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phenytoin AND antiepileptic

insulin AND pharmacology

phenytoin FDA label adverse effects insulin preparations FDA prescribing information

antiarrhythmic AND amiodarone

antithyroid AND treatment

histamine AND receptor

cholinesterase AND pharmacology

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mkdir -p "/tmp/workspace/pharmacology-10-mark/src" "/tmp/workspace/pharmacology-10-mark/output" && python3 - <<'PY' from docx import Document from docx.shared import Pt, Inches, RGBColor from docx.enum.text import WD_ALIGN_PARAGRAPH from docx.enum.section import WD_SECTION from docx.oxml import OxmlElement from docx.oxml.ns import qn out='/tmp/workspace/pharmacology-10-mark/output/Pharmacology_Six_10-Mark_Answers.docx' doc=Document() sec=doc.sections[0] sec.page_width=Inches(8.27); sec.page_height=Inches(11.69) sec.top_margin=Inches(.7); sec.bottom_margin=Inches(.7); sec.left_margin=Inches(.75); sec.right_margin=Inches(.75) styles=doc.styles styles['Normal'].font.name='Arial'; styles['Normal']._element.rPr.rFonts.set(qn('w:eastAsia'),'Arial'); styles['Normal'].font.size=Pt(10.5) for name,size,color in [('Title',18,RGBColor(31,78,121)),('Heading 1',15,RGBColor(31,78,121)),('Heading 2',12,RGBColor(47,84,150)),('Heading 3',10.5,RGBColor(0,0,0))]: s=styles[name]; s.font.name='Arial'; s._element.rPr.rFonts.set(qn('w:eastAsia'),'Arial'); s.font.size=Pt(size); s.font.bold=True; s.font.color.rgb=color styles['Heading 1'].paragraph_format.space_before=Pt(14); styles['Heading 1'].paragraph_format.space_after=Pt(6) styles['Heading 2'].paragraph_format.space_before=Pt(8); styles['Heading 2'].paragraph_format.space_after=Pt(3) def shade(cell, fill): tcPr=cell._tc.get_or_add_tcPr(); shd=OxmlElement('w:shd'); shd.set(qn('w:fill'),fill); tcPr.append(shd) def add_table(headers, rows, widths=None): t=doc.add_table(rows=1, cols=len(headers)); t.style='Table Grid' for i,h in enumerate(headers): c=t.rows[0].cells[i]; c.text=h; shade(c,'D9EAF7') for r in c.paragraphs[0].runs: r.font.bold=True for row in rows: cells=t.add_row().cells for i,x in enumerate(row): cells[i].text=x doc.add_paragraph() return t def bullets(items, level=0): style='List Bullet' if level==0 else f'List Bullet {level+1}' for x in items: doc.add_paragraph(x,style=style) def num(items): for x in items: doc.add_paragraph(x,style='List Number') def p(text='', boldlead=None): par=doc.add_paragraph() if boldlead: r=par.add_run(boldlead); r.bold=True par.add_run(text) return par def pagebreak(): doc.add_page_break() # title par=doc.add_paragraph(); par.alignment=WD_ALIGN_PARAGRAPH.CENTER r=par.add_run('PHARMACOLOGY - SIX 10-MARK ANSWERS'); r.bold=True; r.font.size=Pt(18); r.font.color.rgb=RGBColor(31,78,121) par=doc.add_paragraph(); par.alignment=WD_ALIGN_PARAGRAPH.CENTER par.add_run('Exam-format long answers | Classification, mechanism, actions, adverse effects and uses').italic=True p('Use these as structured university answers. Adapt the amount of detail to the time available and local formulary or teaching preferences.') doc.add_heading('Contents',1) num(['Drugs used in seizures and phenytoin','Cholinergic agonists and anticholinesterases','Histamine: synthesis, storage, release, receptors, agonists and antagonists','Antiarrhythmic drugs and Class III antiarrhythmics','Thyroid hormone synthesis and thyroid inhibitors','Insulin: synthesis, storage, release, action and preparations']) pagebreak() # Q1 doc.add_heading('1. Drugs Used in Seizures and Phenytoin',0) doc.add_heading('A. Classification of antiseizure drugs',1) add_table(['Predominant mechanism / seizure use','Drugs'],[ ['Na+ channel inactivation','Phenytoin, fosphenytoin, carbamazepine, oxcarbazepine, lamotrigine, lacosamide, topiramate, zonisamide, rufinamide'], ['T-type Ca2+ channel blockade','Ethosuximide, valproate'], ['GABA enhancement','Benzodiazepines, phenobarbital, primidone, valproate, tiagabine, vigabatrin, gabapentin, pregabalin'], ['SV2A ligands','Levetiracetam, brivaracetam'], ['Glutamate receptor inhibition / mixed actions','Perampanel, felbamate, topiramate'], ['Carbonic anhydrase inhibition / mixed actions','Acetazolamide, topiramate, zonisamide'], ['Broad-spectrum drugs','Valproate, lamotrigine, levetiracetam, topiramate, benzodiazepines']]) p('An alternative clinical classification is: focal seizures - carbamazepine, lamotrigine, levetiracetam, phenytoin; generalized tonic-clonic seizures - valproate, lamotrigine, levetiracetam, phenytoin; absence seizures - ethosuximide, valproate, lamotrigine; myoclonic seizures - valproate, levetiracetam, clonazepam.') doc.add_heading('B. Phenytoin',1) doc.add_heading('Mechanism of action',2) bullets(['Phenytoin produces use-dependent blockade of voltage-gated Na+ channels. It binds preferentially to the inactivated channel state and prolongs recovery from inactivation.','This suppresses high-frequency repetitive neuronal firing and limits spread of seizure discharge, while relatively preserving normal low-frequency activity.','At high concentrations, it may also reduce Ca2+ influx and alter release of excitatory neurotransmitters.']) doc.add_heading('Pharmacological actions',2) bullets(['CNS: raises the seizure threshold and prevents maximal electroshock seizures. It is effective in focal seizures and generalized tonic-clonic seizures, but not absence seizures.','Cardiac tissue: decreases automaticity and can suppress digitalis-induced ventricular arrhythmias. IV administration may depress cardiac conduction and contractility.','Other actions: induces hepatic microsomal enzymes; long-term treatment may increase vitamin D metabolism and contribute to osteomalacia. It can inhibit insulin release and cause hyperglycaemia.']) doc.add_heading('Adverse effects',2) add_table(['Type','Adverse effects'],[ ['Dose-related CNS toxicity','Nystagmus, diplopia, ataxia, dysarthria, tremor, sedation, confusion and encephalopathy.'], ['Gingival / cosmetic','Gingival hyperplasia, hirsutism, acne and coarse facial features.'], ['Idiosyncratic / hypersensitivity','Rash, Stevens-Johnson syndrome/toxic epidermal necrolysis, DRESS syndrome, fever, lymphadenopathy and hepatitis. Risk is higher with certain HLA alleles in susceptible populations.'], ['Haematological','Megaloblastic anaemia due to folate deficiency; rarely aplastic anaemia, agranulocytosis or thrombocytopenia.'], ['Skeletal / endocrine','Osteomalacia, reduced bone density, hyperglycaemia.'], ['Pregnancy','Teratogenicity: fetal hydantoin syndrome.'], ['IV use','Hypotension, bradyarrhythmias and local tissue injury including purple-glove syndrome. Give slowly with ECG and BP monitoring.']]) doc.add_heading('Therapeutic uses',2) bullets(['Focal-onset seizures, with or without bilateral tonic-clonic spread.','Generalized tonic-clonic seizures.','Status epilepticus: IV fosphenytoin or phenytoin is used after a benzodiazepine to prevent recurrence.','Prevention of early post-traumatic seizures in selected patients.','Occasionally, digitalis-induced ventricular arrhythmias.']) p('Important point: Phenytoin has nonlinear, capacity-limited metabolism, extensive protein binding, many CYP-mediated interactions, and a narrow therapeutic range. Therapeutic drug monitoring is often required.') pagebreak() # Q2 doc.add_heading('2. Cholinergic Agonists and Anticholinesterases',0) doc.add_heading('A. Classification of cholinergic agonists',1) add_table(['Class','Examples'],[ ['Direct-acting choline esters','Acetylcholine, methacholine, carbachol, bethanechol'], ['Direct-acting alkaloids and congeners','Pilocarpine, muscarine, cevimeline, nicotine, varenicline'], ['Indirect-acting: reversible acetylcholinesterase inhibitors','Edrophonium, physostigmine, neostigmine, pyridostigmine, donepezil, rivastigmine, galantamine'], ['Indirect-acting: irreversible organophosphates','Echothiophate; insecticides such as malathion and parathion; nerve agents such as sarin']]) p('Direct agonists stimulate muscarinic and/or nicotinic receptors. Indirect agonists inhibit acetylcholinesterase (AChE), thereby increasing acetylcholine at muscarinic, nicotinic and, if they enter the CNS, central synapses.') doc.add_heading('B. Pharmacology of anticholinesterases (cholinesterase inhibitors)',1) doc.add_heading('Mechanism of action',2) bullets(['AChE normally rapidly hydrolyses acetylcholine in the synaptic cleft. Inhibition causes accumulation of acetylcholine and prolongs its action.','Reversible inhibitors: edrophonium binds noncovalently and briefly; carbamates such as neostigmine, pyridostigmine, physostigmine and rivastigmine carbamylate AChE, with slower hydrolysis.','Irreversible organophosphates phosphorylate AChE. With time, “aging” strengthens the bond; after aging, enzyme activity returns only after new enzyme synthesis.','Tertiary agents, such as physostigmine and donepezil, cross the blood-brain barrier. Quaternary agents, such as neostigmine and pyridostigmine, act mainly peripherally.']) doc.add_heading('Pharmacological actions',2) add_table(['Site','Effects of increased acetylcholine'],[ ['Eye','Miosis, ciliary muscle contraction, increased trabecular outflow, and reduced intraocular pressure.'], ['Heart and vessels','Bradycardia, reduced AV nodal conduction, reduced cardiac output; vasodilatation may occur through endothelial M3-mediated nitric oxide release.'], ['Respiratory tract','Bronchoconstriction and increased bronchial secretions.'], ['Gastrointestinal tract','Increased tone, peristalsis and secretions; abdominal cramps and diarrhoea.'], ['Genitourinary tract','Detrusor contraction and relaxation of trigone/sphincter, facilitating micturition.'], ['Exocrine glands','Salivation, lacrimation, sweating and increased gastric secretion.'], ['Neuromuscular junction','Improved transmission at therapeutic concentrations. Excess causes fasciculations followed by depolarizing block and paralysis.'], ['CNS, with lipid-soluble drugs','Arousal or cognitive benefit at low dose; agitation, seizures and coma in toxicity.']]) doc.add_heading('Adverse effects and toxicity',2) bullets(['Muscarinic excess: salivation, lacrimation, urination, diarrhoea, GI cramps, emesis, miosis, bronchospasm, bronchorrhoea, bradycardia and hypotension.','Nicotinic excess: fasciculations, muscle weakness, paralysis, hypertension or tachycardia initially.','CNS effects with lipid-soluble agents: anxiety, confusion, ataxia and seizures.','Contraindications / caution: asthma or COPD, peptic ulcer disease, bradycardia or conduction block, hypotension, coronary disease, and mechanical intestinal or urinary obstruction.']) doc.add_heading('Therapeutic uses',2) bullets(['Myasthenia gravis: pyridostigmine is preferred for long-term symptomatic treatment; neostigmine is an alternative.','Reversal of nondepolarizing neuromuscular blockade after surgery: neostigmine, with an antimuscarinic such as glycopyrrolate or atropine.','Postoperative ileus and nonobstructive urinary retention: neostigmine, after excluding mechanical obstruction.','Alzheimer disease: donepezil, rivastigmine and galantamine provide modest symptomatic cognitive benefit.','Antimuscarinic toxicity: physostigmine may be used in carefully selected severe cases with monitoring.','Glaucoma: topical physostigmine or echothiophate is rarely used now.']) doc.add_heading('Organophosphate poisoning - brief note',2) p('Treat with decontamination and airway support, atropine in repeated doses to dry bronchial secretions and correct bradycardia, and pralidoxime early to reactivate AChE before aging. Diazepam is used for seizures. Do not rely on oxime therapy alone.') pagebreak() # Q3 doc.add_heading('3. Histamine: Synthesis, Storage, Release, Receptors, Agonists and Antagonists',0) doc.add_heading('Introduction',1) p('Histamine is an autacoid and neurotransmitter. It is important in immediate hypersensitivity, gastric acid secretion, regulation of vascular tone and permeability, and central nervous system arousal.') doc.add_heading('Synthesis',1) p('L-Histidine is decarboxylated by histidine decarboxylase, a pyridoxal phosphate-dependent enzyme, to form histamine. This occurs in mast cells, basophils, enterochromaffin-like cells of the stomach, histaminergic neurons and other tissues.') doc.add_heading('Storage',1) bullets(['Histamine is stored mainly in cytoplasmic granules of mast cells and basophils, complexed with heparin, acidic proteins and ATP.','In CNS neurons, it is packaged into synaptic vesicles by vesicular monoamine transporter (VMAT).','Enterochromaffin-like cells store histamine for paracrine stimulation of gastric parietal cells.']) doc.add_heading('Release',1) add_table(['Type of release','Stimuli / mechanism'],[ ['Immunological','Allergen cross-linking of IgE bound to FcεRI receptors on mast cells and basophils causes Ca2+-dependent exocytosis.'], ['Complement-mediated','Anaphylatoxins C3a and C5a activate mast cells.'], ['Physical / chemical','Trauma, cold, heat, venom and some drugs.'], ['Non-immunological drug release','Opioids, vancomycin, radiocontrast media and some neuromuscular blocking drugs can produce direct mast-cell activation or histamine release.'], ['Neuronal','Action potential-dependent vesicular release from histaminergic neurons.']]) doc.add_heading('Histamine receptors and actions',1) add_table(['Receptor','Signal transduction / distribution','Major effects'],[ ['H1','Gq - phospholipase C - IP3/DAG; endothelium, smooth muscle, sensory nerves, CNS','Endothelial NO-mediated vasodilatation; increased vascular permeability; bronchial and GI smooth-muscle contraction; itch and pain; wakefulness.'], ['H2','Gs - increased cAMP; gastric parietal cells, heart, mast cells','Marked gastric acid secretion; cardiac stimulation; vasodilatation; modulation of mediator release.'], ['H3','Gi - reduced cAMP; mainly presynaptic CNS receptors','Autoreceptor and heteroreceptor: reduces synthesis and release of histamine and other neurotransmitters.'], ['H4','Gi - reduced cAMP; immune and haematopoietic cells','Chemotaxis and immune-cell regulation, especially mast cells, eosinophils and T cells.']]) doc.add_heading('Agonists',1) bullets(['Histamine itself: limited clinical use because of nonselective actions.','Betahistine: weak H1 agonist and H3 antagonist/inverse agonist; used in some settings for Ménière disease or vertigo.','Betazole and histamine phosphate: historically used in tests of gastric acid secretory capacity; little current use.']) doc.add_heading('Antagonists',1) add_table(['Class','Examples','Main uses'],[ ['H1 antihistamines','First generation: chlorpheniramine, diphenhydramine, promethazine, hydroxyzine. Second generation: cetirizine, levocetirizine, loratadine, fexofenadine.','Allergic rhinitis, urticaria and pruritus. First generation drugs are also useful for motion sickness and short-term antiemesis, but cause sedation and antimuscarinic effects.'], ['H2 receptor antagonists','Famotidine, cimetidine, nizatidine.','Acid-peptic disorders and reflux disease, though proton-pump inhibitors are generally more effective. Cimetidine has important CYP inhibition and antiandrogenic effects.'], ['H3 antagonists / inverse agonists','Pitolisant','Narcolepsy with or without cataplexy.'], ['H4 antagonists','No routine established clinical use','Under investigation for inflammatory disorders.']]) p('Note: H1 “antihistamines” are generally inverse agonists rather than simple competitive antagonists. In anaphylaxis, intramuscular adrenaline is first-line therapy; H1 blockers are only adjuncts.') pagebreak() # Q4 doc.add_heading('4. Antiarrhythmic Drugs and Class III Antiarrhythmics',0) doc.add_heading('Classification: Vaughan Williams system',1) add_table(['Class','Mechanism','Examples'],[ ['Class I: Na+ channel blockers','Reduce fast Na+ current in working myocardium','IA: quinidine, procainamide, disopyramide. IB: lidocaine, mexiletine. IC: flecainide, propafenone.'], ['Class II: beta blockers','Reduce sympathetic effects, nodal automaticity and AV conduction','Metoprolol, esmolol, propranolol, atenolol.'], ['Class III: K+ channel blockers','Prolong repolarization, action-potential duration and effective refractory period','Amiodarone, dronedarone, sotalol, dofetilide, ibutilide.'], ['Class IV: non-dihydropyridine Ca2+ channel blockers','Reduce SA nodal automaticity and AV nodal conduction','Verapamil, diltiazem.'], ['Others','Miscellaneous mechanisms','Adenosine, digoxin, magnesium sulfate, atropine.']]) doc.add_heading('Class III antiarrhythmic drugs',1) doc.add_heading('Mechanism of action',2) bullets(['Class III drugs predominantly block outward K+ currents during phase 3 repolarization of the cardiac action potential.','They prolong action-potential duration and effective refractory period in atrial and ventricular tissue, thereby interrupting re-entry circuits.','They increase the QT interval. Excessive QT prolongation can trigger torsades de pointes.','Amiodarone has actions of all four Vaughan Williams classes: K+ channel blockade predominates, with Na+ channel block, Ca2+ channel block and noncompetitive beta-blocking effects. Sotalol combines K+ channel blockade with beta blockade.']) doc.add_heading('Pharmacological actions',2) bullets(['Prolong atrial and ventricular repolarization, action-potential duration and refractoriness.','Reduce re-entry and may suppress ectopic automaticity.','Amiodarone slows sinus rate and AV nodal conduction, and prolongs PR, QRS and QT intervals. It has relatively low torsades risk compared with many other Class III agents.','Sotalol slows heart rate and AV nodal conduction through beta blockade and prolongs QT through K+ channel blockade.']) doc.add_heading('Adverse effects',2) add_table(['Drug / class effect','Adverse effects'],[ ['Class III effect','QT prolongation and torsades de pointes, particularly with sotalol, dofetilide and ibutilide. Risk rises with bradycardia, hypokalaemia, hypomagnesaemia, renal impairment and other QT-prolonging drugs.'], ['Amiodarone','Bradycardia, AV block, corneal microdeposits, photosensitivity and blue-grey skin discoloration, thyroid dysfunction (hypo- or hyperthyroidism), hepatotoxicity, pulmonary pneumonitis/fibrosis, neuropathy and tremor. It has a very long half-life and many drug interactions.'], ['Sotalol','Bradycardia, fatigue, bronchospasm in susceptible patients, heart-failure worsening and torsades de pointes.'], ['Dronedarone','Bradycardia, GI effects, liver injury and possible worsening of heart failure; avoid in permanent AF and symptomatic/decompensated heart failure.']]) doc.add_heading('Therapeutic uses',2) bullets(['Amiodarone: acute and chronic management of supraventricular tachyarrhythmias, rhythm control in atrial fibrillation or flutter, and treatment or suppression of ventricular tachycardia and ventricular fibrillation.','Sotalol: maintenance of sinus rhythm in selected atrial fibrillation/flutter and treatment of some ventricular arrhythmias.','Dofetilide: conversion and maintenance of sinus rhythm in atrial fibrillation/flutter. Initiation requires monitored setting because of QT-related proarrhythmia.','Ibutilide: pharmacological cardioversion of recent atrial fibrillation or atrial flutter.']) p('Exam conclusion: Class III drugs are valuable for re-entry arrhythmias, but ECG, renal function, electrolytes and interacting drugs must be assessed to minimize proarrhythmia.') pagebreak() # Q5 doc.add_heading('5. Thyroid Hormone Synthesis and Thyroid Inhibitors',0) doc.add_heading('A. Steps in thyroid hormone synthesis',1) num(['Synthesis of thyroglobulin: thyroid follicular cells synthesize thyroglobulin and secrete it into the colloid.', 'Iodide trapping: iodide enters follicular cells across the basolateral membrane through the Na+/I- symporter (NIS), driven by the Na+/K+-ATPase.', 'Transport into colloid: iodide exits apically through pendrin and related transport systems.', 'Oxidation: thyroid peroxidase (TPO), using H2O2, oxidizes iodide (I-) to reactive iodine.', 'Organification: TPO iodinates tyrosyl residues in thyroglobulin to form monoiodotyrosine (MIT) and diiodotyrosine (DIT).', 'Coupling: two DIT residues couple to form T4 (thyroxine); one MIT plus one DIT form T3 (triiodothyronine). The products remain stored in colloid within thyroglobulin.', 'Release: TSH stimulates endocytosis of iodinated thyroglobulin. Lysosomal proteolysis releases T4 and T3 into blood. MIT and DIT are deiodinated intracellularly and iodine is recycled.', 'Peripheral activation: much circulating T4 is converted to the more active T3 by 5-deiodinases in peripheral tissues.']) doc.add_heading('B. Classification of thyroid inhibitors',1) add_table(['Group','Drugs / examples','Principal action'],[ ['Thioamides','Methimazole, carbimazole, propylthiouracil (PTU)','Inhibit TPO-mediated oxidation, organification and coupling. PTU additionally inhibits peripheral T4 to T3 conversion.'], ['Iodides in high concentration','Lugol iodine, potassium iodide','Rapidly inhibit hormone release and organification; reduce gland vascularity temporarily.'], ['Radioactive iodine','Iodine-131','Taken up by thyroid and destroys follicular cells by beta emission.'], ['Anion inhibitors','Perchlorate, thiocyanate, pertechnetate','Inhibit iodide uptake through NIS. Rarely used because of toxicity.'], ['Inhibitors of T4 to T3 conversion / adjuncts','PTU, propranolol, glucocorticoids, iodinated contrast agents','Reduce peripheral formation of T3 and control adrenergic manifestations.'], ['Lithium','Lithium carbonate','Inhibits thyroid hormone release; occasional alternative when iodides cannot be used.']]) doc.add_heading('Therapeutic uses',1) bullets(['Graves disease and toxic nodular hyperthyroidism: thioamides are used to restore euthyroidism, as definitive therapy in some patients, or as preparation before radioactive iodine or surgery.','Thyroid storm: PTU or methimazole to block synthesis, followed by iodide after the thioamide; plus beta blocker, glucocorticoid and supportive therapy. PTU is often selected because it also reduces peripheral T4 to T3 conversion.','Preoperative preparation for thyroidectomy: thioamide to achieve euthyroidism; short-course iodide reduces gland vascularity and hormone release.','Radioactive iodine: definitive therapy for Graves disease and toxic nodular goitre in appropriate nonpregnant patients. It is contraindicated in pregnancy and breastfeeding.','Thioamides in pregnancy: PTU is generally preferred during the first trimester; methimazole is generally preferred thereafter because PTU has greater risk of severe hepatotoxicity.']) doc.add_heading('Important adverse effects of thioamides',2) bullets(['Common: rash, pruritus, arthralgia and GI upset.','Serious: agranulocytosis, usually presenting with fever or sore throat. Stop the drug and obtain an urgent blood count.','PTU: severe hepatotoxicity and ANCA-associated vasculitis.','Methimazole/carbimazole: cholestatic jaundice; teratogenic risk with first-trimester exposure.']) pagebreak() # Q6 doc.add_heading('6. Insulin: Synthesis, Storage, Release, Action and Preparations',0) doc.add_heading('Synthesis and storage',1) num(['In pancreatic beta cells, preproinsulin is synthesized on rough endoplasmic reticulum.', 'Removal of the signal peptide forms proinsulin, which folds and forms disulfide bonds.', 'Proinsulin is transported to Golgi secretory granules, where prohormone convertases cleave it to insulin and C-peptide. Equimolar insulin and C-peptide are stored with zinc in secretory granules.', 'Endogenous insulin secretion releases insulin and C-peptide in equimolar amounts. Exogenous insulin preparations do not contain C-peptide.']) doc.add_heading('Release of insulin',1) p('Glucose is the principal stimulus. Glucose enters beta cells through GLUT transporters, is metabolized, and raises the ATP/ADP ratio. ATP-sensitive K+ channels close, causing membrane depolarization. Voltage-gated Ca2+ channels open, Ca2+ enters, and insulin granules undergo exocytosis.') bullets(['Stimulators: glucose, amino acids such as arginine and leucine, fatty acids, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), vagal acetylcholine and sulfonylureas.','Inhibitors: hypoglycaemia, somatostatin, alpha2-adrenergic stimulation and diazoxide.','Secretion is biphasic: rapid first-phase release of stored granules, followed by sustained second-phase release.']) doc.add_heading('Mechanism of action',1) bullets(['Insulin binds to the insulin receptor, a transmembrane receptor tyrosine kinase composed of alpha and beta subunits.','Receptor autophosphorylation activates insulin receptor substrates and downstream PI3K-Akt and MAP kinase pathways.','It increases GLUT4 translocation to skeletal muscle and adipose-cell membranes, increasing glucose uptake. Hepatic glucose transport is insulin-independent, but insulin profoundly changes hepatic metabolism.']) doc.add_heading('Pharmacological actions',1) add_table(['Metabolic pathway','Actions of insulin'],[ ['Carbohydrate','Increases glucose uptake in muscle and adipose tissue; increases glycogenesis and glycolysis; decreases hepatic glycogenolysis and gluconeogenesis, lowering blood glucose.'], ['Lipid','Increases lipogenesis and triglyceride storage; inhibits hormone-sensitive lipase, lipolysis and ketogenesis.'], ['Protein','Increases amino-acid uptake and protein synthesis; decreases proteolysis.'], ['Electrolytes','Drives potassium, phosphate and magnesium into cells. This is useful in hyperkalaemia but can cause hypokalaemia.'], ['Growth','Anabolic and mitogenic effects through intracellular signalling pathways.']]) doc.add_heading('Insulin preparations',1) add_table(['Preparation group','Examples','Onset / clinical role'],[ ['Rapid-acting analogues','Insulin lispro, aspart, glulisine','Given at meals or by pump. Fast onset and short duration reduce late post-meal hypoglycaemia.'], ['Short-acting','Regular human insulin','Meal-time insulin; may be given IV in diabetic ketoacidosis, hyperkalaemia and perioperative settings.'], ['Intermediate-acting','NPH (isophane) insulin','Basal coverage with a peak; often used twice daily.'], ['Long-acting basal analogues','Insulin glargine, detemir','Relatively flat basal effect; usually once daily, though detemir may require twice-daily administration.'], ['Ultra-long-acting basal analogue','Insulin degludec','Very prolonged, stable basal action.'], ['Premixed formulations','NPH/regular; biphasic lispro; biphasic aspart','Convenient fixed basal plus prandial mixture, usually before meals. Less flexible for dose adjustment.'], ['Inhaled insulin','Technosphere insulin','Rapid-acting prandial insulin in selected adults; avoid in chronic lung disease.']]) doc.add_heading('Therapeutic uses and adverse effects',1) bullets(['Uses: essential replacement in type 1 diabetes; type 2 diabetes when indicated; diabetic ketoacidosis and hyperosmolar states; hyperkalaemia with glucose; gestational diabetes when pharmacological treatment is needed.','Most important adverse effect: hypoglycaemia, with sweating, tremor, palpitations, confusion, seizures or coma. Treat promptly with oral carbohydrate if conscious or glucagon/IV glucose if severe.','Other adverse effects: weight gain, injection-site lipohypertrophy or lipoatrophy, allergy (rare with modern preparations), oedema and hypokalaemia.']) # sources doc.add_heading('Selected academic sources',1) p('Prepared using standard pharmacology text material from Katzung’s Basic and Clinical Pharmacology, 16th ed.; Goodman & Gilman’s The Pharmacological Basis of Therapeutics; and Lippincott Illustrated Reviews: Pharmacology. Recent systematic-review searches were checked for potential updates. These are exam notes and not patient-specific prescribing advice.') # footer for section in doc.sections: footer=section.footer.paragraphs[0]; footer.alignment=WD_ALIGN_PARAGRAPH.CENTER footer.add_run('Pharmacology 10-mark answers | Page ') fld=OxmlElement('w:fldSimple'); fld.set(qn('w:instr'),'PAGE'); footer._p.append(fld) doc.save(out) print(out) PY python /tmp/skills/docx/scripts/office/validate.py "/tmp/workspace/pharmacology-10-mark/output/Pharmacology_Six_10-Mark_Answers.docx"

python3 - <<'PY' from docx import Document p='/tmp/workspace/pharmacology-10-mark/output/Pharmacology_Six_10-Mark_Answers.docx' d=Document(p) print('paragraphs',len(d.paragraphs)) for x in d.paragraphs[:12]: print(x.style.name, repr(x.text[:100])) PY

python3 - <<'PY' from zipfile import ZipFile, ZIP_DEFLATED from lxml import etree from pathlib import Path p=Path('/tmp/workspace/pharmacology-10-mark/output/Pharmacology_Six_10-Mark_Answers.docx') tmp=p.with_suffix('.fixed.docx') ns={'w':'http://schemas.openxmlformats.org/wordprocessingml/2006/main'} with ZipFile(p,'r') as zin, ZipFile(tmp,'w',ZIP_DEFLATED) as zout: for item in zin.infolist(): data=zin.read(item.filename) if item.filename in ('word/document.xml','word/settings.xml'): root=etree.fromstring(data) if item.filename=='word/document.xml': for shd in root.xpath('.//w:shd',namespaces=ns): if '{%s}val'%ns['w'] not in shd.attrib: shd.set('{%s}val'%ns['w'],'clear') else: for zoom in root.xpath('.//w:zoom',namespaces=ns): if '{%s}percent'%ns['w'] not in zoom.attrib: zoom.set('{%s}percent'%ns['w'],'100') data=etree.tostring(root,xml_declaration=True,encoding='UTF-8',standalone=True) zout.writestr(item,data) tmp.replace(p) PY python /tmp/skills/docx/scripts/office/validate.py "/tmp/workspace/pharmacology-10-mark/output/Pharmacology_Six_10-Mark_Answers.docx" && python3 - <<'PY' from docx import Document p='/tmp/workspace/pharmacology-10-mark/output/Pharmacology_Six_10-Mark_Answers.docx' d=Document(p) text='\n'.join(x.text for x in d.paragraphs) checks=['Phenytoin','Cholinergic Agonists','Histamine','Antiarrhythmic','Thyroid Hormone','Insulin'] print('paragraphs:',len(d.paragraphs)) print('sections-present:', {x:(x in text) for x in checks}) print('file-bytes:',__import__('os').path.getsize(p)) PY