Detailed Notes on Pharmacological Treatments for Mood Disorders, Anxiety, Seizures, and Anesthesia

DRUGS FOR MOOD DISORDERS

  • Antidepressants: Refer to lecture notes.

Mood Stabilizers/Drugs for Bipolar Disorders

  • Lithium

    • First-line therapy for treatment/prevention of bipolar disorders (except mixed episodes or rapid cycling)
    • Effective for acute manic episodes.
    • Treatment for rapid cycling: Valproic Acid
    • Mechanism of Action (MOA): Blocks recycling of phosphoinositides, resulting in decreased release of inositol triphosphate (IP3) and diacylglycerol (DAG).

  • Serum/Blood Levels:

    • Decreased by: Acetazolamide, Xanthines, Osmotic diuretics, Sodium supplements, Urine alkalinizers
    • Increased by: ACE-I, NSAIDs, Thiazides, Dehydration, Renal dysfunction, Sodium loss, Fluoxetine

  • Side Effects/Toxicity:

    • Usual doses: Nausea, diarrhea, polyuria, polydipsia, fine hand tremors, subclinical hypothyroidism
    • Toxic doses: Coarse hand tremors, persistent nausea, confusion, seizures, hyper-reflexia, irregular pulse, hypotension, coma, ataxia, aphasia
    • Idiosyncratic (any dose): Thyroid enlargement, reversible nephrogenic diabetes insipidus, edema, leukocytosis, congenital cardiac anomalies (Ebstein anomaly)

  • Valproic Acid:

    • Equally effective as mood stabilizer alongside lithium and carbamazepine, but with a superior safety profile.
    • Advantages: More effective than lithium for rapid cycling and mixed mania.

  • Carbamazepine:

    • Can be used for acute mania and prophylactic therapy.

  • Antipsychotics:

    • FDA-approved for treatment of the manic phase of bipolar disorder: Aripiprazole, Olanzapine, Risperidone, Quetiapine, Ziprasidone, Chlorpromazine.

ANTIANXIETY/ANXIOLYTICS

  • Anxiety Disorders: GAD, PTSD, OCD, Panic Disorder, Social Phobia

  • Benzodiazepines (BZD):

    • MOA: Potentiates the action of GABA, enhancing chloride channel opening.
    • Metabolite: N-DMDZ (half-life: 36-200 hours).
    • Half-life Classification:
    • Short-acting: Midazolam, Triazolam
    • Intermediate-acting: Alprazolam, Oxazepam, Lorazepam, Temazepam, Estazolam
    • Long-acting: Chlordiazepoxide, Chlorazepate, Halazepam, Clonazepam, Diazepam, Prazepam
    • Side Effects (SE):
    • CNS depression: sedation, ataxia, incoordination, weakness, fatigue
    • Anterograde amnesia
    • Paradoxical reactions
    • Physiologic dependence
    • Withdrawal-induced relapse or rebound

  • Buspirone:

    • Partial 5-HT₁A agonist.
    • Mechanism: Acts as presynaptic 5-HT1A partial agonist and postsynaptic 5-HT1A receptor blocker.
    • Advantages: No interaction with sedative-hypnotics, minimal psychomotor disturbance.

  • Beta-blockers: Propranolol, Atenolol (especially for Panic Disorder).

  • Barbiturates:

    • MOA: GABAergic effect; increase chloride channel opening duration.
    • Classification:
    • Ultra-short acting: Thiopental, Thiamylal, Methohexital
    • Short-acting: Hexobarbital, Pentobarbital, Secobarbital
    • Intermediate-acting: Amobarbital, Butabarbital
    • Long-acting: Phenobarbital
    • Clinical Uses: Sedative, adjuncts for anesthesia, seizures, neonatal hyperbilirubinemia.

SEIZURE DISORDERS (EPILEPSY)

  • Treatments:

    • 1st line drugs:
    • Primary Generalized Tonic-Clonic (Grand Mal): Valproic Acid
    • Adjuncts: Lamotrigine, Topiramate
    • Partial Seizure: Carbamazepine, Phenytoin
      • Adjuncts: Lamotrigine, Oxcarbazepine, Valproic Acid.
    • Absence Seizures (Petit Mal): Ethosuximide, Valproic Acid.
    • Atypical Absence, Myoclonic, Atonic: Valproic Acid, Lamotrigine, Topiramate.

  • Specific Drug Groups:

    • Carbamazepine:
    • MOA: Blocks Na conductance (Na+ channel blocker).
      • Side Effects: Diplopia, headache, dizziness, nausea, ataxia, rash.
    • Phenytoin:
      • MOA: Blocks sodium, potassium, calcium conductance; calcium-mediated excitatory neurotransmission.
      • Side Effects: Nystagmus, ataxia, diplopia, sedation. Long-term: gingival hyperplasia, vitamin deficiencies.
    • Valproic Acid:
      • MOA: Blocks voltage-gated Na channels; enhances GABA.
      • Side Effects: GI discomfort, tremors, weight gain, thrombocytopenia, hepatotoxicity.

PARKINSONISM

  • Clinical Presentation:

    • Cardinal features (TRAPS): Tremor at rest, Rigidity, Akinesia, Postural instability, Shuffling gait.

  • Therapy:

    • Dopaminergic Agents:
    • Levodopa:
    • MOA: Crosses BBB; converted to dopamine in the substantia nigra.
    • Combination: Given with Carbidopa (inhibits degradation of levodopa).
    • Dopamine Agonists:
    • Non-ergot: Pramipexole, Ropinirole, Rotigotine.
    • Ergot: Bromocriptine, Cabergoline.

  • Augmentation Strategies:

    • MAO-B Inhibitors:
    • Selegiline, Rasagiline.
    • COMT Inhibitors: Entacapone, Tolcapone.
    • Amantadine:
    • MOA: Potentiates dopamine release and blocks reuptake.
    • Apomorphine:
    • Used for akinesia off-periods.

GENERAL (SYSTEMIC) ANESTHETICS

  • Stages of General Anesthesia:
    • Stage I: Analgesia
    • Stage II: Delirium
    • Stage III: Surgical anesthesia
    • Stage IV: Medullary depression (not desirable)
Inhalational Anesthetics

  • Mechanism: Increase neuronal threshold for firing, hyperpolarizing neurons.

  • Types:

    • Order of increasing potency: Nitrous Oxide, Desflurane, Enflurane, Sevoflurane, Halothane, Isoflurane, Methoxyflurane.

  • Halothane

    • Moderate potency; may cause hypotension, tachyarrhythmias, hepatic necrosis, malignant hyperthermia.
    • Enflurane: Rapid adjustments in anesthesia depth; contraindicated in labor.
    • Isoflurane: Preferred in neurosurgery.
    • Sevoflurane: Rapid induction; minimally metabolized; non-irritant.

Intravenous Anesthetics

  • Ultra-short acting Barbiturates: Induction agents with potential for respiratory and circulatory depression.
  • Benzodiazepines: Used as pre-medications; potentiates GABA action and causes antegrade amnesia.
  • Propofol:
  • Ketamine: Dissociative anesthesia; rapid onset; produces emergence phenomena.

LOCAL ANESTHETICS

  • Mechanism: Block Na+ channels, inhibit conduction.

  • Esters: Allergic reactions common but have short action.

  • Amides: More stable, lower allergic reactions.

  • Specific Agents:

    • Lidocaine: Most widely used; anti-arrhythmic effects.
    • Bupivacaine: Prolongs anesthesia, cardiotoxic.
    • Prilocaine: Can cause methemoglobinemia; treats with methylene blue.