Orris

Generate antipsychotics topic from KDT pharmacology in a flow chart manner

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Running Command

ls -la /home/daytona/workspace/ 2>/dev/null && mkdir -p /home/daytona/workspace/antipsychotics-flowchart

Writing File

~/antipsychotics-flowchart/antipsychotics_flowchart.html

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<title>Antipsychotic Drugs - KDT Pharmacology Flowchart</title>
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<body>

<h1 class="main-title">Antipsychotic Drugs</h1>
<p class="subtitle">KDT Pharmacology — Complete Topic Flowchart &nbsp;|&nbsp; Based on Lippincott / Katzung / Goodman &amp; Gilman</p>

<!-- ===================== SECTION 1: CLASSIFICATION ===================== -->
<div class="section-wrapper">
  <div class="section-header sh-purple">
    <span class="num">1</span> Classification of Antipsychotics
  </div>

  <div class="flow-center">
    <div class="box box-root">Antipsychotic Drugs</div>
    <div class="arrow-down" style="height:28px;"></div>
    <div class="grid-2" style="width:100%; max-width:900px;">

      <!-- FGA -->
      <div class="card card-purple" style="border-left: 3px solid #7c4dff;">
        <div class="card-title" style="color:#ce93d8;">🔵 First Generation (FGA) — "Typical" / Neuroleptics</div>
        <div style="margin-bottom:8px; color:#90a4ae; font-size:0.73rem;">Primarily D2 receptor blockers · Higher EPS risk</div>
        <div class="grid-2" style="gap:8px;">
          <div style="background:#200a30; border-radius:8px; padding:8px;">
            <div style="color:#ba68c8; font-weight:700; font-size:0.75rem; margin-bottom:4px;">LOW POTENCY</div>
            <ul class="dot-list">
              <li>Chlorpromazine</li>
              <li>Thioridazine</li>
              <li>Triflupromazine</li>
            </ul>
            <div style="color:#78909c; font-size:0.7rem; margin-top:5px;">More sedation, antimuscarinic, less EPS</div>
          </div>
          <div style="background:#200a30; border-radius:8px; padding:8px;">
            <div style="color:#ba68c8; font-weight:700; font-size:0.75rem; margin-bottom:4px;">HIGH POTENCY</div>
            <ul class="dot-list">
              <li>Haloperidol</li>
              <li>Fluphenazine</li>
              <li>Trifluoperazine</li>
              <li>Pimozide</li>
              <li>Thiothixene</li>
            </ul>
            <div style="color:#78909c; font-size:0.7rem; margin-top:5px;">Less sedation, more EPS</div>
          </div>
        </div>
        <div style="margin-top:10px; color:#78909c; font-size:0.72rem; border-top:1px solid #37474f; padding-top:6px;">
          <span class="highlight">Chemical classes:</span> Phenothiazines · Butyrophenones · Thioxanthenes · Diphenylbutylpiperidines
        </div>
      </div>

      <!-- SGA -->
      <div class="card card-indigo" style="border-left: 3px solid #2979ff;">
        <div class="card-title" style="color:#90caf9;">🔷 Second Generation (SGA) — "Atypical"</div>
        <div style="margin-bottom:8px; color:#90a4ae; font-size:0.73rem;">D2 + 5-HT2A antagonists · Lower EPS · Higher metabolic risk</div>
        <div class="grid-2" style="gap:8px;">
          <div style="background:#0d1840; border-radius:8px; padding:8px;">
            <div style="color:#82b1ff; font-weight:700; font-size:0.75rem; margin-bottom:4px;">D2/5-HT2 BLOCKERS</div>
            <ul class="dot-list">
              <li>Clozapine</li>
              <li>Olanzapine</li>
              <li>Risperidone</li>
              <li>Quetiapine</li>
              <li>Ziprasidone</li>
              <li>Paliperidone</li>
              <li>Lurasidone</li>
            </ul>
          </div>
          <div style="background:#0d1840; border-radius:8px; padding:8px;">
            <div style="color:#82b1ff; font-weight:700; font-size:0.75rem; margin-bottom:4px;">PARTIAL AGONISTS</div>
            <ul class="dot-list">
              <li>Aripiprazole</li>
              <li>Brexpiprazole</li>
              <li>Cariprazine</li>
            </ul>
            <div style="color:#78909c; font-size:0.7rem; margin-top:5px;">D2/D3 partial agonist + 5-HT1A partial agonist</div>
          </div>
        </div>
        <div style="margin-top:10px; color:#78909c; font-size:0.72rem; border-top:1px solid #37474f; padding-top:6px;">
          <span class="highlight">Clozapine:</span> Reserved for refractory cases · Risk of agranulocytosis
        </div>
      </div>

    </div>
  </div>
</div>

<!-- ===================== SECTION 2: SCHIZOPHRENIA & DOPAMINE PATHWAYS ===================== -->
<div class="section-wrapper">
  <div class="section-header sh-blue">
    <span class="num">2</span> Schizophrenia &amp; Dopamine Pathways (Basis of Drug Action)
  </div>

  <div class="grid-4" style="max-width:1100px; margin:0 auto;">
    <div class="card card-blue">
      <div class="card-title" style="color:#42a5f5;">Mesolimbic Tract</div>
      <ul class="dot-list">
        <li>VTA → Nucleus accumbens</li>
        <li><span class="highlight">Hyperdopaminergic</span></li>
        <li>→ <span class="highlight-r">Positive symptoms</span></li>
        <li>Hallucinations, delusions</li>
        <li>Blocking D2 here = <span class="highlight-g">therapeutic effect</span></li>
      </ul>
    </div>
    <div class="card card-indigo">
      <div class="card-title" style="color:#82b1ff;">Mesocortical Tract</div>
      <ul class="dot-list">
        <li>VTA → Prefrontal cortex</li>
        <li><span class="highlight">Hypodopaminergic</span></li>
        <li>→ <span class="highlight-r">Negative symptoms</span></li>
        <li>Avolition, flat affect, alogia</li>
        <li>D2 blockade may <span class="highlight-r">worsen</span> this</li>
      </ul>
    </div>
    <div class="card card-amber">
      <div class="card-title" style="color:#ffa726;">Nigrostriatal Tract</div>
      <ul class="dot-list">
        <li>Substantia nigra → Striatum</li>
        <li>Controls movement</li>
        <li>D2 blockade here →</li>
        <li><span class="highlight-r">EPS (extrapyramidal SE)</span></li>
        <li>Parkinsonism, dystonia, akathisia</li>
      </ul>
    </div>
    <div class="card card-teal">
      <div class="card-title" style="color:#4dd0e1;">Tuberoinfundibular Tract</div>
      <ul class="dot-list">
        <li>Hypothalamus → Pituitary</li>
        <li>DA inhibits prolactin</li>
        <li>D2 blockade →</li>
        <li><span class="highlight-r">↑ Prolactin</span></li>
        <li>Galactorrhea, amenorrhea, gynecomastia</li>
      </ul>
    </div>
  </div>

  <div style="text-align:center; margin-top:16px; padding:12px; background:#0d1621; border-radius:10px; max-width:900px; margin-left:auto; margin-right:auto; border:1px solid #1e3050;">
    <span style="color:#90a4ae; font-size:0.8rem;">
      <span class="highlight">Key concept:</span> Antipsychotics block D2 receptors in all 4 tracts simultaneously —
      therapeutic effects come from mesolimbic blockade, while side effects arise from the other 3 tracts.
      SGAs (D2 + 5-HT2A blockade) reduce EPS because 5-HT2A antagonism in nigrostriatum
      <span class="highlight-g">increases dopamine release</span>, partially counteracting D2 blockade.
    </span>
  </div>
</div>

<!-- ===================== SECTION 3: MECHANISM OF ACTION ===================== -->
<div class="section-wrapper">
  <div class="section-header sh-teal">
    <span class="num">3</span> Mechanism of Action
  </div>

  <div class="grid-3" style="max-width:1050px; margin:0 auto;">
    <div class="card card-purple">
      <div class="card-title" style="color:#ce93d8;">D2 Receptor Antagonism (FGA + SGA)</div>
      <ul class="dot-list">
        <li>Competitive blockade of D2 receptors</li>
        <li>All FGAs — primary mechanism</li>
        <li>Reduces positive symptoms</li>
        <li>D2 occupancy >65% needed for antipsychotic effect</li>
        <li>&gt;78% occupancy → EPS risk</li>
        <li>FGAs bind tightly (slow dissociation)</li>
      </ul>
    </div>
    <div class="card card-indigo">
      <div class="card-title" style="color:#9fa8da;">D2 + 5-HT2A Antagonism (SGA)</div>
      <ul class="dot-list">
        <li>Most SGAs block both receptors</li>
        <li>5-HT2A blockade in cortex</li>
        <li>→ Increases DA in prefrontal cortex</li>
        <li>→ Improves negative symptoms</li>
        <li>→ Reduces EPS (fast D2 dissociation)</li>
        <li>Clozapine: very low D2 affinity, high 5-HT2A</li>
      </ul>
    </div>
    <div class="card card-teal">
      <div class="card-title" style="color:#80cbc4;">D2/D3 Partial Agonism (Aripiprazole class)</div>
      <ul class="dot-list">
        <li>Acts as functional antagonist when DA high</li>
        <li>Acts as agonist when DA low</li>
        <li>"Dopamine system stabilizer"</li>
        <li>Aripiprazole: D2/D3 partial agonist + 5-HT1A partial agonist + 5-HT2A antagonist</li>
        <li>Cariprazine: preferential D3 selectivity</li>
        <li>Least metabolic side effects</li>
      </ul>
    </div>
  </div>

  <div class="grid-3" style="max-width:1050px; margin:12px auto 0;">
    <div class="card card-gray">
      <div class="card-title" style="color:#b0bec5;">Other Receptor Actions (FGA)</div>
      <ul class="dot-list">
        <li><span class="highlight-b">α1 blockade</span> → Orthostatic hypotension, sedation</li>
        <li><span class="highlight-b">H1 blockade</span> → Sedation, weight gain</li>
        <li><span class="highlight-b">M1 blockade</span> → Dry mouth, urinary retention, constipation</li>
        <li>Low-potency FGAs have more of these</li>
      </ul>
    </div>
    <div class="card card-gray">
      <div class="card-title" style="color:#b0bec5;">Clozapine — Unique Profile</div>
      <ul class="dot-list">
        <li>Low D2 affinity, fast dissociation</li>
        <li>High affinity: D4, 5-HT2, H1, M, α1</li>
        <li>No tardive dyskinesia</li>
        <li>Effective in treatment-resistant cases</li>
        <li>Reduces suicidal behavior</li>
        <li><span class="highlight-r">Risk: agranulocytosis (1–2%)</span></li>
      </ul>
    </div>
    <div class="card card-gray">
      <div class="card-title" style="color:#b0bec5;">Glutamate Hypothesis (Adjunctive)</div>
      <ul class="dot-list">
        <li>NMDA receptor hypofunction in schizophrenia</li>
        <li>Phencyclidine (PCP) blocks NMDA → psychosis</li>
        <li>GlyT1 inhibitors (sarcosine) enhance NMDA</li>
        <li>mGluR2/3 agonists under investigation</li>
        <li>None currently approved as primary antipsychotics</li>
      </ul>
    </div>
  </div>
</div>

<!-- ===================== SECTION 4: PHARMACOKINETICS ===================== -->
<div class="section-wrapper">
  <div class="section-header sh-green">
    <span class="num">4</span> Pharmacokinetics
  </div>

  <div class="grid-4" style="max-width:1100px; margin:0 auto;">
    <div class="card card-green">
      <div class="card-title" style="color:#81c784;">Absorption</div>
      <ul class="dot-list">
        <li>Oral absorption: incomplete</li>
        <li>Significant first-pass metabolism</li>
        <li>Chlorpromazine bioavailability: 25–35%</li>
        <li>Haloperidol: ~65% (less first-pass)</li>
        <li>IM route: bypasses first-pass</li>
        <li>Depot (LAI) forms available</li>
      </ul>
    </div>
    <div class="card card-green">
      <div class="card-title" style="color:#81c784;">Distribution</div>
      <ul class="dot-list">
        <li>Highly lipid soluble</li>
        <li>Protein binding: 92–99%</li>
        <li>Vd: very large (&gt;7 L/kg)</li>
        <li>Crosses blood-brain barrier</li>
        <li>Crosses placenta</li>
        <li>Enters breast milk</li>
      </ul>
    </div>
    <div class="card card-green">
      <div class="card-title" style="color:#81c784;">Metabolism &amp; Excretion</div>
      <ul class="dot-list">
        <li>Hepatic: CYP450 (CYP1A2, 2D6, 3A4)</li>
        <li>Chlorpromazine metabolites persist for weeks in urine</li>
        <li>Most excreted in urine and bile</li>
        <li>T½ variable (10–30 hrs for most)</li>
        <li>Clinical effect outlasts plasma half-life</li>
      </ul>
    </div>
    <div class="card card-green">
      <div class="card-title" style="color:#81c784;">Long-acting Injectable (Depot) Forms</div>
      <ul class="dot-list">
        <li>Fluphenazine decanoate: q 2–4 weeks</li>
        <li>Haloperidol decanoate: q 4 weeks</li>
        <li>Paliperidone palmitate: q 1 month or q 3 months</li>
        <li>Aripiprazole lauroxil: q 4–8 weeks</li>
        <li>↑ Adherence, ↓ relapse</li>
        <li>D2 blockade persists 3–6 months post last injection</li>
      </ul>
    </div>
  </div>
</div>

<!-- ===================== SECTION 5: ADVERSE EFFECTS ===================== -->
<div class="section-wrapper">
  <div class="section-header sh-red">
    <span class="num">5</span> Adverse Effects
  </div>

  <!-- EPS FLOWCHART -->
  <div style="background:#1a0a08; border:1.5px solid #c62828; border-radius:12px; padding:18px; max-width:1100px; margin:0 auto 16px;">
    <div style="color:#ef9a9a; font-weight:700; font-size:0.9rem; letter-spacing:1px; margin-bottom:14px; text-transform:uppercase;">⚠ Extrapyramidal Symptoms (EPS) — Nigrostriatal D2 Blockade</div>
    <div class="grid-4" style="gap:10px;">
      <div style="background:#200808; border-radius:9px; padding:10px; border-top:3px solid #e53935;">
        <div style="color:#ef5350; font-weight:700; font-size:0.78rem; margin-bottom:6px;">ACUTE DYSTONIA<br><span style="color:#78909c; font-weight:400;">(Hours–Days)</span></div>
        <ul class="dot-list">
          <li>Involuntary muscle spasms</li>
          <li>Oculogyric crisis</li>
          <li>Torticollis</li>
          <li>Opisthotonos</li>
          <li>More in young males</li>
        </ul>
        <div style="margin-top:6px; background:#2d0a0a; border-radius:6px; padding:5px; font-size:0.72rem; color:#a5d6a7;">
          Rx: Benztropine (IM/IV) or Diphenhydramine
        </div>
      </div>
      <div style="background:#200808; border-radius:9px; padding:10px; border-top:3px solid #fb8c00;">
        <div style="color:#ffa726; font-weight:700; font-size:0.78rem; margin-bottom:6px;">AKATHISIA<br><span style="color:#78909c; font-weight:400;">(Days–Weeks)</span></div>
        <ul class="dot-list">
          <li>Motor restlessness</li>
          <li>Inability to sit still</li>
          <li>Inner sense of unease</li>
          <li>Often misdiagnosed as anxiety</li>
        </ul>
        <div style="margin-top:6px; background:#2d1000; border-radius:6px; padding:5px; font-size:0.72rem; color:#a5d6a7;">
          Rx: Propranolol · Benzodiazepines · Dose reduction
        </div>
      </div>
      <div style="background:#200808; border-radius:9px; padding:10px; border-top:3px solid #8e24aa;">
        <div style="color:#ce93d8; font-weight:700; font-size:0.78rem; margin-bottom:6px;">PARKINSONISM<br><span style="color:#78909c; font-weight:400;">(Weeks)</span></div>
        <ul class="dot-list">
          <li>Tremor (resting), rigidity</li>
          <li>Bradykinesia, shuffling gait</li>
          <li>Mask-like face</li>
          <li>Pill-rolling tremor</li>
        </ul>
        <div style="margin-top:6px; background:#1a0828; border-radius:6px; padding:5px; font-size:0.72rem; color:#a5d6a7;">
          Rx: Benztropine · Biperiden · Amantadine
        </div>
      </div>
      <div style="background:#200808; border-radius:9px; padding:10px; border-top:3px solid #e53935;">
        <div style="color:#ef5350; font-weight:700; font-size:0.78rem; margin-bottom:6px;">TARDIVE DYSKINESIA<br><span style="color:#78909c; font-weight:400;">(Months–Years)</span></div>
        <ul class="dot-list">
          <li>Repetitive involuntary movements</li>
          <li>Lip smacking, tongue protrusion</li>
          <li>Choreoathetosis of limbs</li>
          <li>May be irreversible</li>
          <li><span class="highlight-r">FGAs &gt;&gt; SGAs</span></li>
        </ul>
        <div style="margin-top:6px; background:#2d0a0a; border-radius:6px; padding:5px; font-size:0.72rem; color:#a5d6a7;">
          Rx: Stop drug · Valbenazine/Deutetrabenazine · Switch to clozapine
        </div>
      </div>
    </div>
  </div>

  <!-- NMS -->
  <div style="background:#1a0808; border:2px solid #b71c1c; border-radius:12px; padding:14px; max-width:1100px; margin:0 auto 16px;">
    <div style="color:#ffcdd2; font-weight:700; font-size:0.9rem; letter-spacing:1px; margin-bottom:10px; text-transform:uppercase;">🔴 Neuroleptic Malignant Syndrome (NMS) — EMERGENCY</div>
    <div class="grid-4" style="gap:10px;">
      <div style="background:#220505; border-radius:8px; padding:9px;">
        <div style="color:#ef9a9a; font-size:0.75rem; font-weight:700; margin-bottom:5px;">FEATURES (FALTER)</div>
        <ul class="dot-list">
          <li><span class="highlight">F</span>ever (&gt;38°C)</li>
          <li><span class="highlight">A</span>utonomic instability</li>
          <li><span class="highlight">L</span>eukocytosis</li>
          <li><span class="highlight">T</span>remor</li>
          <li><span class="highlight">E</span>levated CPK</li>
          <li><span class="highlight">R</span>igidity ("lead-pipe")</li>
        </ul>
      </div>
      <div style="background:#220505; border-radius:8px; padding:9px;">
        <div style="color:#ef9a9a; font-size:0.75rem; font-weight:700; margin-bottom:5px;">PATHOPHYSIOLOGY</div>
        <ul class="dot-list">
          <li>Idiosyncratic reaction</li>
          <li>Massive D2 blockade in hypothalamus + striatum</li>
          <li>Dysregulation of temp control</li>
          <li>Rhabdomyolysis → renal failure</li>
          <li>Mortality: 5–20%</li>
        </ul>
      </div>
      <div style="background:#220505; border-radius:8px; padding:9px;">
        <div style="color:#ef9a9a; font-size:0.75rem; font-weight:700; margin-bottom:5px;">TREATMENT</div>
        <ul class="dot-list">
          <li>STOP antipsychotic immediately</li>
          <li>Dantrolene (muscle relaxant)</li>
          <li>Bromocriptine (DA agonist)</li>
          <li>Supportive: IV fluids, cooling</li>
          <li>Monitor renal function/CPK</li>
        </ul>
      </div>
      <div style="background:#220505; border-radius:8px; padding:9px;">
        <div style="color:#ef9a9a; font-size:0.75rem; font-weight:700; margin-bottom:5px;">NMS vs. SEROTONIN SYNDROME</div>
        <ul class="dot-list">
          <li>NMS: onset slow (days), bradyreflexia, lead-pipe rigidity</li>
          <li>SS: onset rapid (hours), hyperreflexia, clonus</li>
          <li>NMS: ↑ CPK markedly</li>
          <li>SS: may not have CPK rise</li>
        </ul>
      </div>
    </div>
  </div>

  <!-- Other AEs -->
  <div class="grid-3" style="max-width:1050px; margin:0 auto;">
    <div class="card card-amber">
      <div class="card-title" style="color:#ffa726;">Metabolic Side Effects (SGAs &gt; FGAs)</div>
      <ul class="dot-list">
        <li><span class="highlight">Weight gain:</span> Clozapine, Olanzapine (most)</li>
        <li>Hyperglycemia / new-onset T2DM</li>
        <li>Hyperlipidemia</li>
        <li>Metabolic syndrome</li>
        <li>Risperidone, Ziprasidone: less weight gain</li>
        <li>Aripiprazole: metabolically neutral</li>
      </ul>
    </div>
    <div class="card card-blue">
      <div class="card-title" style="color:#90caf9;">Endocrine / Cardiac Effects</div>
      <ul class="dot-list">
        <li><span class="highlight">Hyperprolactinemia</span> (FGAs &gt; SGAs)</li>
        <li>Galactorrhea, amenorrhea, gynecomastia</li>
        <li><span class="highlight">QTc prolongation:</span> Ziprasidone, Thioridazine, Haloperidol</li>
        <li>Risk of Torsades de Pointes</li>
        <li>Thioridazine: irreversible pigmentary retinopathy</li>
        <li>Orthostatic hypotension (α1 blockade)</li>
      </ul>
    </div>
    <div class="card card-red">
      <div class="card-title" style="color:#ef9a9a;">Clozapine-Specific Adverse Effects</div>
      <ul class="dot-list">
        <li><span class="highlight-r">Agranulocytosis</span> (1–2%) — weekly WBC monitoring</li>
        <li>Seizures (dose-related)</li>
        <li>Myocarditis / cardiomyopathy</li>
        <li>Severe constipation (bowel obstruction)</li>
        <li>Hypersalivation (sialorrhea)</li>
        <li>Sedation, weight gain</li>
        <li>Never stop abruptly → rapid relapse</li>
      </ul>
    </div>
    <div class="card card-purple">
      <div class="card-title" style="color:#ce93d8;">Anticholinergic Effects (esp. Low-Potency FGAs)</div>
      <ul class="dot-list">
        <li>Dry mouth, blurred vision</li>
        <li>Urinary retention</li>
        <li>Constipation, ileus</li>
        <li>Cognitive blunting</li>
        <li>Contraindicated in BPH, narrow-angle glaucoma</li>
      </ul>
    </div>
    <div class="card card-gray">
      <div class="card-title" style="color:#b0bec5;">Sedation &amp; CNS Effects</div>
      <ul class="dot-list">
        <li>H1 blockade → sedation</li>
        <li>Most sedating: Chlorpromazine, Clozapine, Quetiapine, Olanzapine</li>
        <li>Least sedating: Haloperidol, Aripiprazole</li>
        <li>Seizure threshold lowered</li>
        <li>Clozapine highest seizure risk</li>
      </ul>
    </div>
    <div class="card card-teal">
      <div class="card-title" style="color:#80cbc4;">Other / Rare Effects</div>
      <ul class="dot-list">
        <li>Photosensitivity (chlorpromazine)</li>
        <li>Corneal/lens deposits (chlorpromazine)</li>
        <li>Pigmentary retinopathy (thioridazine)</li>
        <li>Jaundice (cholestatic, chlorpromazine)</li>
        <li>Teratogenicity: avoid in 1st trimester</li>
        <li>Blood dyscrasias (rare, FGAs)</li>
      </ul>
    </div>
  </div>
</div>

<!-- ===================== SECTION 6: CLINICAL USES ===================== -->
<div class="section-wrapper">
  <div class="section-header sh-teal">
    <span class="num">6</span> Clinical Uses
  </div>

  <div class="grid-3" style="max-width:1050px; margin:0 auto;">
    <div class="card card-teal">
      <div class="card-title" style="color:#4dd0e1;">Primary Indications</div>
      <ul class="dot-list">
        <li><span class="highlight">Schizophrenia</span> (first-line: SGAs)</li>
        <li>Schizoaffective disorder</li>
        <li>Acute mania (bipolar disorder)</li>
        <li>Psychotic depression</li>
        <li>Brief psychotic disorder</li>
        <li>Drug-induced psychosis</li>
        <li>Dementia-related psychosis (with caution)</li>
      </ul>
    </div>
    <div class="card card-green">
      <div class="card-title" style="color:#81c784;">Non-Psychotic Uses (FGAs)</div>
      <ul class="dot-list">
        <li><span class="highlight">Nausea &amp; vomiting:</span> Prochlorperazine, Metoclopramide</li>
        <li><span class="highlight">Hiccups:</span> Chlorpromazine</li>
        <li><span class="highlight">Tourette's:</span> Haloperidol, Pimozide</li>
        <li>Huntington's chorea</li>
        <li>Pre-operative anxiety / potentiation of anesthesia</li>
        <li>Acute agitation (haloperidol IV/IM)</li>
      </ul>
    </div>
    <div class="card card-indigo">
      <div class="card-title" style="color:#9fa8da;">Treatment Algorithm</div>
      <ul class="dot-list">
        <li>1st line: Any SGA (except clozapine)</li>
        <li>Inadequate response after 4–6 weeks → switch</li>
        <li>Treatment-resistant (failed 2 antipsychotics): → <span class="highlight">Clozapine</span></li>
        <li>Suicide risk: Clozapine (only FDA-approved for this)</li>
        <li>Depot formulation: For adherence issues</li>
        <li>Maintenance: Continue at least 1–2 years after first episode</li>
      </ul>
    </div>
  </div>
</div>

<!-- ===================== SECTION 7: DRUG COMPARISONS ===================== -->
<div class="section-wrapper">
  <div class="section-header sh-purple">
    <span class="num">7</span> Key Drug Comparison — At a Glance
  </div>

  <div style="overflow-x:auto; max-width:1100px; margin:0 auto;">
    <table style="width:100%; border-collapse:collapse; font-size:0.74rem;">
      <thead>
        <tr style="background:#1a1240; color:#ce93d8;">
          <th style="padding:9px 12px; text-align:left; border-bottom:2px solid #7c4dff; min-width:110px;">Drug</th>
          <th style="padding:9px 12px; text-align:center; border-bottom:2px solid #7c4dff;">Gen</th>
          <th style="padding:9px 12px; text-align:center; border-bottom:2px solid #7c4dff;">EPS</th>
          <th style="padding:9px 12px; text-align:center; border-bottom:2px solid #7c4dff;">Sedation</th>
          <th style="padding:9px 12px; text-align:center; border-bottom:2px solid #7c4dff;">Wt Gain</th>
          <th style="padding:9px 12px; text-align:center; border-bottom:2px solid #7c4dff;">Prolactin</th>
          <th style="padding:9px 12px; text-align:center; border-bottom:2px solid #7c4dff;">QTc ↑</th>
          <th style="padding:9px 12px; text-align:left; border-bottom:2px solid #7c4dff;">Notes</th>
        </tr>
      </thead>
      <tbody>
        <tr style="background:#100c20;">
          <td style="padding:7px 12px; color:#e0e0e0; font-weight:600;">Chlorpromazine</td>
          <td style="padding:7px 12px; text-align:center;"><span class="badge badge-fga">FGA</span></td>
          <td style="padding:7px 12px; text-align:center; color:#ffa726;">++</td>
          <td style="padding:7px 12px; text-align:center; color:#ef5350;">+++</td>
          <td style="padding:7px 12px; text-align:center; color:#ffa726;">++</td>
          <td style="padding:7px 12px; text-align:center; color:#ffa726;">++</td>
          <td style="padding:7px 12px; text-align:center; color:#ffa726;">+</td>
          <td style="padding:7px 12px; color:#90a4ae;">Photosensitivity, cholestasis, corneal deposits</td>
        </tr>
        <tr style="background:#0d0c1a;">
          <td style="padding:7px 12px; color:#e0e0e0; font-weight:600;">Thioridazine</td>
          <td style="padding:7px 12px; text-align:center;"><span class="badge badge-fga">FGA</span></td>
          <td style="padding:7px 12px; text-align:center; color:#66bb6a;">+</td>
          <td style="padding:7px 12px; text-align:center; color:#ef5350;">+++</td>
          <td style="padding:7px 12px; text-align:center; color:#ffa726;">++</td>
          <td style="padding:7px 12px; text-align:center; color:#ffa726;">++</td>
          <td style="padding:7px 12px; text-align:center; color:#ef5350;">+++</td>
          <td style="padding:7px 12px; color:#90a4ae;"><span class="highlight-r">Pigmentary retinopathy</span> — not first-line</td>
        </tr>
        <tr style="background:#100c20;">
          <td style="padding:7px 12px; color:#e0e0e0; font-weight:600;">Haloperidol</td>
          <td style="padding:7px 12px; text-align:center;"><span class="badge badge-fga">FGA</span></td>
          <td style="padding:7px 12px; text-align:center; color:#ef5350;">+++</td>
          <td style="padding:7px 12px; text-align:center; color:#66bb6a;">+</td>
          <td style="padding:7px 12px; text-align:center; color:#66bb6a;">+</td>
          <td style="padding:7px 12px; text-align:center; color:#ef5350;">+++</td>
          <td style="padding:7px 12px; text-align:center; color:#ffa726;">+</td>
          <td style="padding:7px 12px; color:#90a4ae;">Gold standard FGA; Tourette's, acute agitation (IV)</td>
        </tr>
        <tr style="background:#0d0c1a;">
          <td style="padding:7px 12px; color:#e0e0e0; font-weight:600;">Clozapine</td>
          <td style="padding:7px 12px; text-align:center;"><span class="badge badge-sga">SGA</span></td>
          <td style="padding:7px 12px; text-align:center; color:#66bb6a;">0/+</td>
          <td style="padding:7px 12px; text-align:center; color:#ef5350;">+++</td>
          <td style="padding:7px 12px; text-align:center; color:#ef5350;">+++</td>
          <td style="padding:7px 12px; text-align:center; color:#66bb6a;">+</td>
          <td style="padding:7px 12px; text-align:center; color:#ffa726;">++</td>
          <td style="padding:7px 12px; color:#90a4ae;"><span class="highlight-r">Agranulocytosis</span>; refractory/suicidal; no TD</td>
        </tr>
        <tr style="background:#100c20;">
          <td style="padding:7px 12px; color:#e0e0e0; font-weight:600;">Olanzapine</td>
          <td style="padding:7px 12px; text-align:center;"><span class="badge badge-sga">SGA</span></td>
          <td style="padding:7px 12px; text-align:center; color:#ffa726;">+</td>
          <td style="padding:7px 12px; text-align:center; color:#ef5350;">+++</td>
          <td style="padding:7px 12px; text-align:center; color:#ef5350;">+++</td>
          <td style="padding:7px 12px; text-align:center; color:#ffa726;">++</td>
          <td style="padding:7px 12px; text-align:center; color:#66bb6a;">+</td>
          <td style="padding:7px 12px; color:#90a4ae;">Helps positive &amp; negative symptoms; metabolic risk high</td>
        </tr>
        <tr style="background:#0d0c1a;">
          <td style="padding:7px 12px; color:#e0e0e0; font-weight:600;">Risperidone</td>
          <td style="padding:7px 12px; text-align:center;"><span class="badge badge-sga">SGA</span></td>
          <td style="padding:7px 12px; text-align:center; color:#ffa726;">++</td>
          <td style="padding:7px 12px; text-align:center; color:#ffa726;">++</td>
          <td style="padding:7px 12px; text-align:center; color:#ffa726;">++</td>
          <td style="padding:7px 12px; text-align:center; color:#ef5350;">+++</td>
          <td style="padding:7px 12px; text-align:center; color:#ffa726;">+</td>
          <td style="padding:7px 12px; color:#90a4ae;">Highest prolactin among SGAs; available as LAI</td>
        </tr>
        <tr style="background:#100c20;">
          <td style="padding:7px 12px; color:#e0e0e0; font-weight:600;">Quetiapine</td>
          <td style="padding:7px 12px; text-align:center;"><span class="badge badge-sga">SGA</span></td>
          <td style="padding:7px 12px; text-align:center; color:#66bb6a;">+</td>
          <td style="padding:7px 12px; text-align:center; color:#ef5350;">+++</td>
          <td style="padding:7px 12px; text-align:center; color:#ffa726;">++</td>
          <td style="padding:7px 12px; text-align:center; color:#66bb6a;">0/+</td>
          <td style="padding:7px 12px; text-align:center; color:#ffa726;">+</td>
          <td style="padding:7px 12px; color:#90a4ae;">Bipolar depression; sedating; low prolactin</td>
        </tr>
        <tr style="background:#0d0c1a;">
          <td style="padding:7px 12px; color:#e0e0e0; font-weight:600;">Ziprasidone</td>
          <td style="padding:7px 12px; text-align:center;"><span class="badge badge-sga">SGA</span></td>
          <td style="padding:7px 12px; text-align:center; color:#ffa726;">+</td>
          <td style="padding:7px 12px; text-align:center; color:#ffa726;">+</td>
          <td style="padding:7px 12px; text-align:center; color:#66bb6a;">0</td>
          <td style="padding:7px 12px; text-align:center; color:#66bb6a;">+</td>
          <td style="padding:7px 12px; text-align:center; color:#ef5350;">+++</td>
          <td style="padding:7px 12px; color:#90a4ae;"><span class="highlight-r">QTc prolongation</span>; take with food; weight neutral</td>
        </tr>
        <tr style="background:#100c20;">
          <td style="padding:7px 12px; color:#e0e0e0; font-weight:600;">Aripiprazole</td>
          <td style="padding:7px 12px; text-align:center;"><span class="badge badge-sga">SGA</span></td>
          <td style="padding:7px 12px; text-align:center; color:#66bb6a;">+</td>
          <td style="padding:7px 12px; text-align:center; color:#66bb6a;">+</td>
          <td style="padding:7px 12px; text-align:center; color:#66bb6a;">0/+</td>
          <td style="padding:7px 12px; text-align:center; color:#66bb6a;">↓</td>
          <td style="padding:7px 12px; text-align:center; color:#66bb6a;">0</td>
          <td style="padding:7px 12px; color:#90a4ae;">Partial D2 agonist; metabolically neutral; akathisia common</td>
        </tr>
        <tr style="background:#0d0c1a;">
          <td style="padding:7px 12px; color:#e0e0e0; font-weight:600;">Cariprazine</td>
          <td style="padding:7px 12px; text-align:center;"><span class="badge badge-sga">SGA</span></td>
          <td style="padding:7px 12px; text-align:center; color:#66bb6a;">+</td>
          <td style="padding:7px 12px; text-align:center; color:#66bb6a;">+</td>
          <td style="padding:7px 12px; text-align:center; color:#66bb6a;">+</td>
          <td style="padding:7px 12px; text-align:center; color:#66bb6a;">+</td>
          <td style="padding:7px 12px; text-align:center; color:#66bb6a;">0</td>
          <td style="padding:7px 12px; color:#90a4ae;">D3 preferring partial agonist; negative symptoms</td>
        </tr>
      </tbody>
    </table>
    <div style="font-size:0.68rem; color:#546e7a; margin-top:6px; text-align:right;">0 = none, + = mild, ++ = moderate, +++ = high</div>
  </div>
</div>

<!-- ===================== SECTION 8: IMPORTANT MNEMONICS ===================== -->
<div class="section-wrapper">
  <div class="section-header sh-orange">
    <span class="num">8</span> High-Yield Points &amp; Mnemonics
  </div>

  <div class="grid-3" style="max-width:1050px; margin:0 auto;">
    <div class="card card-amber">
      <div class="card-title" style="color:#ffb74d;">EPS Timeline Mnemonic<br><span style="color:#78909c; font-weight:400; font-size:0.72rem;">"ADAPT"</span></div>
      <ul class="dot-list">
        <li><span class="highlight">A</span>cute dystonia — hours to days</li>
        <li><span class="highlight">D</span>rug-induced parkinsonism — weeks</li>
        <li><span class="highlight">A</span>kathisia — days to weeks</li>
        <li><span class="highlight">P</span>rolactinemia — immediate</li>
        <li><span class="highlight">T</span>ardive dyskinesia — months to years</li>
      </ul>
    </div>
    <div class="card card-purple">
      <div class="card-title" style="color:#ce93d8;">Clozapine Remember: "CLOZAPINE"</div>
      <ul class="dot-list">
        <li><span class="highlight">C</span>BC (WBC) monitoring weekly</li>
        <li><span class="highlight">L</span>ow D2 affinity</li>
        <li><span class="highlight">O</span>nly for treatment-resistant cases</li>
        <li><span class="highlight">Z</span>ero tardive dyskinesia</li>
        <li><span class="highlight">A</span>granulocytosis risk</li>
        <li><span class="highlight">P</span>revents suicidal behaviour</li>
        <li><span class="highlight">I</span>llness relapses rapidly if stopped</li>
        <li><span class="highlight">N</span>ever stop abruptly</li>
        <li><span class="highlight">E</span>pilepsy risk (seizures)</li>
      </ul>
    </div>
    <div class="card card-teal">
      <div class="card-title" style="color:#80cbc4;">Key Exam Facts</div>
      <ul class="dot-list">
        <li>Most weight gain: <span class="highlight">Clozapine &gt; Olanzapine</span></li>
        <li>Most EPS (FGAs): <span class="highlight">Haloperidol</span></li>
        <li>Most QTc prolongation: <span class="highlight">Thioridazine, Ziprasidone</span></li>
        <li>Most prolactin elevation: <span class="highlight">Risperidone, FGAs</span></li>
        <li>Lowers prolactin: <span class="highlight">Aripiprazole</span></li>
        <li>No tardive dyskinesia: <span class="highlight">Clozapine</span></li>
        <li>Best for negative symptoms: <span class="highlight">Clozapine, Cariprazine</span></li>
        <li>NMS treatment: <span class="highlight">Dantrolene + Bromocriptine</span></li>
        <li>Acute dystonia antidote: <span class="highlight">Benztropine</span></li>
        <li>Antiemetic FGA: <span class="highlight">Prochlorperazine</span></li>
      </ul>
    </div>
  </div>
</div>

<!-- ===================== SECTION 9: CONTRAINDICATIONS ===================== -->
<div class="section-wrapper">
  <div class="section-header sh-red">
    <span class="num">9</span> Contraindications &amp; Drug Interactions
  </div>

  <div class="grid-2" style="max-width:900px; margin:0 auto;">
    <div class="card card-red">
      <div class="card-title" style="color:#ef9a9a;">Contraindications</div>
      <ul class="dot-list">
        <li>CNS depression (alcohol, barbiturates)</li>
        <li>Narrow-angle glaucoma (anticholinergic agents)</li>
        <li>Bone marrow suppression (clozapine)</li>
        <li>Parkinson's disease (D2 blockers worsen symptoms)</li>
        <li>Prolonged QTc / cardiac arrhythmia (ziprasidone, thioridazine)</li>
        <li>Dementia-related psychosis in elderly: <span class="highlight-r">↑ mortality (Black Box)</span></li>
        <li>Pregnancy (1st trimester): teratogenic risk</li>
      </ul>
    </div>
    <div class="card card-blue">
      <div class="card-title" style="color:#90caf9;">Important Drug Interactions</div>
      <ul class="dot-list">
        <li><span class="highlight">CNS depressants</span> + antipsychotics → additive sedation</li>
        <li><span class="highlight">Anticholinergics</span> → additive antimuscarinic effects</li>
        <li><span class="highlight">Antihypertensives</span> → additive hypotension (α1 blockade)</li>
        <li><span class="highlight">CYP1A2 inhibitors</span> (e.g., fluvoxamine) → ↑ clozapine levels</li>
        <li><span class="highlight">Carbamazepine</span> → ↓ clozapine levels; also agranulocytosis risk</li>
        <li><span class="highlight">QTc-prolonging drugs</span> (macrolides, quinolones) + ziprasidone/thioridazine → Torsades de pointes</li>
        <li><span class="highlight">Antacids</span> → ↓ absorption of FGAs</li>
      </ul>
    </div>
  </div>
</div>

<footer>
  Compiled from Lippincott Illustrated Reviews Pharmacology · Katzung's Basic &amp; Clinical Pharmacology 16e · Goodman &amp; Gilman's Pharmacological Basis · Maudsley Prescribing Guidelines<br>
  For educational purposes only. Always verify drug information against current guidelines.
</footer>

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Antipsychotics Flowchart - KDT Pharmacology

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antipsychotics flowchart

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What's covered (9 sections):

1. Classification
  • FGA (Typical): Low potency (Chlorpromazine, Thioridazine) vs. High potency (Haloperidol, Fluphenazine, Pimozide)
  • SGA (Atypical): D2/5-HT2 blockers vs. Partial agonists (Aripiprazole, Cariprazine, Brexpiprazole)
  • Chemical classes: Phenothiazines, Butyrophenones, Thioxanthenes
2. Dopamine Pathways - All 4 tracts (Mesolimbic, Mesocortical, Nigrostriatal, Tuberoinfundibular) with clinical implications
3. Mechanism of Action - D2 blockade, D2 + 5-HT2A (SGAs), partial agonism, glutamate hypothesis, clozapine's unique profile
4. Pharmacokinetics - Absorption, distribution, metabolism, depot (LAI) forms
5. Adverse Effects (most detailed section):
  • EPS flowchart with onset timing: Acute dystonia → Akathisia → Parkinsonism → Tardive dyskinesia
  • NMS (FALTER mnemonic) with NMS vs. Serotonin Syndrome comparison
  • Metabolic effects, QTc prolongation, clozapine-specific effects
6. Clinical Uses - Primary indications, non-psychotic uses, treatment algorithm
7. Drug Comparison Table - 10 major drugs compared across EPS, sedation, weight gain, prolactin, QTc
8. Mnemonics - EPS timeline (ADAPT), Clozapine features (CLOZAPINE mnemonic), high-yield exam facts
9. Contraindications & Drug Interactions
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