Exam 4 Medchem 2 v.10 FINAL

N₂O

Nitrous Oxide

• Class: Gaseous anesthetic

• MOA: disrupts protein/lipid membranes

• Clinical Use: Analgesia in combination

• Onset/Duration: Very rapid onset/recovery

• MAC: 104% (very weak)

• BGPC: 0.47 (fast recovery)

• Not muscle Relaxing

Halothane

• Class: Volatile anesthetic

• Clinical Use: General anesthesia

• MAC: 0.74% (high potency)

• BGPC: 2.5 (rapid induction, slower recovery)

• Metabolism: ~20% → TFA (toxic metabolite), Cl⁻, Br⁻; hepatotoxicity

• Side Effects: Cardiac sensitization (arrhythmia), liver/kidney damage

• BP 50.2 C

• Muscle Relaxing

Enflurane

• Class: Volatile anesthetic

• Clinical Use: General anesthesia

• MAC: 1.7%

• BGPC: 1.9

• Metabolism: ~5%; toxic metabolites

  • 2nd highest F toxicty

• BP 56,5 C

• Muscle relaxing

Isoflurane

• Class: Volatile anesthetic

• Clinical Use: General anesthesia

• MAC: 1.17%

• BGPC: 1.4

• Metabolism: 0.2%

• SM relaxation: Yes

• BP 48.5C

• Commonly used

Desflurane

• Class: Volatile anesthetic

• Clinical Use: maintenance of anesthesia in combo

  • outpatient surgery due to rapid recovery

• MAC: 6% (least potent)

• BGPC: 0.42 (fastest recovery)

• Metabolism: <0.02%

  • Least F toxicity

• Notes: Airway irritant, requires special packaging due to BP

• BP 23.5 C

Sevoflurane

• Class: Volatile anesthetic

• Clinical Use: Induction/Maintenance of Anesthesia

• MAC: 2.05%

• BGPC: 0.68

  • Rapid recovery from anesthesia

• Metabolism: ~5%; fluoride release (renal risk)

  • Highest F toxicty

• Notes: Pleasant taste, low airway irritation

• BP 58.6 C

Cyclopropane

• Clinical Use: Historical general anesthesic

• MAC: 17.5%

• SM relaxation: Yes

• Safety: Explosive with O₂

Ethylene

• Clinical Use: Historical general anesthesia

• MAC: Higher than cyclopropane (less potent)

• Safety: Explosive with O₂

Ketamine C-III

• Class: NMDA receptor antagonist

• MOA: Non-competitive NMDA antagonist

• Clinical Use: dissociative anesthetic, causes amnesia

• Onset/Duration: Rapid onset, short duration

• SM relaxation: No

• Side Effects: Hallucinations, emergence reactions

• Formulations: IV

• Metabolism: dealkylation to ACTIVE metabolite

• S > R enantiomer activity (racemic mix)

Esketamine C-III

• Class: NMDA receptor antagonist

• MOA: Non-competitive NMDA antagonist

• Clinical Use: Treatment-resistant depression

• Onset: Fast (intranasal)

• Admin: Under healthcare supervision only (2x per week)

• Formulations: Intranasal only

• S enantiomer only

Propofol

• Class: IV anesthetic

• MOA: Enhance GABA transmission

• Clinical Use: Induction, maintenance, of anesthesia + ICU

• Fast onset: ~40 sec, 2-24hr duration

  • Rapid recovery from anesthesia

• Muscle Relaxing

• Metabolism: Hepatic glucuronidation/sulfation

• Properties: Anti-emetic, lipid emulsion, non-controlled

• Formulations: IV

• Pain in inj site

Fospropofol C-IV

• Class: IV anesthetic prodrug

• MOA: Prodrug of propofol

• Onset: 4–8 min

• Properties: Water-soluble, requires alkaline phosphatase

• Discontinued

Midazolam C-IV

• Class: Benzodiazepine

• Clinical Use: pre op Sedation (Muscle Relaxing)

  • induction of anesthesia,

  • anxiety,

  • seizures

• Onset: IV ~5 min, 10-20 min IM

  • Long recovery time for PTs

  • amnesia affect

• Formulations: IV, PO, IM

• Metabolism: hydroxylation ACTIVE metabolite

Remimazolam C-IV

• Class: Softdrug benzodiazepine

  • gives predictable PK

• MOA: GABA-A potentiation

• Clinical Use: Short procedures, procedural sedation

• Rapid Onset , Short duration

• Muscle Relaxing

• Metabolism: Tissue esterases create charged carbolic acids which prevents CNS penetration

• Formulations: IV

Etomidate

• Class: IV anesthetic (imidazole)

• MOA: GABA-A receptor enhancement

• Clinical Use: induction of general anesthesia for short procedures

• Rapid onset, short duration: 3–5 min

• Notes: No analgesia, nausea/vomiting common, No Muscle relaxing

• Formulations: IV

Methohexital C-IV

• Class: Ultra-short Barbiturate

• Clinical Use: Induction of anesthesia

• Rapid onset, short duration: 20 min

• No Muscle Relaxing

• Formulations: IV

Thiopental C-III

• Class: Ultra-short Barbiturate

• MOA: GABA-A agonist

• Clinical Use: Induction of anestheisa, (now propofol is favored)

• Duration: Ultra-short (lipophilic)

  • can have long term sedating effect

• Formulations: IV

Secobarbital (C-II)

• Class: Short-acting barbiturate

• MOA: GABA-A receptor agonist

• Clinical Use: Hypnotic, preanesthetic

• Onset/Duration: Onset 10–15 minutes; Duration 3–4 hours

• Metabolism: Epoxide formation → hydrolysis deactivates it

• Formulation: PO

• Notes: Branching and unsaturation promote metabolism; epoxide may covalently bind CYP450; two hydroxyl groups increase water solubility

Pentobarbital (CII)

• Class: Short-acting barbiturate

• MOA: Enhances GABA-A receptor activity (↑ Cl⁻ influx)

• Clinical Use: Hypnotic and preanesthetic

• Onset/Duration: 10–15 min onset, 3–4 hr duration

• Metabolism: Hepatic; includes oxidation and glucuronidation

• Formulation: PO/IV

• Notes: One chiral center (racemic)

Amobarbital (CII)

• Class: Intermediate-acting barbiturate

• MOA: GABA-A receptor enhancer

• Clinical Use: Sedative-hypnotic

• Onset/Duration: 45–60 min onset, 6–8 hr duration

• Metabolism: Hepatic oxidation/conjugation

• Formulation: PO/IV

• Notes: no chiral center due to symmetry

Butabarbital C-III

• Class: Intermediate-acting barbiturate

• MOA: GABA-A receptor enhancer

• Clinical Use: Sedative-hypnotic

• Onset/Duration: 45–60 min onset, 6–8 hr duration

• Formulation: PO

Phenobarbital (CIV)

• Class: Long-acting barbiturate

• MOA: GABA-A agonist (↑ Cl⁻ channel open duration)

• Clinical Use: sedative hypnotic + Grand mal seizure

• Onset/Duration: 30–60+ min onset, 10–16 hr duration; half-life 53–118 hrs

• Metabolism: oxidation, glucuronidation at 3-N (preferrs S enantiomer at 6.8 S/R ratio) sulfation

• Formulation: PO/IV

• Notes: Benzene ring allows conjugation;

Chloral Hydrate (CIV)

• Class: Old (1832) sedative-hypnotic

• MOA:(GABA-A enhancer)

• Use: Sedation, helping sleep, especially in children

• Favored formation from trichloracetaldehyde

• Gemdiol is reduced to active Metabolite

• Synergism CNS depression with alcohol

  • also prevents alcohol withdrawl

• misued as roofie drug

• Issues: Bitter taste (given with fruit juice), GI irritation

• Formulations: PO

Diphenhydramine

• Class: 1st-gen antihistamine

• MOA: H1 antagonist, anticholinergic

• Clinical Use: Allergy, insomnia (structurally non specific)

• Controlled in Zambia

• Not used in children less than 6 y/9

• Formulations: PO, IV

Zolpidem Tartrate (Ambien) (CIV)

• Class: Z-drug

• MOA: BZT1 (GABA-A α1) receptor agonist

• Selective for type 1 receptor

• Clinical Use: Short-term insomnia, no go pill for military

• Half-life: 2 hrs

• extensively metabolized (hydroxilation, oxidation)

• Non chiral

• Formulations: 2:1 Salt with Tartrate PO (IR, ER)

Zaleplon (CIV)

• Class: Z-drug

• MOA: BZT1 receptor agonist

• Clinical Use: Sleep-onset insomnia

• Half-life: ~1 hr

• Metabolism: Extensively metabolized, hydroxylation, dealkylation

• PO

Eszopiclone (CIV)

• Class: Z-drug

• MOA: selective BZT1 receptor agonist

• Clinical Use: Sleep onset + maintenance

• Metabolism: demethylation of N gives ACTIVE metabolite (weaker)

• Formulations: PO (once-daily oral)

• S enantiomer

Dexmedetomidine

• Class: sedative hypnotic

• MOA: alpha a2 adrenergic agonist

• Clinical Use: ICU sedation, adjunct to anesthesia

• Metabolism: Extensive metabolism, oxidation, glucuronidation

• Formulations: IV
  Onset/Duration: Onset 5–10 min, duration 1–2 hrs

• Notes: More sedative, less hypotensive than clonidine

• S enantiomer

Ramelteon

• Class: Melatonin receptor agonist

• MOA: MT1 (sleep onset) and MT2 (circadian rhythm) agonist

• Use: Chronic insomnia (sleep onset)

• Half-life: 1–2.6 hrs

• Metabolism: hydroxylation → ACTIVE metabolite (10× conc, 1/10 activity)

  • high first pass OBA, much lower 2nd pass

• Formulations: PO (once-daily)

Tasimelteon

• Class: Melatonin receptor agonist

• MOA: MT1 and MT2 agonist (MT2 Selective)

• Use: Non-24-hour sleep-wake disorder (blind patients), Smith-Magenis syndrome, night time sleep disturbances

• Half-life: ~1.3 hrs

• R, R enantiomer

• Formulations: PO (once-daily) Taken WITHOUT food

Suvorexant (CIV)

• Class: Orexin receptor antagonist (DORA)

• MOA: OX1R & OX2R antagonist

• Use: Insomnia (onset + maintenance)

• Half-life: ~12 hrs

• Notes: Take 30 min before bed, not with food

  • 30 min before sleep

• Negative food effect, take WITHOUT food

• Formulations: PO (once-daily), no generic available

• R enantiomer

Daridorexant (CIV)

• Class: DORA

• MOA: Dual orexin antagonist

• Use: non-first line tx Insomnia (for ≥7 hr sleep)

• Half-life: ~8 hrs

• Formulations: PO (once-daily) high cost, no generic

Lemborexant (CIV)

• Class: DORA

• MOA: Dual OX1R/OX2R blocker; stronger OX2R affinity

• Use: Insomnia (sleep onset + maintenance)

  • 30 min before bedtime

• Half-life: 17–19 hrs (due to F)

• Extensively Metabolized,

  • Negative food effect, take WITHOUT food

• Formulations: PO (once-daily) high cost, no generic

Chlordiazepoxide (Librium) (C-IV)

• Benzodiazepine

• MOA: Type 1+2 BZ binding and enhancing of GABA binding

• Use: Anxiety, alcohol withdrawal

• Metabolism: dealkylation, hydrolysis, oxidation and reduction are all ACTIVE.

  • hydroxylation on phenol is INACTIVE

• Formulations: PO, IM, IV

Diazepam (Valium) C-IV

• Benzodiazepine

• MOA: Type 1+2 BZ binding and enhancing of GABA binding

• Use: Anxiety, seizures, muscle spasms, alcohol withdrawal

• Metabolism: demethylation to ACTIVE → nordiazepam with longer (t½ ~200 hrs)

  • Hydroxylated to temazepan which is also active

• Half-life: 60–72 hrs

• Formulations: PO, IV, IM

Temazepam C-IV

• Benzodiazepine

• Use: Insomnia (preferred hypnotic)

  • Hydroxylated metabolite of diazepam

• Half-life: 4–18 hrs

• PO

Oxazepam C-IV

• Benzodiazepine

• Use: Anxiety, alcohol withdrawal

  • hydroxylated and demethylated metabolite of diazepam

• Half-life: 6–8 hrs

• PO

Clorazepate C-IV

• Benzodiazepine

• MOA: Type 1+2 BZ binding and enhancing of GABA binding

• Use: Anxiety, alcohol withdrawal, seizures

• Notes: Prodrug; decarboxylated in stomach → nordiazepam

• Half-life: Long (~200 hrs)

• PO

Flurazepam C-IV

• Benzodiazepine

• MOA: Type 1+2 BZ binding and enhancing of GABA binding

• Notes: Prodrug; active N-desalkyl metabolite

• Use: sedative hypnotic, Insomnia (maintains REM)

• Half-life: 47–100 hrs

• PO

Quazepam C-IV

• Benzodiazepine

• MOA: Type 1+2 BZ binding and enhancing of GABA binding

• Use: Insomnia (frequent waking)

• Metabolized by hydrolysis (removal) of sulfur to ACTIVE metabolite.

  • sulfur gives higher CNS pen (lipophilicity)

• Half-life: 47–100 hrs

Lorazepam C-IV

• Benzodiazepine

• MOA: Type 1+2 BZ binding and enhancing of GABA binding

• Use: Anxiety, seizures, delirium

• Half-life: 10–20 hrs

• Notes: Glucuronidated

• Chlorines give higher lipophilicity

• Formulations: PO, IV, IM

Alprazolam C-IV

• Triazolobenzodiazepine

• Use: Anxiety, panic disorder, agoraphobia

• Dose: 0.25–2.5 mg TID

• Metabolism: aHydroxylation gives ACTIVE metabolite, hydroxylation of phenol gives inactive

• Formulations: PO

Estazolam C-IV

• Triazolobenzodiazepine

• Use: Insomnia

• Dose: 1–2 mg at bedtime

• weaker than alprazolam

• Formulations: PO

Triazolam C-IV

• Triazolobenzodiazepine

• Use: Insomnia

• Dose: 0.25 mg at bedtime

• Notes: Highly potent (more than alprazolam), narrow therapeutic index (more sides)

• Formulations: PO

Flumazenil

• Class: GABA-A receptor antagonist

• Use: Benzo OD reversal, anesthetic awakening

• Metabolism: Ester hydrolysis

• Half-life: 7–15 min (peripheral), 20–30 min (CNS), terminal 40–80 min

• Notes: May precipitate seizures

• Formulations: IV

Buspirone Hydrochloride

• Class: Anxiolytic (non-BZD)

• MOA: 5-HT1A partial agonist; D2 antagonist

• Use: short term anxiety tx (non-sedating)

• Metabolism: CYP3A4, becomes α2 antagonist

• Formulations: PO

Gepirone Hydrochloride (Exxua)

• MOA: 5-HT1A partial agonist; no D2 binding

• Use: Major depressive disorder MDD (FDA approved 2023)

• Formulations: PO

• more potent than buspirone

Hydroxyzine

• Class: H1 antihistamine (mild tranq)

• MOA: H1 antagonist

• Use: Anxiety, sedation, pruritus

• Notes: Teratogenicity concern

Meprobamate (Miltown) (CIV)

• MOA: GABA-A enhancer (exact binding unclear)

• Use: Anxiety, sedative

• Metabolism: hydroxylation→ inactive

• Formulations: PO

• NON chiral

Methocarbomal (Robaxin)

• Class: Centrally acting skeletal muscle relaxant

• Clinical Use: Relief painful musculoskeletal conditions; tetanus-induced spasm

• Metabolism: not converted to guaifenesin although similar looking

  • has metabolically stable carbamate

• with acetaminophen (Robaxacet),

  • ibuprofen (Robax Platinum),

  • aspirin (Robaxisal)

  • PO
    

Carisoprodol (C-IV)

• Class: Centrally acting skeletal muscle relaxant

• Clinical Use: Adjunct treatment for acute musculoskeletal conditions

• Onset/Duration: Not specified

• Metabolism: N-dealkylation of isopropyl gives active meprobamate (PRODRUG)

• PO

Metaxalone

• Class: Centrally acting skeletal muscle relaxant

• MOA: Unknown

• Clinical Use: Adjunct for acute musculoskeletal pain

• Notes: Contains internal carbamate group

• PO

Baclofen

• Class: Centrally acting antispasmodic

• MOA: GABA-B receptor agonist (GABA analog)

• Clinical Use: Spasticity due to MS and spinal cord trauma

• Notes: Cl at para position confers resistance to metabolic hydroxylation

• Eliminated unchanged

• racemic mixture (chiral)

• does not reduce muscle strength like other agents

• less sedation than diazepam

• PO

Chlorzoxazone

• Class: Centrally acting skeletal muscle relaxant

• Clinical Use: Muscle spasms, strains, back pain

• Notes: Contains carbamate

• PO

Cyclobenzaprine

• Class: Centrally acting muscle relaxant (TCA analog)

• Clinical Use: Skeletal muscle spasms

• Onset/Duration: Long duration; available in once-daily formulations

• Metabolism: (extensive) sulfated, glucuronidated, hydroxylated or demethylated (also epoxide formation)

• without double bond = nortriptyline

• PO

Dantrolene

• Class: Peripherally acting muscle relaxant

• MOA: Ryanodine receptor (RYR) antagonist → inhibits Ca²⁺ release from sarcoplasmic reticulum

• Clinical Use: Spasticity from spinal cord injury, MS, cerebral palsy, malignant hyperthermia

• Metabolism: oxidation of nitro group to hydroxy amine is carcinogen and hepatically toxic

• muscle weakness

• IV/PO

Orphenadrine

• Class: Centrally acting skeletal muscle relaxant

• Clinical Use: Adjunct for acute musculoskeletal pain, leg cramps

• Notes: Structural analog of diphenhydramine;

  • Sedative and anticholinergic effects

• PO

Tizanidine

• Class: Centrally acting muscle relaxant

• MOA: α2-adrenergic agonist, similar to clonidine

• Clinical Use: Spasticity due to MS, spinal cord injury;

• Extensively metabolized to inactive in liver

• Notes: Structural analog of clonidine;

  • less BP effect, 1/10 to 1/50 th

  • more CNS sedation;

  • acts on spinal cord

• PO

Chlorpromazine

• Class:typical antipsychotic

  • Aliphatic Phenothiazine

• MOA: D2 receptor antagonist

• Use: antiemetic/antipsycotic

• Metabolism: Oxidation of sulfur in air to→ sulfoxide/sulfone

  • can also be demethylated and hydroxylated

  • Cl blocks hydroxylation

Triflupromazine

• Class: Typical antipsychotic

  • Aliphatic Phenothiazine

• MOA: D2 antagonist

• Use: antiemetic/antipsycotic

• Structure: Trifluoromethyl enhances potency (lipophilicity)

• Oxidation of sulfur in air + hydroxylation and demethylation

Promethazine

• Aliphatic Phenothiazine

• Use: antiemetic in motion sickness and post operative patients 

  • low antipsychotic activity (~1/10 chlorpromazine)

  • Also anti histamine activity

• Racemic mixture

Thioridazine

• Class: typical antipsychotic

  • Piperidine Phenothiazine

• MOA: D2 antagonist

• Use: 2nd line schizophrenia

  • weak antipsycotic

• Metabolism: sulfide is oxidized sulfoxide (activex2), and then sulfone (more active x8)

• Side Effect: QT prolongation

• Oxidation of sulfur in air + hydroxylation and demethylation

Trifluoperazine

• Class: typical antipsychotic

  • piperazine phenothiazine

• MOA: D2 antagonist

• Use: Schizophrenia 2nd line, short-term anxiety

• Side Effects: More EPS, less sedation

• Oxidation of sulfur in air + hydroxylation and demethylation

Prochlorperazine

• Class: Typical antipsychotic

  • piperazine phenothiazine

• MOA: D2 antagonist

• Use: short term treatment of non psycotic anxiety, N/V

• Oxidation of sulfur in air + hydroxylation and demethylation

Perphenazine

• Class: typical antipsycotic

  • Piperazine Ethanol Phenothiazine

• MOA: D2 antagonist

• Use: antipsycotic, N/V

Fluphenazine

• Class: typical antipsycotic

  • Piperazine Ethanol Phenothiazine

• MOA: D2 antagonist

• Use: antipsycotic + n/v

• Formulations: 2 prodrugs available

  • enanthate IM every 2 weeks

  • decanoate IM/SubQ every 3-4 weeks

  • 3-4x per day of oral

Thiothixene

• Class: typical antipsycotic

  • (bioisosteric phenothiazine)

• MOA: D2 antagonist

• Use: antipsycotic

• Double bond is sp2 hybridized in Z config

• solfonamid is non oxidizable

Molindone (Moban)

• Class: typical antipsychotic

  • Indole

• MOA: unknown MOA, suspected D2

• Use: antipsycotic

• Notes: Extensive hepatic metabolism; only 2–3% unchanged

Haloperidol

• Class: Typical antipsycotic

  • Butyrophenone

• MOA: inverse agonist (↑cAMP)

• Use: Schizophrenia, Tourette's

• Metabolism: 50–60% conjugation, 20–30% N-dealkylation, 23% reduction

• Half-life: 12–38 hrs;

• Formulations: PO 2-3x per day,

  • IM deconate formulation dosed monthly

Droperidol

• Class: Typical antipsycotic

  • Butyrophenone

• MOA: D2 antagonist

• Use: Post-op nausea or chemo nausea,

• Half-life: 2 hr

• Formulations: IV, IM
  

Piomozide

• Class: Typical antipsycotic

  • Butyrophenone

• MOA: D2 antagonist

• Use: Tourette’s

• Metabolism: C–N bond cleavage

  • split down middle

• Half-life: 29 ± 10 hrs

• Notes: No ketone; limited metabolism

Li₂CO₃

Lithium Carbonate

• Class: Mood stabilizer

• MOA: Increases norepinephrine reuptake and increases serotonin receptor sensitivity

• Clinical Use: manic episodes of Bipolar disorder

• effects sodium levels

Lithium Citrate

• Class: Mood stabilizer

• MOA: Increases norepinephrine reuptake and increases serotonin receptor sensitivity

• Clinical Use: Bipolar disorder

• effects sodium levels

Loxapine

• typical antipsycotic

• MOA: unknown

• Use: schizophrenia

• rremoval of methyl group gives ACTIVE amoxipine (depression drug)

• Extra Pyrmidal

Clozapine

• Atypical antipsycotic (2nd gen)

• MOA: D2 antagonist

• Use: antipsycotic

  • both + and - sypmtoms

• Agranulocytosis

Risperidone

• 2nd Gen antipsycotic

• MOA: D2 and 5-HT2A antagonist

• Use: Schizophrenia, bipolar

• Metabolites:

  • 9-hydroxy active metabolite (Paliperidone - marketed as drug) once a day dosing

  • PRODRUG paliperidone Palmitate ,nanocrystal IM monthly

  • also er tablet available

• EPS side effect

• Notes: PO ODT IM

• contains benzoisoxazole
  

Iloperidone

• 2nd gen antipsycotic

• MOA: D2, 5-HT2A antagonist

• Use: Schizophrenia

• Extensive Metabolism, Ketone reduction, hydroxylation, demethylation. ACTIVE metabolites

• contains benzoisoxazole

Ziprasidone

• 2nd gen antipsycotic

• MOA: D2, 5-HT2A, 5-HT2B antagonist; 5-HT1A agonist

• Use: Schizophrenia, bipolar

• extensively metabolized

• positive food effect

• benzisothiazol

Lurasidone

• 2nd gen antipsycotic

• MOA: D2, 5-HT2A, 5-HT7 antagonist

• Use: Schizophrenia, bipolar depression

• positive food effect

• benzisothiazol

Olanzapine

• 2nd gen antipsycotic

• MOA: D2, 5-HT2A antagonist

• Use: Schizophrenia, bipolar

• Structure: bioisostere Thiophene ring (less oxidizable)

• Half-life: 21–54 hrs

• uncommon agranulocytosis

• similar to clozapine

Quentiapine

• 2nd gen antipsycotic (atypical)

• MOA: D2, 5-HT2A antagonist

• Use: Schizophrenia, bipolar, depression

• Notes: Sulfur in ring oxidation possible

• 2:1 quentiapine to fumarate salt

Aripiprazole

• 2nd gen antipsycotic

• MOA: D2 partial agonist, 5-HT1A agonist, 5-HT2A antagonist

• Use: Schizophrenia, bipolar, Tourette’s

• Metabolism: Dealkylation, hydroxylation, hydrogenation to ACTIVE metabolite (40%)

• Half-life: ~75 hrs

• Forms: PO (High OBA), IM (Maintena, Lauroxil)

Brexpiprazole

• 2nd gen antipsycotic

• MOA: D2 partial agonist, 5-HT1A agonist, 5-HT2A antagonist

• Use: Depression, schizophrenia

• High oral bioavailability

• Half-life: ~91 hrs

Cariprazine (vraylar)

• 2nd gen antipsycotic

• MOA: D2, 5HT1a partial agonist, 5HT2b and 5HT2a antagonist

• Use: Schizophrenia, bipolar, MDD

• demethylated to ACTIVE metabolite

• Half-life: 2–4 days; active metabolite: ~8 days

Asenapine

• 2nd gen antipsycotic

• MOA: D2, 5-HT2A antagonist

• Use: Schizophrenia, bipolar

• 2 chiral centers gives 4 enantiomers

• Mirtazepine is an antidepressant drug that looks similar

• Formulations: Sublingual tablet

  • Avoids 1st-pass metabolism

Lumateperone

• 2nd gen antipsycotic (atypical)

• MOA: D2 and 5-HT2A antagonist

• Use: Bipolar, schizophrenia

• Metabolism: reduction at ketone and demethylation by CYP3A4 (extensively metabolized), avoid grapefruit juice

• Half-life: ~18 hrs

Ethosuximide

• Class: Succinimide

  • anti seizure

• MOA: Inhibits T-type Ca²⁺ channels in thalamic neurons

• Use: Absence seizures (petit mal)

• Metabolism: no dealkylation

• Notes: Less adverse effects than valproate

Methsuximide

• Class: Succinimide

• MOA: T-type Ca²⁺ channel blocker

• Use: Absence seizures (petit mal)

• Metabolism: demethylation → active metabolite (N-desmethylmethsuximide)

Trimethadione

• Class: Oxazolidinedione

• MOA: T-type Ca²⁺ channel inhibitor

• Use: Absence seizures (petit mal)

• Metabolism: Hepatic demethylation to active metabolite

Valproic Acid

• MOA: unknown

• Use: First Line for Absence (petit mal) seizure, also partial, complex seuziures.also bipolar disorder

• Metabolism: omega and β-oxidation, glucuronidation

• BBW for

  • hepatotoxicity

  • teratogenic

  • fatal pancreatitis

• banned in france and europe

Acetazolamide

• Class: Carbonic anhydrase inhibitor

• Use: absence seizure (petit mal) glaucoma, mountain sickness

• diuretic effect, raises urine pH
  

Clonazepam C-IV

• Class: Benzodiazepine

• MOA: GABA-A enhancement (binding to BZ site)

• Use: absence seizures (petit mal) and status epilepticus

• Chorazepate is prodrug for seizures too 

Primidone

• Class: isoteric barbituarate

• Use: petit and grand mal seizure, weak anticonvulsant

• metabolized by hydroxylation and hydrolysis to active metabolites

• Parent and all metabolites are active

Phenytoin

• Class: Hydantoin

• Use: grand mal seizure

• Metabolism: S-enantiomer preferred formation after hydroxylation

• Formulations: PO (poor OBA), IV (alkaline, painful 50mg/ml and pH12)

• resembles barbituates

Fosphenytoin

• Class: Prodrug of phenytoin

• MOA: Converts to phenytoin in vivo by alkaline phosphatase

• Use: Status epilepticus, neuro surgery seizures

• Formulations: IV

• very water soluble

Ethotoin

• Class: Hydantoin

• Use: grand mal, petit mal, psychomotor seizures

• Metabolism: N-demethylation, ring hydroxylation

Carbamazepine

• Class: Dibenzazepine

• Use: grand mal seizure, bipolar

• Metabolism: CYP3A4 → epoxide (active), induces own metabolism

• Side Effects:

  • Aplastic anemia,

  • agranulocytosis

Perampanel

• Non competetive AMPA receptor antagonist (allosteric)

• use for grand mal seizure in people 12 and older

• partial onset in people 4 and older

• once daily dosing

Lacosamide

• Partial + grandmal seizure

• amino acid derivative of d-serine

• high oral bioavailability

• 40% elim unchanged

• t1/2 12-16 hours

Oxcarbazepine

• Class: Dibenzazepine

• Use: Partial seizures

• reduced to active metabolite

• can be acetylated to make a Prodrug Eslicarbazepine (aption) which has once a day dosing