uses:

Negative symptoms of schizophrenia or patients that don't respond to typical antipsychotics

Autism

Manic/mixed bipolar episodes in children and adolescents

Side Effects:

Sedation: 0/+

EPS: 0/+

Hypotension: 0/+

Weight gain: 0/+

Diabetes: 0

Worsening lipid profile: 0

Low toxicity!! :)

Headache, akathisia, n/v

Interactions:

3A4 inhibitors: clarithromycin, itraconazole, ketoconazole

2D6 inhibitors: fluoxetine, paroxetine, quinidine

Class: Atypical antipsychotic; benzapine

MOA: D₂ dopamine receptor antagonist and 5-HT 2A, 2C, and 1A antagonist

Kinetics:

Highly lipophilic

Typical half life = 20-40 h

Metabolized by P450

Uses:

Resitant schizophrenia or schizophrenia with suicidal ideation

Side Effects:

Sedation: +++

EPS: 0

Hypotension: +++

Weight gain: +++

Diabetes: +

Worsening lipid profile: +

Autonomic effects (block M receptor and α adrenoceptor)

Myocarditis and myopathy

Severe ileus and sialorrhea (salivation); sweating

Neutropenia (3%) and agranulocytosis (1%)

Weekly blood count monitoring for 6 months and bi-weekly thereafter

Dose-dependent seizure risk

Contraindications:

Bone marrow disorder, severe CNS depression, uncontrolled epilepsy

Class: Atypical antipsychotic

MOA: Blocks 5-HT_2A/2C receptors

Kinetics:

Highly lipophilic

Typical half life = 20-40 h

Metabolized by CYP1A2

Uses:

Negative symptoms of schizophrenia or resistant schizophrenia

Mood stabilizer

Bipolar

Acute agitation (IM injection)

Pregnancy! (Category C; others are D)

Side Effects:

Sedation: +

EPS: +

Hypotension: ++

Weight gain: +++

Diabetes: +

Worsening lipid profile: +

Stroke; torsades de pointes

Coma and autonomic effects upon overdose

Class: Atypical antipsychotic

MOA: Blocks 5-HT_2A, D2, α1, and H1 receptors

Kinetics:

Highly lipophilic

Typical half life = 20-40 h

Metabolized by CYP2D6

Active metabolite = paliperidone

Higher dose makes it act like a typical antipsychotic

Uses:

Negative symptoms of schizophrenia or resistant schizophrenia

Bipolar (manic and mixed)

Irritability associated with autism

Can be used in children and teens

Side Effects:

Sedation: ++

EPS: ++

Hypotension: +++

Weight gain: ++

Diabetes: ?

Worsening lipid profile: ?

Stroke

Block α receptors

Hyperprolactinemia

Interactions:

CYP2D6 inhibitors: fluoxetine, paroxetine

Class: Atypical antipsychotic

MOA: Blocks 5-HT_2A receptors; partial agonist of 5-HT_1A receptor

Kinetics:

Highly lipophilic

Typical half life = 20-40 h

Metabolized by CYP3A4

Uses:

Negative symptoms of schizophrenia or resistant schizophrenia

Drug of choice for antipsychotic in Parkinson's

Bipolar

Adjuvant for major depressive disorder

Side Effects:

Sedation: +++ (highly sedating)

EPS: 0

Hypotension: ++

Weight gain: ++

Diabetes: ?

Worsening lipid profile:? (Elevated cholesterol and TG)

Dry mouth; constipation

Risk of suicide in children, adolescents, and young adults

Interactions:

CYP3A4 inhibitors: erythromycin, fluvoxamine, itraconazole

Class: Atypical antipsychotic

MOA: "Antidepressant-like"

D2 and 5-HT₂ antagonist

5-HT_1A agonist

Moderate inhibitor of 5-HT and dopamine reuptake

Kinetics:

Highly lipophilic

Typical half life = 20-40 h

Metabolized by CYP1A2

Uses:

Negative symptoms of schizophrenia or resistant schizophrenia

Bipolar

Acute agitation (IM injection)

Side Effects:

Sedation: +/++

EPS: 0/+

Hypotension: +

Weight gain: 0/+

Diabetes: 0

Worsening lipid profile: 0

QT prolongation

Contraindications:

Hx QT prolongation, heart failure, MI, any other drug that prolongs QT interval

Class: Atypical antipsychotic

MOA: Blocks 5-HT_2A and D2 receptors; partial agonist at 5-HT_1A receptor

Kinetics:

Highly lipophilic

Typical half life = 20-40 h

Metabolized by CYP3A4

Uses:

Negative symptoms of schizophrenia or resistant schizophrenia

Side Effects:

CNS: EPS (akathisia, parkinsonism, agitation); somnolence

GI: n/v, dyspepsia

Dermatologic: Rash, pruritis

Weight gain

Interactions:

CYP3A4 inducers: rifampin, carbamazepine, phenytoin

CYP3A4 inhibitors: ketoconazole, nefazodone, itraconazole

MOA: Unknown, but several theories

Competes with monovalent and divalent cations at tissues and receptor sites

Inhibits inositol-1-phosphatase, causing reduction in synaptic transmission

Inhibits PKC and glycogen synthase kinase

Kinetics:

Absorbed from GI

Renal elimination (Contra for renal failure, but good for liver failure!)

Half life = 20-24 h

Distributed through body water; plasma levels altered by changes in body fluid or sodium depletion

Uses:

Bipolar disorder

Acute mania treatment and prevention of recurrence

Long-term prevention of recurrence of major affective illness (mania and depression)

Depression

Adjunct for melancholic, recurrent depression and acute major depression

Reduces suicide risk

Episodic disorders: premenstrual dysphoria, episodic alcohol abuse, episodic violence

Mania

Long-term mood stabilization (not given acutely)

For acute tx: use antipsychotics, sedating benzos (lorazepam or clonazepam), or sodium valproate

Side effects:

GI: n/v/d

CNS stimulation: tremor, ataxia, coma, comvulsions

Daytime drowsiness, polyuria, polydipsia, weight gain, acne

Inhibits thyroid hormone release --> thyroid enlargement and hypothyroidism

Leukocytosis/leukemia: must test blood every 2 weeks

Interactions:

Loop and thiazide diurectics: decrease secretion

COX-1 and COX-2 inhibitors: decrease renal blood flow

ACE-I, AT1R antagonist, and diuretics: increase blood volume

Contraindications:

Pregnancy (3rd trimester?)

Neonatal goiter, CNS depression, hypotonia, cardiac murmur

Acute renal failure

Class: Dibenzazepine derivative (similar to TCAs)

MOA: Unknown

Block NE reuptake and release

Decrease doapmine and GABA turnover

Block NMDA receptor (prevent Ca²⁺ influx)

Decrease adenylyl cyclase activity

Kinetics:

Excreted in breast milk--hepatitis and jaundice in infants

Induces P450 (decrease OC levels)

Metabolized by CYP3A4

Side effects:

CNS toxicity: drowsiness, dizziness, fatigue, clumsiness, ataxia, vertigo, blurred vision, diplopia, nystagmus, dysarthria, confusion, headache

GI: n/v/d, abdominal pain, constipation, anorexia

Liver toxicity*

Leukopenia (severe bone marrow depression)*

Do not give with clozapine!

Dermatologic: rash, uritcaria, photosensitivtiy, lupus-like syndrome

Pregnancy category D

*Requires frequent monitoring!!!

Use: acute antimanic and prophylactic effects; similar to lithium or VPA (bipolar)

Especially good for early-onset manic episodes and negative family history of mood disorders

MOA: Induce GABA-ergic transmission, decrease dopamine turnove, decrease NMDA-mediated depolarization, block voltage-gated Na⁺ channels and T-type Ca²⁺ channels

Kinetics:

Highly bound to albumin

Metabolized in liver (Contra--liver dysfunction!!)

Side effects:

GI

CNS: tremor, sedation, ataxia, weight gain

Agranulocytosis and thrombocytopenia

Hepatitis and pancreatitis

Teratogenic (category D)

OK in breastfeeding, but must monitor infant regularly

Uses:

Acute manic/mixed bipolar episodes

Seizures

Migraine

MOA: Unknown; may inhibit voltage-gated Na⁺ channels or reduce release of excitatory AAs

Side effects:

Common: HA, nausea, dizziness, ataxia, drowsiness, tremor, diplopia

Special: Stevens-Johnson syndrome

Uses:

Treatment-resistant bipolar I and II

Rapid-cycling dysphoric mania

Mixed states

INX:

Valproate decreases clearance

Decreases plasma levels of valproate