Corticosteroid Pharmacology — Study Notes

# -*- coding: utf-8 -*-
from reportlab.lib.pagesizes import letter
from reportlab.lib.units import inch
from reportlab.lib import colors
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, Image,
    ListFlowable, ListItem, HRFlowable, PageBreak
)
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.enums import TA_CENTER, TA_LEFT

OUT = "/tmp/workspace/corticosteroid-notes/Corticosteroid_Pharmacology_Notes.pdf"
IMG = "/tmp/workspace/corticosteroid-notes/assets/mechanism.png"

styles = getSampleStyleSheet()

navy = colors.HexColor("#1a2b4c")
teal = colors.HexColor("#0f6d66")
lightband = colors.HexColor("#eef3f8")

title_style = ParagraphStyle("TitleX", parent=styles["Title"], textColor=navy,
                              fontSize=22, spaceAfter=4, alignment=TA_LEFT)
subtitle_style = ParagraphStyle("SubtitleX", parent=styles["Normal"], textColor=teal,
                                 fontSize=11, spaceAfter=14, alignment=TA_LEFT)
h1 = ParagraphStyle("H1", parent=styles["Heading1"], textColor=navy, fontSize=14.5,
                     spaceBefore=14, spaceAfter=6, borderPadding=0)
h2 = ParagraphStyle("H2", parent=styles["Heading2"], textColor=teal, fontSize=11.5,
                     spaceBefore=8, spaceAfter=4)
body = ParagraphStyle("BodyX", parent=styles["Normal"], fontSize=9.7, leading=13.5,
                       spaceAfter=4)
bullet = ParagraphStyle("BulletX", parent=body, leftIndent=14, bulletIndent=4, spaceAfter=3)
note_style = ParagraphStyle("NoteX", parent=body, fontSize=9.3, leading=12.5,
                             textColor=colors.HexColor("#333333"), backColor=lightband,
                             borderPadding=8, spaceAfter=8, spaceBefore=4)
caption_style = ParagraphStyle("Caption", parent=styles["Normal"], fontSize=8.3,
                                textColor=colors.grey, alignment=TA_CENTER, spaceAfter=10)
cite_style = ParagraphStyle("Cite", parent=styles["Normal"], fontSize=7.8,
                             textColor=colors.grey, spaceBefore=16)

def P(text, style=body):
    return Paragraph(text, style)

def bullets(items, style=bullet):
    return ListFlowable(
        [ListItem(P(it, style), leftIndent=14) for it in items],
        bulletType="bullet", start="•", leftIndent=10, spaceBefore=2, spaceAfter=6
    )

story = []

# ---------- Header ----------
story.append(P("Corticosteroid Pharmacology", title_style))
story.append(P("Handwritten-style study notes — classification, mechanism, potency, uses, adverse effects", subtitle_style))
story.append(HRFlowable(width="100%", thickness=1.2, color=navy, spaceAfter=10))

# ---------- 1. Classification ----------
story.append(P("1. Classification", h1))
story.append(P("Corticosteroids are adrenal cortex steroid hormones, divided by receptor and dominant action:", body))

t1_data = [
    ["Class", "Main receptor", "Examples", "Main use"],
    ["Glucocorticoids", "GR", "Cortisol, prednisone, prednisolone,\nmethylprednisolone, dexamethasone, hydrocortisone", "Anti-inflammatory /\nimmunosuppressive"],
    ["Mineralocorticoids", "MR", "Aldosterone, fludrocortisone", "Na\u207a / water retention,\nK\u207a excretion"],
]
t1 = Table(t1_data, colWidths=[1.3*inch, 0.9*inch, 2.6*inch, 1.6*inch])
t1.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,0), navy),
    ("TEXTCOLOR", (0,0), (-1,0), colors.white),
    ("FONTSIZE", (0,0), (-1,-1), 8.6),
    ("FONTNAME", (0,0), (-1,0), "Helvetica-Bold"),
    ("GRID", (0,0), (-1,-1), 0.5, colors.grey),
    ("ROWBACKGROUNDS", (0,1), (-1,-1), [colors.white, lightband]),
    ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
    ("TOPPADDING", (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
]))
story.append(t1)
story.append(Spacer(1, 8))
story.append(bullets([
    "Cortisol = principal endogenous glucocorticoid; secretion is <b>diurnal</b> (peak early morning, small secondary peak late afternoon), driven by stress and negative feedback on ACTH/CRH.",
    "GR is widely distributed; MR is largely confined to kidney, colon, salivary/sweat glands (both also present in brain).",
]))

# ---------- 2. Mechanism of Action ----------
story.append(P("2. Mechanism of Action (MOA)", h1))

story.append(P("Genomic pathway (classic, slow &mdash; hours to days)", h2))
story.append(bullets([
    "Lipophilic steroid diffuses across cell membrane &rarr; binds cytoplasmic <b>glucocorticoid receptor (GR)</b> &rarr; complex dimerizes &rarr; recruits coactivators/corepressors &rarr; translocates to nucleus &rarr; binds <b>glucocorticoid response elements (GREs)</b> on DNA.",
    "<b>Transactivation</b> &rarr; switches ON anti-inflammatory genes (e.g. lipocortin-1/annexin A1, I\u03baB).",
    "<b>Transrepression</b> &rarr; switches OFF pro-inflammatory genes (cytokines, COX-2, adhesion molecules) &mdash; thought to be the primary anti-inflammatory route.",
    "Key effect: induces <b>lipocortin</b>, which inhibits <b>phospholipase A2</b> &rarr; blocks arachidonic acid release &rarr; \u2193 prostaglandins and leukotrienes.",
]))

story.append(P("Non-genomic pathway (rapid, high-dose)", h2))
story.append(bullets([
    "Membrane-bound GR and direct membrane insertion of steroid produce faster effects &mdash; relevant to pulse/IV steroid therapy.",
]))

story.append(P("Cellular / immune effects", h2))
story.append(bullets([
    "\u2193 T-cell function and circulating lymphocyte number (redistribution to lymphoid tissue, not destruction).",
    "\u2193 eosinophils, basophils, monocytes; \u2191 neutrophils (demargination); \u2191 Hgb / platelets.",
    "\u2193 Fc receptor expression, \u2193 cytokine production, stabilizes mast cell / basophil membranes (\u2193 histamine release).",
]))

# Mechanism image
try:
    img = Image(IMG, width=4.6*inch, height=4.6*inch*0.62)
    img.hAlign = "CENTER"
    story.append(Spacer(1, 4))
    story.append(img)
    story.append(P("Fig. Mechanisms of the cellular actions of glucocorticoids.", caption_style))
except Exception:
    pass

story.append(PageBreak())

# ---------- 3. Potency table ----------
story.append(P("3. Relative Potency &amp; Duration of Action", h1))
story.append(P("All potencies relative to hydrocortisone = 1", body))

t2_data = [
    ["Drug", "Anti-inflammatory potency", "Duration"],
    ["Cortisone", "0.8", "Short"],
    ["Hydrocortisone", "1", "Short"],
    ["Prednisone", "4", "Intermediate"],
    ["Prednisolone", "4", "Intermediate"],
    ["Methylprednisolone", "5", "Intermediate"],
    ["Triamcinolone", "~5", "Intermediate"],
    ["Dexamethasone", "25", "Long"],
    ["Betamethasone", "~25", "Long"],
]
t2 = Table(t2_data, colWidths=[2.1*inch, 2.5*inch, 1.8*inch])
t2.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,0), teal),
    ("TEXTCOLOR", (0,0), (-1,0), colors.white),
    ("FONTNAME", (0,0), (-1,0), "Helvetica-Bold"),
    ("FONTSIZE", (0,0), (-1,-1), 9),
    ("GRID", (0,0), (-1,-1), 0.5, colors.grey),
    ("ROWBACKGROUNDS", (0,1), (-1,-1), [colors.white, lightband]),
    ("TOPPADDING", (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
]))
story.append(t2)
story.append(Spacer(1, 6))
story.append(bullets([
    "Prednisone (PO) and methylprednisolone (IV) preferred clinically for cost / half-life balance.",
    "Mineralocorticoid activity is highest with hydrocortisone / fludrocortisone, minimal with dexamethasone &mdash; important when choosing an agent for adrenal insufficiency vs. pure anti-inflammatory use.",
]))

# ---------- 4. Therapeutic uses ----------
story.append(P("4. Therapeutic Uses", h1))
story.append(bullets([
    "<b>Replacement therapy</b> &mdash; Addison disease (hydrocortisone, mimicking diurnal rhythm: 2/3 dose AM, 1/3 PM) &plusmn; fludrocortisone for mineralocorticoid deficiency.",
    "<b>Anti-inflammatory / immunosuppressive</b> &mdash; asthma, allergic rhinitis, RA, IBD, autoimmune disease, transplant rejection, vasculitis.",
    "<b>Allergic emergencies</b> &mdash; anaphylaxis, drug / serum / transfusion reactions.",
    "<b>Malignancy</b> &mdash; component of chemo regimens (lymphoma, leukemia).",
    "<b>Route-specific use minimizes systemic exposure</b>: inhaled (e.g. fluticasone) for asthma/rhinitis, topical for dermatoses, intra-articular for joint flares.",
]))

# ---------- 5. Adverse effects ----------
story.append(P("5. Adverse Effects", h1))
story.append(P("Dose- and duration-dependent; significant risk generally above ~10 mg/day prednisone-equivalent.", body))

t3_data = [
    ["System", "Effects"],
    ["Endocrine / metabolic", "Hyperglycemia, weight gain, iatrogenic Cushing syndrome, dyslipidemia"],
    ["Bone", "Osteoporosis; avascular necrosis (femoral/humeral head, tibial plateau)"],
    ["Cardiovascular", "Hypertension, fluid retention"],
    ["Ophthalmic", "Cataracts, glaucoma"],
    ["Immune", "\u2191 infection risk (TB reactivation, fungal, PCP); fever may be masked"],
    ["Dermatologic", "Acne, purpura, skin atrophy, striae"],
    ["Psychiatric", "Euphoria, insomnia, mood lability, depression, psychosis"],
    ["Musculoskeletal", "Steroid myopathy (proximal, painless, normal CK/EMG)"],
    ["GI", "Dyspepsia (take with food)"],
]
t3 = Table(t3_data, colWidths=[1.6*inch, 4.8*inch])
t3.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,0), navy),
    ("TEXTCOLOR", (0,0), (-1,0), colors.white),
    ("FONTNAME", (0,0), (-1,0), "Helvetica-Bold"),
    ("FONTSIZE", (0,0), (-1,-1), 8.8),
    ("GRID", (0,0), (-1,-1), 0.5, colors.grey),
    ("ROWBACKGROUNDS", (0,1), (-1,-1), [colors.white, lightband]),
    ("VALIGN", (0,0), (-1,-1), "TOP"),
    ("TOPPADDING", (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
]))
story.append(t3)
story.append(Spacer(1, 6))
story.append(P("Bone protection: give calcium + vitamin D \u00b1 bisphosphonate prophylaxis. Consider PJP prophylaxis if \u226520 mg prednisone-equivalent for &gt;1 month.", body))

story.append(PageBreak())

# ---------- 6. HPA axis suppression ----------
story.append(P("6. HPA Axis Suppression &amp; Withdrawal", h1))
story.append(bullets([
    "Exogenous glucocorticoids suppress CRH/ACTH via negative feedback &rarr; adrenal cortisol production falls.",
    "<b>Suppression risk</b> rises with dose &gt;7.5&ndash;10 mg/day prednisone-equivalent and duration &gt;2&ndash;3 weeks.",
    "Abrupt discontinuation after prolonged use &rarr; <b>adrenal crisis</b> (hypotension, hypoglycemia, nausea, weakness &mdash; can be fatal). Must <b>taper</b> gradually.",
    "Under physiologic stress (surgery, infection) in a patient with HPA suppression, give <b>stress-dose steroids</b>.",
]))

# ---------- 7. Quick memory points ----------
story.append(P("7. Quick Memory Points", h1))
story.append(note_style if False else None)  # placeholder no-op
mem_items = [
    "&ldquo;Steroids don&rsquo;t cure, they control&rdquo; &mdash; suppress inflammation, don&rsquo;t fix underlying disease.",
    "<b>MOA in one line</b>: lipophilic &rarr; cytoplasmic GR &rarr; nuclear translocation &rarr; GRE binding &rarr; transactivation (anti-inflammatory genes \u2191) / transrepression (cytokine genes \u2193).",
    "<b>Potency order (low&rarr;high)</b>: cortisone &lt; hydrocortisone &lt; prednisone &asymp; prednisolone &lt; methylprednisolone &asymp; triamcinolone &lt; dexamethasone &asymp; betamethasone.",
    "<b>Never stop abruptly</b> if on &gt;3 weeks / &gt;20 mg prednisone-equivalent &rarr; taper to avoid adrenal crisis.",
]
story.append(bullets(mem_items))

story.append(Spacer(1, 6))
story.append(P(
    "<b>Recent evidence note:</b> A 2024 systematic review / meta-analysis (PMID: 38038629, <i>J Clin Endocrinol Metab</i>) "
    "quantified neuropsychiatric adverse effects of synthetic glucocorticoids, reinforcing that mood/psychiatric effects are "
    "frequent and clinically significant even at moderate doses.",
    note_style
))

story.append(HRFlowable(width="100%", thickness=0.7, color=colors.grey, spaceBefore=14, spaceAfter=6))
story.append(P(
    "Sources: Lippincott Illustrated Reviews &ndash; Pharmacology (Ch. 26); The Washington Manual of Medical Therapeutics; "
    "Rheumatology, 2-Volume Set (Elsevier); Goodman &amp; Gilman&rsquo;s The Pharmacological Basis of Therapeutics; "
    "Katzung&rsquo;s Basic and Clinical Pharmacology. PubMed PMID 38038629.",
    cite_style
))

doc = SimpleDocTemplate(
    OUT, pagesize=letter,
    leftMargin=0.7*inch, rightMargin=0.7*inch, topMargin=0.6*inch, bottomMargin=0.6*inch,
    title="Corticosteroid Pharmacology Notes"
)
doc.build(story)
print("PDF built at", OUT)